Biomedical subjects
Publications and source records attributed to H Nara.
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We investigated the aetiological role of group A rotavirus in adults with acute diarrhoea in a 4-year prospective study. Of 683 patients with acute diarrhoea, 97 (14%) shed rotavirus as a sole agent, whereas six (5%) of 115 patients without diarrhoea shed rotavirus. Half of patients with rotavirus diarrhoea required admission to hospital. Unlike rotavirus diarrhoea in children, the occurrence of rotavirus-positive cases did not show a significant winter seasonality. Rotavirus infection should be included in the differential diagnosis of diarrhoeal diseases in adults.
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Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.
Symbiobacterium thermophilum is a tryptophanase-positive thermophile which shows normal growth only in coculture with its supporting bacteria. Analysis of the 16S rRNA gene (rDNA) indicated that the bacterium belongs to a novel phylogenetic branch at the outermost position of the gram-positive bacterial group without clustering to any other known genus. Here we describe the distribution and diversity of S. thermophilum and related bacteria in the environment. Thermostable tryptophanase activity and amplification of the specific 16S rDNA fragment were effectively employed to detect the presence of Symbiobacterium. Enrichment with kanamycin raised detection sensitivity. Mixed cultures of thermophiles containing Symbiobacterium species were frequently obtained from compost, soil, animal feces, and contents in the intestinal tracts, as well as feeds. Phylogenetic analysis and denaturing gradient gel electrophoresis of the specific 16S rDNA amplicons revealed a diversity of this group of bacteria in the environment.
Sulfamethoxazole (SMX), a hormone-mediated rodent-specific nongenotoxic carcinogen, was administered to CB6F1 mice carrying a human prototype c-Ha-ras gene (Tg-rasH2) at doses of 0, 25, 100 or 400 mg/kg/day and to the wild-type mice at a dose of 400 mg/kg/day in feed for 26 weeks to evaluate the carcinogenicity and to validate the Tg-rasH2 model. N-Methyl-N-nitrosourea was administered at an intraperitoneal dose of 75 mg/kg to Tg-rasH2 as a positive control and the experimental system was confirmed to be valid. Histopathological examination revealed adenomas of the lung and Harderian gland and hemangiosarcoma of the spleen at low frequencies in the Tg-rasH2 treated with SMX; however, no statistically significant differences were observed either in the onset or prevalence rates of these neoplasms compared with that in the control group. Between the wild-type mice and Tg-rasH2, the onset rate and prevalence of the neoplasms were not significantly different, but the neoplasms tended to be more frequent in Tg-rasH2 mice showing a sensitivity to tumorigenicity. Follicular epithelial cell hyperplasia was observed in the thyroid gland in the groups of Tg-rasH2 given 100 mg/kg SMX or more, but no neoplastic lesion was observed. SMX was judged to be negative for carcinogenic potential in Tg-rasH2 in the present study.
A nephrotoxicity study of Cefmatilen hydrochloride hydrate (S-1090) was conducted in rabbits at single oral doses of 250, 500 and 1000 mg potency/kg. All treated groups showed a decreased food consumption and a tendency for the body weight to decrease. Urinary protein and glucose were detected and slight increases of plasma creatinine and urea nitrogen were observed in the 500 mg potency/kg group. Urinary protein was also detected in the 1000 mg potency/kg group. In the histopathological examination of the kidney, tubular necrosis was observed in the 500 and 1000 mg potency/kg groups. No nephrotoxic signs were observed in the 250 mg potency/kg group. The NOAEL on the nephrotoxicity of S-1090 in rabbits was estimated to be 250 mg potency/kg.
The frequency, clinical profile, treatment and outcome of subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) were assessed retrospectively, based on the case records of SLE of the Jichi Medical School Hospital over a 20 year period. Clinically defined SAH was found in 10 (3.9%) out of 258 SLE patients, which represented a frequency higher than previously assumed. Five patients had active SLE and lacked an apparent cause of SAH, other than SLE. A high mortality rate (5/5), no visible aneurysm on angiogram (3/4), and an onset during intractable SLE or after discontinued or no steroid therapy because of medical noncompliance (4/5) were characteristic of patients with active SLE, and thus an earlier successful suppression of SLE, if possible, might have prevented their SAH. In contrast, in the 5 patients with inactive SLE, 2 out of 3 saccular aneurysms were successfully clipped and small bleeding of one patient without aneurysms remitted spontaneously without the need for additional steroid therapy. When one death, which occurred outside of medical care, was excluded, the survival ratio of the hospitalized SAH patients with inactive SLE was significantly better than that with active SLE (3/4 versus 0/5, P=0.0476). In conclusion, the relatively common occurrence of SAH in SLE patients, and a significantly different clinical impact of SAH in respect to active and inactive SLE, were suggested from the results.
We report three female patients with systemic lupus erythematosus complicated by massive intestinal hemorrhage during the recovery from lupus nephritis (case 1, 2) or central nervous system lupus (case 3) on high dose corticosteroid therapy. Large number of cytomegalovirus (CMV) antigen-positive leukocytes and cessation of bleeding with concurrent disappearance of the viral antigens after ganciclovir therapy indicated CMV colitis in all of the three patients. No recurrence of the symptom and a favorable response to ganciclovir without reduction in steroid regimen was common to these patients.
Clinical profiles and the treatment process of three female patients with systemic sclerosis (cases 1, 2, and 3) complicated by thrombotic microangiopathic hemolytic anemia (TMHA) were described. Thrombocytopenia preceded renal damage and hypertension in cases 1 and 2, although the chronological relationship between these parameters were unknown in case 3. Plasma exchange therapy using fresh frozen plasma was beneficial in cases 1 and 2. Cases land 3 presented with delirium and fluctuating psychosis, respectively. Early detection of thrombocytopenia and insidious hemolysis might be essential for starting effective plasmapheresis treatment in a part of patients with scleroderma kidney who present with thrombotic thrombocytopenic purpura (TTP) like disorder.
A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.
PURPOSE: To investigate the effects of an imaginary and a visual target on torsional optokinetic nystagmus (tOKN) and directional symmetry of tOKN. METHODS: Torsional OKN was induced by a rotating random dot pattern (52 degrees in diameter, constant angular velocity: +/-30 deg/sec to +/-52 deg/sec) with an imaginary or a visual target in 11 eyes of 10 healthy humans by dual-search coil methods. RESULTS: Intorsional OKN and extorsional OKN were symmetrical in their slow-phase gain. The mean slow-phase gain (0. 037/0.041, intorsion/extorsion) of tOKN during fixation on a visual target at the center of the rotating random dot pattern was significantly (P: < 0.002) smaller than that (0.051/0.052, intorsion/extorsion) during fixation on an imaginary target at the center of the rotating random dot pattern. The mean tOKN slow-phase beat duration (840 msec/724 msec, intorsion/extorsion) during fixation on the visual target was significantly (P: < 0.002) longer than that (585 msec/543 msec, intorsion/extorsion) during fixation on the imaginary target. In seven eyes of six subjects, the mean slow-phase gain and beat duration (0.034 and 812 msec) of tOKN during fixation on a visual target 6.5 degrees left or right from the center of the rotating random dot pattern were not significantly different from those (0.037 and 825 msec) with a visual target at the center of the rotating random dot pattern (P: > 0.3). CONCLUSIONS: A visual target spot suppresses tOKN by a nonpursuit visual system. Intorsional and extorsional OKNs were symmetrical.
Adult onset Still's disease was first reported by Bywaters in 1971. It is a systemic inflammatory disorder of unknown etiology, characterized by spiking fever, macular rash and polyarthritis. Although the prognosis is generally good, severe cases have been published. They include those with disseminated intravascular coagulation (DIC), hemophagocytosis, amyloidosis and respiratory failure. Among them, DIC is not uncommon. Prednisolone in a dose of 20-60 mg/day is required when patients fail to respond to nonsteroidal anti-inflammatory drugs (NSAIDs) or when they are accompanied by complications including pleuritis, pericarditis, liver dysfunction, severe arthritis and DIC. Recently, disease-modifying antirheumatic drugs (DMARDs) and immunosuppressive agents including cyclophosphamide and methotrexate have been shown to be effective for alleviating refractory cases and chronic arthritis.
BACKGROUND: Osteoclasts play crucial roles in bone resorption, which triggers bone remodeling. Molecular mechanisms underlying these osteoclast-specific biological functions remain elusive because only a limited number of osteoclast-specific genes have been identified. To circumvent this, we isolated a large number of osteoclast-specific genes by preparing a subtracted cDNA library of high quality. RESULTS: We first constructed a plasmid expression vector (pAP3neo) that allowed an efficient subtraction. Then, we improved the standard protocols for preparation of the cDNA library and the subsequent subtraction procedure. Using our protocol, we prepared a rabbit osteoclast cDNA library of high complexity. Subsequently, we prepared an osteoclast-specific cDNA library of high complexity by subtracting it with biotin-labelled mRNA, derived from rabbit spleen through the biotin-avidin method. The resulting library included a high proportion of full-length cDNA inserts. Using DNA dot blot analysis, we found that the osteoclast-specific cDNA clones were highly enriched in this subtracted cDNA library, i.e. nearly 70% of the analysed clones were primarily detected in osteoclasts but not in spleen. Multiple-tissue Northern analysis also showed that many of these clones were expressed almost exclusively in osteoclasts. DNA sequencing of randomly selected clones showed that 424 cDNA species out of 1136 analysed were novel. DNA sequencing also showed that our subtracted cDNA library was almost equalized, suggesting that the library may contain almost all of the osteoclast-specific genes. CONCLUSION: From these data, we conclude that our subtraction protocols, and the subsequent procedure for the analysis of the isolated clones developed here, are useful for the comprehensive isolation and identification of transcriptionally up- or down-regulated genes in general.
BACKGROUND: Many patients who require endoscopic treatments such as biopsy and polypectomy are given antiplatelet agents reluctantly. We have studied the effects of aspirin on colonic mucosal hemostasis. METHODS AND PATIENTS: We developed a new endoscopic device to make a standard incision (7-mm length) on the colonic mucosa to study colon bleeding time. We measured the colon bleeding time of normal colonic mucosa in 47 cases. The colon bleeding time and skin bleeding time (Simplate method) were measured before and one hour after aspirin ingestion (990 mg) in ten healthy subjects. RESULTS: The bleeding time of normal colonic mucosa was 156 +/- 71 (mean +/- standard deviation) seconds. Significant prolongation was noted in both skin bleeding time (357 +/- 192 vs. 477 +/- 183 seconds; P < 0.05) and colon bleeding time (155 +/- 47 vs. 244 +/- 169 seconds; P < 0.05) after aspirin ingestion. CONCLUSIONS: Bleeding time was measured safely under direct colonoscopic visualization. Aspirin prolonged the colon bleeding time. Therefore, endoscopists should be aware of a risk of abnormal bleeding after endoscopic biopsy and polypectomy in patients with aspirin use. Two days were necessary for colon bleeding time to become normalized in patients with aspirin use.
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It seems desirable to conduct as many function tests as possible in repeated dose toxicity studies, but is it practicable? The current status of conducting function tests in repeated dose toxicity studies in Japan was investigated by a literature survey of more than one thousand papers published in seven Japanese toxicology journals during the past 10 years and by a questionnaire survey directed to toxicologists among the Japan Pharmaceutical Manufacturers Association (JPMA) member companies. The function tests often carried out in repeated dose toxicity studies were, for example: 1) electro-retinography (ERG) and visually evoked potential (VEP) for visual test and tonometer for intraocular pressure; 2) auricular reflex, evoked response audiometry (ERA) and auditory brainstem response (ABR) to sound stimuli; 3) respiration and heart rate, electrocardiogram (ECG) and blood pressure by noninvasive cuff methods or using electronic devices such as telemetry; 4) body temperature, spontaneous motility and some adaptation tests (using rotarod and sloped plate in rats); 5) indocyanin (ICG) or bromosulfophtalein (BSP) for hepatic test; 6) phenolsulfonphtalein (PSP) and creatinine clearance for renal test; and 7) immunoglobulin, leukocyte phagocytosis, lymphocyte blastgenesis and natural killer cell (NK) for immuno-reaction test. Limitations to conducting function tests in repeated dose toxicity studies and issues to be resolved were discussed, based on questions and suggestions given by the respondents to the questionnaire. Although it certainly seemed desirable to conduct as many function tests as possible in repeated dose toxicity studies, most of the function tests so far introduced into toxicity studies were not satisfactory, because those tests could not be carried out under the restricted conditions of repeated dose toxicity studies, and not much reliable data from function tests were obtainable. A variety of function tests should firstly be incorporated into single dose toxicity studies together with development of a new concept for methodology in safety pharmacology.