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Biomedical subjects

T Hanafusa

Publications and source records attributed to T Hanafusa.

At least 199 records · Page 11Linked to original sources
PubMed1985

Decreased incidence of diabetes mellitus by monosodium glutamate in the non-obese diabetic (NOD) mouse.

Subcutaneous administration of monosodium glutamate (MSG) to neonatal female non-obese diabetic (NOD) mice resulted in obesity associated with stunting and hyperinsulinemia. However, the cumulative incidence of diabetes mellitus at 25 weeks of age in the MSG group was significantly lower than in the control group (10.3% vs. 43.6%, P less than 0.005). The immunoreactive insulin content of the pancreas from the 13- to 20-week-old MSG-treated mice was higher than that of the control mice (P less than 0.005). Immunohistochemistry showed that the number of pancreatic B-cells was well preserved and insulitis was attenuated in the MSG-treated mice. Plasma corticosterone and 3, 5, 3'-triiodothyronine levels were elevated in the MSG group. These results suggested that, by the MSG treatment, the B-cell functions were maintained through the modification of the degenerative process of the islets in the NOD mouse.

Aging↗
PubMed1984

Decreased response of epinephrine and norepinephrine to insulin-induced hypoglycemia in diabetic autonomic neuropathy.

The responses of epinephrine, norepinephrine and other counter-regulatory hormones to insulin-induced hypoglycemia were investigated in 5 diabetics who showed signs of autonomic neuropathy, in 7 age-matched diabetics without autonomic neuropathy and in 7 healthy subjects. The presence of autonomic neuropathy was evaluated by decreased beat-to-beat variation in heat rates during hyperventilation or orthostatic hypotension. Catecholamines were determined by a totally automated plasma catecholamine analyzing system using a two-column system of high performance liquid chromatography. Plasma epinephrine and norepinephrine responses to hypoglycemia in diabetics with autonomic neuropathy were significantly lower than those in diabetics without autonomic neuropathy. Plasma glucagon response in diabetics was apparently attenuated compared to normal controls and there was no significant difference in glucagon response between the two patient groups. Other counter-regulatory hormone responses did not differ among the three groups. The data demonstrate that the responses of plasma epinephrine and norepinephrine to insulin-induced hypoglycemia are impaired in diabetics with autonomic neuropathy.

Adult↗
PubMed1984

Rous sarcoma virus variants that carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts.

The transforming activity of the cellular src (c-src) gene as well as of hybrid genes between viral and cellular src was tested by constructing derivatives of Rous sarcoma virus DNA in which all or part of the viral src gene (v-src) was replaced by the corresponding portion of the c-src gene. After these derivatives were introduced into chicken embryo fibroblasts by transfection, replication-competent virus was recovered, which induced the expression of p60src at a level equivalent to p60v-src expression in cells infected with Rous sarcoma virus wild type. Replacement of the portion of the v-src gene, either upstream or downstream of the Bgl I site, with the homologous portion of the c-src gene resulted in fully transforming viruses. On the other hand, the virus stock obtained from cells transfected with Rous sarcoma virus DNA containing the entire c-src gene had a very low titer of focus-forming virus, while it contained a high titer of infectious virus. We present evidence that the rare small foci are formed by mutant viruses generated from the original c-src-containing virus. These results indicate that overproduction of the c-src gene product does not cause cell transformation, and that this proto-oncogene is subject to a relatively high rate of mutation when incorporated in a retrovirus genome, resulting in the acquisition of transforming capacity.

Animals↗
PubMed1984

Asialoagalactothyroglobulin binds to the surface of human thyroid cells at a site distinct from the 'microsomal' autoantigen.

Human thyroglobulin has been shown for the first time to bind to the surface of cultured human thyroid follicular cells. Binding was only observed with partially glycosylated asialoagalactothyroglobulin, not with the fully glycosylated iodoprotein. The binding site for asialoagalactothyroglobulin in the cell membrane is distinct from membrane associated microsomal/microvilli antigen. Since asialoagalactothyroglobulin bears the autoantigenic determinants of the parent molecule, its ability to bind to the thyroid cell surface suggests a possible role for this protein in the pathogenesis of human thyroiditis.

Antigens↗
PubMed1984

In vitro and in vivo reversal of thyroid epithelial polarity: its relevance for autoimmune thyroid disease.

A method is described for culturing intact human thyroid follicles, based on the study of 40 thyroidectomy specimens from normal (n = 18) and diseased glands (n = 22). Reversal of the normal polarity of thyrocytes, whereby the microvilli move from the colloid edge to the vascular pole of the cells, occurs gradually when the amount of fetal calf serum (FCS) is changed from 0.5% to 10%. The translocation of thyroid 'microvillar' antigens, (surface expression of 'microsomal' and a separate surface antigen) from the follicular to the vascular pole of thyrocytes was assessed by indirect immunofluorescence with human sera containing microsomal antibodies, as well as by electron microscopy. In normal and diseased thyroid glands up to 80% of follicles became reversed after 5-10 days in high FCS and the microsomal/microvillar antigen persisted for about twice as long as in monolayer cultures. Spontaneous reversal of polarity was observed in six of eight glands from patients with Graves' thyrotoxicosis or toxic nodular goitre in freshly dispersed tissues or after 2 days in 0.5% FCS, unlike normal tissues where only a trace of reversal appeared after 7 days of culture under these conditions. It is postulated that polarity reversal may play a role in human thyroid autoimmunity as the normally secluded 'microvillar' antigens becomes transposed to the vascular pole of thyroid follicles where they are in direct contact with cytotoxic antibodies or sensitized immunocytes. This could initiate lesions in intact follicles. Inappropriate HLA-DR expression on thyrocytes, either stimulated by phytohaemagglutinin (PHA) or appearing spontaneously as an early marker of thyroiditis, did not correlate with reversal of polarity.

Antigens, Surface↗
PubMed1984

[Local administration of anti-cancer drugs].

Anti-cancer drugs in the forms of an emulsion, a microsphere, and of conjugates with high molecular dextran have been developed in our laboratories, namely a fat emulsion of anticancer drug, MMC-microsphere, or MMC-dextran conjugates. The main advantages of these forms of pharmaceutical preparation are that they give prolongation of pharmacological actions by slow release and that they are applicable for topical use because of their reduced toxicities to local tissue yet maintaining local therapeutic potency. In this study we found that the rate of sustained release of drugs and antitumor effects were enhanced when used in such modified forms of drugs for topical injections. Results of clinical trials of those drugs have been promising. However, the number of trials has been limited so far. Further studies would be required for evaluating on of their clinical utilities.

Adult↗
PubMed1984

[Experimental and clinical studies on the intestinal anastomosis and reconstruction of the alimentary tract].

Healing process of anastomosis and its procedure were studied in following points: Four-interrupted sutures anastomosis in the Wistar rats revealed recanalization without leakage in 64 out of 69. Lymphangial recanalization through the anastomosis was completed within 21 days after operation by Gambee' layer-to-layer anastomosis. While 8 weeks were required by everted or inverted anastomosis. Serosal surface of invaginated intestinal segment of which length corresponded to x1-x2 luminal diameter in the telescoping anastomosis was covered within 8 weeks by the proliferated mucosae of the both proximal and distal segments. Telescoping anastomosis was found to be useful to make an intestinal valve which worked just the same as ileocoecal junction. IVH and elementary diet were effective on the healing of anastomosis. According to the above mentioned findings, following operative procedures were recommended: Esophago-jejunal conduit duodenostomy following total gastrectomy. Choledocho-jejunal conduit duodenostomy with the intestinal valve as bile duct reconstruction. Construction of the intestinal valve and an artificial sphincter using rectus abdominis muscle fibers for ileostomy or short bowel syndrome. Endorectal pull-through operation for anterior-resection of the rectum as well as for radical treatment of Hirschsprung' disease.

Animals↗
PubMed1983

Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity.

To investigate the expression of class II histocompatibility antigens HLA-DR in the thyrocytes in autoimmune thyroid diseases, 47 thyroidectomy specimens were examined by immunofluorescence with monoclonal antibodies to the nonpolymorphic region of the DR molecule. Aberrant DR expression was most marked in the Hashimoto gland, with the entire section being strongly stained. DR expression was seen in discrete groups of follicles in 20/26 thyroids from patients with Graves' disease, in 2/9 non-toxic nodular goitres, and in none of 11 specimens of "normal" thyroid. The presence of lymphoid foci, "activated" T-cells, and immune complexes on the follicular basement membrane were not regularly associated with the DR-positive thyroid acini. HLA-A,B,C expression was also increased in the diseased glands. Expression of HLA-DR thus seems to be one of the earliest manifestations of autoimmune lymphocytic thyroiditis.

Adult↗
PubMed1983

Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity.

Immune responses are initiated by HLA-DR+ cells, which present antigen to T cells. Observations that HLA-DR may be experimentally induced on thyroid epithelium and that HLA-DR occurs on thyrocytes in autoimmune thyroid diseases suggest a mechanism of autoimmunity with special relevance to organ-specific diseases. This involves the local aberrant expression of HLA-DR antigens by epithelial cells and their subsequent capacity to present autoantigens occurring on their surfaces to T lymphocytes. For autoantigens which T cells recognise infrequently because of their restricted tissue location and low concentration in the circulation, T-cell tolerance is unlikely, and so induction of autoreactive T cells would occur. Because interferon is the best known inducer of DR antigen expression and viral infections may predate endocrine autoimmunity, the following sequence seems likely: local viral infection which causes interferon production, or other local environmental factors which would induce DR expression, presentation of autoantigens, and subsequent autoimmune T-cell induction. These T cells would activate effector B and T cells. Whether the initial induction of autoimmune T cells leads to autoimmune disease would depend on factors such as abnormalities of the suppressor T-cell pathway, reported to coexist with autoimmunity and necessary to induce autoimmune disease in mice. This mechanism of autoimmune disease induction explains vague associations with viral infections and long latency periods before disease becomes manifest and gives a simple explanation for the well-documented association between HLA-DR and autoimmune diseases in man.

Autoantigens↗
PubMed1983

Detection of thyroid growth immunoglobulins (TGI) by [3H]-thymidine incorporation in cultured rat thyroid follicles.

A new bioassay is described for detecting the growth stimulating immunoglobulins (TGI) that contribute to goitre formation in human thyroid autoimmune diseases. It measures the incorporation of tritiated thymidine into intact rat thyroid follicles grown in tissue culture. This radiometric assay demands much less technical skill than the cytochemical bioassays (CBA) previously employed. It has good reproducibility and the techniques and apparatus are available in many clinical laboratories. Immunoglobulins (Igs) from 68% of patients with goitrous Graves' disease were positive, in proportion with goitre size, and this showed no correlation with T3 levels, or three accepted methods for conventional thyroid stimulating antibodies. Non-toxic nodular goitre cases gave positive results in 3/9 who had recurrences after one or more thyroidectomies and in 1/10 cases of familial simple goitre. All normal subjects and all endemic goitre cases were negative as well as 21 cases of sporadic non-toxic nodular goitre. Although it is less sensitive than the 'growth CBA' it clearly emphasizes the essential difference between the intensity of growth stimulus which leads to the regular hyperplasia of thyroid epithelium seen in Graves' thyrotoxicosis and the disorganized and metabolically uncoordinated hyperplasia typical of non-toxic nodular goitre.

Adult↗
PubMed1982

Isolation of 16L virus: a rapidly transforming sarcoma virus from an avian leukosis virus-induced sarcoma.

We have isolated a replication-defective rapidly transforming sarcoma virus (designated 16L virus) from a fibro-sarcoma in a chicken infected with td107A, a transformation-defective deletion mutant of subgroup A Schmidt-Ruppin Rous sarcoma virus. 16L virus transforms fibroblasts and causes sarcomas in infected chickens within 2 wk. Its genomic RNA is 6.0 kilobases and contains sequences homologous to the transforming gene (fps) of Fujinami sarcoma virus (FSV). RNase T1 oligonucleotide analysis shows that the 5' and 3' terminal sequences of 16L virus are indistinguishable from (and presumably derived from) td107A RNA. The central part of 16L viral RNA consists of fps-related sequences. These oligonucleotides fall into four classes: (i) oligonucleotides common to the putative transforming regions of FSV and another fps-containing avian sarcoma virus, UR1; (ii) an oligonucleotide also present in FSV but not in UR1; (iii) an oligonucleotide also present in UR1 but not in FSV; and (iv) an oligonucleotide not present in either FSV, UR1, or td107A. Cells infected with 16L virus synthesize a protein of Mr 142,000 that is immunoprecipitated with anti-gag antiserum. This protein has protein kinase activity. These results suggest that 16L virus arose by recombination between td107A and the cellular fps gene.

Animals↗
PubMed1982

Islet-activating protein (IAP) reduces bethanechol-stimulated release of pancreatic polypeptide in the dog.

The effect of islet-activating protein (IAP) purified from culture medium of Bordetella pertussis was examined in dogs. This was assessed by the levels of pancreatic polypeptide (PP) as well as the responses of plasma insulin and glucagon to a parasympathomimetic agent, bethanechol. Plasma responses of these pancreatic hormones were measured before and 5 days after IAP injection. Although IAP had no significant effect on the bethanechol-stimulated increase in plasma glucose, insulin and glucagon, the PP response to bethanechol was significantly reduced after IAP treatment compared with that before IAP (p less than 0.05). In conclusion, IAP significantly and selectively reduced bethanechol-stimulated PP release in the dog although the mechanism remained to be elucidated.

Animals↗
PubMed1982

Impaired response of human pancreatic polypeptide to insulin-induced hypoglycemia in chronic pancreatitis without diabetes mellitus.

In order to clarify the pancreatic endocrine functions in mild chronic pancreatitis, the response of insulin to oral glucose load and the response of glucagon and human pancreatic polypeptide (HPP) to insulin-induced hypoglycemia were investigated in five normal controls and eight patients with chronic pancreatitis but without diabetes mellitus. Although insulin and glucagon responses in patients with chronic pancreatitis tended to be lower than those in normal subjects, the differences between the two groups were not statistically significant. In contrast, HPP response to hypoglycemia in the patients was markedly impaired and significantly lower than that in normals (p less than 0.02). This finding indicates that the impairment of HP response is the earliest and most definite manifestation among pancreatic endocrine abnormalities in chronic pancreatitis.

Adult↗
PubMed1982

Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. An observation in nonobese diabetic (NOD) mice.

This experiment was undertaken to explore a novel method of therapy for insulin-dependent diabetes mellitus (IDDM), using nonobese diabetic (NOD) mice that had symptoms and histologic changes similar to those of human IDDM patients. We examined preventive and therapeutic effects of large-dose nicotinamide administration on diabetes in NOD mice. Eighteen young female NOD mice without glycosuria were randomly divided into two groups; nine received subcutaneous nicotinamide (0.5 mg/g body wt) injections every day and the other nine were maintained as a control group and not injected. After 40 days, all of the mice given nicotinamide showed almost normal glucose tolerance and only mild insulitis on histologic study. On the other hand, marked glycosuria and severe insulitis were observed in six of the nine mice not injected. Four of six NOD mice given nicotinamide from the day of the first occurrence of marked glycosuria displayed a disappearance of glycosuria and an improvement in glucose tolerance during the therapy; however, urine sugar became negative in only one of six mice that received nicotinamide from 1 to 2 wk after the onset of marked glycosuria. These results indicate that nicotinamide has preventive and therapeutic effects on diabetes in NOD mice, and suggest the reversibility of B-cell damage, at least at a very early stage of IDDM.

Animals↗