Biomedical subjects

G Komaki

Publications and source records attributed to G Komaki.

At least 37 records · Page 2Linked to original sources

PubMed1992

Aldosterone responses to angiotensin II in anorexia nervosa.

Patients with anorexia nervosa (AN) tend to have renin-angiotensin-aldosterone (RAA) abnormalities caused by abnormal behaviors such as strict dieting, fasting, vigorous exercise, self-induced vomiting and abuse of laxatives and/or diuretics. Adrenal responsiveness to angiotensin II (A II) was studied in 13 AN patients before and after therapy and in 6 normal sex- and age-matched controls: adrenal responses to postural change (1 h of walking following 1 h in a supine position) and to exogenous A II injection (A II: 10 ng/kg/min intravenous infusion for 30 min). The 24-h urine sodium concentration was significantly lower in AN patients before therapy than after therapy. Plasma aldosterone secretory response to A II was significantly higher in AN patients before therapy in both postural change and exogenous A II injection tests compared with after therapy response and that of controls. On the other hand, there was no significant difference in adrenal response to postural change or to exogenous A II between AN patients after therapy and controls. In conclusion, increased A II sensitivity caused by chronic sodium deficiency in AN patients normalized over time as the patients recovered.

Adult↗

PubMed1992

Effect of intravenous injection of IL-1 beta on PGE2 levels in several brain areas as determined by microdialysis.

Using perfusion microdialysis, the effect of intravenous injection of recombinant human interleukin-1 beta (IL-1 beta) on prostaglandin E2 (PGE2) release into the interstitial fluid of the organum vasculosum laminae terminalis (OVLT), medial preoptic area (MPOA), paraventricular nucleus (PVN), dorsal hippocampus (HPC), and cerebrospinal fluid (CSF) of the lateral ventricle (LV) was examined. Artificial CSF was perfused through the dialysis probe and collected at 20-min intervals before and after IL-1 beta (1 microgram/100 g body wt iv). The results showed that 1) IL-1 beta induced a significant increase in PGE2 levels in the OVLT and the medial part of the MPOA in the first 20 min, which is more rapid and to a greater extent than that in PVN, HPC, and LV; 2) inclusion of indomethacin in the perfusate abolished the IL-1 beta-induced PGE2 response in the OVLT, but a suppressive effect in the PVN was insignificant. These results suggest that OVLT may be a gate for the entry of blood-borne IL-1 beta into the brain and a site where the initial biochemical response to IL-1 beta occurs.

Animals↗

PubMed1992

Increased circulating interleukin-1 and interleukin-6 after intracerebroventricular injection of lipopolysaccharide.

Recently, it was demonstrated that intracerebroventricular (icv) injection of interleukin-1 (IL-1) stimulated circulating interleukin-6 (IL-6) to a greater degree than intravenous (i.v.) injection of IL-1. The goal of this study was to compare the efficacy of lipopolysaccharide (LPS), injected both icv and i.v., on circulating concentrations of IL-1 and IL-6. Both i.v. and icv injection of LPS stimulated plasma levels of IL-1 to a similar degree. However, i.v. injection of LPS was significantly more efficacious than icv injection of LPS in elevating circulating IL-6. These results demonstrate that like i.v. injection of LPS, icv injection of LPS stimulates plasma levels of IL-1 and IL-6. Increases in circulating cytokines during infectious diseases which are limited to the central nervous system may serve to activate peripheral functions of an acute phase response.

Animals↗

PubMed1991

Heterogeneity of serum prolactin in patients with menstrual disorder in conjunction with hyperthyroxinemia.

Since the secretion of PRL is regulated by the hypothalamic-pituitary axis, an increase in large molecular size PRL in the serum is most likely due to secretion by the pituitary itself. The present study was performed to investigate the possible occurrence of PRL heterogeneity in 128 subjects with menstrual disorder in conjunction with hyperthyroxinemia (88 with untreated Graves' disease, 40 with subacute thyroiditis) and 50 age- and sex-matched healthy controls. All 128 patients in this study were suffering from amenorrhea or oligomenorrhea at the time of their initial visit. PRL heterogeneity was found in the sera of 5 of 88 (5.7%) patients with untreated Graves' disease, in 2 of 40 (5.0%) patients with subacute thyroiditis, but in none of the normal controls. PRL heterogeneity remained essentially unchanged in patients with Graves' disease over 6 months of treatment; however, in patients with subacute thyroiditis, either big-big PRL or big PRL decreased significantly along with a corresponding increase in little PRL associated with recovery from the illness within 6 months. The menstrual disorders in all patients were restored to normal after restoration to a euthyroid state. The underlying cause of the occurrence of PRL heterogeneity in patients with menstrual disorder in conjunction with hyperthyroxinemia is not known.

Adolescent↗

PubMed1991

Responses of growth hormone and cortisol to intravenous glucose loading test in patients with anorexia nervosa.

The hypothalamic satiety and hunger centers appear to be affected by changes in circulating blood glucose concentrations. The response of the centers, in turn, is reflected by alterations in growth hormone (GH) and cortisol levels. There are no studies attempting to relate blood glucose and GH and cortisol changes in patients with anorexia nervosa (AN) during an intravenous glucose tolerance test (IVGTT). In the present inquiry, IVGTT (10 g) were performed on AN patients to characterize the satiety and hunger centers' responses to changes in glucose and insulin levels as reflected by GH and cortisol levels. Study participants were 15 female AN patients and eight healthy female volunteers. No significant differences in blood glucose levels were observed between the two groups. However, immunoreactive insulin (IRI) levels in AN patients were significantly lower than those in the control group. Although GH and cortisol concentrations were significantly suppressed after the infusion in the control group, the AN patients' GH levels paradoxically increased, and cortisol levels did not change. Moreover, a negative correlation was observed between delta GH and delta IRI in all individuals in this study (r = -.61, P less than .01). In conclusion, abnormal GH and cortisol responses to a 10-g IVGTT were found in patients with AN. delta GH levels correlated negatively with delta IRI levels. These data suggest that hypothalamic satiety and hunger centers in AN respond abnormally to change in blood glucose levels.

Adolescent↗

PubMed1990

Sensitivity of thyroids to endogenous thyrotrophin in patients with Graves' disease.

T3 nonsuppressibility and TSH nonresponsiveness to TRH are characteristics of untreated hyperthyroid Graves' disease. Although the tests are commonly restored to normal during antithyroidal drug therapy, dissociation of TRH and T3 suppression tests have been observed in euthyroid Graves' disease and during drug therapy. Abnormalities of pituitary-thyroidal regulation and persistence of thyroid autoimmune disease have been found in Graves' patients following various modalities of therapy. The present study investigated in vivo sensitivity to endogenous TSH of thyroids in 144 Graves' disease patients following treatment with subtotal thyroidectomy, 131I, or antithyroidal drugs. After administration of TRH, thyroidal sensitivity to TSH was determined by the following: delta T3 (peak T3 minus basal T3), % increase in T3 (peak over basal), and the ratio of delta T3 to delta TSH. Significant differences in sensitivity to TSH in T3 nonsuppressible patients were found compared to suppressible patients regardless of their TSH responses to TRH or modality of therapy. These data suggest that measurements of serum T3 and TSH following TRH administration to determine in vivo thyroidal sensitivity may be substituted for the T3 suppression test as a confirmatory test for Graves' disease or as a prognosticator of relapse following therapy.

Adolescent↗

PubMed1990

Plasma beta-endorphin during fasting in man.

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.

Adolescent↗

PubMed1990

Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH)-releasing hormone-(1-44)-induced GH secretion in anorexia nervosa.

The presence of hypothalamic disturbances affecting GH secretion in anorexia nervosa has been suggested, although a normal GH response to GH-releasing hormone (GHRH) administration has been shown in these patients. The present study was performed to investigate the role of acetylcholine in regulating GH secretion by using pirenzepine, which selectively blocks muscarinic cholinergic receptors. Paired tests were performed in nine anorexia nervosa patients (age +/- SEM, 19.1 +/- 1.2 yr; percent ideal body weight, -32.7 +/- 2.2%) and in six normal controls (20.1 +/- 0.3 yr; -3.1 +/- 1.8%). GHRH-(1-44) (1 microgram/kg) was infused iv with and without pirenzepine pretreatment (0.6 mg/kg, iv). Basal levels of GH were not different in anorexia nervosa compared to normal controls, whereas, somatomedin-C levels were significantly lower in anorexia nervosa patients. However, after pirenzepine administration, the GHRH-stimulated GH responses were completely blocked in normal controls, but not in anorexia nervosa patients. These results suggested that altered muscarinic cholinergic mechanism are involved in the modulation of GH secretion in patients with anorexia nervosa.

Acetylcholine↗

PubMed1990

Thyroid-stimulating antibody and thyrotropin-binding inhibitory immunoglobulin activity in hypothyroid patients who subsequently developed thyrotoxicosis.

Although abnormal thyroid-stimulating and -blocking antibodies have been demonstrated in hyperthyroid and hypothyroid patients with autoimmune thyroid disorders, a direct correlation is not always observed. Thyroid-stimulating antibody, thyrotropin-binding inhibitory immunoglobulin, and thyroid-stimulating blocking antibody levels were determined in three hypothyroid patients who subsequently developed hyperthyroidism. Thyroid-stimulating antibodies levels were normal in one, elevated in another, and unmeasured in the third hypothyroid patient, but became elevated in all patients with the onset of hyperthyroidism. There was discordance, however, in one patient who had markedly elevated thyroid-stimulating antibodies and TSH-binding inhibitory immunoglobulin levels when she was hypothyroid. The data indicate that thyroidal responses to the abnormal stimulating antibodies may differ among patients with autoimmune thyroid disease.

Adult↗

PubMed1990

The clinical efficacy of a 5-HT1A agonist, SM-3997, in the treatment of bulimia.

Psychotherapeutic and pharmacological treatment of bulimia and vomiting require long duration and frequently entail considerable obstacles in patience compliance, making such regimens difficult to pursue. The regulating mechanism of the appetite center is recognized to be complex and recently an important role of serotonin (5-HT), a neurotransmitter, has been shown in rats. In the present study a newly developed 5-HT1A agonist, SM-3997, was administered to 12 patients with bulimia and its clinical efficacy was evaluated. The patients were treated on an open basis with SM-3997, 30-40 mg/day, for 6-15 weeks. Bulimic behavior stopped completely in 4 patients, was improved in 4 others and was unchanged in the remaining 4. These results suggest that the administration of a 5-HT1A agonist, SM-3997, may be effective in the treatment of bulimia and vomiting and that further investigation is warranted.

Administration, Oral↗

PubMed1989

Methimazole-induced agranulocytosis in Japanese patients with Graves' disease.

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

Adult↗

PubMed1989

Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroidal drugs: clinical, immunological, and histological findings in 26 patients.

Graves' disease may result eventually in hypothyroidism in approximately 5-20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5-10 yr or more after discontinuation of antithyroid drug therapy. Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia. We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

Adolescent↗

PubMed1989

Changes in serum thyroid hormone, thyrotropin and thyroglobulin concentrations during thyroxine therapy in patients with solitary thyroid nodules.

We studied the effect of therapy with 0.1 mg/day T4 for 3 months on goiter size in 49 patients with solitary thyroid nodules. The nodule volume in 18 patients (responders) decreased by more than 50%. In this group the mean serum thyroglobulin (Tg) levels decreased significantly (from 425 to 61 micrograms/L; P less than 0.01). In the nonresponders the mean serum Tg levels did not change significantly (145 vs. 250 micrograms/L). The mean serum T4, free T4, free T3, and rT3 concentrations increased significantly in both groups during T4 therapy, serum T3 levels did not change, and serum TSH decreased. These findings demonstrate that serum Tg levels decrease when T4 therapy is effective. Thus, serum Tg measurements may prove a useful indicator of the efficacy of T4 therapy in patients with solitary nodules.

Adolescent↗

PubMed1988

Changes in serum angiotensin-converting enzyme in acutely starved non-obese patients. A possible dissociation between angiotensin-converting enzyme and the thyroid state.

We investigated changes in the serum angiotensin-converting enzyme, as an index of thyroid hormone action, before, during and after fasting in 15 non-obese, hospitalized patients. Serum angiotensin-converting enzyme decreased significantly from 14.6 +/- 1.1 U/l before fasting to 13.2 +/- 1.1 U/l on the 5th day (P less than 0.05, N = 15) during fasting, and to 10.6 +/- 1.0 U/l on the 10th day (P less than 0.05, N = 8). The serum TSH and T3 levels decreased significantly to below the normal range, and the serum T4 level decreased gradually during fasting, whereas free T4 (Amerlex) changed slightly, but within normal range. Although re-feeding did not lead to any reduction in the serum TSH, T3, or T4 level, the serum angiotensin-converting enzyme further decreased to 8.7 +/- 0.9 U/l on the 5th day of re-feeding compared with that on the 10th day of fasting (P less than 0.01, N = 8). There was a delay in the re-elevation of serum angiotensin-converting enzyme following a rise in serum T3. No correlations were found between serum angiotensin-converting enzyme levels and thyroid hormone levels throughout the study period. It is concluded that a significant reduction in the serum angiotensin-converting enzyme level occurs under a 'low T3' state during acute starvation, although there is no clear association between serum angiotensin-converting enzyme and thyroid hormone levels.

Adolescent↗

PubMed1987

HLA and thyrotoxic periodic paralysis in Japanese patients.

Periodic paralysis (PP) is a well recognized although rare and peculiar complication of thyrotoxicosis, especially among Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked to certain immunogenetic factors, and increased frequency of certain HLA antigens has been found in patients with Graves' disease. This study was, therefore, undertaken to determine HLA haplotypes in Japanese men with thyrotoxic periodic paralysis (TPP). HLA typing in 35 TPP patients and 263 normal men and women demonstrated highly significant increases (P less than 0.01) in HLA-A2, Cw3, and DRw8 in the TPP patients. In comparing TPP patients with thyrotoxic men who did not have PP, the frequency of DRw8 antigen was 2.5-fold greater in patients with PP than in those without it (62.8% vs. 28.6%). The data suggest that the HLA-DRw8 gene itself may play a significant role in the susceptibility to TPP among Japanese men.

Adult↗

PubMed1986

Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients.

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.

Adolescent↗

PubMedDate not supplied

Pancreatic abnormalities in patients with eating disorders.

In patients with eating disorders, we evaluated pancreatic abnormalities using serum elastase 1 measurement by RIA and the 50 g oral glucose tolerance test (50 g OGTT). Twenty-one patients had anorexia nervosa (AN) with bulimia and vomiting (AN-B group), 30 had AN without bulimia or vomiting (AN-R group), and 25 had bulimia with normal body weight (B group). The serum elastase 1 level was determined on admission and repeated after body weight gain in 43 anorectic patients. The 50 g OGTT was performed within 2 weeks after admission. The serum elastase 1 level in the AN-B group (363 +/- 47 ng/dl, M +/- SE), and in the AN-R group (352 +/- 37) were significantly higher than that in the B group (242 +/- 18) or in the healthy female controls (191 +/- 10; n = 13). A significant decrease of serum elastase 1 was observed before and after body weight gain; however, there was no significant correlation between the serum elastase 1 level and insulin response to the 50 g OGTT. Elevation of the serum elastase 1 level in AN suggests pancreatic abnormalities other than those related to endocrinological events.

Adult↗

PubMedDate not supplied

The restraint stress-induced elevation in plasma interleukin-6 negatively regulates the plasma TNF-alpha level.

Although a considerable amount of evidence has shown that physical and psychological stress elevates the plasma interleukin 6 (IL-6) levels, the physiological significance of such an elevation remains to be elucidated. In this study, in order to determine whether the restraint stress-induced elevation of plasma IL-6 contributes to the activation of the hypothalamic-pituitary-adrenal axis, and whether or not such elevation can affect the inflammatory processes, the plasma levels of ACTH, corticosterone, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in mice pretreated with anti-IL-6 antibody (MP5-20F3 monoclonal antibody) were compared with those in mice pretreated with rat IgG (control antibody) both during and after stress. Both the anti-IL-6-antibody- and control-antibody-pretreated mice showed the same extent of plasma ACTH and corticosterone increases during stress, and no significant difference was found between the two groups of animals. On the other hand, the level of plasma TNF-alpha in the anti-IL-6-treated animals was also significantly higher than that in the control animals both immediately after cessation of stress and 60 min after the cessation of the 120-min period of restraint. Plasma IL-1 activity, however, did not reach a detectable level in either group of animals at any time point examined. These results thus indicate that the restraint-stress-induced elevation of plasma IL-6 negatively regulates the plasma TNF-alpha levels and may thus contribute to the maintenance of homeostasis.

Adrenocorticotropic Hormone↗