OBJECTIVE

Transnasal esophagoscopy (TNE) is rapidly becoming integrated into otolaryngological practice. A recent report has shown an incongruence between an endoscopic diagnosis of Barrett's esophagus and biopsy-proven Barrett's esophagus in patients with laryngopharyngeal reflux (LPR). The goal of this study was to determine whether performing TNE with narrowband imaging (NBI) improves on the diagnostic yield in the otolaryngologist's hands. Narrowband imaging involves the use of filtered light to enhance the mucosal microvasculature pattern and has been shown to be highly sensitive to detecting Barrett's esophagus under conventional esophagoscopy.

METHODS

A retrospective chart review of 111 patients with LPR who underwent TNE by the same otolaryngologist was carried out. Pentax EE-1580K (white light only) and Olympus GIF-N180 (with NBI) endoscopes were used in 58 and 53 patients, respectively. Microcup biopsy of the squamocolumnar junction was obtained when Barrett's esophagus was suspected.

RESULTS

Biopsy-proven Barrett's esophagus was found in 13.5% of the patients. According to white light only and NBI, 7 of 58 (12.1%) and 8 of 53 (15.1%), respectively, had biopsy-proven Barrett's esophagus. Three patients had dysplasia on biopsy (2.7%), and all of these cases were detected under NBI (5.7%).

CONCLUSIONS

Narrowband imaging may be a useful adjunct in increasing the diagnostic sensitivity of TNE in the hands of the otolaryngologist.

Orf virus (ORFV) is the etiological agent of contagious ecthyma (CE), a pustular dermatitis of sheep and goats. Outbreaks of ORFV have been observed in all geographical regions of the world, including Argentina. The origin and identity of Argentinian ORFVs are unknown, and no comparative or phylogenetic studies of these viruses have been performed. In this study, we described the sequencing and analysis of five ORFV molecular markers: a partial B2L gene (ORF011), VIR (ORF020), an envelope mature protein (ORF109), vIL10 (ORF127), and GIF (ORF117) from two particular Argentinian outbreaks of CE.

BACKGROUND

In tilting trains partial alignment to the gravito-inertial force (GIF) in the curves seems to be the best tilt compensation to reduce the incidence of motion sickness. We investigated the effect of alignment to the GIF on the development of motion sickness during low-frequency horizontal motion.

METHODS

There were 12 healthy subjects who participated. The design was a three-period, single-blind, crossover trial, counterbalanced for order. Cardiopulmonary measurements, Misery SCores (MISC), and questionnaire data (Motion Sickness Susceptibility Questionnaire, Nijmegen Questionnaire for Hyperventilation) were obtained. The stimulus was a sinusoidal movement (0.176 Hz, 0.2 g peak acceleration) on the ESA-sled. The cabin was compensated for 0% (A-0), 50% (A-50), and 100% (A-100) to the GIF. Runs were 1 wk apart.

RESULTS

The A-50 condition may delay the development of motion sickness. Based on the survival curves the possible effect seems temporary. However, MISC 2 early in the runs resulted in high positive and negative predictive values for dropout and survival during the runs. No synchronization of the respiratory frequency with the sled motion was observed. There was a significant (P = 0.002) drop in relative end-tidal CO2 levels.

CONCLUSIONS

There seems to be a rationale for partially compensating to the GIF while trying to prevent motion sickness in tilting trains. Sitting comfort is just better than without compensation at all and Coriolis effects are not as nauseating as with complete tilt compensation. Also, a drop in end-tidal CO2 levels might be a sign of pulmonary compensation for the nauseating stimulus.

This study presents the development and optical engineering of stacked nanoporous anodic alumina gradient-index (NAA-GIFs) filters with tunable multispectral photonic stopbands for sensing applications. The structure of these photonic crystals (PC) is formed by stacked layers of NAA produced with sinusoidally modified effective medium. The progressive modification of the sinusoidal period during the anodization process enables the generation and precise tuning of the characteristic photonic stopbands (PSB) (i.e., one per sinusoidal period in the anodization profile) of these PC structures. Four types of NAA-GIFs featuring three distinctive PSBs positioned within the visible spectral region are developed. The sensitivity of the effective medium of these NAA-GIFs is systematically assessed by measuring spectral shifts in the characteristic PSBs upon infiltration of their nanoporous structure with analytical solutions of d-glucose with several concentrations (0.025-1 M). This study provides new insights into the intrinsic relationship between the nanoporous architecture of these PCs and their optical properties, generating opportunities to fabricate advanced optical sensing systems for high-throughput and multiplexed detection of analytes in a single sensing platform.

The endoscopic pneumatic dilation (EPD) procedure introduces an instrument which can be used in combination with fiberoptic-endoscopes types GIF-P and GIF-P2. The dilator is characterized by simple, easy, and gentle handling, even with extreme deviation at the gastro-esophageal junction. In daily clinical routine it has been shown to be effective in the treatment of achalasia.

Stoffregen and Riccio (1988) have presented a theory of orientation that dismisses the role of otolithic information in the perception of the direction of the gravitoinertial force (GIF). Their dismissal of otolithic involvement in GIF perception is not warranted because (a) the logic associated with their analysis is flawed. (b) the underwater experiments they analyzed do not reflect the isolated operation of otolithic function, and (c) they do not cite a large body of relevant evidence on otolithic function.

Gait Initiation Failure (GIF) is one of the most disabling gait disturbances seen in advanced Parkinson's disease (PD). Gait Initiation is a complex motor task that requires motor and cognitive processing to enable the correct selection, timing and scaling of movement. Failure to initiate the first step often precipitates falls and leads to significant morbidity. However, the brain mechanisms underlying GIF remain unknown. This study utilized an ambulatory electroencephalography (EEG) technique to investigate the brain dynamic changes underlying GIF and aims to detect the occurrence of GIF in four PD patients. We sought to determine whether episodes of GIF might be associated with a characteristic brain signal that could be detected by surface EEG. This preliminary investigation analyzed the EEG signals through power spectra density (PSD) and centroid frequency (CF) to show that the GIF episodes were associated with significant increases in the high beta band (21-38Hz) across the central, frontal, occipital and parietal EEG sites. By implementing PSD and CF as input features with two-layer Back Propagation neural networks as a classifier, the proposed system was able to detect GIF events with a classification performance of 84.27% sensitivity and 84.80% accuracy. This is the first study to show cortical dynamic changes associated with GIF in Parkinson's disease, providing valuable information to enhance the performance of future GIF detection that could be translated into clinical practice.

One male rat pituitary placed in a chamber was perifused with cyclic somatostatin (GIF) for 30 min. Either 160 nM or 1.6 muM GIF caused a decrease in the release of GH. The release of TSH was also decreased by 160 nM GIF, and paradoxically increased by 1.6 muM GIF. Increasing the dose of GIF to 16 muM resulted in an abrupt rise in the release of both GH and TSH during the perfusion; then the level of GH decreased to the nadir level followed by an elevation above the base line, while that of TSH promptly fell back toward the base line. The release of PRL was not clearly affected by 16 muM GIF. [Tyr8]-GIF did not have such stimulatory activities. These results indicate that GIF not only inhibits the release of GH and TSH, but also stimulates that of GH and TSH in this system, depending on its dose.

OBJECTIVE

To investigate the relationship of the BP response to the Valsalva maneuver (VM) to parameters of congestive heart failure (CHF) other than hemodynamic measures.

METHODS

Comparison of neurohormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], norepinephrine [NE]), parameters of spiroergometry, and clinical parameters with BP response to the VM.

METHODS

Tertiary care center.

METHODS

Forty-five patients with stable CHF (ejection fraction, 28 +/- 7%).

METHODS

Pulse amplitude ratio (PAR) calculated between the end and the beginning of the VM using the last two and the first three beats of the straining phase. Failure of the systolic BP to fall below the resting level during the VM.

RESULTS

Patients in the New York Heart Association class III (n = 15) had a higher PAR than those in class II (0.82 +/- 0.21 vs 0.63 +/- 0.20; p < 0.01). There was a close correlation between PAR and ANP (r = 0.76) and BNP (r = 0.62), whereas other parameters were less well correlated (eg, for peak f1.gif" BORDER="0">O(2), r = -0.35; p < 0.05). Patients with failure of the systolic BP to fall below the resting level (n = 24) had higher neurohormones (mean ANP, 246 +/- 158 vs 84 +/- 43 pg/mL; mean BNP, 282 +/- 289 vs 81 +/- 85 pg/mL; p < 0.001; mean NE, 3.9 +/- 1.7 vs 3.4 +/- 1.5 nmol/L; nanosecond), lower exercise capacity (19.8 +/- 5.2 vs 23.0 +/- 3.7 mL/kg/min; p < 0.05), and their quality of life (Minnesota questionnaire) was more compromised (31 +/- 19 vs 18 +/- 15; p < 0. 05).

CONCLUSIONS

The BP response to the VM is related to a broad range of clinical and neurohumoral parameters of CHF. Whether or not it is also related to prognosis remains to be determined. Nevertheless, this easily applicable test should be part of the assessment of patients with CHF.

This article describes the isolation and identification of contagious pustular dermatitis virus/orf virus (ORFV) from an outbreak of contagious pustular dermatitis (orf) in flocks of goats, in the north western region of India (Rajasthan). The virus was isolated in Vero cell cultures from scab and swab suspensions and has been identified using GIF/IL-2 and B2L gene specific primers in PCR and sequencing. The virus showed high nucleotide identity with previously reported Chinese, far eastern, Brazilian and Indian isolates. This report described the use of molecular tools for fast, reliable and confirmatory diagnosis of ORFV infection.

OBJECTIVE

Endoscopic submucosal dissection (ESD) technique requires special skill and involves a prolonged procedure time. Therefore, the present study aim is to increase the efficiency of endoscopic treatment techniques by vibrating the endoscope scope itself. The usefulness of this vibration endoscopy for ESD was evaluated in 6 porcine stomachs.

METHODS

Vibration endoscope modified a commercial endoscope (Olympus: GIF-Q200). Investigations to measure procedure time were conducted separately with and without vibration of 5,000 or 10,000 rpm applied at the time of circumferential incision and submucosal dissection.

RESULTS

Among circumferential incisions, submucosal dissection and a total of both, the average procedure durations with vibration at 10,000 rpm were significantly shorter than that without vibration.

CONCLUSIONS

When performing peripheral incisions and submucosal dissection with a knife in ESD, the time for the procedure was reduced by adding vibration.

The small caliber peroral endoscope (GIF-P2) was efficient and safe in the detection of lesions in a series of 69 patients with acute upper gastrointestinal hemorrhage. The authors describe a technique of examination that they have found appropriate to this problem.

Using THA as a proxy for underlying osteoarthritis, we describe population-based familial clustering of osteoarthritis of the hip. The GIF test for excess relatedness on 1049 patients that underwent THA (and do not have a diagnostic code for other conditions leading to THA) showed excess relatedness (P<0.001). Even when close relationships were ignored (closer than third-degree relationships), excess relatedness was observed (P=0.020). Relative risk was elevated in first-degree (RR 2.59; 95% CI 1.84-3.53, P=2.0e(-7)), second-degree (RR 1.66; 95% CI 1.11-2.39; P=0.0075) and third-degree relatives (RR 1.46; 95% CI 1.17-1.81; P=5.7e(-4)). Excess relatedness of individuals who had undergone THA for osteoarthritis and elevated risks to both near and distant relatives were observed.

Mice sensitized with frozen-thawed Toxoplasma antigen emulsified in Freund's Incomplete Adjuvant (FIA) showed high resistance against Plasmodium berghei infection, but not in mice sensitized with paraformaldehyde-fixed. Toxoplasma or saline plus FIA. However, mice which survived from malaria infection did not show any protective reaction against the RH strain inoculation. Furthermore, an immune interferon activity was detected in the supernatant of the spleen cells collected from the mice sensitized with frozen-thawed Toxoplasma and cultured with the specific antigen, however, no Toxoplasma growth inhibitory factor (Toxo-GIF) was found in the same supernatant of lymphokines. From these results, it is suggested strongly that frozen-thawed Toxoplasma antigen could confer nonspecific resistance in mice against Plasmodium infection.

A 54-year-old woman with severe abdominal distention suffered from massive ascites. Cytological examination revealed adenocarcinoma cells, leading to a diagnosis of peritonitis carcinomatosa. Gastrointestinal fiberscopy (GIF) resulted in a histological diagnosis of type 4 advanced gastric cancer with signet-ring cell carcinoma. The clinical diagnosis was confirmed to be cT3(SE)cN1cM0cH0cP1, cStage IV gastric cancer, type 4, according to the Japanese classification of gastric carcinoma. The patient was treated with S-1 and low-dose cisplatin (CDDP) in order to alleviate the critical state of the disease. After the third cycle of the regimen, the clinical response of P1 was classified as a partial response (PR) according to the World Health Organization (WHO) criteria. The patient's appetite loss and abdominal discomfort were markedly alleviated. The patient experienced grade 2 leukocytopenia throughout the regimen. Surgery was performed. Ascites and peritoneal disseminated lesions were not observed, and cytological examination of the peritoneal washes was negative. Total gastrectomy with D1 lymph node dissection was performed, and the surgical diagnosis was sT3(SE)sN0sM0sH0sP0; sStage II. Microscopically, viable cancer cells were found to be scattered throughout the subserosal-serosal layers in the resected stomach. All of the samples from lesions that were potentially cancers involving peritoneal dissemination were diagnosed as fibrous scar tissues without any viable cancer cells. The patient is alive without recurrence at 10 months after surgery and 14 months after the initial chemotherapy. Thus, systemic chemotherapy with S-1/low-dose CDDP achieved desirable control of peritoneal disseminated cells, as assessed microscopically, suggesting that the regimen may be an effective strategy for the treatment of advanced gastric cancer with peritonitis carcinomatosa.

T helper 2 (Th2) cells are critical to the induction of IgE antibody and allergic inflammation, but how the pathological pathways are controlled in nonallergic individuals remains unclear. Here we report that glycosylation-inhibiting factor (GIF) suppresses Th2 effector generation. GIF is a cytokine encoded by the same gene that codes for macrophage migration inhibitory factor (MIF). GIF-deficient mice demonstrated enhanced T-dependent antibody formation especially of IgE isotype and allergic airway inflammation with the generation of regulatory T cells unaffected. GIF-deficient macrophages and dendritic cells revealed normal responsiveness to toll-like receptor (TLR) ligands. GIF undergoes a unique posttranslational modification, cysteinylation. The modified GIF, mainly secreted by activated T cells derived from CD4(+)CD25(-) cells, inhibited IL-4 production by the same cells whereas the unmodified GIF showed no effect. Bone marrow chimera experiment demonstrated that T cell-derived GIF suppressed the generation of Th effectors that secrete IL-4. During the first 24 h of CD3/CD28 stimulation in vitro, GIF secreted from naïve CD4 cells acted on the same cells, maintained nuclear factor of activated T cells (NFAT)c2 in the nucleus, and repressed IL-4 mRNA levels. Thus, GIF represents a self-regulatory mechanism of Th2 cell generation from naïve CD4 cells, in which the posttranslational modification plays a crucial role.

Prostate-specific antigen (PSA) is a protease able to bind to serum antiproteases as alpha 1 antichymotrypsin (ACT). Free PSA (FPSA) corresponds to the fraction of total PSA (TPSA) which is unbound to ACT. Specific detection of the FPSA seems to be a valuable tool in the distinction between prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). Our aim was to evaluate retrospectively the FPSA/TPSA ratio in comparison to TPSA or FPSA determination, using two new immunoradiometric assays (PSA-RIACT and FPSA-RIACT, CIS bio international, Gif Sur Yvette, France) in the early diagnosis of PCa. 256 men, with TPSA levels between 0.7 and 44.7 ng/ml (median age = 69 years), including 164 sera obtained from patients with BPH and 92 sera from patients with untreated PCa were assayed. All diagnoses were histologically confirmed and patients tested before any adjuvant treatment. The evaluation of the median FPSA/TPSA ratio in the two groups showed significantly different values (BPH group: 24.2%, PCa group: 12.1%, P < 0.0001). By R.O.C. (Receiver-Operating-Characteristics) analysis, we show that the FPSA/TPSA ratio is the method of choice for discriminating BPH and PCa, since the area under curve is the greatest for the FPSA/TPSA ratio curve, as compared to the TPSA or FPSA curves (P < 0.0001). The best accuracy (number of true positive + true negative/total = 82.4%) was obtained with a FPSA/TPSA ratio < or = 15% with high odds ratio (20.5; confidence interval (CI): 11.2; 37.7). Of interest, similar results were also confirmed even in the subpopulation with serum TPSA levels between 2.5 and 10 ng/ml (161 patients including 99 BPH and 62 PCa). We thus confirm that combined serum measurement of FPSA and TPSA is of particular interest in the early diagnosis of PCa for patients with non-suspicious digital rectal examination and a TPSA value between 2.5 and 10 ng/ml. In those patients, biopsy should be reserved to the cases with FPSA/TPSA below 15%, which allows significant odds ratio (12.8; CI: 5.2; 31.4). Otherwise, to avoid the risk of missing any PCa, usual follow-up with combined TPSA and FPSA determination would be required with the same criteria of biopsy (i.e. FPSA/TPSA ratio < or = 15% when TPSA value is between 2.5 and 10 ng/ml; or TPSA>> 10 ng/ml).

Granuloma initiation factor (GIF), which elicits a granulomatous reaction in naive murine skin, contains low-molecular-weight proteins partially purified from organized granulomas developed in livers of mice with schistosomiasis. In this study, we found that 10- and 14-kDa proteins in the GIF are highly homologous to mouse migration inhibitory factor-related protein (MRP) 8 and MRP 14. Compared with the N-terminal amino acid sequence deduced from each corresponding cDNA, the 10-kDa protein from the granuloma lacks the first methionine, whereas the 14 kDa misses methionine, alanine, and asparagine. Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated blood vessels and at the edge of granulomas. The staining of differentiated macrophages and epithelioid cells located in the center of the granulomas was negative. Immunoreactivity of peritoneal exudate cells also was found to gradually disappear with time in cell culture. Furthermore, in vivo effects of the recombinant proteins in murine skin were described histologically. Both MRPs caused severe infiltration of neutrophils and monocytes during 7-14 days. The reaction resulting from individual MRP implantation became minimal after 50 days but inoculation of the Ca2+-dependent heterodimers showed an extensive eosinophil accumulation.

BACKGROUND

Ketamine is an increasingly popular drug of abuse in China but there is currently no method for classifying the psychological effects of ketamine in individuals with ketamine dependence.

OBJECTIVE

Develop a scale that characterizes the acute and long-term psychological effects of ketamine use among persons with ketamine dependence.

METHODS

We developed a preliminary symptom checklist with 35 dichotomous ('yes' or 'no') items about subjective feelings immediately after ketamine use and about perceived long-term effects of ketamine use that was administered to 187 inpatients with ketamine dependence recruited from two large hospitals in Guangzhou, China. Exploratory factor analysis (EFA) was conducted on a randomly selected half of thesample to reduce the items and to identify underlying constructs. Confirmatory factor analysis (CFA) was conducted on the second half of the sample to assess the robustness of the identified factor structure.

RESULTS

Among the 35 symptoms, the most-reported acute effects were 'floating or circling' (94%), 'euphoric when listening to rousing music' (86%), and 'feeling excited, talkative, and full of energy' (67%). The mostreported long-term symptoms were 'memory impairment' (93%), 'personality changes' (86%), and 'slowed reactions' (81%). EFA resulted in a final 22-item scale best modelled by a four-factor model: two factors representing chronic symptoms (social withdrawal and sleep disturbances), one about acute psychoticlike symptoms, and one that combined acute drug-related euphoria and longer-term decreased libido. CFA showed that these 4 factors accounted for 50% of the total variance of the final 22-item scale and that the model fit was fair (Goodness of Fit Index, GIF=83.3%; Root Mean Square Error of Approximation, RMSEA=0.072).

CONCLUSIONS

A four-factor model including social withdrawal, sleep disturbance, psychotic-like symptoms, and euphoria at the time of drug use provides a fair description of the short-term and long-term psychological symptoms associated with ketamine use. Future work on the 22-item version of the scale with larger samples is needed to confirm the validity of this 4-factor structure, to assess the scale's test-retest reliability, and to determine whether or not it can be useful in the differential diagnosis and monitoring of treatment of individuals with ketamine dependence.

In a previous study, we developed newly synthesized arylthio derivatives of cyclopentenone prostaglandins (GIF-0642, GIF-0643, GIF-0644, GIF-0745 and GIF-0747), which are neuroprotective against both manganese toxicity in PC12 cells and glutamate toxicity in HT22 cells. In the present study, we showed that these compounds and their lead compound, NEPP11, are potent inducers of glial cell line-derived neurotrophic factor (GDNF) expression in C6 glioma cells and primary astrocytes. These neuroprotective cyclopentenone prostaglandins also induced the gene expression of nerve growth factor and, to a lesser extent, brain-derived neurotrophic factor. The induction of GDNF mRNA was transcription-dependent, and the overexpression of dominant-negative Nrf2 attenuated the ability of the (arylthio)cyclopentenone prostaglandins to stimulate GDNF gene expression. These results suggest that (arylthio)cyclopentenone prostaglandins increase GDNF gene expression partly via the Keap1/Nrf2 pathway. A growing number of reports demonstrate the importance of increasing the amounts of neurotrophic factors, especially GDNF, in neuropathological states. Although the precise mechanisms by which the GIF compounds inhibit cell death are under investigation, an increase in neurotrophic factors may contribute to the diverse pharmacological properties of (arylthio)cyclopentenone prostaglandins in vivo and will make them potentially valuable in the treatment of neurodegenerative disorders.

In this work five peptides with Cys-Xaa-Cys motif were studied including Ac-Cys-Gly-Cys-NH(2), Ac-Cys-Pro-Cys-Pro-NH(2), their N-unprotected analogues and the N-terminal fragment of metallothionein-3, Met-Asp-Pro-Glu-Thr-Cys-Pro-Cys-Pro-NH(2). All these peptides were found to be very effective ligands for Ni(2+), Zn(2+) and Cd(2+) ions. Potentiometric and spectroscopic (UV-Vis, CD and MCD) studies have proved that sulfur atoms are critical donors for the metal ions coordination. The amide nitrogen may participate in the metal ion binding only in the case when Gly is adjacent to Cys residues. Ac-Cys-Gly-Cys-NH(2) may serve as a low molecular weight model for cluster A, which is a binding unit of nickel ion in acetyl coenzyme A synthase. This bifunctional enzyme from anaerobic microorganisms catalyzes the formation of acetyl coenzyme A from CO, a methyl group donated by the corrinoid-iron-sulfur protein and coenzyme A. Other peptides studied in this work were Ac-Cys-Pro-Cys-Pro-NH(2) and Met-Asp-Pro-Glu-Thr-Cys-Pro-Cys-NH(2) originating from metallothionein sequence. These motifs are characteristic for the sequence of cysteine rich metallothionein-3 (MT-3) called also neuronal growth inhibitory factor (GIF). Cys-Pro-Cys-Pro fragment of protein was demonstrated to be crucial for the inhibitory activity of the protein.

Serum human growth hormone (hGH) levels were measured with three different commercial kits, comprising a radioimmunoassay (RIA) (bioMérieux, Marcy-l'Etoile, France, 'bmpoly') and two immunoradiometric assays (IRMA) (bioMérieux, 'bmmono', and CIS bioInternational, Gif-sur-Yvette, France, 'cismono'). Samples were collected after various stimulation tests [arginine-insulin, growth hormone-releasing hormone (GHRH), L-dopa and glucagon-beta-axolol] from children who were undergoing evaluation for short stature. Values obtained with the IRMAs were consistently lower than those obtained with the RIA. Furthermore, the cismono/bmmono and cismono/bmpoly values ratios were always significantly higher when samples were collected during GHRH stimulation than during the other stimulation tests. These data indicate that GHRH could induce a particular form of hGH molecule (in nature or in amount), recognized by the monoclonal antibodies in the cismono kit and that a specific form of hGH may be released by GHRH stimulation.

Growth inhibitory factor (GIF) is highly expressed in the CNS under physiological conditions, but its expression is reduced in neurodegenerative diseases, such as Alzheimer's disease. The results of this study show that the levels of GIF and GIF mRNA were not influenced by neuroglial interactions. GIF was highly expressed in confluent astrocytes, but the expression was down-regulated in low-density growing astrocytes. A high level of GIF was not observed in serum-starved low-density cultures. These findings suggest that GIF is a quiescent state-specific protein and that two different mechanisms may exist for the cells to enter the quiescent state. Among interleukin-1beta (IL-1beta), fibroblast growth factor-2, epidermal growth factor (EGF), amyloid beta1-42, and 50% O2, only EGF and IL-1beta altered the level of GIF in confluent astrocytes: EGF increased both GIF mRNA and protein, and IL-1beta decreased GIF mRNA, but did not alter GIF protein. Kinetic analysis of the GIF mRNA level revealed the biphasic regulation of GIF mRNA expression by IL-1beta, i.e., a transient up-regulation followed subsequently by down-regulation, explaining in part the discrepancy between the levels of GIF mRNA and protein in astrocytes treated with IL-1beta.

Medium (MCM, 20% human serum), conditioned for 24 h by mononuclear human blood cells, had no colony-forming ability when tested in the mouse CFU-C assay. However, when combined with L-CSF, which predominantly generates macrophage colonies, MCM increased the colony number and size. Even more significant was the increased cellularity with a striking shift towards granulocyte production. Some human sera induced GIF formation without additives, but mostly LPS was required. After heat inactivation, all sera became dependent on LPS to yield an active MCM. Lithium, PHA, Con A and PMW also stimulated GIF formation, which itself depended upon protein synthesis. Heat inactivation of LPS and serum did not reduce their ability, in combination, to yield an active MCM. However, when serum and LPS were mixed before heat treatment, the ability to induce GIF production was abolished, but could be restored by adding intact LPS. This may indicate that LPS exerts its effect by combining with a serum factor yielding a heat-sensitive complex. However, even in the absence of serum, LPS had a stimulatory effect when used in large concentrations, but still the MCM was less active than MCM with serum.