BACKGROUND

Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy.

METHODS

This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT.

RESULTS

Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations.

CONCLUSIONS

Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum.

Training on a motor task results in performance improvements that are accompanied by increases in motor cortex excitability. Moreover, periods of afferent stimulation result in increased motor cortex excitability. There is increasing evidence to suggest that raised motor cortical excitability may facilitate movement and learning. Here we examined whether a period of electrical stimulation of hand afferents ("associative stimulation"), known to increase motor cortex excitability, facilitated the performance of a complex sensorimotor task. Three groups of nine normal subjects participated in these studies. All subjects were trained on the grooved pegboard test (GPT). Training consisted of three blocks, each of five trials, of placing pegs as quickly as possible. The time to complete each block was recorded. One group of subjects had a 1-h period of associative stimulation prior to training on the GPT. A second group received non-associative stimulation (which does not change cortical excitability) of the same hand afferents while a third group received no stimulation prior to training. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and abductor digiti minimus (ADM) muscles both prior to and following stimulation and performance of the GPT. In contrast to non-associative stimulation, associative stimulation increased motor cortical excitability, as evidenced by an increase in the amplitude of MEPs evoked in the FDI, one of the stimulated muscles, but not the ADM. Training on the GPT resulted in significant improvements in the time taken to complete the task for all three groups. However, in subjects who had preconditioning associative stimulation, performance on the GPT improved more rapidly. Additionally, there was a strong trend for the improvement in the performance of the stimulated group to be greater than that of the control group. The results of the present study suggest that increased motor cortical excitability, induced by associative stimulation, may facilitate the performance of a novel complex sensorimotor task.

OBJECTIVE

To identify the roles of serum IL-18, IL-10, TNF-alpha and sIL-2R in the pathogenesis of chronic hepatitis C and the effects of interferon on the mentioned serum cytokines.

METHODS

The levels of IL-18, IL-10, TNF-alpha and sIL-2R were detected in 10 healthy controls, 24 asymptomatic HCV carriers, and 27 patients with chronic hepatitis C (before and after IFN treatment) by enzyme linked immunosorbent assay (ELISA).

RESULTS

The levels of IL-18, IL-10, TNF-alpha and sIL-2R in the patients of chronic hepatitis C were higher than those in the healthy controls (P<0.05) and in asymptomatic HCV carriers (P<0.05). The values of the mentioned cytokines showed a significant positive correlation to GPT. The levels of the mentioned cytokines decreased obviously after IFN treatment (P<0.05), while the serum levels of IL-10 and sIL-2R reduced in sequence in no-response group, partial-response group and complete-response group.

CONCLUSIONS

IL-18, IL-10, TNF-alpha and sIL-2R co-participate in the pathogenesis of chronic hepatitis C, and are used to evaluate the effect of IFN on the immune state of organisms, and IL-10 and sIL-2R are important for predicting the anti-viral efficacy of IFN.

Noninvasive evaluation of organ redox states provides invaluable information in many clinical settings. We evaluated a newly developed reduction/oxidation-sensitive green fluorescent protein (roGFP) probe that reports cellular redox potentials and their dynamic changes in live cells. On hypoxia/reoxygenation (H/R) of AML12 liver cells, roGFP indicated mild reduction during hypoxia, but immediate transient oxidation after reoxygenation. The roGFP probe confirmed the antioxidative effects of N-acetylcysteine, catalase, redox factor-1, and Mn-SOD/CuZn-SOD against H/R-induced cellular oxidative stress (OS). In a mouse liver ischemia/reperfusion (I/R) model, roGFP transduced by using an adenoviral vector revealed immediate reduction of the liver under ischemia, and two distinct peaks of OS: (a) early, observed within 60 min after reperfusion, similar to the in vitro study; and (b) later, at 24 h. The early peak levels paralleled the ischemic time up to 75 min and the postischemic liver injury (sGOT/GPT/LDH) in the later phase (6 and 24 h after I/R). The roGFP probe successfully indicated postischemic OS of the liver in living mice, accurately predicting postischemic liver injury. This probe may represent an effective OS marker indicating organ redox states and also predicting the damage/function.

We describe two retroviral vector-based recombination substrate systems designed to assay for lymphoid VDJ recombinase activity in cultured cells. Both substrates incorporate a constitutive dominant marker gene (the simian virus promoter-driven neo gene) to allow selection of cells that stably integrate the substrate. Both substrates also include a second marker gene that becomes transcriptionally active only when inverted by a site-specific recombination event between flanking immunoglobulin variable-region gene segments. The first vector, similar in structure to previous retrovirus-based recombination substrates, utilizes the bacterial guanine-xanthine phosphoribosyltransferase gene (gpt) as its activatable marker; detection of inversion (VDJ recombinase activity) involves drug selection and Southern blotting analyses. We have used this vector to make a more extensive and quantitative survey of VDJ recombinase activity in B-lineage cell lines than has previously been performed with stable substrates, and we have compared our results with those of other studies that use transient recombination substrates. In the second vector, the activatable gene is the bacterial beta-galactosidase gene (lacZ). Detection for inversional activation of this gene is achieved by a fluorogenic assay, termed FACS-Gal, that detects beta-galactosidase activity in viable cells. The latter assay has the unique advantage of rapidly detecting cells that undergo recombination and also allows viable sorting of cells on the basis of the presence or absence of VDJ recombinase activity. We have used the lacZ vector to rapidly quantitate VDJ recombinase activity in B-lineage cell lines and compared the results with those obtained with the gpt vector. We have also used the lacZ vector to isolate variant pre-B-cell lines with low and high levels of VDJ recombinase activity.

OBJECTIVE

To explore putative cytoprotective functions of biliverdin during hepatic ischemia/reperfusion (I/R) injury in rat models.

METHODS

Male Sprague Dawley (SD) rat livers were harvested and stored for 24 hours at 4 degrees C in University of Wisconsin (UW) solution (n=18), and then perfused with blood for 2 hours on an isolated rat liver perfusion apparatus equipped for temperature (37 degrees C), pressure (13 cm H2O), and pH (7.3) maintenance. Biliverdin was added to the blood at concentrations of 10 and 50 micromol in two groups of six animals. Portal vein blood flow, bile production, and GOT/GPT levels were assessed serially. At the conclusion of the experiment, liver samples were collected for histologic evaluation using Suzuki criteria.

RESULTS

BV exerted protective effects against liver I/R injury. Adjunctive biliverdin improved portal venous blood flow (mL/min/g) from the beginning of reperfusion (1.33+/-0.17 versus 0.98+/-0.15; P<.001) and increased bile production (mL/g) as compared with the control group (3.40 versus 1.88; P<.003). I/R-induced hepatocellular damage as measured by GOT/GPT release (IU/L) was diminished in the biliverdin group (91 versus 171 and 46 versus 144, respectively; P<.0001). Improved liver function by biliverdin was accompanied by preservation of the histologic structure as assessed by Suzuki criteria (3.7+/-1.4 versus 6.8+/-0.8 in untreated controls; P<.005).

CONCLUSIONS

Biliverdin attenuates the ischemia/early reperfusion injury of rat liver grafts as assessed by hemodynamics, function, enzyme analysis, and histology. This study provides the rationale for novel therapeutic approaches using biliverdin to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.

A girl with partial deletion of the short arms of one chromosome 7 is described. Among many other symptoms she has craniosynostoses. Early closure of cranio-sutures has previously been described in 2 of 3 patients with partial deletion 7. Investigation of a number of genetic marker systems shows that the HL-A, MN, AcP, and GPT loci are not located in the deleted segment.

A strain of Salmonella typimurium LT2 has been isolated which carries an insertion of approximately 700 bp in the gpt gene. The insertion in the gpt gene was shown to be the Salmonella-specific element IS200. The mutation in strain CR1 arose without selection during storage and is only the second phenotypically identified mutation caused by the insertion of IS200.

We have recently proposed total hydroxyoctadecadienoic acid (HODE) as a biomarker for oxidative stress in vivo. The biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert the oxidation products of linoleate to HODE. In the present study, this method was applied to measure the oxidative damage induced by the administration of carbon tetrachloride to mice and also to evaluate the capacity of antioxidant to inhibit the above damage. alpha-Tocopherol transfer protein knock out (alpha-TTP-/-) mice were used to evaluate antioxidant effect in the absence of alpha-tocopherol. The intraperitoneal administration of carbon tetrachloride to mice induced the increase in HODE in liver and plasma, which was followed by an increase in plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). F2-isoprostanes, another prevailing biomarker, were also increased similarly, but their concentration was approximately two to three orders of magnitude smaller than that of HODE. The lipophilic antioxidants such as gamma-tocopherol, gamma-tocotrienol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) were effective in suppressing the formation of HODE.

Rat embryo fibroblast cell line 6 was transfected with plasmid pT24, which contains the activated human bladder c-Ha-ras oncogene, and the cells were grown continuously in the absence or presence of the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) or teleocidin. The presence of TPA or teleocidin led to a 6- to 14-fold increase in the number of morphologically transformed foci. No transformed foci were seen when rat 6 cells were transfected with the normal c-Ha-ras oncogene in the absence or presence of TPA, or in cells simply treated with TPA or teleocidin. Enhancement of pT24-induced foci was seen even when the addition of TPA was delayed until day 16. In transfection studies with the drug resistance genes gpt and neo, TPA and teleocidin did not increase the number of Gpt+ or Neo+ colonies. When rat 6 cells were cotransfected with pT24 and neo genes and grown in the absence or presence of TPA, the presence of TPA did not increase the yield of Neo+ colonies but caused a fivefold increase in the number of Neo+ colonies that displayed a transformed morphology. Southern blot analyses of DNAs obtained from these clones indicated that TPA treatment did not influence the extent of integration of either the pT24 or neo gene. DNA samples from all of the morphologically transformed cells displayed a characteristic 2-kilobase SacI fragment homologous to pT24 DNA and expressed relatively high levels of the corresponding mRNA. Our findings indicate that in this system tumor promoters do not simply enhanced the process of DNA transfection per se. Thus, this model system may be useful for analyzing synergistic interactions between tumor promoters and activated oncogenes during multistage carcinogenesis. It may also serve as a simple screening test for detecting new tumor promoters.

Male rats provided with a 5 or 15% (v/v) ethanol solution as the sole source of fluid consumed ethanol at a rate of 11.4 or 24.9% of total calories (4.2 or 8.3 g/kg daily). After ethanol consumption lasting 1, 2 and 3 weeks the hepatotoxicity of CCl4 (0.1 ml/kg i.p.) was elevated by determination of serum activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase ( GPT), sorbitol dehydrogenase (SDH) and histological investigations. Carbon tetrachloride (CCl4)-induced liver damage was significantly greater in rats provided with ethanol than in the tap-water consuming controls. This potentiation of CCl4 hepatotoxicicty was fully developed already after a 1-week exposition to ethanol and was greater in the 15% than in the 5% ethanol group. Ethanol alone did not influence serum enzyme activities but increased microsomal aniline hydroxylation. There was, however, no clear-cut parallelism between potentiation of CCl4 hepatotoxicity and activation of aniline hydroxylation.

Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist. By inhibiting nuclear factor κB (NF-κB), it decreases tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) and has an anti-inflammatory effect. Endotoxin shock can induce the production of several inflammatory mediators such as TNF-α and IL-6, leading to multiple organ dysfunction and death. We investigated the effects of rosiglitazone (.3 mg/kg, intravenous administration) on the physiologic attributes and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae lipopolysaccharides (LPSs; 10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 24 hr after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, TNF-α, and IL-6 were measured at 0, 1, 3, 6, 12, and 24 hr after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, glucose, TNF-α, and IL-6 levels and HR, while also decreasing MAP. Rosiglitazone diminished the increase in HR, decreased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, CPK, glucose) and inflammatory biomarkers (TNF-α, IL-6), and did not affect MAP after LPS. In conclusion, rosiglitazone ameliorated endotoxin shock-induced markers of organ injury and suppressed the release of TNF-α and IL-6 in conscious rats.

OBJECTIVE

Peripancreatic fluid collections are common complications of acute pancreatitis or acute exacerbations of chronic pancreatitis. Surgery is required when these fluid collections become infected or cause obstruction or pain. However, morbidity and mortality after surgery in these cases are still too high, therefore minimally invasive approaches have been encouraged. The aim of this study was to evaluate the feasibility of endoscopic ultrasound-guided transmural drainage with intracystic endoscopy and necrosectomy.

METHODS

From 2000 to 2006 30 patients (age: 57 +/- 10 years, range: 34 - 74 years) with an infected pancreatic pseudocyst or infected pancreatic necrosis were included in the study. The diagnosis of infection in patients who had fever despite an adequate antibiotic regime was confirmed by endoscopic fine needle aspiration with a positive bacterial or mycological result. The mean C-reactive protein value before treatment was 202 +/- 58 mg/L and the mean leukocyte count was 13.25 +/- 4.75 GPt/L. Transgastric cyst drainage was performed using a therapeutic endoscopic ultrasound probe (Pentax 38 UX or Olympus GF UCT 140) with insertion of an 8-Fr double pigtail prosthesis. After balloon dilatation (12 mm) a normal gastroscope was inserted into the cavity and all the fluid and easy removable necrosis were removed. The prosthesis was removed 4 weeks after the end of the endoscopic treatment. Clinical and ultrasound follow-up were carried out 3 and 6 months after removal of the prosthesis. The mean follow-up was 60 weeks.

RESULTS

The technical success of the procedure was 96.7 %, the long-term success was 83.4 %. On average 2.7 (range: 1 - 16) procedures were necessary for complete removal of necrosis and the remaining fluid. Major complications (bleeding, perforation, fistulation) occurred in 10 %. In 10 % a secondary operation was necessary. The overall mortality rate was 6.6 %.

CONCLUSIONS

Endoscopic treatment of infected pseudocysts and infected postacute pancreatic necrosis using transgastral retroperitoneal endoscopy with fluid and necrosis removal is a minimally invasive and effective procedure in patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. However, the mortality rate of 6.6 % has to be taken into account.

The inducible crassulacean acid metabolism (CAM) plant Mesembryanthemum crystallinum accumulates malic acid during the night and converts it to starch during the day via a pathway that, because it is located in different subcellular compartments, depends on specific metabolite transport across membranes. The chloroplast glucose transporter (pGlcT) and three members of the phosphate translocator (PT) family were isolated. After induction of CAM, transcript amounts of the phosphoenolpyruvate (PEP) phosphate translocator (PPT) and the glucose-6-phosphate (Glc6P) phosphate translocator (GPT) genes were increased drastically, while triose phosphate (TP) phosphate translocator (TPT) and the pGlcT transcripts remained unchanged. PPT- and GPT-specific transcripts and transporter activities exhibited a pronounced diurnal variation, displaying the highest amplitude in the light. pGlcT transcripts were elevated towards the end of the light period and at the beginning of the dark period. These findings, combined with diurnal variations of enzyme activities and metabolite contents, helped to elucidate the roles of the PPT, GPT, TPT and pGlcT in CAM. The main function of the PPT is the daytime export from the stroma of PEP generated by pyruvate orthophosphate:dikinase (PPDK). The increased transport activity of GPT in the light suggests a higher requirement for Glc6P import for starch synthesis rather than starch mobilization. Most likely, Glc6P rather than 3-phosphoglycerate or triose phosphates is the main substrate for daytime starch biosynthesis in M. crystallinum plants in which CAM has been induced (CAM-induced), similar to non-green plastids. In the dark, starch is mobilized both phosphorylytically and amylolytically and the products are exported by the GPT, TPT and pGlcT. The transport activities of all three phosphate translocators and the transcript amounts of the pGlcT adapt to changing transport requirements in order to maintain high metabolic fluxes during the diurnal CAM cycle.

Apoptosis (AO) is a process by which cells typically undergo a form of nonnecrotic cellular suicide. AO normally allows the host to selectively delete cells from a given tissue site without producing bystander injury associated with necrosis. However, inappropriate induction of AO has been associated with a variety of acute as well as chronic pathological states and may contribute to the therapeutic nonresponsiveness frequently encountered in the septic animal/patient's organ function. In this respect, while AO has been demonstrated in a variety of immune cell tissues of septic animals it is unclear if it is present in the septic liver. Therefore, it was the aim of our study to determine if AO is evident in hepatocytes of polymicrobial septic animals. To assess this, C3H/HeN male mice were subjected to polymicrobial sepsis (cecal ligation and puncture) or sham- CLP (Sham). Hepatocytes were then harvested at 4 h (early hyperdynamic phase) or 24 h (late hypodynamic state) later, and indices of AO were assessed [cell cycle analysis of Annexin V/propidium iodide (PI) staining for flow cytometric analysis, DNA extracted, and cell death ELISA]. Plasma glutamic pyruvic transaminase (GPT) was also colorimetrically assessed as well as total viable cell yield as an index of hepatocellular necrosis. The results indicate that indices of hepatocellular AO, as determined by cell cycle analysis and cell death ELISA, were markedly increased in polymicrobial septic mice at 24 h. However, while an increase in DNA fragmentation/degradation could be consistently detected, the pattern was typically faint. Similarly, although there was an increase in Annexin V staining it was not dissociated from that of PI (necrotic index). Alternatively, necrosis (as evidenced by increased GPT levels at both 4 and 24 h) preceded the induction of all the indices of AO. Taken together, these data suggest a role for both necrosis and apoptosis in the evolution of hepatocellular injury encountered in the polymicrobial septic animal/patient which may represent a unique pattern of cell death under such conditions.

More than 11000 blood samples have been examined for glutamicpyruvic transaminase (<em>GPT</em>) and almost 9000 for Esterase D(EsD) in the Asian-Pacific area; <em>GPT</em>3 and <em>GPT</em>6 were detected in several population groups in New Guinea, Singapore and some Pacific islands. No previously undescribed alleles were found in either system.

The present study, conducted over a time course of 36 hr after CCl4 administration, describes sequential morphometric and biochemical changes which occur in livers of rats exposed to a combination of low levels of chlordecone (10 ppm for 15 days) and a single ip injection of CCl4 (0.1 ml/kg). Those changes were compared to hepatic alterations which occur in rats that received the same dose of chlordecone or CCl4 alone. Biochemical studies showed only trivial increases in levels of glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), and moderate but temporary increases in isocitrate dehydrogenase (ICD) after CCl4 alone. The combination of chlordecone and CCl4 resulted in significantly greater elevations of all three serum enzymes at all time intervals examined. Morphometric data showed no difference between normal diet controls and animals exposed to chlordecone alone as far as numerical density of hepatocytes or volume densities of hepatocytes with glycogen, lipid, dilated rough endoplasmic reticulum (RER), pyknosis, or mitoses. Morphometric analysis of livers from animals that received CCl4 alone showed decreases in numerical density, temporary decrease in percentage of hepatocytes containing glycogen, an increase in hepatocytes containing lipid, temporary increase in hepatocytes with dilated RER, and temporary increases in pyknotic nuclei. Soon after the initial hepatic injury was histologically evident between 4 and 6 hr, the number of mitoses increased dramatically and this progressed until complete recovery from CCl4 damage. From all indices of damage, complete recovery was evident by 36 hr after CCl4 administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Individuals with inflammatory bowel disease (IBD) are at increased risk of developing gastrointestinal cancer. Here, we have tested the possibility that chronic inflammation could trigger mutations. For this, we have used IL-10-deficient (IL-10-/-) mice, which spontaneously develop intestinal inflammation, in combination with a transgenic gpt gene and red/gam gene (gpt+IL-10-/-), which is a well-characterized mutation reporter locus. The total mutation frequency in the colon of gpt+IL-10-/- mice was about five times higher than that in normal gpt+IL-10+/+ mice. In the particular case of G:C to A:T transitions, the frequency of mutations in gpt+IL-10-/- mice was 4.1 times higher than that in control mice. Interestingly, the frequency of small deletions and insertions was also strikingly increased (approximately 10 times). The majority of the deletion or insertion mutations were observed in the monotonous base runs or adjacent repeats of short tandem sequences. In contrast, the frequency of large deletions, detected by loss of the Spi marker present in the red/gam transgene, was similar among the mouse strains. Finally, as a control, the mutation frequency in non-inflamed tissues, such as the liver, were similar between gpt+IL-10-/- mice and gpt+IL-10+/+ mice. Our data demonstrate that the chronic inflammatory environment in the colon promotes the generation of mutations.

We have identified a gene on 6q14-21 which restores senescence to immortal ovarian tumor cells. Single gpt tagged human chromosomes, present in mouse/human monochromosomal hybrids, were introduced into immortal human and rat ovarian tumor cells via microcell fusion. Analysis of chromosome transfer clones for cell morphology and growth properties revealed that chromosome 6 or 6q restored senescence to both human and rat ovarian tumor cells while chromosomes 10 or 14 did not affect the proliferative potential of these cells. Reversion to immortal growth concordant with loss of the donor chromosome confirmed the presence of a senescence gene on 6q. During continuous maintenance of microcell hybrids in MX medium, rare immortal revertant clones grew out of the human and rat senescent cell populations. Analysis of independent revertant clones of rat cells, for chromosome 6 markers, revealed a common deletion of chromosomal region 6q14-21 in all revertants. Restoration of senescence following introduction of a gpt tagged chromosome segment 6q13-21 into human and rat ovarian tumor cells confirmed the location of a senescence gene in this region. In contrast, introduction of a chromosome 6 lacking the region 6q14-21 did not impart senescence in these cells. Based on these results we assigned the senescence gene (SEN 6A) to region 6q14-21.

BACKGROUND

We have investigated the variation of acute radiation reactions in medium-risk patients with postmastectomy radiotherapy with regard to a possible correlation between radiation reaction of normal tissues and local tumor control.

METHODS

From 1985 through 1991, a total number of 194 patients received postmastectomy radiotherapy for breast cancer pT1-2pN0-2M0 at the University of Halle-Wittenberg. The lymphatics were irradiated by an anterior 9-MV photon field and the chest wall by an individually shaped anterior field with 9-MV electrons. Both fields received single doses of 2 Gy 5 times weekly up to a total dose of 44 Gy to the chest wall and 50 Gy to the lymphatics. All patients were routinely evaluated once weekly during radiotherapy for acute side effects by one examiner. Skin erythema was classified as mild, moderate or severe, esophagitis as being present in form of dysphagia or not and pneumonitis, if present, as asymptomatic (visible only on repeated chest X-rays) or clinically symptomatic. A differential blood count was also carried out once weekly. For this analysis, the records of all patients were retrospectively reviewed. The median follow-up at the time of analysis was 4.2 years.

RESULTS

Of the patients, 98 (51%) had a mild, 53 (27%) moderate and 43 (22%) a severe erythema. Furthermore, 38 patients (20%) had signs of esophagitis, 13 (7%) had asymptomatic and 26 (13%) symptomatic pneumonitis. Patients with severe erythema or erythema plus esophagitis and pneumonitis had a more pronounced decrease in lymphocyte count during treatment than patients with mild erythema: the lymphocyte nadir was 0.14 vs 0.73 Gpt/l in patients with severe vs mild erythema, and 0.36 vs 0.69 Gpt/l in patients with erythema plus esophagitis plus pneumonitis vs patients with erythema only, p < 0.05. Of the patients, 44 (22%) developed chronic side effects, mostly arm edema. There was no correlation between acute and late effects. An overall number of seven local recurrences (3.6%) occurred. The risk of developing a local recurrence within 5 years after treatment was 0% in patients with severe erythema or erythema plus esophagitis/pneumonitis vs 7% in patients with mild erythema only; this difference was marginally significant, p = 0.055.

CONCLUSIONS

This analysis showed a trend towards better local control in patients with severe acute radiation reaction of normal tissue. The data support a recent publication by Dahl and coworkers showing a linkage between acute radiation reaction of normal tissue and tumor response in patients with preoperative radiotherapy for rectal cancer. The correlation between acute normal tissue reaction and local control might be explained by interindividual variations in the intrinsic, genetically determined radiosensitivity. However, local factors might also be involved, e.g. induction of a cytokin cascade in cases of acute reactions in normal tissues.

OBJECTIVE

To perform a retrospective study to evaluate the long-term outcome of systemic cyclosporine treatment as an adjunct to topical corticosteroid treatment after penetrating keratoplasty (PKP).

METHODS

Twenty-six high-risk patients (27 eyes) who received systemic cyclosporine following PKP for an average of 5.4 months were compared with another series of 57 patients (57 eyes) who did not receive cyclosporine after PKP.

RESULTS

Endothelial rejection developed in 2 cases during cyclosporine treatment and in 6 cases after discontinuation. The rate of rejection-free graft survival was similar between the treated and the control groups. The control group showed a significantly higher rate of graft survival than the treated group. As side effects in the treatment group, transient elevation in blood urea nitrogen or creatine developed in 7 cases. Increase in glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT) developed in 4 cases. Severe side effects were absent throughout the series in both groups of patients.

CONCLUSIONS

Systemic cyclosporine treatment for several months did not reduce the incidence of rejection nor improve the rate of graft clarity in the long term in high-risk patients after PKP.

The effect of nonhistone protein HMG1 and HMG2 from pig thymus on the in vitro nucleosome assembly has been examined with plasmid pSV2-gpt DNA and pig thymus core histones in the presence of DNA topoisomerase I. In the absence of core histones, the direct binding of HMG proteins could induce negative superhelical turns in DNA at low ionic strength, but not at physiological ionic strength. The nucleosome formation in the higher histone-to-DNA ratios at physiological ionic strength was not facilitated by HMG proteins, in contrast to poly(L-glutamic acid). HMG proteins suppressed the nucleosome assembly in the moderate histone-to-DNA ratios, resulting in the reduction of fully supercoiled DNA topoisomers. The suppression by HMG proteins was not cancelled by poly(L-glutamic acid). These suggest that the highly acidic carboxy terminal of HMG proteins does not act as an assembly factor, and that the HMG proteins, on the contrary, suppress the nucleosome formation, probably by binding to DNA in a way to inhibit the assembly into core particles.

A single oral dose of the lyophilized deathcap fungus Amanita phalloides (85 mg/kg body wt) caused gastrointestinal signs of diarrhea, retching, and vomiting in beagles after a latent period of 16 hr. The pathologic lesions; the increases in serum transaminase (GOT, GPT), alkaline phosphatase, and bilirubin, as well as the fall in prothrombin time all indicated that liver damage was maximal at about 48 hr after poisoning. Four of twelve dogs given A. phalloides died with signs of hepatic coma within 35 to 54 hr with the biochemical values in the survivors reverting to normal by the ninth day. Silibinin administration (50 mg/kg) 5 and 24 hr after intoxication suppressed the serum changes and the fall in prothrombin time. The degree of hemorrhagic necrosis in the liver was markedly reduced, and none of the silibinin-treated dogs died.