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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 649 records · Page 36Linked to original sources

[A case of adult onset hypophosphatemic vitamin D resistant osteomalacia].

A case of adult onset hypophosphatemic vitamin D resistant osteomalacia is described. A 40-year-old female who complained of thorax and lumbar pain and gait disturbance was admitted to our hospital on 7 November, 1988. The patient had hypophosphatemia with normal plasma calcium, parathyroid hormone and 25-hydroxy vitamin D3 concentrations, but had decreased tubular reabsorption of phosphate and decreased plasma 1, 25-dihydroxy vitamin D3 concentrations. The iliac crest bone biopsy showed osteomalacic changes. The 99mTc-MDP bone scintigram showed evidence of increased bone turnover with raised plasma alkaline phosphatase concentrations. After treatment with oral 1 alpha-hydroxy vitamin D3 (3-6 micrograms/day) and intravenous or oral phosphate supplement (0.47-1.74g/day), the subjective and clinical findings improved.

Adult↗

[Enhanced production of in vitro tumor necrosis factor-alpha from monocytes in Behçet's disease].

In vitro tumor necrosis factor-alpha (TNF-alpha) production from peripheral blood monocytes (PBMC) was investigated among 12 patients (male: 7, female: 5) with uveoretinitis of Behçet's disease and 6 age-matched healthy controls. TNF-alpha production of PBMC after the stimulation with lipopolysaccharides (LPS) was significantly enhanced in Behçet's disease patients with active uveoretinitis (21.5 +/- 2.8 U/ml) compared with both controls (5.7 +/- 1.8 U/ml) (p < 0.01) and inactive cases (5.1 +/- 1.4 U/ml) (p < 0.01). In the cases with active uveoretinitis, TNF-alpha production in the period of ocular attack (7.2 +/- 6.2 U/ml) was significantly lower than that of the post-attack period (24.4 +/- 13.9 U/ml) (p < 0.02). These results may indicate that TNF-alpha plays an important role in the immunopathogenesis of uveoretinitis in Behçet's disease.

Adult↗

[A case of sarcoidosis associated with Sjögren's syndrome].

A 49-year-old woman, who has had a past history of Raynaud's phenomenon since 1981, dry mouth since 1987 and dry eyes since 1990, was admitted to our hospital complaining of general fatigue, bilateral gonalgia, and shortness of breath in April 1991. Physical examinations revealed bilateral parotid gland enlargement and bilateral uveitis. Her family history included mixed connective tissue disease in her eldest daughter. Laboratory findings indicated an elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and elevation of serum lysozyme and angiotensin converting enzyme levels. Antinuclear antibodies, anti-SSA antibodies, anti-SSB antibodies were positive, while tuberculin test was negative. Chest X-rays showed bilateral hilar lymphadenopathy and small nodular shadows in both lung fields. Increases in lymphocytes and the CD4/CD8 ratio of T cells were noted in alveolar lavage fluid. Renal biopsy revealed non-caseous granulomas. Other remarkable findings included positive Schirmer's test, apple tree lesions by sialography and chronic sialoadenitis by biopsy of the labial minor salivary gland. On the basis of all these findings, we diagnosed her as suffering from sarcoidosis with Sjögren's syndrome. After oral administration of prednisolone, her shortness of breath, hilar lymphadenopathy and small nodular shadows in the lung field disappeared, but the patient was transferred to the department of urology due to the onset of hydronephrosis. This case is noteworthy because sarcoidosis associated with Sjögren's syndrome has been reported in only 11 cases in the literature.

CD4-CD8 Ratio↗

An ultrastructural study of the cytoplasmic aspects of erythrocyte membranes by a quick-freezing and deep-etching method.

A novel method for preparing exposed cytoplasmic aspects of erythrocyte membranes is described which improves the resolution in direct electron microscope images. Normal human erythrocytes were briefly fixed with paraformaldehyde and pelleted. Glass coverslips were coated with 3-aminopropyl triethoxysilane and glutaraldehyde to make erythrocytes stick to them. A drop containing the erythrocyte pellets was sandwiched between 2 coverslips. The attached erythrocytes were split open mechanically and postfixed with glutaraldehyde. Some were treated with Triton X-100 or postfixed with osmium tetroxide. All specimens were quickly frozen in an isopentane-propane mixture, deeply etched and rotary shadowed with platinum and carbon. Filamentous structures were seen to form networks on the cytoplasmic sides of the erythrocyte membranes. Triton X-100 and osmium tetroxide fixation distorted the fine network structure. This quick-freezing and deep-etching method will be useful in the analysis of the in situ ultrastructure of the cytoplasmic sides of erythrocyte membranes.

Cytoskeleton↗

A case of endogenous Enterococcus faecalis endophthalmitis.

A case of successful treatment by vitrectomy and lensectomy of early-stage endogenous endophthalmitis caused by Enterococcus faecalis was reported. The case was a 50-year-old man with poorly controlled diabetes. Following T-tube drainage for a necrotic cholecystitis operation, he developed iridocyclitis in both eyes as well as fever. At the time of his first visit to our clinic, his right eye had already lost light perception. His left eye had visual acuity recognizing hand movement, marked uveitis, complicated cataract, and dense vitreous opacity. As gram-positive cocci were isolated from the aspirated vitreous, lensectomy and vitrectomy under irrigation with antibiotics were conducted. After the administration of systemic postoperative antibiotics and human immunoglobulin, the patient showed remarkable improvement in the state of his ocular fundus. By 60 days after the surgery, the visual acuity of his left eye recovered to 0.2. Endogenous Enterococcus faecalis endophthalmitis has rarely been reported in Japan. The diagnosis and treatment of this disease with reference to the above findings were discussed.

Cataract Extraction↗

[A case of juvenile rheumatoid arthritis with panuveitis].

An association of bilateral panuveitis and juvenile rheumatoid arthritis (JRA) was recognized in a case which had an acute onset of systemic JRA without ocular manifestations 3 years previously. On the present occasion she had no active systemic inflammation at the onset of panuveitis. Fluorescein angiography demonstrated bilateral hypo-fluorescent patches at the posterior pole in the early stage and corresponding window defects in the late stage. Topical corticosteroid treatment and oral non-steroid therapy resulted in clinical improvement of the uveitis. It is concluded that ophthalmologic examinations, including fundus ophthalmoscopy, are important in patients with JRA, since there is a possibility of ocular symptoms, even in the systemic type in which ocular complications are rare, as well as in cases with a long interval since the onset of arthritis.

Adolescent↗

[An HLA-B27 negative case of ankylosing spondylitis with acute iridocyclitis].

The author experienced a 34-year-old male case of acute iridocyclitis with fibrinous exudates accompanied by ankylosing spondylitis with negative HLA-B27. Who was diagnosed definite ankylosing spondylitis by the New York criteria. The cause of ankylosing spondylitis was postulated to be a cross reaction between HLA-B27 and a certain Gram-negative bacillus. However, our case with negative HLA-B27 suggested the causes could comprise multiple factors in addition to HLA-B27. Since the clinical picture of iridocyclitis observed in our case showed no difference with those of HLA-B27 positive cases, iridocyclitis associated with ankylosing spondylitis is considered to be the same entity regardless of HLA-B27 being present or not.

Acute Disease↗

Stereoscopic study of renal proximal tubular basement membrane by quick-freezing and deep-etching method.

Rat kidney tissue was quickly frozen, fractured and deeply etched. A replica was prepared by shadowing with platinum and carbon. The proximal tubular basement membrane was found to be different from that in conventional ultrathin sections. The lamina lucida was not electron translucent but filled with a traversing filamentous structure, which connected the tubular cell membranes with the lamina densa. The lamina densa had a three-dimensional polygonal meshwork structure. This meshwork was composed of fibrils (6-9 nm in thickness). In the lamina reticularis, collagen fibrils and micro-threads formed a loose network structure. The traversing filamentous structure in the lamina lucida might serve as an anchorage for the cell membranes and extracellular matrices.

Animals↗

[Gene organization of HLA and its association with ocular disease].

It is now evident that the human major histocompatibility complex (MHC), human leucocyte-associated antigen (HLA), regulates the immune response through discrimination between autologous and non autologous substances thereby displaying a high degree of genetic polymorphism. In recent years, the three-dimensional structure of HLA has been clarified by crystal analysis and provides the attractive hypothesis, the so-called hotdog model, explaining the interactions of foreign antigens (or autologous antigens), HLA and T cell receptors and has a great impact on various studies on immunogenetic mechanisms underlying the development of many diseases. Thus, several HLA-associated ocular diseases such as Behçet's disease and Harada's disease have also been analyzed from this point of view by means of recombinant DNA techniques, enabling elucidation of molecular mechanisms of susceptibility to these diseases. This paper describes a general outline of HLA, especially its genetical structure, as well as recent analysis of molecular mechanisms of the predisposition to representative ocular diseases.

Eye Diseases↗

Increase in intracellular calcium induced by stimulating histamine H1 receptors in macrophage-like P388D1 cells.

The addition of histamine to macrophage-like P388D1 cells resulted in a dose-dependent increase in intracellular calcium [Ca2+]i measured by fura-2 in single cells. The maximum level of [Ca2+]i was obtained by addition of 1 x 10(-4) M histamine. The increase was primarily due to release from the intracellular store. The addition of an H1 specific antagonist pyrilamine before histamine treatment inhibited the increase reversibly, while an H2 specific antagonist cimetidine had no inhibitory effect. Histamine also resulted in a dose-dependent increase in cGMP but not in cAMP. These data suggest the existence of histamine H1 receptors in these cells and histamine may have some biological effect on the function of macrophages via [Ca2+]i and cGMP as the second messengers.

Animals↗

Structure and properties of a ubiquitously expressed protein kinase C, nPKC delta.

cDNA clones coding for novel protein kinase C delta (nPKC delta) were isolated from a mouse brain cDNA library. Mouse nPKC delta consists of 674 amino acid residues and has sequence identity of 95% with rat nPKC delta. Antiserum raised against a C-terminal peptide of rat nPKC delta identified a 79-kDa protein in COS cells transfected with a mouse nPKC delta cDNA expression plasmid. nPKC delta expressed in COS1 cells had phorbol-ester-binding activity and protein kinase activity in a phorbol-ester- or diacylglycerol-dependent manner, like conventional protein kinase C (cPKC) isozymes and nPKC epsilon. However, nPKC delta, like nPKC epsilon, is not activated by Ca2+, a known activator of cPKCs, and requires lower concentrations of Mg2+ for full activation than cPKCs. Moreover, apparent kinetic constants for synthetic oligopeptides (MBP4-14, EGFR peptide and epsilon-peptide) were quite different between nPKC delta and cPKC in two different conditions. Among various phospholipids tested, phosphatidylinositol is the most potent activator of nPKC delta, in clear contrast to cPKCs and nPKC epsilon. Limited proteolysis of nPKC delta generated a C-terminal active fragment with a cofactor-independent kinase activity. Northern blot analysis indicated that nPKC delta, like cPKC alpha, is widely distributed in almost all the tissues and cells examined and, in some cases such as fibroblast cells, exists as a major PKC type. These results suggest that nPKC delta is involved in fundamental cellular functions regulated by diacylglycerols and mimicked by phorbol esters.

Amino Acid Sequence↗

Overexpression of a beta-galactoside binding protein causes transformation of BALB3T3 fibroblast cells.

Overexpression of an animal lectin, rat beta-galactoside binding protein (GBP) in mouse BALB3T3 fibroblast cells by stable introduction of a GBP cDNA expression plasmid results in the acquisition of transformed phenotype which includes a loss of anchorage dependence, reduced contact inhibition, colony formation in soft agar, and tumor formation in nude mice. The transformation depends on the level of the expression of both GBP and TGF gamma 2 activities confirming that both activities are ascribable to a single bifunctional protein TGF gamma 2/GBP. The results indicate that GBP acts as a growth regulator and is directly involved in regulation of cell proliferation.

Animals↗

c-myc gene in a murine plasmocytoma without visible chromosomal translocations moves to chromosome 12F1 with Pvt-1 and rearranges with IgH enhancer-S mu sequences.

The DCPC 21 plasmocytoma lacks any of the MPC-associated chromosomal translocations. However, the c-myc gene has been transposed to the IgH locus on chromosome 12 by an Ig switch-region-mediated recombination mechanism. DNA sequencing analysis, further, revealed that this recombination is consistent with an insertion of the IgH enhancer (E mu)-S mu sequences, 2341 bp in length, into the c-myc 5'-flanking region, resulting in 5': c-myc 5'-flanking-E mu-S mu-c-myc 5'-flanking-c-myc exon-1: 3' segment. In situ molecular hybridization of DCPC 21 metaphase chromosome spreads using a Pvt-1 probe demonstrated that Pvt-1 has also moved to the F1 sub-band region of chromosome 12 where the IgH genes are located. These results indicate that the c-myc gene has been inserted into the IgH locus together with the Pvt-1, regardless of whether plasmocytoma has cytogenetically identifiable translocations. The possible interaction between c-myc activation and Pvt-1 in the development of MPCs is discussed.

Animals↗

Growth patterns and prognosis of submucosal carcinoma of the esophagus. A pathologic study.

Sixteen cases of esophageal carcinoma invading the submucosa were analyzed in terms of growth patterns. Seven were classified into the massively penetrating (down growth) type, four into the superficially spreading (spreading growth) type, and five into the unclassified type. In the down growth type, the ratio of the submucosal area to the total (mucosa and submucosa) area was more than 0.2 (one fifth), and in the others that ratio was less than 0.2. The down growth type is characterized by a tendency toward elevated lesions, a high incidence of vessel invasions and lymph node metastasis, and a poor prognosis after surgery. Lymphatic and/or vascular invasions were recognized in six of seven cases, and the 5-year survival rate was 0%. In contrast, the spreading growth and unclassified types was characterized by superficial lesions, a low incidence of vessel invasions and lymph node metastasis, and a favorable prognosis. In only one with the spreading growth type was there lymphatic invasion. Three of the four with the spreading growth type survived over 5 years, and the other one with the spreading growth type and all of five with the unclassified type are alive without recurrences 15 to 52 months after surgery. Thus, growth patterns reflect well the prognosis of the submucosal carcinoma of the esophagus.

Aged↗

Detection of antibodies against Borrelia burgdorferi in patients with uveitis.

We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects.

Antibodies, Bacterial↗

Protective effect of ICRF-187 against normal tissue injury induced by adriamycin in combination with whole body hyperthermia.

The use of [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)]propane (ICRF-187) as a protective agent against normal tissue toxicity caused by combined Adriamycin (ADR) and whole body hyperthermia (WBH; 2 h at 41.5 degrees C) was assessed in a rat model. The effect of ICRF-187 on the antitumor response induced by the combination of ADR and WBH was also investigated in order to assess alterations in the therapeutic index of this combined therapeutic modality treatment. ICRF-187 significantly reduced ADR-mediated body weight loss, renal toxicity, and cardiomyopathy under both normothermic and hyperthermic conditions as shown by morphological and functional assays. ADR-induced neuropathy (seen only in normothermic rats) was also ameliorated by ICRF-187. Although this study did not show a pronounced effect of ICRF-187 on ADR-induced acute myelosuppression, ADR-mediated chronic anemia, leukocytosis, and thrombocytosis were reduced by ICRF-187 in both normothermic and WBH-treated rats. The effect of ICRF-187 on antitumor response was evaluated with a tumor growth delay assay using an in vivo transplantable fibrosarcoma. ICRF-187 caused no significant change in tumor growth delay induced by either ADR alone or ADR combined with WBH. Indeed, the only complete tumor regression following treatment resulted from the combination of ICRF-187 plus ADR plus WBH. Thus, ICRF-187 significantly increases the therapeutic index of the combined modality treatment of ADR and WBH by selectively reducing normal tissue toxicity without interfering with antitumor efficacy.

Animals↗

Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.

Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for "acute" hematological changes were 1.3, whereas those estimated for "late" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.

Animals↗