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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 739 records · Page 41Linked to original sources
PubMed1981

3,3',5'-triiodothyronine (reverse T3) in human cerebrospinal fluid.

To examine the metabolic products of thyroid hormones in the central nervous system, total and free rT3 as well as T4 in human cerebrospinal fluid (CSF) were determined in 41 patients. Total T4, T3, and rT3 concentrations in CSF were determined by RIA, and free T4, T3, and rT3 fractions were analyzed by the magnesium precipitation method. The mean (+/- SE) total T4 and T3 concentrations in CSF were 166 +/- 24 and 2.6 +/- 1.5 ng/dl, respectively; the values were approximatey 2% of those in normal control pooled sera. Total rT3 concentrations in CSF from 29 clinically euthyroid patients who were apparently in a normal nutritional state ranged from 5.2-23 ng/dl (mean +/- SE, 11.2 +/- 0.9 ng/dl); the value was approximately 40% of that in sera. A patient with primary hypothyroidism had a markedly diminished CSF rT3 concentration (1.1 ng/dl), and the remaining 11 patients, suffering from severe diseases such as meningitis and cerebrovascular accident, had significantly higher CSF rT3 concentrations (37.5 +/- 6.6 ng/dl) than the clinically euthyroid patients. Although free T4 and T3 concentrations in CSF (5.9 +/- 1.1 and 0.16 +/- 0.05 ng/dl, respectively) were similar to those in serum (2.1 +/- 0.2 and 0.22 +/- 0.01 ng/dl, respectively), the free rT3 concentration in CSF (0.70 +/- 0.12 ng/dl) was approximately 20 times higher than that (0.044 +/- 0.016 ng/dl) in serum. Furthermore, the reciprocal relationship was observed between CSF total rT3 concentrations and free rT3 percentages in CSF. These data suggest the possibility that rT3 may be produced from T4 in human brain and that there may be a transport mechanism regulating free rT3 in CSF.

Humans↗
PubMed1981

Cushing's syndrome associated with corticogenic hypothyroidism: a case study.

Described here is a 27-year-old female, who had centripetal obesity, broad reddish-purple striae on the lower abdomen and hypertension. Serum cortisol levels, the results of a dexamethasone suppression test and an adrenal scintigram with 131I-19-iodocholesterol were all compatible with Cushing's syndrome due to an adrenal adenoma that secretes cortisol autonomously. This was confirmed by gross and microscopic examination of the removed adrenal tumor. In addition, the patient had markedly diminished T4 and T3 concentrations in serum. Basal TSH levels were not elevated and did not rise significantly after TRH injection. Serum T4 and T3 concentrations were elevated to the normal range when the hyperadrenocorticism was corrected. The results indicate that the patient had "'corticogenic hypothyroidism."

Adenoma↗
PubMed1981

Reciprocal relation between serum thyrotropin levels and intrapituitary 3,5,3'L-triiodothyronine generating activity from thyroxine in perinatal rats.

Thyroxine (T4) 5'-monodeiodinating activity in rat pituitary was studied, using paper chromatography. Rat anterior pituitary homogenates were incubated with 125I-T4, dithiothreitol and unlabeled L-T4 at 37 degrees C. The incubation mixture was extracted by ethanol and the extracts were subjected to descending paper chromatography. The conversion ratio of T4 to 3, 5, 3'L-triodothyronine (T3) was calculated from the radioactivity of T3 spot to total radioactivity on the paper strip. The T3 amount generated was estimated from the T4 concentration in the incubation mixture and the conversion ratio. The T3 generating activity from T4 increased as the amount of tissue increased. It was temperature-and pH-dependent, and thiol sensitive. These results suggest the enzymatic nature of T4 5'-monodeiodinating activity of the anterior pituitary. A kinetic study revealed low Km for T4 (7.9 +/- 1.6 nM, Mean +/- SE), with Vmax of 68.0 +/- 12.7 fmoles T3/mg protein/min. T4 monodeiodinating activity was consistently, though minimally, detected in fetal rat pituitaries and increased after birth, reaching the maximum at 22 days. It declined thereafter to the young adult level. Serum TSH levels were markedly elevated in fetus. They decreased after birth, reaching the nadir at 22 days, and then increased to young adult levels. Serum T4 and T3 levels were markedly diminished in fetus and gradually increased after birth, reaching the young adult levels at 17 days. Thus, a reciprocal relationship was observed between intrapituitary T3 generating activity from T4 and serum TSH levels in developing rats. It suggests that the conversion of T4 to T3 in the pituitary plays a role in regulating TSH secretion.

Animals↗
PubMed1981

Sex- and age-related changes of exophthalmos in graves' disease.

In order to evaluate the effect of sex and age on the protrusion of the eyes in patients with Graves' disease, exophalmometry was performed on 95 patients, aged 16-73. The mean (+/- SE) protrusion in the 190 eyes was 17.5 +/- 0.2 mm, being significantly higher than those in normal subjects (14.9 +/- 0.2 mm) and patients with Hashimoto's disease (14.3 +/- 0.2 mm). No significant difference existed in the degree of protrusion between thyrotoxic Graves' disease patients and those maintained in an euthyroid state during treatment with antithyroid drugs. When compared in terms of the duration of the treatment, the protrusion became prominent with the increased duration of the treatment, especially in male patients, although statistically not significant. The protrusion in male patients tended to increase, though not significantly, with increasing age, whereas it decreased significantly with increasing age in female patients.

Adolescent↗
PubMed1981

Primary aldosteronism associated with a primary double cancer of the thyroid and rectum: report of a case.

A variety of complications are encountered in primary aldosteronism. Among them, less well known is the association of functioning adrenocortical adenoma with neoplasia of other organs. Described here is a patient with primary aldosteronism who had undergone a surgical operation for thyroid cancer and died of meningoencephalitis due to Listeria monocytogenes. Moreover, the autopsy revealed that he had an adenocarcinoma of the rectum. To our knowledge, this is the first documented case of a patient who had both primary aldosteronism and a primary double cancer of the thyroid and rectum.

Adenocarcinoma↗
PubMed1981

Modulation of T4 5'-monodeiodination in rat anterior pituitary and liver homogenates by thyroid states and fasting.

In order to clarify the role of the pituitary conversion of L-thyroxine (T4) to 3, 5, 3'-L-triiodothyronine (T3) in regulating thyrotropin (TSH) secretion, the effect of altered thyroid states and fasting on intrapituitary T3 generation was investigated by a paperchromatographic procedure using the anterior pituitary homogenates. Hepatic T3 generation was also studied for comparison. The rate of pituitary and hepatic T3 generation in normal rats averaged 25.2 +/- 12.4 (mean +/- SE) fmoles T3/mg protein/min and 33.8 +/- 12.7 fmoles T3/mg protein/min, respectively. T4 treatment raised the hepatic T3 generation from T4 (46.7 +/- 3.1 fmoles T3/mg protein/min) and lowered the intrapituitary T3 generation (4.5 +/- 0.2 fmoles T3/mg protein/min). On the contrary, thyroidectomy slowed the hepatic T4 5'-deiodination (11.0 +/- 2.8 fmoles T3/mg protein/min), and accelerated the pituitary T4 5'-deiodination (64.3 +/- 1.4 fmoles T3/mg protein/min). In 48 h fasted rats, serum T4, T3 and TSH concentrations were all lower than those in fed rats, and both pituitary and hepatic T3 generations were also suppressed. Thus, altered thyroid states cause an opposite effect on pituitary and liver 5'-monodeiodination, whereas fasting causes similar changes. The findings suggest the existence of an autoregulatory mechanism for thyroid hormone activation within the target tissues.

Animals↗
PubMed1980

Ca2+-calmodulin-dependent phosphorylation and platelet secretion.

Protein phosphorylation may play a critical role in stimulus-coupled secretion of platelets. Some platelet proteins become phosphorylated on exposure to agents such as thrombin and collagen, and the smallest of these phosphoproteins (molecular weight 20,000), has been identified as a light chain of myosin. Phosphorylation of myosin light chain increases the activity of actin-activated myosin ATPase and the resultant contraction of the actomyosin presumably mediates the release reaction. Platelet myosin light chain kinase has been identified as a calcium-dependent enzyme requiring calmodulin for its activity. Calmodulin is a Ca2+-binding protein with a molecular weight of approximately 18,000 which seems to be involved in a wide variety of cellular processes. Although a growing body of evidence suggests that non-muscle actomyosin, such as that isolated from platelets, is regulated by Ca2+-calmodulin-dependent light chain phosphorylation, the precise relationship between the phosphorylation and the function of platelets is not clearly established. We now present pharmacological evidence that a calmodulin-mediated system, such as Ca2+-dependent myosin light chain phosphorylation, also plays an important role in the phenomenon of the release reaction. N-(6-aminohexyl)-5-chloro-1-napthalene-sulphonamide (W-7) (refs 13-15) is shown to bind selectively to calmodulin in vitro and inhibit its biological activity.

Adenosine Triphosphate↗
PubMed1980

Morphological changes of the liver in uremic patients treated with chronic hemodialysis--laparoscopic observations and light- and electron-microscopic studies.

In order to clarify morphological changes of the liver in the uremic state, 16 uremic patients treated with chronic hemodialysis were studied. Biopsy was performed in 14 cases under laparoscopic observation and in two on the occasion of renal transplantation. One uremic patients not being treated with dialysis was also studied for comparison. All biopsy specimens were examined by light and electron microscopy. The liver usually appeared mildly or moderately swollen under laparoscopic observations, which was considered at least partially due to the enlargement of the hepatocytes. All patients had hepatocytes with an Orcein-negative "ground glass" appearance, in which marked proliferation of smooth endoplasmic reticulum (SER) was found by electron microscopy. Since the patient not being on dialysis also had such hepatocytes, this finding may be characteristic of uremia. With electron microscopy, in addition to proliferation of SER, alteration of mitochondria and rough endoplasmic reticulum (RER) and an increase in cytoplasmic lipid droplets were observed. Hypertrophy of the Golgi apparatus containing electron-dense particles (VLDL) was often found in patients associated with hypertriglyceridemia. Amorphous electron-dense inclusions in microbodies were occasionally observed. Siderosis was observed in nine patients including three having parenchymal siderosis. With electron microscopy, various siderosomes were seen in the cytoplasm of hepatocytes in patients with parencymal siderosis. Conclusively, these histological and ultrastructral features of hepatocytes are rather associated with several metabolic abnormalities in uremia.

Adolescent↗
PubMed1980

Phosphatidylcholine liposomes containing cholesterol analogues with side chains of various lengths.

The effect of the length of the side chain of sterols on their interaction with phosphatidylcholine was studied by measuring the permeability properties of liposomes constituted with sterol analogues with side chains of various lengths. The sensitivities of liposomes constituted with these sterol analogues toward digitonin and polyene antibiotics were also examined. The effects of sterols on phase transition of phosphatidylcholine were examined by measuring their effects on permeability increase due to perturbation of phase equilibrium and by differential scanning calorimetry. An analogue with a short side chain, isopropyl (C-22), had a very similar effect to cholesterol in suppressing the permeability increase, suggesting that the full length of the side chain is not necessary for this effect. The permeability of egg yolk phosphatidylcholine at 42 degrees C was suppressed as much by the analogue C-22 as by cholesterol. Androstene-3-beta-ol, an analogue without a side chain, however, had little suppressive effect. Thus it is concluded that the condensing effect of sterol requires a side chain, but not the full length of side chain. Liposomes constituted with analogues having a side chain with more than 5 carbon atoms showed maximum reactivity with a polyene antibiotic, amphotericin B, whereas those constituted with analogues having a side chain with less than 4 carbon atoms showed weaker reactivity. These findings indicate that a side chain with more than 5 carbon atoms is essential for the maximum interaction of liposomes with amphotericin B. Unlike amphotericin B, filipin reacted almost equally well with liposomes containing C-22 and with those containing cholesterol. Thus the chain length of the side chain of sterol is less important for interaction of liposomes with filipin than for their interaction with amphotericin B. Liposomes containing analogues having a side chain with more than 6 carbon atoms showed maximum reactivity with digitonin. Thus for the maximum interaction of liposomes with digitonin, the side chain of sterol should be longer than 6 carbon atoms.

Anti-Bacterial Agents↗
PubMed1980

Effect of normal C10:0-C20:0 fatty acids and their related compounds on gastric secretion and experimental ulceration in rats.

Fatty acids of C10:0, C12:0, C13:0, C14:0 and C16:0 significantly inhibited the amount of gastric juice, total acid output, and total peptic activity, but fatty acids of C17:0-C20:0 entirely failed to show significant inhibitory activity. Only the methyl ester of C14:0 showed significant inhibition of these parameters at the dose of 100 mg/kg, while at the dose of 200 mg/kg, methyl esters of fatty acids of fatty acids of C10:0, C12:0, C14:0, and C16:0 significantly inhibited these three parameters. alpha-Monoglyceride of C14:0 significantly inhibited the amount of gastric juice at the dose of 100 mg/kg, while alpha-monoglycerides of C10:0, C12:0', C13:0, C14:0, and C16:0 significantly inhibited the amount of gastric juice, total acid output, and total peptic activity at the dose of 200 mg/kg. In the case of intraduodenal administration, myristic acid also showed significant inhibition of these parameters at 100 and 200 mg/kg doses. The dose-activity correlation in gastric secretion inhibitory activity was examined with myristic acid and this activity was found to increase with increasing dose of the acid administered. Myristic acid significantly decreased the ulcer index in aspirin-induced ulcer, it was entirely ineffective in preventing histamine-induced ulcer. Finally, inhibitory effect of myristic acid on pepsin and histidine decarboxylase was examined in vitro and it was found that myristic acid inhibited peptic activity, but it had almost no effect of inhibiting the histidine decarboxylase activity.

Animals↗
PubMed1980

Effect of 3,5,3'L-triiodothyronine administration on serum thyroid hormone levels in hypothyroid patients maintained on constant doses of thyroxine.

In order to investigate the effect of 3,5,3'L-triiodothyronine (T3) administration on thyroid hormone concentrations in serum, thyroxine (T4), T3, 3,3',5'L-triiodothyronine (reverse T3, rT3) and thyroid stimulating hormone (TSH) concentrations in serum were determined before and after T3 administration in 10 hypothyroid patients maintained on constant doses of T4. Ten hypothyroid patients given 100 micrograms of T4 for approximately 3 months had almost normal T4 and T3 concentrations in serum. Seven patients showed almost normal rT3 concentrations in serum and they were slightly diminished in the remaining 3 patients. TSH levels in serum were almost within the normal limit in 7 out of 10 patients. However, despite the elevation of T4 and T3 levels, 3 patients had markedly elevated TSH levels. Values for serum T4 concentrations were decreased 4 weeks after the administration of 50 micrograms T3 in all patients maintained on constant doses of T4, although they were almost within the normal range. T3 concentrations in serum, which was obtained just before the administration of the next daily doses of T3, were markedly elevated in 6 of 10 patients after T3 administration and the remaining 4 patients had also slightly higher T3 concentrations than those before T3 administration. On the other hand, serum rT3 concentrations were diminished in 5 patients during T3 ingestion. They were somewhat diminished or almost unchanged before and after T3 administration in the remai T3 administration and the remaining 4 patients had also slightly higher T3 concentrations than those before T3 administration. On the other hand, serum rT3 concentrations were diminished in 5 patients during T3 ingestion. They were somewhat diminished or almost unchanged before and after T3 administration in the remaining 5 patients. Moreover, 3 patients with elevated TSH levels during T4 administration showed almost normal TSH levels after T4 and T3 ingestion. The results showed the reciprocal relationship between T3 and rT3 levels in serum after T3 administration in hypothyroid patients maintained on constant doses of T4. Furthermore, the present findings suggest that the administration of both T4 and T3 might be a more suitable replacement therapy in the patients with hypothyroidism than T4 alone.

Drug Therapy, Combination↗
PubMed1980

Clinical evaluation of measuring glycosylated hemoglobin levels for assessing the long-term blood glucose control in diabetics.

The glycosylated hemoglobin levels were determined in the hemolysates obtained from 14 normal subjects and 67 patients with adult-onset diabetes mellitus, using the column chromatographic procedure of Trivelli et al. The levels of hemoglobin A1a+b (HbA1a+b) and HbA1c and the sum of HbA1a+b and HbA1c (HbA1a+b+HbA1c) in normal subjects averaged 2.3 +/- 0.4 (SD)%, 5.3 +/- 0.8% and 7.6 +/- 1.0%, respectively. Although a slight increase in HbA1a+b was found in patients with diabetes mellitus (mean +/- SD=2.8 +/- 0.7%), it was not significantly different from that in normal subjects. Despite the wide range, HbA1c and HbA1a+b+HbA1c were significantly increased in patients with diabetes mellitus (6.9 +/- 1.8% for HbA1c, p < 0.01 and 9.7 +/- 2.2% for HbA1a+b+HbA1c, p < 0.01). A significant correlation existed between the glycosylated hemoglobins and plasma glucose levels determined in the same blood (r = +0.57, p < 0.001). Moreover, the glycosylated hemoglobin levels correlated significantly with the average glucose levels for several months preceding the hemoglobin measurements. In particular, a striking correlation was evident in the plots of HbA1a+b+HbA1c against the mean plasma glucose for 3 months prior to the hemoglobin measurements, which had a correlation coefficient of 0.79 (p < 0.001). The present findings revealed that the glycosylated hemoglobins reflect the time-averaged blood glucose levels in diabetics for during approximately the proceeding 3 months, indicating the usefulness of measuring the glycosylated hemoglobins in assessing the long-term blood glucose control in diabetics.

Adult↗