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Biomedical subjects

S Nagafuchi

Publications and source records attributed to S Nagafuchi.

At least 91 records · Page 5Linked to original sources

Immunohistochemical study of insulitis induced by multiple low doses of streptozocin in CD-1 mice.

In an attempt to characterize insulitis induced by multiple low doses of streptozocin (SZ), we immunohistochemically examined sequential changes of the subsets of lymphocytes infiltrating the pancreatic islets in CD-1 mice. Daily intraperitoneal injections of 30 mg/kg body wt of SZ for five consecutive days led to lymphocytic infiltration around the islets. Most of the infiltrated cells were initially CD4 positive (helper/inducer) T-lymphocytes and no immunoglobulin-bearing cells were detected. The number of helper/inducer T-lymphocytes increased with progression of the insulitis, then surface immunoglobulin-positive cells (B-lymphocytes) accumulated around the area of CD4 positive T-lymphocytes. CD8 positive (suppressor/cytotoxic) T-lymphocytes were seen scattered throughout the study and only a few asialo GM1 positive (natural killer) cells existed in the area of insulitis. Subsequently, the pancreatic insulin contents were considerably decreased and diabetes occurred on day 21. These observations suggest that CD4 positive T-lymphocyte-dependent B-lymphocyte infiltration in and around islet cells may be associated with islet cell destruction and the development of diabetes in CD-1 mice treated with multiple low doses of streptozocin.

Animals↗

[Transient dysfibrinogenemia and cerebral thrombosis following remission induction therapy for acute lymphoblastic leukemia].

A 38-year-old female with acute lymphoblastic leukemia developed monoplegia of the left upper extremity following chemotherapy for remission induction consisting of vincristine, prednisolone, cyclophosphamide, adriamycin and methotrexate. Hemorrhagic infarction due to thrombosis of the right cortical vein was diagnosed by brain images using computed tomography and magnetic resonance imaging in addition to the clinical course. At this time, a plasma level of fibrinogen measured by the thrombin time method had decreased to 84 mg/dl, while its antigenicity was 276 mg/dl. There was no evidence of activation of the blood coagulation and fibrinolysis system nor of abnormal liver function. A mixing test with normal plasma disclosed the absence of an inhibitory factor against fibrin polymerization in her plasma. Fibrinogen levels as assessed by the thrombin time method recovered to the antigenicity level one and half months later. The discrepancy between the activity and antigenicity of fibrinogen indicated the occurrence of acquired dysfibrinogenemia, probably induced by antileukemic agents. Thus, it is suggested that dysfibrinogenemia is a possible cause of cerebral thrombosis in this patient.

Adult↗

Characterization of a newly established, TA-4-producing squamous carcinoma cell line derived from metastatic tongue carcinoma.

A human squamous carcinoma cell line was established from the pleural effusion of a patient with recurrent squamous carcinoma of the tongue. The cell line, designated HST-I, has been passaged 82 times over a period of 4 years. The cells have been shown by light and electron microscopy to be of the squamous epithelial type. Immuno-histochemical staining was positive for keratin. When these cells were transplanted into athymic nude mice, tumors developed at the site of inoculation, which on histological examination were shown to be well-differentiated squamous carcinomas. Karyotypic analysis of cells from the cell line demonstrated an aneuploid human type with a modal chromosome number of 71, with both numerical and structural aberrations. HST-1 cells produce and secrete TA-4, a squamous-cell carcinoma-related antigen, in vitro in culture and in vivo in nude mice bearing the tumors produced by inoculation of cultured cells. Thus, the HST-1 cell line represents a new human tongue squamous carcinoma producing TA-4. This cell line appears useful for facilitating therapeutic investigations as well as biological studies on the association between cancerous growth and circulating TA-4 levels.

Adult↗

Prolonged suppression of gonadotropin secretion after weight recovery in an anorectic patient with Turner's syndrome: reduced gonadal function in anorexia nervosa is independent in part on nutrition.

Two hypotheses have been postulated as to the pathogenesis of hypogonadotropinemia in anorexia nervosa; one is starvation and weight loss and the other is a psychological factor to influence gonadotropin secretion. Our patient suffered from very rare concurrence of Turner's syndrome and anorexia nervosa and a study of this experiment in nature provided important evidences concerning decreased secretion of gonadotropins in the eating disorder. The patient was diagnosed as Turner's syndrome when she was 6 years old. Her gonadotropin levels were elevated to the castrated ranges (LH 61.8 IU/l; FSH 175.8 IU/l) after 8 years of age. She was noticed to be anorectic at the age of 13 years. Serum levels of the pituitary gonadotropins were lowered (LH 2.9 IU/l; FSH 3.0 IU/l) and their responses to luteinizing hormone-releasing hormone were decreased beneath the normal prepubertal limits. After one year of the anorectic period, she recovered the weight though her gonadotropin levels remained in the very low ranges (LH 2.7 IU/l; FSH 2.5 IU/l). The results suggest that hypogonadism in anorexia nervosa is not solely caused by nutritional deficiency but rather by other factors such as psychological abnormalities.

Adolescent↗

Delayed-type hypersensitivity skin reaction to HBsAg and immunohistopathologic study of liver in patients with acute type B viral hepatitis.

In an attempt to clarify the role of cellular immunity in the pathogenesis of acute type B viral hepatitis (AHB, we studied delayed-type hypersensitivity (DTH) skin reaction to hepatitis B surface antigen (HBsAg) and immunohistopathology of livers in patients with AHB. DTH skin reaction to HBsAg developed early in the convalescent phase in all 14 patients with AHB. In contrast, the production of anti-HBs was significantly delayed in these patients, compared with healthy controls immunized with HB vaccine intradermally (P less than 0.001). These observations suggest that DTH to HBsAg but not anti-HBs may be associated with recovery from AHB. In the biopsied livers obtained from patients with AHB, the proliferation of Kupffer cells was extensive and immunohistopathologic studies revealed an accumulation of CD-4 positive lymphocytes in the portal area, a finding which suggested a DTH reaction in the liver with AHB. CD-8 positive cells had infiltrated the lobule and made contact with affected hepatocytes, thereby indicating that a cytotoxic T cell response is involved in damaging of the infected cells. All these observations taken together, we propose that not only a cytotoxic T cell response but also a DTH reaction may be involved in the pathogenesis of AHB.

Acute Disease↗

Inhibition of streptozocin-induced insulitis and diabetes with lobenzarit in CD-1 mice.

When multiple low doses (30 mg/kg body wt) of streptozocin were given to CD-1 mice, diabetes associated with L3T4 T-lymphocyte- and B-lymphocyte-predominant insulitis occurred. Thus, a model of type I (insulin-dependent) diabetes was obtained. To treat these diabetic mice, we administered lobenzarit (CCA), a newly synthesized immunomodulator. CCA (2 or 10 mg/kg body wt) significantly inhibited the progression of diabetes by suppressing the severity and incidence of insulitis. Insulin contents of the pancreas were preserved. The possibility that autoimmune-related diabetes can be treated with CCA warrants further attention.

Animals↗

Cyclosporin A enhances streptozocin-induced diabetes in CD-1 mice.

Cyclosporin A (CYA), when administered to CD-1 mice treated with a subdiabetogenic dose of Streptozocin (STZ), exacerbated the STZ-induced insulitis and elevated the plasma glucose levels, parallel to a reduction of the insulin content of the pancreas. The possible mechanisms of CYA-mediated aggravation of STZ-induced diabetes are discussed.

Animals↗

High-resolution cytogenetic studies in patients with Prader-Willi syndrome.

We investigated 24 patients with Prader-Willi syndrome by the high-resolution banding technique. Their history and clinical findings were also examined in some detail. Twelve had interstitial deletion of 15q; del(15) (q11.2q13) in 11 cases and del(15) (q11.2q12) in one case. Six revealed normal karyotypes at about 500-850 bands per haploid-set level. In an additional six cases, no deletion was detected. However, we took the results as tentative, as the observed karyotypes were at the 400-bands level. During the course of this study, it was realized that a small deletion in the proximal 15q could be easily overlooked when a mitotic spread around 400-bands or less per haploid-set level was used. There was no distinct difference in the clinical features of patients with interstitial deletion and those with a normal karyotype. Two cases in the latter group lacked some of the typical features of the former group, e.g. poor fetal vigor, neonatal feeding difficulty, hypotonia, and delayed motor development.

Adolescent↗

Identification and partial purification of a low-molecular-weight growth inhibitor formed by density-inhibited, tumorigenic V79 Chinese hamster cells.

Medium conditioned by exposure to density-inhibited, tumorigenic V79 Chinese hamster cell cultures reversibly inhibited the growth and DNA synthesis of sparse, proliferating cultures, not only of the same cell line but also of the BALB/c 3T3 A31 murine cell line. This species nonspecific inhibitory activity was found to be mediated by the soluble inhibitor produced endogenously by V79 cells at the time of density inhibition. The molecular weight of this inhibitor is approximately 2000, and production of this compound seems to be serum dependent. Partial purification was done by reverse-phase fast protein liquid chromatography. The inhibitory activity was linearly dependent on the concentration in the inhibitory fraction. This partially purified inhibitor did not include lactic acid, a growth-inhibitory metabolite. These data indicate that a growth-regulatory factor is also operant in tumorigenic V79 cells and suggest that growth of neoplastic cells cannot only be explained by an enhanced positive growth potential but rather by the balance between a positive and negative growth potential.

Animals↗