OBJECTIVE

To evaluate the effectiveness of combined peripheral blood T-SPOT.TB and cerebrospinal fluid interferon-γ (cIFN-γ) detection methods in the diagnosis of tuberculous meningitis (TBM).

METHODS

A total of 30 individuals with TBM and 39 control individuals without TBM participated in this study. IFN-γ-secreting T cells were detected by enzyme-linked immunospot (ELISPOT), and cIFN-γ was detected by enzyme-linked immunosorbent assay (ELISA). We collected cerebrospinal fluid from 10 patients in the TBM group on initial visit and at 4 weeks, to observe changes.

RESULTS

The sensitivity and specificity of peripheral-blood T-SPOT.TB testing in the diagnosis of TBM were 70% and 87%, respectively. The area under the ROC curve of cIFN-γ for TBM diagnosis was 0.819, and the corresponding sensitivity and specificity were 83% and 85%, respectively. When T-SPOT.TB and cIFN-γ results were positive, the specificity and positive predictive value of TBM diagnosis reached 100%.

CONCLUSIONS

Combined use of T-SPOT.TB and cIFN-γ could improve the diagnosis efficiency of TBM. Dynamic observation of cIFN-γ is also important in monitoring TBM because the level of this analyte significantly decreases after treatment.

A 53-yr-old woman with end-stage renal disease was admitted for renal transplantation (RTX). About a decade ago, she had presented with urinary abnormalities. Monoclonal IgA lambda was detected. Renal biopsy showed nodular glomerulosclerosis, and an immunohistochemical study for lambda was negative. Fibrillary glomerulonephritis was suggested as the most likely diagnosis. RTX was successfully performed, and graft function was stable for the first half year. Graft biopsy was performed at one yr post-transplant. Glomeruli showed nodular lesion similar to native kidney biopsy findings. Immunofluorescence microscopy (IF) indicated strong lambda staining along the glomerular basement membrane, the tubular basement membrane (TBM), and the peritubular capillary. The diagnosis of recurrent light chain deposition disease (LCDD) was confirmed. A series of biopsies are available to conduct studies on the recurrent process of LCDD. Light microscopy showed no remarkable changes up to six months post-RTX. However, the IF study revealed evident granular depositions of lambda along the TBM only at the one-h biopsy. Typical IF staining pattern of lambda and EDD compatible with LCDD were noted after six months post-transplant. This is the first case report that elucidated the details of the recurrent process of LCDD at one yr after the operation.

A monoclonal antibody (A8) to a basement membrane component (TIN antigen), which is associated with autoimmune tubulointerstitial nephritis, was developed and utilized to characterize tissue distribution and properties of TIN antigen by immunofluorescence microscopy and immunoblotting. Results were confirmed with polyclonal goat anti-rabbit and human autoantibodies. TIN antigen was found in basement membranes of kidney cortex, small intestines, skin, and cornea, but was not detected in the renal medulla. Within the kidney cortex proximal tubular basement membrane (TBM) showed the strongest staining. TIN antigen was also detected in Bowman's capsule, distal TBM, peritubular capillaries, and focally in the interstitium, but not in glomerular basement membrane or mesangial matrix. Immunoblotting of SDS-extracted human, rabbit, mouse, and Brown Norway rat TBM with A8 revealed predominantly a 58 kD TIN antigen; however, other reactive components were detected in minor quantities. Bovine TBM contained components of 52 kD, 45 kD and 35 kD in varying concentrations. Immunoblotting of isolated rabbit TIN antigen revealed the major 58 kD component that was characterized previously, and minor components of 300 kD, 175 kD, 160 kD and 50 kD. TIN antigen was not detected in Lewis rat TBM by immunofluorescence or immunoblotting. These studies suggest the following: 1) TIN antigen may be synthesized as a high molecular weight glycoprotein that is processed to smaller forms; 2) it may be covalently associated with other basement membrane components; 3) the antibody reactive epitope may be present on multiple TBM components; and 4) high molecular weight forms may represent aggregates of TIN antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.

Serum specimens from 99 selected renal patients were examined over a 3-year period by both a hemagglutination technique (HA) and an indirect immunofluorescent (IIF) method for the presence of circulating antibody against tubular basement membrane (TBM). 11 patients were found with anti-TBM antibodies. 6 of them also had antibody against glomerular basement membrane (GBM). The other 5 with anti-TBM antibody alone, had a unique natural history and response to therapy which suggested that the antibody was important in the pathogenesis of their disease. The variation seen in end organ damage may indicate that other factors, possibly genetic, are involved in the pathophysiology.

C3H, CBA (H-2k) and NZB (H-2d) mice were immunized with dog insoluble glomerular (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble antigenic fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. After immunization with insoluble GBM, animals from all three strains develop antibodies mainly directed against collagenous antigenic determinants shared by GBM and TBM. After immunization with insoluble TBM, the antibodies are directed in NZB mice against non-collagenous TBM-specific determinants, in C3H mice against collagenous determinants and in CBA mice against both types of antigenic determinants. Thus the ability to respond to the various antigens of GBM and TBM is genetically determined and does not depend only on the major histocompatibility complex.

IgA, IgM and IgG concentrations and their bacterial antibodies to E. coli, group B streptococci and Brucella abortus were measured in human breast milk collected from the 1st to 10th day post-partum from mothers delivered of 'preterm' infants (Premature Breast Milk or PBM) and from mothers delivered of term infants (Term Breast Milk or TBM). Reverse passive haemagglutination tests (RPH), rocket immuno-electrophoresis and mixed reverse passive antiglobulin haemagglutination tests (MRPAH) were employed. PBM at 2-5 days post-partum (though not beyond this period) contained higher IgA levels than did TBM, and this difference persisted even when total IgA was expressed as a proportion of total milk protein: in contrast the IgM and IgG contents of PBM and TBM were the same at both these postnatal ages. The titre of IgA antibody to E. coli, which was absorbable only by the corresponding bacteria, showed no significant difference between PBM and TBM, whereas the titres of IgA reacting with Br. abortus and, to a lesser extent group B streptococci, were higher in PBM than those in TBM. However the IgA which reacted with Br. abortus and group B streptococci was not specific to those organisms but was absorbed by all three bacteria studied. It is speculated that the high IgA content of early preterm milk and perhaps the presence of especially high titres of what appears to be a non-specific or cross-reacting bacterial IgA in such milk, may be immunologically advantageous to low birthweight infants fed on their own mother's milk.

A case of diffuse mesangial sclerosis (DMS) associated with Kawasaki disease is reported. A previously healthy Japanese girl, aged 4 months, presented with clinical features of Kawasaki disease. At week 10 of the illness, she developed the nephrotic syndrome, which was refractory to steroid therapy. Renal biopsy demonstrated a diffuse mesangial proliferative glomerulonephritis with microcystic tubular dilatation and, ultrastructurally, marked thinning of the lamina densa in the glomerular basement membrane (GBM) and the tubular basement membrane (TBM) of the proximal tubule. She went into chronic renal failure and died at the age of 11 months. At autopsy, the kidney revealed DMS. Histologically, we found Finnish microcystic disease in its early stages in the biopsy. Using a newly developed monoclonal antibody, we analysed the alpha chains (alpha 1-alpha 6) of type IV collagen in the GBM and TBM. There was no defective constitution of alpha chains on the thin GBM, but the thin TBM of the microcystic proximal tubule showed a weak or discontinuous reactivity for alpha 1 and alpha 2 chains, suggesting faulty formation of the basement membrane. The sclerosing glomeruli of the DMS did not depend on collapse of the GBM, which was positive for alpha 3-alpha 5 chains, but mainly on the proliferation of mesangial matrix, which was positive for alpha 1 and alpha 2 chains.

Disease in the brain is often associated with subtle, spatially diffuse, or complex tissue changes that may lie beneath the level of gross visual inspection, even on magnetic resonance imaging (MRI). Unfortunately, current computer-assisted approaches that examine pre-specified features, whether anatomically-defined (i.e. thalamic volume, cortical thickness) or based on pixelwise comparison (i.e. deformation-based methods), are prone to missing a vast array of physical changes that are not well-encapsulated by these metrics. In this paper, we have developed a technique for automated pattern analysis that can fully determine the relationship between brain structure and observable phenotype without requiring any a priori features. Our technique, called transport-based morphometry (TBM), is an image transformation that maps brain images losslessly to a domain where they become much more separable. The new approach is validated on structural brain images of healthy older adult subjects where even linear models for discrimination, regression, and blind source separation enable TBM to independently discover the characteristic changes of aging and highlight potential mechanisms by which aerobic fitness may mediate brain health later in life. TBM is a generative approach that can provide visualization of physically meaningful shifts in tissue distribution through inverse transformation. The proposed framework is a powerful technique that can potentially elucidate genotype-structural-behavioral associations in myriad diseases.

To label heparan sulfate proteoglycans and other strong anions within glomerular basement membranes (GBM) during assembly, cationized ferritin (CF), with a narrow isoelectric range of 7.7 to 8.2, was intravenously injected into newborn rats. Kidneys were then fixed and processed for electron microscopy at intervals ranging from 1 to 72 h after CF injection. One hour after injection, CF bound extensively to the lamina rara interna and externa of developing GBM and mesangial matrix and to tubular basement membranes (TBM). In double basement membranes of early stage glomeruli, large amounts of CF were also seen in central areas between the endothelial and epithelial basement membranes. In maturing-stage glomeruli, CF bound throughout interior regions of GBM outpockets projecting into the epithelial side of capillary walls as well as to the laminae rarae. Because in adult rats CF binds only to the laminae rarae, the abundant anionic sites seen here in newborns between double basement membranes and within GBM outpocket interiors may be subsequently neutralized or removed during the GBM assembly process. In addition to basement membranes, CF was also located intracellularly within endocytic vesicles and lysosomes of glomerular endothelial, mesangial, and epithelial cells 1 h postinjection. CF was also present in similar structures within the tubular epithelium. In contrast to these findings, CF was gradually lost from developing GBM 5, 15, and 24 h after injection and was essentially cleared from all GBM, mesangial matrices, and TBM after 48 h. Large CF aggregates were progressively accumulated within mesangial lysosomes, however. The transient binding of CF to GBM anionic sites seen here was most likely due to its endocytic removal by developing glomerular endothelial, mesangial, and epithelial cells. Anions in the circulation probably also competed effectively with the GBM and TBM for bound CF.

Inland water ecosystems dynamically process, transport, and sequester carbon. However, the transport of carbon through aquatic environments has not been quantitatively integrated in the context of terrestrial ecosystems. Here, we present the first integrated assessment, to our knowledge, of freshwater carbon fluxes for the conterminous United States, where 106 (range: 71-149) teragrams of carbon per year (TgC⋅y(-1)) is exported downstream or emitted to the atmosphere and sedimentation stores 21 (range: 9-65) TgC⋅y(-1) in lakes and reservoirs. We show that there is significant regional variation in aquatic carbon flux, but verify that emission across stream and river surfaces represents the dominant flux at 69 (range: 36-110) TgC⋅y(-1) or 65% of the total aquatic carbon flux for the conterminous United States. Comparing our results with the output of a suite of terrestrial biosphere models (TBMs), we suggest that within the current modeling framework, calculations of net ecosystem production (NEP) defined as terrestrial only may be overestimated by as much as 27%. However, the internal production and mineralization of carbon in freshwaters remain to be quantified and would reduce the effect of including aquatic carbon fluxes within calculations of terrestrial NEP. Reconciliation of carbon mass-flux interactions between terrestrial and aquatic carbon sources and sinks will require significant additional research and modeling capacity.

BACKGROUND

There is increasing evidence that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. We have reported a positive relationship between the concentrations of eosinophils and neutrophils in sputum from severe asthmatics, suggesting a possible role of eosinophils in regulating neutrophilic inflammation. The aim of this study was to investigate whether activated eosinophils modify the trans-basement membrane migration (TBM) of neutrophils.

METHODS

Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils in response to a variety of chemoattractants was evaluated in the presence or absence of eosinophils by using the chambers with a Matrigel-coated Transwell insert.

RESULTS

As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8 (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the TBM of neutrophils. When eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the other hand, when neutrophils were coincubated with eosinophils and stimulated with eotaxin or RANTES, the TBM of neutrophils was not modified.

CONCLUSIONS

Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of patients with severe asthma. On the other hand, it is unlikely that eosinophils migrated by chemoattractants such as CC chemokines regulate neutrophilic inflammation.

OBJECTIVE

The present study is aimed at describing electroencephalographic (EEG) changes in the tubercular meningitis (TBM) and correlating these with clinical and radiological findings.

METHODS

All the patients underwent a detailed neurological evaluation, CSF analysis, EEG and CT scan studies. Outcome was assessed by the Barthel index (BI) score at the end of 3 months, into good (BI>> or = 12) and poor (BI < 12). Thirty-two patients with TBM have been included of which 3 were definite and the remaining highly probable. Their mean age was 28 (range 8-62) years and 8 of whom were females. The majority of these patients were in stage III.

RESULTS

Clinical signs of raised intracranial tension were present in 9 and history of seizure in 11 patients. Cranial CT scan was abnormal in 22 patients. The CT scan abnormalities included hydrocephalus in 20, infarction in 11, exudates in 7 and tuberculoma in 4 patients. The EEG was abnormal in 24 patients. The EEG abnormalities included diffuse theta to delta slowing in 22 patients, intermittent rhythmic delta activity in frontal region in 15, right to left asymmetry in 5 and epileptiform discharges in 4 patients. At the end of 3 months, 5 patients died, 13 had poor, 3 partial and 11 complete recovery. The EEG findings correlated with the severity of meningitis, the degree of coma and outcome at 3 months as assessed by Barthel index score.

This study was prompted by the observation that cells in mouse lymph nodes (LN) with cytological characteristics of tingible body macrophages (TBM) appeared to be Thy-1 positive. The objective of this study was to determine if these large cells were TBM and to conclusively demonstrate their reactivity for Thy-1. The cells were studied using monoclonal antibodies (MoAb) against Thy-1 and macrophage markers including F4/80 and Ia antigens at both light microscopic (LM) and electron microscopic (EM) levels. Immunocytochemical reactivity by TBM for Thy-1 antigen specific MoAb was demonstrated by LM in both in situ and in vitro LN preparations. Furthermore, ultrastructural examination of these germinal center cells in situ demonstrated that the Thy-1 reactivity visualized at the LM level was associated with ribosomes and endoplasmic reticulum as well as their plasma membrane. Similarly, these cells expressed intracytoplasmic and membrane reactivity for Ia antigens and also for the macrophage specific antigen F4/80. This indicates that the reactivity is due to active synthesis of the Thy-1 antigen and not attributable to reactivity of any phagocytosed Thy-1 positive cells. As defined by their germinal center location and morphological characteristics, these Thy-1 reactive macrophages were identified as TBM. Germinal center TBM thus represent a unique, vigorously phagocytic subset of mature macrophages which express both macrophage and thymocyte markers.

For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects. TBM, and MSCs committed or not, and cultured in two- or three-dimensions were mixed with BCP and implanted in bilateral parietal bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant de novo bone formation was observed in rhBMP-2 and BG groups, and in a lesser amount, when BCP biomaterials were mixed with TBM or committed MSCs cultured in three-dimensions. Due to the efficacy and safety of the TBM/BCP combination approach, we recommend this one-step procedure for further clinical investigation.

UNASSIGNED

For craniofacial repair, total bone marrow (BM) and BM mesenchymal stem cell (MSC)-based regenerative medicine have shown to be promising in alternative to bone grafting (BG). Therefore, clinicians might be unsure as to which approach will offer the most benefit. Here, BM and MSCs committed or not were mixed with calcium phosphate ceramics (CaP) and implanted in bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant bone formation was observed in rhBMP-2 and BG groups, and when CaP were mixed with BM or committed MSCs. Since the BM-based procedure does not require bone harvest or cell culture, but provides de novo bone formation, we recommend consideration of this strategy for craniofacial applications.

BACKGROUND

Radiological studies on HIV infection in tuberculous meningitis (TBM) in children are limited to small, retrospective studies using CT features. They report that HIV-infected children are less likely to display meningovascular enhancement, tuberculoma formation and obstructive hydrocephalus. No similar MRI-based studies were found in the literature.

OBJECTIVE

The purpose of this study is to compare the MRI features of TBM in HIV-infected and uninfected children.

METHODS

Retrospective descriptive study comparing clinical, laboratory and MRI features of 8 HIV-infected and 19 HIV-uninfected children with TBM.

RESULTS

Intense basal meningeal enhancement occurred less frequently (p = 0.31) in HIV-infected children whilst cerebral atrophy was more commonly encountered (p = 0.06) Neither finding was however of statistical significance. All HIV-infected children had visible meningeal nodules on MR imaging compared to 72% in HIV-uninfected children with TBM. No differences were noted regarding number or location of infarcts and presence of hydrocephalus. Hydrocephalus in HIV-infected children was exclusively of communicating nature.

CONCLUSIONS

The MRI criteria for diagnosis of TBM apply to HIV-infected children. The presence of nodular meningeal disease in all HIV-infected children has not previously been reported and requires further investigation.

The primary aim was to investigate whether the reduction in resting metabolic rate (RMR) and fat free mass (FFM) associated with a short-term very low kilojoule diet (VLKD) is altered by concurrent resistance exercise. Twenty overweight, premenopausal women were pair matched on body surface area and randomly assigned to either diet only (3,400 kJ/day) or diet combined with resistance training. Before and after 4 weeks of treatment, RMR was assessed by indirect calorimetry; total body mass (TBM), FFM, and fat mass (FM) by dual energy x-ray absorptiometry; total body water (TBW) by bioelectrical impedance; and strength by a weight-lifting test. Both groups had significantly lower TBM, FFM, FM, TBW, absolute RMR, and RMR, with FFM as the covariate, in the posttests than the pretests with no significant differences between groups. It was concluded that 4 weeks of resistance training did not prevent or reduce the decline in FFM and RMR observed with a VLKD.

The mucin gene is up-regulated in diseases such as cystic fibrosis (CF) and asthma. To understand the mechanisms involved in transcriptional regulation of mucin gene expression we have characterized the region of the mucin gene up-stream of the transcriptional start site and analysed the cis-acting elements required for mucin promoter activity. We isolated clones from a dog genomic library containing the promoter region for the tracheobronchial mucin gene (TBM). The authenticity of the promoter was tested by nucleotide sequencing, primer extension analysis, electrophoretic mobility shift assay (EMSA) and reporter gene expression analysis. The canine TBM promoter is different from housekeeping gene promoters (as it is not rich in GC content and contains TATA- and CAAT-like sequences) and different from that of regulatory genes (because it contains many TATA- and CAAT-like sequences and multiple transcriptional initiation sites). Reporter gene analysis using canine TBM promoter-chloramphenicol acetyltransferase (CAT) fusion plasmids established the regions responsible for promoter activity and verified the positions of the major mucin transcriptional initiation sites. Reporter gene analysis also established that a region of the canine TBM promoter and first exon containing all of the transcriptional initiation sites is more active in mucin expressing cells (e.g. CT1 cells-immortalized canine tracheal epithelial cells, human CFT1 cells-immortalized tracheal epithelial cells from a CF subject, or HBE1 cells-immortalized tracheal epithelial cells from non-CF subject) than in mucin non-expressing cells (COS7, 3T3), suggesting cell specificity. The promoter region contained cAMP response element (CRE) sequences, and the TBM gene transcription was enhanced when cAMP analogs were added to transfected cells. EMSA indicated the presence of at least two DNA binding proteins in CT1 cells. This is the first report describing the characterization of a TBM gene promoter. The information obtained in the present studies will be valuable in understanding mucin gene regulation in normal and pathological conditions.

Alpha-1-antitrypsin (A-1-AT) and A-1-AT-elastase complex levels in cerebrospinal fluid have been evaluated in 11 children with viral meningitis (VM), 14 with bacterial meningitis (BM), 10 with tuberculous meningitis (TBM) and 10 investigated for, but found not to have meningitis (NM). A-1-AT concentrations in the NM group were lower than in the BM group (P = 0.0002) and the TBM group (P = 0.0005) but did not differ from the concentrations in VM; those in the VM group were lower than in the BM group (P = 0.0001) and the TBM group (P = 0.003) but no difference was found between the BM and TBM groups. A-1-AT-elastase complex concentrations in CSF were lower in the NM group than the BM group (P = 0.0001) or the TBM group (P = 0.0089), however those in the BM group were significantly higher than in the TBM group (P = 0.0001). A significant correlation existed in CSF between the protein concentrations and neutrophil counts as well as the A-1-AT and A-1-AT-elastase complex concentrations.

Plants typically expend a significant portion of their available carbon (C) on nutrient acquisition - C that could otherwise support growth. However, given that most global terrestrial biosphere models (TBMs) do not include the C cost of nutrient acquisition, these models fail to represent current and future constraints to the land C sink. Here, we integrated a plant productivity-optimized nutrient acquisition model - the Fixation and Uptake of Nitrogen Model - into one of the most widely used TBMs, the Community Land Model. Global plant nitrogen (N) uptake is dynamically simulated in the coupled model based on the C costs of N acquisition from mycorrhizal roots, nonmycorrhizal roots, N-fixing microbes, and retranslocation (from senescing leaves). We find that at the global scale, plants spend 2.4 Pg C yr(-1) to acquire 1.0 Pg N yr(-1) , and that the C cost of N acquisition leads to a downregulation of global net primary production (NPP) by 13%. Mycorrhizal uptake represented the dominant pathway by which N is acquired, accounting for ~66% of the N uptake by plants. Notably, roots associating with arbuscular mycorrhizal (AM) fungi - generally considered for their role in phosphorus (P) acquisition - are estimated to be the primary source of global plant N uptake owing to the dominance of AM-associated plants in mid- and low-latitude biomes. Overall, our coupled model improves the representations of NPP downregulation globally and generates spatially explicit patterns of belowground C allocation, soil N uptake, and N retranslocation at the global scale. Such model improvements are critical for predicting how plant responses to altered N availability (owing to N deposition, rising atmospheric CO2 , and warming temperatures) may impact the land C sink.

Authors measured the thickness of the basement membranes of the proximal and distal tubuli in the renal cortex in 20 patients with verified diabetes mellitus. The test group consisted of 20 patients with small abnormalities of glomeruli (or in the range of variable norm), of the same sex and comparable age. Measurements were performed in locations without tubulo-interstitial changes. The average thickness of TBM in patients with diabetes mellitus was 1540 +/- 616 nm, and in the test group 360 +/- 86 nm, which is a statistically significant difference (p < 0.000000). In spite of the small number of cases and possible error in the manual measurement of electron microscopic pictures, a significant thickening of TBM in diabetes mellitus has been found. We consider this to be of diagnostic value.

BACKGROUND

Task-based measurement (TBM) is a method to assess the eight-hour A-weighted equivalent noise exposure level (L(Aeq.8h)) besides dosimeter. TBM can be better used in factories by non-professional workers and staffs. However, it is still not clear if TBM is equal or similar with dosimeter for L(Aeq.8h) measurement in general. This study considered the measurement with dosimeter as real personal noise exposure level (PNEL) and assessed the accuracy of TBM by comparing the consistencies of TBM and dosimeter in L(Aeq.8h) measurement.

METHODS

The study was conducted in one automobile firm among 387 workers who are exposed to unstable noise. Dosimeters and TBM were used to compare the two strategies and assess the degree of agreement and causes of disagreement. Worker's PNEL was measured via TBM for noise; the real PNEL was also recorded. The TBM for noise was computed with task/position noise levels measured via sound level meter and workers' exposure information collected via working diary forms (WDF) filled by participants themselves. Full-shift noise exposure measurement via personal noise dosimeters were taken as the real PNEL. General linear model (GLM) was built to analyze the accuracy of TBM for noise and the source of difference between TBM for noise and real PNEL.

RESULTS

The L(Aeq.8h) with TBM were slightly higher than the real PNELs, except the electricians. Differences of the two values had statistical significance in stamping workers (P < 0.001), assembly workers (P = 0.015) and welding workers (P = 0.001). The correlation coefficient of L(Aeq.8h) with TBM and real PNELs was 0.841. Differences of the two results were mainly affected by real PNEL (F = 11.27, P = 0.001); and work groups (F = 3.11, P < 0.001) divided by jobs and workshops were also independent factors. PNEL of workers with fixed task/position ((86.53 ± 8.82) dB(A)) was higher than those without ((75.76 ± 9.92) dB(A)) (t = 8.84, P < 0.01). Whether workers had fixed task/position was another factor on the accuracy of TBM for noise (F = 4.36, P = 0.038).

CONCLUSIONS

TBM for noise has acceptable accuracy on workers' PNEL measurement. The accuracy is affected by job categories, workshops and variability of task/position. TBM for noise can yield a relatively conservative result of worker's PNEL in most cases, so it can be used to measure and assess workers' real PNEL.

Tracheobronchomalacia (TBM) is a common congenital disorder in which the cartilaginous rings of the trachea are weakened or missing. Despite the high prevalence and clinical issues associated with TBM, the etiology is largely unknown. Our previous studies demonstrated that Wntless (Wls) and its associated Wnt pathways are critical for patterning of the upper airways. Deletion of Wls in respiratory endoderm caused TBM and ectopic trachealis muscle. To understand mechanisms by which Wls mediates tracheal patterning, we performed RNA sequencing in prechondrogenic tracheal tissue of Wlsf/f;ShhCre/wt embryos. Chondrogenic Bmp4, and Sox9 were decreased, while expression of myogenic genes was increased. We identified Notum, a deacylase that inactivates Wnt ligands, as a target of Wls induced Wnt signaling. Notum's mesenchymal ventral expression in prechondrogenic trachea overlaps with expression of Axin2, a Wnt/β-catenin target and inhibitor. Notum is induced by Wnt/β-catenin in developing trachea. Deletion of Notum activated mesenchymal Wnt/β-catenin and caused tracheal mispatterning of trachealis muscle and cartilage as well as tracheal stenosis. Notum is required for tracheal morphogenesis, influencing mesenchymal condensations critical for patterning of tracheal cartilage and muscle. We propose that Notum influences mesenchymal cell differentiation by generating a barrier for Wnt ligands produced and secreted by airway epithelial cells to attenuate Wnt signaling.

OBJECTIVE

Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area.

METHODS

This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated.

RESULTS

Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %).

CONCLUSIONS

Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.