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Biomedical subjects

Y Koide

Publications and source records attributed to Y Koide.

At least 235 records · Page 13Linked to original sources

Restriction molecules involved in the interaction of human T cell clones with antigen-presenting cells.

Two of three distinct human Ia molecules detected by murine monoclonal antibodies (MoAb) have been suggested to be involved in antigen presentation for T cell responses to purified protein derivatives (PPD) and herpes simplex virus (HSV). This observation was first suggested from studies on the inhibition of proliferative responses of whole T cell populations with MoAb against human Ia molecules. To determine whether a single T cell recognizes the antigen in the context of both Ia molecules or in the context of each one of two Ia molecules, we isolated and propagated PPD-reactive T cell clones from an HLA-DR heterozygous individual. They showed four different restriction patterns: type I and type II clones each appeared to be restricted to one of two HLA-DR antigens, type III clone gave anomalous patterns of response and seemed to be restricted to non-DR antigens, and type IV clone recognized antigen when both DR antigens were presented on the same antigen-presenting cells (APC) surface. Blocking study with monoclonal anti-Ia antibodies suggested that type I, II and IV clones are restricted to DR molecules and type III clones are restricted to 1B4 molecules distinct from DR or MB1 molecules. These data imply that human T cell clones recognizing PPD in the context of each one of two Ia molecules are clonally distributed.

Antibodies, Monoclonal↗

Clonal distribution of human T cells recognizing PPD in the context of each of two distinct Ia molecules.

Participation of two of three distinct human Ia molecules, HLA-DR and the Ia molecule detected by monoclonal antibody (MoAb) 1B4 (1B4 molecules), in antigen presentation for T cell responses to purified protein derivative (PPD) and herpes simplex virus (HSV) was first suggested from studies on the inhibition of proliferative responses of whole T cell populations with MoAb against human Ia molecules. To determine whether a single T cell recognizes the antigen in the context of both Ia molecules or in the context of each one of two Ia molecules, we isolated and propagated PPD-reactive T cell clones from an HLA-DR heterozygous individual. The clones showed four different restriction patterns: type I and type II clones appeared to be restricted to one of two HLA-DR antigens, type III clones gave anomalous patterns of response and seemed to be restricted to non-DR antigens, and type IV clone recognized antigen when both DR antigens were presented on the same APC surface. Blocking study with MoAb to Ia molecules suggested that type I and type II clones are restricted to DR molecules and type III clones are restricted to 1B4 molecules distinct from DR or MB1 molecules. Furthermore, it is most likely that type IV clone was restricted to the interaction molecule associated with DR antigens. These data imply that human T cell clones recognizing PPD in the context of each one of two Ia molecules are clonally distinct.

Antibodies, Monoclonal↗

A case of glycogen storage disease type I associated with an incomplete type of Fanconi syndrome; the protective role of lysosomal alpha 1,4-glucosidase and insulin deficiency against hypoglycemia.

A 59-year-old Japanese farmer with asymptomatic fasting hypoglycemia and with exaggerated hypoglycemic episodes induced by insulin and oral hypoglycemic agent administered for his postprandial hyperglycemia was diagnosed as glycogen storage disease type I. This diagnosis was suggested by unresponsiveness of blood glucose level to glucagon and confirmed by 13% normal level of glucose 6-phosphatase activity in liver biopsy specimen and by the presence of PAS positive amylase digestable glycogen in liver specimen. This case was associated with an incomplete type of Fanconi syndrome characterized by hyperphosphaturic hypophosphatemia, partial aminoaciduria, mild proteinuria and hyperuricosuric normouricemia in spite of the lactic acidemia due to glycogen storage disease type I. The etiology for the absence of hypoglycemia and other typical manifestations of glycogen storage disease type I was studied. The glucose production from glycogen by lysosomal alpha 1,4-glucosidase especially at prolonged fasting and the presence of postprandial hyperglycemia by insulin deficiency are regarded as responsible for keeping this patient free from typical manifestations of glycogen storage disease type I.

Biopsy↗

Inhibitory effects of active vitamin D preparations on PTH secretion in rats.

To study the effects of various vitamin D preparations on PTH secretion, serum calcium and urinary excretion of cAMP were monitored in conscious perfused rats, and the influences of a bolus iv injection of the preparations on these parameters were examined. Three hours after the administration of 0.25 microgram/kg (0.6 nmol/kg) of 1 alpha, 24(R)-dihydroxycholecalciferol [1 alpha, 24(OH)2D3], the urinary excretion of cAMP decreased to a level compatible with that of parathyroidectomized (PTX) rats (50% of initial value; p less than 0.05) with no change in the concentration of serum calcium (total and ionized). In PTX rats supplemented with bovine PTH (1 U/h), the vitamin D preparation showed no significant effects either on the urinary excretion of cAMP or on serum calcium. These effects were rather specific for active vitamin D preparations, i.e. 1 alpha, 25(OH)2D3 (0.25 micrograms/kg) and 1 alpha OHD3 (1.25-6.25 micrograms/kg). However, 24,25(OH)2D3 (up to 25 micrograms/kg) had no significant effect on these parameters. These results suggest that, in rats, active vitamin D preparations specifically inhibit PTH secretion without causing a significant increase in the serum calcium concentration, reflecting a direct feedback mechanism between active vitamin D metabolite and the parathyroid glands.

24,25-Dihydroxyvitamin D 3↗

The capacity of antigen-presenting cells is fully preserved in childhood cancer patients.

T cells from 19 out of 25 childhood cancer patients showed impaired proliferative responses to purified protein derivatives (PPD)-pulsed antigen-presenting cells (APC) although all of the patients had been immunized with BCG. To test whether such low responsiveness of T cells results from the dysfunction of T cells or from that of APC, the experiment was designed to assess the proliferative response of T cells from patients or their parents to PPD-pulsed APC from patients or parents. These combinations seem to be suitable to assess the activity of T cells or APC since at least partial identity of HLA-D/DR antigens is required for T cell-APC interactions. Although T cells from patients who showed low responsiveness to PPD failed to respond even to PPD-pulsed APC from parents, T cells from parents were able to respond to PPD-pulsed APC from patients as well as to autologous APC. These observations strongly suggest that the low responsiveness to PPD in childhood cancer patients results from the dysfunction of T cells, and the capacity of APC is fully preserved. In other words, it appears that the capacity of APC is not impaired by chemotherapy, neoplastic cells, or other factors. Suppressor T cells appeared not to be involved in such dysfunction of T cells.

Adolescent↗

Effects of substance P on thyroidal cyclic AMP levels and thyroid hormone release from canine thyroid slices.

A neuropeptide, substance P (1-50 microM) caused a prompt but transient rise in tissue cyclic AMP levels and also increased the release of thyroid hormones from canine thyroid slices. While norepinephrine markedly inhibited the stimulation by TSH of such parameters as reported previously, substance P had no effect. These results suggest that substance P may play a regulatory role in thyroid gland functions in a manner different from norepinephrine.

Animals↗

Activation of glycogenolysis by the reduction in the extracellular calcium concentration in verapamil-perfused rat liver.

In an attempt to elucidate the role of Ca2+ flux in the initial events of hepatic glycogenolysis, extracellular Ca2+ concentration was manipulated in rat liver perfused with Ca2+ antagonistic drugs. After the liver had been perfused with a buffer containing verapamil and 1 mM CaCl2, either the addition of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid to the perfusate or the replacement of the perfusate with Ca2+-free buffer caused a rapid increase in glucose output as well as 45Ca2+ efflux. Substitution of diltiazem, but not 5-20 mM LaCl2, for verapamil also stimulated glucose output and 45Ca2+ efflux. However, when Ca+-free buffer was used throughout the experiment, any modes of verapamil or diltiazem perfusion were without significant effects on glucose output or Ca2+ efflux. The increases in glucose output and 45Ca2+ efflux were not affected by either 20 microM phentolamine or 300 microM ouabain, but they were inhibited significantly by 10-100 microM trifluoperazine. These results indicate that rapid decline in the extracellular Ca2+ concentration in verapamil- or diltiazem-perfused liver initiates the change in Ca2+ equilibrium on or across plasma membrane and activates glycogenolysis through a Ca2+-dependent mechanism.

Animals↗

Association of isolated adrenocorticotropin deficiency with a variety of neuro-somatic abnormalities in congenital facial diplegia (Moebius) syndrome.

A male patient with recurring episodes of hypoglycemic attacks was diagnosed as having isolated ACTH deficiency as well as renal glycosuria and ichthyosis vulgaris. In addition, he had facial diplegia and abducens palsy consistent with Moebius syndrome, muscle atrophy with proximal dominancy, high arched palate, hammer toes, and mental retardation. There was electrophysiological evidence of peripheral neuropathy. Muscle biopsy of the deltoid showed mild myofiber atrophy with occasional cylindrical laminated bodies. The association of these disorders has never been reported and it could be coincidental. However, considering the high rate of association of isolated hypogonadotropic hypogonadism and Moebius syndrome with peripheral neuropathy, the present case may indicate a causal relationship between isolated ACTH deficiency and Moebius syndrome, reflecting the disorders in the organ systems derived from a common ectoderm.

Adrenocorticotropic Hormone↗

[Basic and clinical studies on metastatic cancer--with special reference of multidisciplinary treatment of gastric and colorectal cancer patients with hepatic metastasis].

We studied 161 gastric cancer patients with P0, H(+) and 51 colorectal cancer patients with P0, H(+) from among cancer patients of the digestive organs and obtained the following conclusions. The effective treatment for synchronous hepatic metastasis was regarded as the group with surgical removal of the primary lesion plus hepatic resection plus chemotherapy, demonstrating most favorable prognosis in both gastric and colorectal cancer patients. Prognosis of the group treated with surgical removal of the primary lesion plus hepatic resection plus chemotherapy, was the most excellent and was followed by the group with surgical removal of the primary lesion plus chemotherapy and group with surgical removal of the primary lesions and group surgical removal of the primary lesion in this order. Concerning chemotherapy after surgical removal of the primary lesion, continuous intraarterial infusion therapy with FML regimen combining Lentinan revealed more favorable prognosis also in both gastric and colorectal cancer patients. Hepatic resection with aggressive reduction surgery was of significance in the treatment for the patients with hepatic metastasis of H1 and H2. Long-term survival is also expected for the patients with metachronous hepatic metastasis of H1 by hepatic resection plus chemotherapy.

Colonic Neoplasms↗

[Report on 15 cases of multiple primary cancers in our department].

Of 512 gynecological malignant cases treated in our department, 22 were suspected of multiple primary cancer; 15 were confirmed by clinical and pathological findings, representing an incidence of 2.9% (15/512) of all malignant cases. The most frequent sites of other cancers in patients with cervical cancer were intestinal (5/15), mammary (3/15) and urinary (2/15). Nine (60%) of 15 multiple primary cancers were noted within 12 months. Two rare combinations are also reported. There was a patient with Grawitz's tumor (kidney) and epidermoid cancer (uterine cervix) and one with leiomyosarcoma (uterine corpus) and epidermoid cancer (uterine cervix).

Aged↗

Determination of p-hydroxyphenylacetic acid in cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection.

Using reversed-phase high-performance liquid chromatography and electrochemical detection with a rapid one-step purification on a Sephadex G-10 column, we have developed a sensitive technique to measure p-hydroxyphenylacetic acid, the oxidatively deaminated metabolite of p-tyramine. The metabolite was measured in cerebrospinal fluid with high recovery and precision. Concentrations of p-hydroxyphenylacetic acid ranged from 4.2 to 17.0 ng/ml with a mean value of 7.8 ng/ml +/- 1.1 SEM in lumbar cerebrospinal fluid of 11 control patients. In a preliminary analysis, the concentrations in schizophrenic patients were significantly lower than those in controls. Since p-hydroxyphenylacetic acid in cerebrospinal fluid seems to be derived from the brain, this finding may indicate a decrease in brain formation. The present method should be useful in clinical investigations to clarify a functional role of p-tyramine in the brain.

3,4-Dihydroxyphenylacetic Acid↗

Paradoxical response to parathyroid hormone of renal handling of phosphate in hyperparathyroid rats.

The effect of PTH given as a bolus on renal handling of phosphate in rats was studied by a perfusion balance study method. In vitamin D-fed rats, iv PTH as a bolus (10 USP units) elicited a phosphaturic response and an increase in urinary cAMP, whether or not the rats were thyroparathyroidectomized. When given to thyroparathyroidectomized rats receiving continuous infusion of PTH (2.5 USP units/h) for 16 h, PTH led to a paradoxical decline of phosphate clearance in spite of an increase in urinary cAMP. Vitamin D-deficient intact rats also showed this paradoxical response. Vitamin D-deficient thyroparathyroidectomized rats showed an ordinary phosphaturic response. When PTH had been supplied continuously (2.5 USP units/h) to these rats, the PTH bolus again produced the paradoxical response. Phosphate supplementation did not restore the phosphaturic response. (Bu)2cAMP infusion reproduced the paradoxical effect in vitamin D-fed, thyroparathyroidectomized rats receiving continuous infusion of PTH. These data indicate that a long-lasting excess of circulating PTH alters the nature of the response of the kidney to an iv bolus of PTH, so that PTH leads to a paradoxical decline of phosphate clearance, and that the mechanism responsible for the paradox may lie in a step (or steps) subsequent to cAMP production.

Animals↗

A case of pituitary adenoma with possible simultaneous secretion of thyrotropin and follicle-stimulating hormone.

A TSH- and FSH-screening pituitary adenoma was demonstrated in a 23-yr-old man who presented with bitemporal hemianopsia, but without clinical or laboratory evidences of hyper- or hypothyroidism or hypogonadism. Basal TSH (29-45 microunits/ml) and FSH (44-63 mIU/ml) were moderately elevated. GH and ACTH secretion were impaired, and basal PRL and testosterone were normal. TRH and LRH elicited a significant increase in TSH and FSH, respectively. The plasma glycoprotein alpha-subunit concentration was normal, and its response to simultaneous administration of TRH and LRH was low. Plasma TSH was not suppressed completely by exogenous T3. After operation and radiotherapy, elevated TSH and FSH as well as failure of T3 to suppress TSH were corrected. No significant changes in thyroid hormone concentration in the blood were detected in spite of the reduction of TSH. TSH and FSH concentrations in the tumor extract were lower than those in normal pituitaries. Histologically, the tumor was very vascular and consisted mostly of a single type of cell. The tumor cells were positively stained for FSH beta-subunit by immunohistochemical study, but for none of other pituitary hormones or subunits examined. Electron microscopic examination revealed relatively abundant single type secretory granules of high electron density. It is possible that the tumor simultaneously secreted TSH and FSH, the former possibly being immunologically active, but biologically inactive.

Adenoma↗

Hyponatremia without inappropriate secretion of vasopressin in a case of myxedema coma.

A 45-year-old woman with myxedema coma due to primary hypothyroidism manifested hyponatremia, impaired water excretion, and elevated urine osmolarity as well as natriuresis suggestive of a syndrome of inappropriate antidiuretic hormone secretion. However, plasma vasopressin was undetectable or very low and plasma aldosterone levels were suppressed in the presence of hyponatremia. Subsequent replacement therapy with levothyroxine caused a rapid decline in sodium clearance which was independent of the change in glomerular filtration rate, and corrected the impaired water excretion and hyponatremia. Plasma vasopressin levels returned to the normal range after the correction of hyponatremia. Thus, the results indicate that neither vasopressin nor aldosterone plays a dominant role in the pathogenesis of the hyponatremia in this patient. It appears that thyroid hormone deficiency itself caused the derangement of tubular cell function, which resulted in the development of the impaired water excretion and hyponatremia.

Coma↗