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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 595 records · Page 33Linked to original sources

Demonstration of antigen-specific immune response against Streptococcus sanguis.

The genetic control of Streptococcus sanguis antigen response was studied. Mice sensitized with inactivated S. sanguis organisms antigen-injected at the base of the tail developed footpad swelling. Those with an I-Ak,q,r region of H-2 showed a strong footpad response, whereas those with an I-Ab,d,s region showed a weak response to S. sanguis cell wall antigen. Footpad response was mediated by CD4+,8- T cells by using in vitro monoclonal antibody treatment. Similar evidence of genetic control was obtained with an in vitro T cell proliferation assay. However, quantitation of antibodies against S. sanguis showed that antibody production was not controlled by H-2. These results indicated that both in vivo footpad swelling and in vitro T cell proliferation responses were functions of helper (CD3+,4+,8-) T cells and controlled by the I-A region of H-2.

Animals↗

Patterns in genome evolution.

Among the recent advances that have furthered our understanding of genome evolution, some of the most important information has come from studies on the conservation of the mammalian X chromosome and the conservation of several linkage groups in divergent mammalian species. In addition, I believe that studies on gene duplication by tetraploidy in teleost fish provide evidence that the mammalian ancester underwent a round or two of tetraploid evolution, presumably at the stage of fish. It is possible that we might soon be able to deduce the genomic structure of the Devonian fish ancestor.

Animals↗

Crystallization and preliminary X-ray diffraction studies of a mammalian steroid dehydrogenase.

20 beta-Hydroxysteroid dehydrogenase from the cytosolic fraction of neonatal pig testis is a NADPH-dependent enzyme that catalyzes the reduction of the C-20 ketone of C21-steroids. It is 85% homologous in amino acid sequence to the human enzyme, carbonyl reductase. The enzyme has been crystallized from 36% saturated ammonium sulfate in 10 mM 2-[N-Morpholino]ethanesulfonic acid buffer. The size and the quality of nicely formed square bi-pyramidal crystals were improved by using a "seeding" technique. The crystals diffract X-rays to at least 2.5 A resolution. The space group is P4(1)2(1)2 (or P4(3)2(1)2) and the unit-cell dimensions are a = b = 58.53 A, c = 165.64 A. There is one molecule (M(r) = 30.5 kDa; 289 amino acid residues) in the asymmetric unit. An intensity data set to 2.5 A has been collected with an overall Rmerge of 6.6% for all reflections.

Animals↗

Sequence dependence of the hyperthermic potentiation of carboplatin-induced cytotoxicity and intracellular platinum accumulation in HeLa cells.

We have examined the enhancement of cytotoxic effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin) by hyperthermia in HeLa cells using different regimes of timing and sequence. The results were compared with those obtained with cis-diamminedichloroplatinum(II) (cisplatin). We found that cisplatin simultaneously combined with heat was the most cytotoxic toward HeLa cells of the various timing and sequencing conditions studied. On the other hand, for carboplatin, drug treatment immediately following or during heat exposure showed the greatest effect. Intracellular platinum concentration in HeLa cells treated with heat before carboplatin showed a 2.75-fold increase over that in cells treated with the drug alone. The ratios for carboplatin given before, or during heating, were 0.67 and 1.42 respectively. Simultaneous exposure of cells to cisplatin and heat led to a 1.64-fold enhancement in cisplatin accumulation, compared to 0.92- and 1.24-fold increase for cells treated with cisplatin before and after heat respectively. Although each drug exposure prior to heat was less cytotoxic toward HeLa cells than any other heat/drug combination sequences, the platinum concentration was less than seen with each drug alone. Even though heat exposure prior to and during carboplatin showed a similar toxicity, platinum concentration in cells treated with heat prior to carboplatin was higher than that in cells treated with heat and carboplatin simultaneously. Thus, increased cytotoxicity cannot always be explained on the basis of intracellular platinum concentration. It is clear however that, differing from cisplatin, exposure of cells to heat prior to or during carboplatin administration results in the greatest cell kill.

Biological Transport↗

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats.

Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41.5 degrees C) was examined using a F344 rat model. The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts. Carboplatin produced profound depression of platelet counts which was over three-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin-mediated haematological toxicities were significantly enhanced by WBH. The depth of decrease in platelet, RBC and WBC counts induced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) combined with WBH was identical to that induced by the MTD of carboplatin (70 mg kg-1) alone. The TERs of carboplatin-mediated thrombocytopenia, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The thermal enhancement of cisplatin mediated haematological toxicity was similar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2.4 for anaemia and 1.9 for leukopenia. These data, demonstrating thermal enhancement of cisplatin or carboplatin-mediated haematological toxicity, must be taken into account in the clinical application of the combination therapy of platinum and WBH.

Anemia↗

Cytophotometric DNA content and argyrophilic nucleolar organiser regions of oesophageal carcinoma.

The cytophotometric DNA content and the argyrophilic nucleolar organiser regions (AgNORs) of biopsy specimens taken before undergoing any treatment were examined in 91 surgically treated oesophageal carcinoma cases. There was a significant linear dependence between the mean DNA content and the number of AgNOR per nucleus (AgNOR number) (r = 0.615, P < 0.001). The DNA distribution pattern and the range of the AgNOR number also showed a significant correlation (P < 0.01). Twenty three of 28 cases with a low AgNOR number (< 4) were then determined to have a diploid pattern (type II), while 17 out of 22 cases with a high AgNOR number (> or = 6) had high ploidy values (type IV). The patients with a type II DNA distribution pattern and a low AgNOR number thus showed a good post-operative course with a 5 year survival rate of 55.2%, whereas no patients survived over 4 years among the 17 cases with both a type IV DNA pattern and a high AgNOR number (P < 0.001). These data thus demonstrate the close relationship between cytophotometric DNA content and AgNOR number and suggest that the combined detection of these two parameters, using biopsy specimens, should be of benefit in making an accurate preoperative evaluation of prognosis for patients with oesophageal carcinoma.

Adult↗

Differentiation-associated localization of nPKC eta, a Ca(++)-independent protein kinase C, in normal human skin and skin diseases.

The expression of nPKC eta, a Ca(++)-independent isoform of protein kinase C in normal human skin, and skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, nevus pigmentosus, and seborrheic keratosis, were examined by immunohistochemical staining using a polyclonal antibody raised against a synthetic peptide at a diverse region of the nPKC eta molecule. In normal epidermis, the strongest staining was observed in the uppermost granular layer with no staining of the spinous or basal layers. The inner layer of the intra-epidermal eccrine duct was also strongly stained. Weak staining was observed in several layers of the outer root sheath of the follicular infundibulum. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, intradermal eccrine duct, arrectores pilorum, melanocytes, Langerhans cells, fibroblasts, or blood vessels. In psoriatic skin, stained keratinocytes were distributed in the suprabasal layers with the most being observed in the uppermost layer and the least in layers closed to the basal layer. In squamous cell carcinoma, weak staining was observed in the keratotic cells around horny pearls. In the basal cell epithelioma and nevus pigmentosus, the cells were not stained, whereas in seborrheic keratosis, cells that stained were located in the granular layer. We conclude from the evidence presented above that nPKC eta is expressed in close association with epidermal differentiation in normal skin and skin diseases.

Adult↗

Glycogenosis type V (McArdle's disease) with hyperuricemia. A case report and clinical investigation.

A 28-year-old male with glycogenosis type V associated with continuous hyperuricemia during mild daily activities is reported. An aerobic exercise test using a bicycle ergometer revealed that purine metabolites, i.e., ammonia, inosine, hypoxanthine and xanthine, were transiently increased by the exercise and that a subsequent increment in uric acid continued until the following day. The accelerated purine degradation by the muscle exercise was thus shown to be able to cause the overt hyperuricemia in a patient with glycogenosis type V. Therapeutic use of fructose for glycogenosis was disappointing due to fructose-induced hyperuricemia. A search for myogenic hyperuricemia is essential for therapeutic trials.

Adult↗

Three-dimensional study of glomerular lesions in murine chronic graft-versus-host reaction by the quick-freezing and deep-etching method.

In murine chronic graft-versus-host reaction (GVHR), the immune complex composed of antoantibodies has been considered to induce human lupus-like nephritis. We prepared the replica membranes and immunoelectron-microscopic specimens of glomeruli of GVHR mice. The immunoelectron-microscopic examination revealed that immune deposits were noted mainly in the mesangial matrices and subepithelial area. The replica membranes showed various sizes of the deposits in the same portions. Moreover, fine fibrils around the deposits were strongly disrupted. Microfilaments were increased in the cytoplasm of podocytes and endothelial cells were slightly detached from glomerular basement membrane. In this model system, the immune deposits might play an important role in keeping the glomerular integrity.

Animals↗

Survival rate after vitreous surgery in patients with diabetic retinopathy.

We studied factors affecting the survival rate after vitreous surgery in 73 patients with diabetic retinopathy, who had undergone vitreous surgery between 1982 and 1987, according to the life-table theory and multivariate analysis. The 5-year survival rate was 84.8%; the mean age at death was 62.1 +/- 7.1 (mean +/- SD) years; the mean postoperative survival time was 34.0 +/- 25.2 months; the most common cause of death having been cardiovascular disease, which occurred in 5 of the 13 (38.5%) patients who had died. Patients with triopathy essentially require very careful systemic management, because this state was definitively associated with a decline in postoperative survival.

Aged↗

[Successful treatment with lobenzarit disodium in case of Churg-Strauss syndrome].

In this case the patient was a 62-year-old male with a chief complain of sensory disturbance of the extremities. In January 1987 he was diagnosed as having bronchial asthma by a neighboring doctor and began to receive prednisolone (PSL) therapy at his hospital on an ambulatory basis. Later on, in January 1990, he developed dyspnea, epigastralgia, ecchymoses and muscle weakness of the lower extremities, with which he was admitted to the neighboring hospital, where he was started on treatment of asthmatic attacks with 30 mg/day of PSL. However, because muscle weakness of his extremities became gradually worse, he was transferred to our hospital. Physical examination on admission revealed an absence of knee and ankle jerk, sensory loss in the bilateral hands, legs and feet and diminished muscle strength of the extremities. Significant laboratory findings included leukocytosis, eosinophilia (4743/mm) and elevated serum IgE concentration (4900 IU/ml). Histologic evidence of vasculitis with an associated infiltration by eosinophils was noted on skin biopsy. These findings led to a diagnosis of Churg-Strauss syndrome. Treatment was started with PSL at 40 mg/day. However, as asthmatic attacks and eosinophilia were refractory to the conventional therapies, concomitant lobenzarit disodium (CCA), 240 mg/day was initiated. On increasing the dosage of CCA to 320 mg/day because of unsatisfactory symptomatic responses elicited at the initial dose level, the patient became free from an asthmatic attack with a return to normal of his eosinophilic count. He was discharged virtually asymptomatic while being placed on a regimen of PSL at 5 mg/day.

Churg-Strauss Syndrome↗

Vitreous hemorrhage associated with acute posterior vitreous detachment--a case report.

A case of vitreous hemorrhage associated with acute posterior vitreous detachment was reported. The patient was a 64-year-old man who complained of floaters in his left eye of one-week duration. His previous medical and ocular histories were unremarkable. Slit-lamp examination with Goldmann three-mirror contact lens showed complete posterior vitreous detachment in both eyes. Ophthalmoscopic examination and fluorescein angiogram revealed a partial defect in retinal blood flow in the midperipheral area of the superotemporal region of the left fundus. On follow-up examination, recovery of the retinal circulation was observed in that region and the vitreous hemorrhage had spontaneously resolved. The diagnosis was made in the left eye of rupture of retinal vein due to vitreous traction associated with acute posterior vitreous detachment without retinal break formation.

Acute Disease↗

[Clinical effects of low-dose and long-term erythromycin in diffuse panbronchiolitis with chronic respiratory failure].

We studied the effects of erythromycin (EM) in diffuse panbronchiolitis (DPB) with chronic respiratory failure. Seventeen patients with DPB or sinobronchial syndrome receiving home oxygen therapy (HOT) were treated with EM of 400-600 mg/day for twelve months. Five patients discontinued HOT, and hypoxemia was improved in five other patients. Clinical effects were evident at one month after the start of EM administration, and a stable state was achieved after six months of EM therapy. FEV1 was significantly increased in pulmonary function tests. Factors which influenced the effects of EM included the period between onset of clinical symptoms and commencement of HOT and/or between commencement of HOT and administration of EM. EM was effective for patients with obstructive, but not constrictive impairment in pulmonary function tests. These findings indicate that EM is effective for DPB even in patients with chronic respiratory failure.

Adult↗

[Serological diagnosis of adenovirus conjunctivitis].

We compared the serum antibody titers against adenoviruses of pair sera and the identification of isolated adenovirus from 17 patients with acute conjunctivitis. Isolated adenoviruses were Ad3 in ten cases, Ad8 in four cases, Ad37 in two cases, and Ad4 in one case. Among these cases, eleven cases showed identical results in a neutralization test. In one patient from whom Ad3 was isolated, no neutralizing antibody was found. In 3 patients from whom Ad8 or Ad37 was isolated, there were discrepancies between serological results of the neutralization test or the haemagglutination inhibition test, and viral isolation. Antibody titers against adenoviruses subgenus D, such as Ad8, 19 and 37 were increased not only for the isolated serotypes, but also for other serotypes of this subgenous.

Adenovirus Infections, Human↗

The dysfunction of peripheral blood dendritic cells in patients with mixed connective tissue disease.

The morphological findings and functions of peripheral blood dendritic cells (DC) from patients with mixed connective tissue disease (MCTD) were compared with those of DC from normal subjects. DC from both groups possessed typical dendritic processes and showed HLA-DR antigens and C3bi receptor. The autologous mixed lymphocyte reaction (MLR) and autologous concanavalin A (Con A)-induced T cell proliferation using DC as stimulating cells and accessory cells were significantly depressed in patients with MCTD. In the allogeneic MLR and allogeneic Con A responses, DC from patients with MCTD were poorer stimulating cells and accessory cells. The dysfunction of DC also, as one of the various immune abnormalities, must play a role in the appearance of clinical features.

Adolescent↗

A song in praise of peptide palindromes.

Peptide palindromes are invariably found in all proteins, and long palindromes exceeding 10 residues in length are not rare. They are particularly abundant in DNA-binding proteins such as H1 histone. When a complementary strand of the coding sequence is translatable being free of a chain terminator, a complementary protein encode by it becomes equally abundant in peptide palindromes. The simultaneous musical transformation of both strands of mouse H1 histone variety-1 DNA enable us to appreciate the symmetrical beauty of successive palindromes appearing in both H1 histone and its complementary protein.

Amino Acid Sequence↗