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Biomedical subjects

T Mitsuhashi

Publications and source records attributed to T Mitsuhashi.

At least 127 records · Page 7Linked to original sources
PubMed1989

Pulmonary embolization-induced thymus hyperplasia in rabbits.

The effects of pulmonary embolization on the thymus glands of rabbits were studied morphologically, morphometrically and immunohistochemically. Pulmonary embolization was induced by an intravenous injection of 0.4 ml of Sephadex bead suspension (particle size; 150 to 300 microns, about 2,000 per ml). Both mean weight and volume of the thymus of rabbits killed at 2 weeks after embolization, were about 1.5 times more than those in control animals treated with physiologic saline. Histological examinations showed enlargement of the cortex and medulla of the thymus, and the embolized Sephadex beads in the branches of pulmonary arteries of the lung. The area ratios of medulla/cortex, in the embolization group and in control, were not significantly different. The cells with immunohistochemically positive staining of anti-nuclear antigen of monoclonal antibody of Ki-67, were found in both portions of the medulla and cortex. These data suggest that pulmonary embolization in the rabbit induces true thymic hyperplasia. An intravenous injection of India ink into the right highest intercostal artery revealed the distribution of bronchial arteries, which send the branches to the right lobe of the thymus. In 2 out of 4 animals killed 2 weeks after pulmonary embolization, the left lobe of the thymus as well as the right were stained with the injected ink. As it is known that pulmonary vascular obstruction caused a marked increase in the bronchial blood flow, these data suggest that the thymus blood supply from the bronchial arteries increases in the conditions of pulmonary embolization, which might contribute to thymus hyperplasia.

Animals↗
PubMed1988

Intracellular Ca2+ requirement for activation of the Na+/H+ exchanger in vascular smooth muscle cells.

The role for intracellular Ca2+ in modulating activity of the Na+/H+ exchanger was studied in cultured vascular smooth muscle cells. Na+/H+ exchange was activated by four distinct stimuli: 1) phorbol 12-myristate 13-acetate, 2) thrombin, 3) cell shrinkage, and 4) intracellular acid loading. [Ca2+]i was independently varied between 40 and 200 nM by varying the bathing Ca2+ from 10 nM to 5.0 mM. Thrombin-induced intracellular Ca2+ transients were blocked with bis(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (MAPTAM). In the absence of stimulators of Na+/H+ exchange, varying [Ca2+]i above or below the basal level of 140 nM did not activate Na+/H+ exchange spontaneously. However, varying [Ca2+]i did affect stimulus-induced activation of Na+/H+ exchange. Activation of the exchanger by phorbol 12-myristate 13-acetate was blunted by reduced intracellular Ca2+ (half-maximal activity at 50-90 nM [Ca2+]i), consistent with a Ca2+ requirement for protein kinase C (Ca2+/phospholipid-dependent enzyme). Activation of the exchanger by thrombin in protein kinase C-depleted cells was also sensitive to reduced intracellular Ca2+ (half-maximal activity at 90-140 nM [Ca2+]i) and was increased 40% by raising [Ca2+]i to 200 nM. Activation of the exchanger by cell shrinkage or intracellular acid loads was not significantly affected over the range of [Ca2+]i tested. Thus, altered [Ca2+]i does not itself affect Na+/H+ exchange activity in vascular smooth muscle but instead modulates activation of the transporter by particular stimuli.

Animals↗
PubMed1988

Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone.

The nucleotide and predicted amino acid sequences of two variant cDNAs [rat brain thyroid hormone receptor (rTR alpha) vI and vII], isolated from a rat brain cDNA library by using the Pst I fragment of v-erbA, showed virtual identity with the rat brain thyroid hormone receptor (rTR alpha) [Thompson, C. C., Weinberger, C., Lebo, R. & Evans, R. M. (1987) Science 237, 1610-1614] in the putative DNA binding domain and in the first 180 amino acids of the hormone binding domain but no similarity except for 5 amino acids at the extreme 3' end. Isolation and sequencing of the 3' end of the gene coding for rTR alpha, vI and vII mRNAs revealed that the 3' heterogeneity is due to alternative splicing of the primary transcripts of the same gene. RNA transfer blot analyses with probes unique to rTR alpha, rTR alpha vI, and rTR alpha vII showed that only the variant mRNAs are abundantly expressed in rat brain, contrary to the previously reported high-level expression of rTR alpha. Since in vitro translation products of rTR alpha vI and rTR alpha vII did not bind thyroid hormones specifically, our findings explain the discrepancy between the reported abundance of the receptor mRNA and the low receptor levels determined by ligand binding studies in rat brain. These variant mRNAs are also expressed in kidney, heart, spleen, and liver, albeit at lower levels. The presence of an intact DNA binding domain in rTR alpha vI and rTR alpha vII suggests that the variants might have modulating functions in thyroid hormone action.

Amino Acid Sequence↗
PubMed1988

[A case of plasmacytoma (IgD lambda) of the breast associated with multiple myeloma].

A case of secondary plasmacytoma (Ig. D. lambda) of the breast, associated with multiple myeloma, is reported, involving a 60-year-old woman in whom multiple tumors of the right breast appeared during the course of her treatment for multiple myeloma. These breast tumors were firm, non-tender, clear-margined, smooth-surfaced, and showed good mobility. An ultrasonogram revealed that the tumors had the shape of a clear-margined anechoic mass like a cyst. A histological diagnosis of a biopsied specimen determined plasmacytoma (Ig. D, lambda) and the patient was treated with chemotherapy which caused the tumors to greatly reduce.

Breast↗
PubMed1987

n-Butyrate increases the level of thyroid hormone nuclear receptor in non-pituitary cultured cells.

The thyroid hormone nuclear receptor is a chromatin-associated protein regulating expression of specific genes. Acetylation of nucleosomal core histones is thought to be one of the factors regulating transcriptional activity of chromatin, and it is suggested that this reaction negatively regulates thyroid hormone receptor levels in GH1 cells (Samuels, H.H., Stanley, F., Casanova, J., and Shao, T. C. J. Biol. Chem. 255, 2499-2508). In the present study, we found that n-butyrate, a potent inhibitor of histone deacetylase, increases thyroid hormone receptor levels in three distinct non-pituitary cells without changing binding affinity. This effect appeared within 30 min and reached a plateau (240% of control) after a 6-h treatment, before important cellular functions were affected. This effect was time-dependent, dose-dependent, reversible, and paralleled the changes in the electrophoretic mobilities of histones H3 and H4. n-Butyrate prolonged the receptor half-life, and this prolongation corresponded to the increase of receptor levels. Thyroid hormone did not reduce its own receptor levels or influence the effect of n-butyrate. Considering the difference between GH1 cells and non-pituitary cells in the regulation of thyroid hormone receptor levels, our observations, together with those of Samuels et al., suggest the possibility that the acetylation of chromatin-associated proteins has a physiological significance in the regulation of thyroid hormone nuclear receptor levels.

Acetylation↗
PubMed1987

Thyroglobulin release-stimulating activity in immunoglobulin G from patients with Graves' disease studied by human thyroid cells in vitro.

The ability of TSH or immunoglobulin G (G-IgG) from untreated patients with hyperthyroidism due to Graves' disease to stimulate thyroglobulin (Tg) release from human thyroid cells was studied. Thyroid tissue obtained from antithyroid drug-treated Graves' hyperthyroid patients was dispersed enzymatically and cultured in monolayers; medium was changed every 3 days. The cultured cells initially released large but declining amounts of Tg, independent of the presence of TSH (approximately 5 micrograms/dish on day 3 and approximately 1.5 micrograms/dish on day 6). After 6 days, TSH had a dose-dependent stimulatory effect on Tg release, and the peak response occurred on day 15. G-IgG-induced Tg release was found on the 12th day of culture and was maximal on day 18. Thyroid cells cultured for 12 days in the absence of TSH responded to TSH and G-IgG in a time- and dose-dependent fashion. Using 12-day cultures, Tg release-stimulating activity (Tg-RSA) was tested using 5 mg/ml (7.5 mg/dish) G-IgGs from 20 patients and 72-h incubation. The Tg-RSA of individual patients varied. However, significant correlations were found between Tg-RSA values and serum Tg concentrations or Tg-RSA and thyroid-stimulating immunoglobulin activities. No correlation was found between Tg-RSA and TSH binding inhibitor immunoglobulin activities. These results suggest that Tg-RSA can be an indicator of abnormal IgG of hyperthyroid Graves' patients. Whether the activity is identical with thyroid-stimulating activity remains to be clarified.

Adolescent↗
PubMed1987

Mechanical production of pleural cysts in isolated rat lungs: an experimental model for pleural blebs.

In an effort to establish the pathogenesis and developmental mechanisms of pleural blebs, which are not well understood, I attempted to produce bleb-like lesions experimentally in isolated rat lungs, and observed them histologically and ultrastructurally. One to 2 ml of the Dulbecco's phosphate-buffered saline or a mixture of sodium citrate, citric acid and dextrose was injected in usual speed into the subpleural lung parenchyma while the hilum of the lung was lightly pinched with forceps. This treatment induced one of two kinds of pleural cysts near the site of injection; one, in which a space was produced between the pleural connective tissues and lung parenchyma, and the other, in which it was between mesothelial cell layer and the pleural connective tissues. These observations suggested that some of the blebs in humans may arise on mechanical stress, and that there may be two different types of blebs in humans, too.

Animals↗
PubMed1987

[A case of a carcinoid of the duodenum (somatostatin-, serotonin- and ACTH-producing) with carcinoma of the stomach].

A case of a duodenal carcinoid which was producing somatostatin, serotonin and ACTH in a 65-year-old man is reported. The patient was found to have a submucosal protruded mass of the duodenal bulb and a tumor mass-like IIa + IIc in the antral portion of the stomach. Subtotal gastrectomy was performed and the histological diagnosis of the tumors were found to be a classical carcinoid of the duodenum and a well-differentiated tubular adenocarcinoma of the stomach. The carcinoid cells of the duodenum had numerous cyto-plasmic granules which were positive by Grimelius staining and negative by Hellerström-Hellmann staining, and 200-300 nm in size, electronmicroscopically. These cells were shown to contain somatostatin, serotonin or ACTH-positive cells by means of monoclonal immunohistochemistry, however, results were negative for gastrin, insulin, glucagon, calcitonin, VIP or PP.

Adenocarcinoma↗
PubMed1987

[Dialysis versus renal transplantation; a comparative study on medical cost and quality of life in patients with chronic renal failure].

We studied the medical costs of hemodialysis, CAPD and renal transplantation in our patients with chronic renal failure. The cost per patient averaged 660,000 yen for hemodialysis (760,000 yen for CAPD) in the first month when dialysis was started and 460,000 yen for routine maintenance hemodialysis (240,000 yen for CAPD). There was a difference in cost between recipients treated with conventional immunosuppressants (conventional group) and those receiving cyclosporine (Cs-group). That is, the estimated average cost for the conventional group was 3,800,000 in the first month after kidney grafting and at 60,000 yen in the subsequent months when the patient is cared for at the outpatient clinic; that of Cs-group was at 2,710,000 yen and 170,000 yen. This difference is due to the high cost of cyclosporine. The cumulative cost of maintenance hemodialysis is on a constant linear increase. Recently, clinical results of renal transplantation have improved markedly. Furthermore, our analysis of questionnaires to patients shows that renal transplantation is far superior to hemodialysis on the aspect of the quality of life. Thus, renal transplantation should be promoted further, and then the combined treatment of a low dose of cyclosporine and other immunosuppressants might be recommended to reduce the cost of cyclosporine.

Adult↗
PubMed1986

Changes in thyrotropin binding inhibiting immunoglobulins (TBII) in sera of patients with Graves' disease at the time of relapse or exacerbation.

Thyrotropin Binding Inhibiting Immunoglobulins (TBII) were measured in sera of 240 patients with Graves' disease who were followed 0-25 yr as a cross-sectioned study (21 untreated, 189 under therapy and 30 T3-suppressible and drug-discontinued patients) by using solubilized porcine thyroid TSH receptor. Assays were performed by using 50 microliter of serum. All untreated 21 patients showed positive TBII. Frequency of positive patients decreased yearly with treatment although 36% of patients remained positive after 6 yr of therapy. After that time TBII were positive in 61% of follow-up patients and in 16 positive patients who have been treated for more than 10 yr, drug therapy could not be stopped because of recurrence. TBII were positive in 6 of 30 T3-suppressible patients. As a longitudinal study changes in TBII were studied in 10 patients at the time of relapse or exacerbation. TBII increased in parallel with increases in thyroid hormone concentrations in 3 of 10 patients. Six of the others showed earlier or later TBII increases than those in thyroid hormones. One patient did not show any change in TBII, albeit thyroid hormone concentrations were found to be increased. Our observations suggest that abnormal IgGs detected as TBII in sera of patients with Graves' disease by the present method do not explain the occurrence of hyperthyroidism.

Adult↗