BACKGROUND: Previous studies have identified the association between diabetes mellitus and liver cancer. However, the detail of this association is still unclear, in terms of confounding factors, the trend according to the duration of diabetes, and the interaction between diseases associated with the liver cancer and this association. The purpose of the present study was to examine the association between diabetes and liver cancer in view of the trend and the interaction. METHODS: The baseline survey was conducted during the period 1986-1989 among the general population of Fukuoka Prefecture, Japan (15 417 persons aged 30-79 years). The respondents were assessed for history of diabetes, age at which they had had diabetes, and other covariates by means of a baseline questionnaire. A total of 7308 persons aged 40-79 years were retrieved for the main analysis and 4902 persons for a subcohort from which the information on history of diseases associated with liver cancer were obtained. The relative risks (RRs) and their 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model. RESULTS: After adjustment for smoking, alcohol and the diseases associated with liver cancer, the RR for liver cancer was 2.06 (95% CI=1.01-4.19). Diabetes increased the risk of liver cancer in persons with hepatitis and/or cirrhosis (RR=2.90, 95% CI=1.13-7.41). However, the RR of diabetes for liver cancer was 1.35 (95% CI=0.41-4.43) in persons without hepatitis and cirrhosis. The trend according to the duration of diabetes was not seen. CONCLUSIONS: A significant association between diabetes and liver cancer was observed. Moreover, this association was modified by hepatitis and cirrhosis.

Adult↗

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The micronucleus test of methyl methanesulfonate with mouse peripheral blood reticulocytes using acridine orange-coated slides.

The usefulness of the micronucleus assay using mouse peripheral blood erythrocytes and acridine orange (AO)-coated slides was evaluated with methyl methanesulfonate (MMS). The micronucleus test was carried out at doses ranging from 20 to 80 mg/kg body weight in CD-1 mice by intraperitoneal injection. Peripheral blood cells were examined from 0 to 72 h after treatment at 12- or 24-h intervals. Bone marrow cells from other mice treated with 80 mg/kg MMS were also sampled at the same times. The frequency of micronucleated reticulocytes (MNRETs) increased dose-dependently at every sampling time except 72 h, and the maximum frequency of MNRETs was observed at about 36 h after treatment. Micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow after a dose of 80 mg/kg were significantly induced at 12 h to 36 h, and the maximum frequency of MNPCEs was observed at 24 h after treatment. The induction of MNRETs was delayed by about 12 h compared to that of MNPCEs in bone marrow, and the maximum frequencies of MNRETs were lower than those of MNPCEs, but the induction of MNRETs by MMS was significant and dose-dependent. It is concluded, therefore, that bone marrow cells could be replaced by peripheral blood cells as material for the micronucleus assay using AO-coated slides.

Acridine Orange↗

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Morphological studies of growth and aging in the lungs of Fischer 344 male rats.

Observations by light microscopic morphometry and scanning electron microscopy were performed on the lungs from 86 specific pathogen-free Fischer 344 male rats between 1 day and 32 months of age. The distribution curve of the mean chord length of the gas exchanging area appeared as a single peak (approximately 70 microns) at day 1, and two peaks (approximately 50 and 90 microns) were seen at day 7 when the first alveoli appeared. At 3 months of age, the distribution curve peaks began to decrease gradually, becoming more flattened with a wide base to a maximum 200 microns. Between 27 and 32 months of age, ductectasia occurred and the alveolar surface appeared more irregular and rough, but no destruction of the alveolar wall was observed. From these observations, it was concluded that the first alveoli appear by 7 days of age in male Fischer 344 rats, that the alveolar size gradually increases after 3 months of age, and that ductectasia appears after 27 months of age. These changes might reflect changes in the matrix of the alveolar walls due to nutritional deterioration in old age, concomitant with cellular atrophy of this zone.

Aging↗

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Augmentation of tissue ATP level during digestion using preoxygenated perfluorocarbon results in high islet yield-new strategy for islet isolation.

BACKGROUND: Recently, preservation using oxygenated perfluorocarbon (the two-layer method) has shown beneficial effects on islet yield and viability. In this paper, we apply this concept on isolation processes to examine the effectiveness of oxygenation. METHODS: Rat pancreata were digested using four different methods: (groups 1A, 1B, 2A, and 2B) with or without oxygenated perfluorocarbon in groups 1 and 2, respectively. Adenosine was added into the collagenase solution in subgroup A whereas it is not added in subgroup B. RESULTS: Tissue oxygen tension in group 1 was about 0 during digestion; whereas it rapidly reached about 300 mm Hg and was maintained in group 2. Tissue ATP level just after laparotomy (control) was 4.2 +/- 0.7 micromol/g dry weight. The ATP levels after digestion were 0.12 +/- 0.03 in group 1A (P < 0.01 vs control); 0.70 +/- 0.10 in group 1B (P < 0.01 vs control); 0.30 +/- 0.18 in group 2A (P < 0.01 vs control); and 2.90 +/- 0.80 in group 2B (P = 0.19 vs control). Islet yields (IEQ/pancreas) were 1600 +/- 400 in group 1B; 1400 +/- 400 in group 1B; 1300 +/- 400 in group 2A; and 2400 +/- 100 in group 2B. The amount in group 2B was significantly greater than that in the other three groups. CONCLUSIONS: Oxygen provision by preoxygenated perfluorocarbon itself showed no beneficial effect on islet yield. However, if oxygen provision was associated with adenosine administration into the pancreas, tissue ATP levels after digestion were well maintained, and a greater number of islets were retrieved.

Adenosine Triphosphate↗

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Two cases of frosted branch angiitis with central retinal vein occlusion.

BACKGROUND: Frosted branch angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted branch angiitis in adults. Both had poor visual outcomes because of associated central retinal vein occlusion and neovascular glaucoma. CASES: Case 1 was a 36-year-old woman. Almost all retinal veins and some retinal arteries showed vasculitis in her right eye, and veins were slightly dilated and sheathed. Case 2 was a 23-year-old woman. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandering, and sheathed. Retinal hemorrhages were also observed. In both cases, after systemic steroid therapy the retinal vasculitis gradually decreased, but central retinal vein occlusions gradually developed. Despite systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity diminished in both cases. CONCLUSIONS: Two cases of frosted branch angiitis complicated by retinal vein occlusion are reported. Careful observation of retinal blood flow is necessary in frosted branch angiitis in adults.

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Synthetic lipid A-induced uveitis and endotoxin-induced uveitis--a comparative study.

Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation induced by lipopolysaccharide (LPS). The lipid A (LA) region of the LPS chemical structure is believed to be responsible for virtually all the biological activities induced by LPS. The aim of this study was to perform a more detailed investigation of the potency of LA in reproducing EIU. Various doses of either LPS or LA were injected into the footpad of an inbred strain of Lewis rat and the inflammation patterns were compared by assessing the protein concentration, by cytological study, and by determining the inflammatory cell content in samples of aqueous humor obtained during 96-hour follow-up. Evaluation of the cell number and protein concentration ratio of both groups showed the LA-stimulated group presented a higher ratio than the LPS group (Welch's t-test, (P < 0.00001). It was noteworthy that even the injection of high doses of LPS could not reproduce the level of cellular infiltration induced by LA. Histological study confirmed the enhanced cellularity in the LA group, neutrophils being predominant in both the LPS- and the LA-stimulated groups. The divergent findings in these two models of uveitis may be valuable to further investigations of the process of inflammatory cell migration into the anterior chamber of the eye.

Animals↗

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Immunogenetics of episcleritis in leprosy.

Human leukocyte antigens (HLA) were analyzed among Japanese leprosy patients to identify any possible determinants in the development of episcleritis in leprosy patients. Seventy-nine Japanese leprosy patients (33 patients with history of episcleritis and 46 patients without episcleritis) and 114 healthy control subjects were investigated. Human leukocyte antigen-class I and class II specificities were determined serologically by the standard microcytotoxicity test. The HLA-DRB1, -DRB5, -DQA1, and -DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism analyses. The frequency of HLA-Cw3 was significantly increased among the patients with episcleritis (66.7%) compared to patients without episcleritis (43.5%; odds ratio = 2.6, P < 0.05). The frequency of HLA-DR4 was significantly decreased among the patients with episcleritis (15.2%) compared to patients without episcleritis (39.1%; odds ratio = 0.28, P < 0.05) and the controls (46.5%; odds ratio = 0.21, P < 0.001). At the genomic level, frequencies of the HLA-DRB1*0405, -DQB1*0401, and -DQB1*0302 alleles were significantly decreased among the patients with episcleritis (0%, 0%, and 6.1%, respectively) compared to patients without episcleritis (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09, and 0.18, P < 0.05). HLA-DRB1*0405 and -DQB1*0401 were also significantly decreased among the patients with episcleritis compared to the controls (29.8% and 29.8%; odds ratio = 0.04, P < 0.0001). Our results suggest that HLA-Cw3 antigen confers the susceptibility to the development of episcleritis among Japanese leprosy patients. Concurrently, the DRB1 (the -DBR1*0405), and/or DQB1 (the -DQB1*0401 and -DQB1*0302) alleles might provide protection against leprous episcleritis.

Alleles↗

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Ciclosporin microemulsion preconcentrate treatment of patients with Behçet's disease.

PURPOSE: The new microemulsion preconcentrate (MEPC) formulation of ciclosporin has been developed to reduce problems in intestinal absorption and to stabilize fluctuations in blood levels. A multicenter, open-label clinical trial of MEPC was conducted to assess its efficacy and safety in Behçet's disease patients with ocular involvement. METHODS: The patient population comprised 17 de novo patients (patients not previously treated with ciclosporin in the currently available formulation) and 30 patients whose ciclosporin formulation was switched from the conventional formulation to MEPC. The patients were treated with the test formulation for 16 weeks in the former (de novo) group and for 12 weeks in the latter (switched) group. RESULTS: In the de novo group, ocular attacks decreased significantly as compared to the pretreatment incidence in 11 of the 14 patients (78.6%) evaluated after MEPC therapy. Ocular attacks also decreased significantly in the switched group. In the de novo group, visual acuity improved with MEPC therapy in 20 of the 28 eyes (71.4%) examined, and the overall efficacy evaluation was "improved" or "markedly improved" in 13 of the 16 patients evaluated (81.3%). The one case each of onset of neuro-Behçet's disease and intestinal Behçet's disease observed in the de novo group were regarded as adverse reactions. CONCLUSION: It was concluded that ciclosporin MEPC is useful for controlling the ocular symptoms of Behçet's disease, and that it can be used as effectively and safely as the conventional formulation.

Adult↗

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Epidemiological features and visual prognosis of Behçet's disease.

PURPOSE: Retrospective evaluation of epidemiological features and visual prognosis of patients with Behçet's disease (BD) who visited the University of Tokyo Hospital between 1974 and 1993. OBSERVATIONS: During the survey period, more than 100 new patients with BD visited the uveitis clinic in each 5-year period. The number of new patients decreased in the most recent 5-year period from 1989 to 1993. Although BD has always been more prevalent in men, the percentage of women has increased to 24.7% (19/77) in the most recent 5-year survey period. The percentage of patients who initially manifested ocular symptoms in their third or fourth decade was more than 70%. The proportion of the incomplete type of BD gradually had increased to 62.3% (48/77) by 1993. Among the extraocular major symptoms, oral aphtha and skin lesions have been frequent and genital ulcer has become less frequent in the last 20 years. The patients whose visual acuity was better than 0.4 at the first visit in the 1984-1993 period had a significantly better visual prognosis than the patients in the previous 10-year period. The main drug therapy consisted of colchicine and cyclophosphamide in the earlier 10-year period, and of colchicine and ciclosporin in the later 10-year period. CONCLUSIONS: Behçet's disease is still one of the most frequently encountered types of endogenous uveitis. There have been some changes in the epidemiological features of the patients with BD over the past 20 years. The introduction of ciclosporin in 1985 is probably responsible for the improvement of the visual prognosis in BD patients.

Adult↗

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Experimental uveitis induced by intravitreal or intravenous lipoteichoic acid in rabbits.

PURPOSE: To investigate the role of lipoteichoic acid (LTA), one of the cell wall components in gram-positive bacteria in uveitis. METHODS: Intraocular inflammation in rabbit eyes was induced by intravitreal or intravenous injections of LTA from Staphylococcus aureus or Streptococcus sanguis. The inflammation was monitored progressively with the laser flare-cell photometer, and examined by periodic clinical observations. Histological examinations were performed 24 hours after administration, and aqueous protein concentrations and cell counts were also determined. RESULTS: Intraocular inflammation appeared within 6-9 hours of LTA intravitreal injection. became maximal at about 24-48 hours postinjection, and lasted for nearly 6 days. Intraocular inflammation was also induced by intravenous injection of LTA at a higher dose. Inflammation reached a peak 4-5 hours after injection, and rapidly disappeared in 24 hours. No cellular response was observed in intravenous LTA-treated eyes. CONCLUSIONS: This study demonstrates that LTAs from gram-positive bacteria have the biological activity to induce intraocular inflammation in rabbits by intravitreal or intravenous injection. Therefore, we suggest that LTA may play a role in the pathogenesis of uveitis as one of the etiological factors.

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Detection of the integrated feline leukemia viruses in a cat lymphoid tumor cell line by fluorescence in situ hybridization.

Feline leukemia virus (FeLV) is a type-C retrovirus associated with lymphoid and hematopoietic malignancies in cats. The FeLV-induced tumors are thought to be caused, at least in part, by somatically acquired insertional mutagenesis in which the integrated provirus may activate a proto-oncogene or disrupt a tumor suppressor gene. This study was undertaken to enumerate and map the acquired proviral insertions in the genome of a feline thymic lymphoma cell line (FT-1) infected with FeLV. Fluorescence in situ hybridization (FISH) combined with tyramide signal amplification was applied on the chromosome specimen of FT-1 cells and normal cat lymphocytes, with an entire FeLV-A genome used as a probe. Specific hybridization signals were detected from only the metaphases of the FT-1 cells, not from those of normal cat lymphocytes. Statistically based on the Poisson's distribution, at least six loci of chromosomal regions, A2p23-p22, B2p15-p14, B4p15-p14, D4q23-q24, E1p14-p13, and E2p13-p12, appeared to be positive for FeLV integration. Consistently, Southern blot hybridization analysis using an FeLV LTR-U3 probe specific for exogenous FeLV showed the integration of at least six FeLV proviral genomes in FT-1 cells. The cytogenetic technique employed here will provide valuable molecular tags to reveal unidentified tumor-associated genes in FeLV-associated tumor cells.

Animals↗

PubMedDate not supplied

Hematologic abnormalities and outcome of 16 cats with myelodysplastic syndromes.

We investigated the hematologic abnormalities and prognoses in 16 cats with myelodysplastic syndromes (MDS). Nonregenerative anemia, thrombocytopenia, and neutropenia were observed in 15, 13, and 4, respectively, of the 16 cats with MDS. Morphologic abnormalities characteristic of MDS included megaloblastoid rubricytes (9 cats), hyposegmentation of neutrophils (7 cats), nuclear abnormality of rubricytes (10 cats) and neutrophils (13 cats), and micromegakaryocytes (10 cats). Disease in these 16 cats was subclassified into refractory anemia (RA; 8 cats), RA with excess of blasts (RAEB; 5 cats), RAEB in transformation (RAEB in T; 1 cat), and chronic myelomonocytic leukemia (CMMoL; 2 cats), according to the human French-American-British (FAB) classification. In the cats in which the clinical outcome was known, 3 of 6 cats with high blast cell count MDS, including RAEB, RAEB in T, and CMMoL, developed acute myeloid leukemia, but only 1 of 8 cats with low blast cell count MDS (RA) developed acute myeloid leukemia. Based on the Dusseldorf scoring system for the prognosis of human MDS, the survival times of the cats showing high scores (> or =3 points) were significantly shorter than those of the cats with low scores (<3 points). The FAB classification and Dusseldorf scoring system were considered to be useful for predicting the prognosis of feline MDS. Furthermore, 15 of the 16 cats with MDS in this study were infected with feline leukemia virus, indicating its possible etiologic role in the pathogenesis of feline MDS.

Anemia↗