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Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 883 records · Page 49Linked to original sources

Fluorometric determination of gizzerosine, a histamine H2-receptor agonist discovered in feedstuffs, employing high-performance liquid chromatography.

Gizzerosine (2-amino-9-(4-imidazolyl)-7-azanonanoic acid) was discovered in fish meal as a causative material of gizzard erosion in chicks. This compound stimulates gastric acid secretion as a histamine H2-receptor agonist and induces gizzard erosion in chicks. A method of fluorometric determination of this compound was developed employing high-performance liquid chromatography. By this method, 0.2 to 5.0 micrograms of gizzerosine in fish meals was quantitated with the recovery of 95-102%. Fish meals, which induced severe gizzard erosion in chicks, contained more than 20 mg/kg of gizzerosine. The present method will be useful in preventing gizzard erosion in chicks, which is a big problem in the poultry industry all over the world.

Animals↗

Transcriptional and post-transcriptional regulation of L-type pyruvate kinase in diabetic rat liver by insulin and dietary fructose.

Regulation of the expression of the hepatic L-type pyruvate kinase gene by insulin and dietary fructose was studied in diabetic rats. Insulin increased the levels of putative nuclear RNA precursor species of this enzyme in parallel with that of total cellular pyruvate kinase L mRNA. These changes occurred more slowly than those induced by dietary fructose. Insulin caused a 3-fold increase in transcription of the pyruvate kinase L gene after 6 h and a 6-fold increase after 16 h. The increase caused by insulin was inhibited by glucagon, but not by adrenalectomy. Cycloheximide inhibited the induction caused by insulin, suggesting that insulin may stimulate transcription of the pyruvate kinase L gene by stimulating synthesis of some unknown protein. On the other hand, feeding fructose had no effect on transcription of the pyruvate kinase L gene. We previously showed that increases in the levels of putative nuclear RNA precursor species of the pyruvate kinase L after fructose feeding preceded changes in the levels of cytosolic pyruvate kinase L mRNA (Inoue, H., Noguchi, T., and Tanaka, T. (1984) J. Biochem. (Tokyo) 96, 1457-1462). Thus, dietary fructose may increase the levels of pyruvate kinase L mRNA by stabilizing nuclear RNA species. Glucagon inhibited the increase in pyruvate kinase L mRNA caused by dietary fructose. However, plasma levels of glucagon and thyroid hormones were not decreased in diabetic rats after fructose feeding. In addition, treatment with triiodo-L-thyronine caused no change in the pyruvate kinase L mRNA level. Furthermore, adrenalectomy did not impair enzyme induction by fructose in diabetic rats. Thus, the effect of fructose on pyruvate kinase L seems to be directly on the liver.

Adrenalectomy↗

Characteristics of alanine: glyoxylate aminotransferase from Saccharomyces cerevisiae, a regulatory enzyme in the glyoxylate pathway of glycine and serine biosynthesis from tricarboxylic acid-cycle intermediates.

Alanine: glyoxylate aminotransferase (EC 2.6.1.44), which is involved in the glyoxylate pathway of glycine and serine biosynthesis from tricarboxylic acid-cycle intermediates in Saccharomyces cerevisiae, was highly purified and characterized. The enzyme had Mr about 80 000, with two identical subunits. It was highly specific for L-alanine and glyoxylate and contained pyridoxal 5'-phosphate as cofactor. The apparent Km values were 2.1 mM and 0.7 mM for L-alanine and glyoxylate respectively. The activity was low (10 nmol/min per mg of protein) with glucose as sole carbon source, but was remarkably high with ethanol or acetate as carbon source (930 and 430 nmol/min per mg respectively). The transamination of glyoxylate is mainly catalysed by this enzyme in ethanol-grown cells. When glucose-grown cells were incubated in medium containing ethanol as sole carbon source, the activity markedly increased, and the increase was completely blocked by cycloheximide, suggesting that the enzyme is synthesized de novo during the incubation period. Similarity in the amino acid composition was observed, but immunological cross-reactivity was not observed among alanine: glyoxylate aminotransferases from yeast and vertebrate liver.

Alanine Transaminase↗

Vasodilatory and diuretic actions of alpha-human atrial natriuretic polypeptide (alpha-hANP).

Vascular and diuretic actions of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were studied using anesthetized dogs and isolated canine arterial strip preparations. alpha-hANP, when given intra-arterially or intravenously, dilated the renal artery more selectively than the vertebral, femoral, common carotid and coronary arteries. alpha-hANP selectively relaxed the high K+-contracted renal artery strip as compared with the basilar, coronary and femoral arterial strips. Intravenous alpha-hANP also increased urine volume and urinary excretion of electrolytes at doses, at which it increased renal blood flow and lowered systemic blood pressure without changing heart rate. It is concluded that alpha-hANP has a vasodilatory property relatively specific for the renal artery, and that it possesses diuretic, natriuretic, kaliuretic, magnesiuretic, calciuretic and chloruretic activities concomitantly with a definite hypotensive activity.

Animals↗

Cerebral myelinogenesis in the Snell dwarf mouse: stimulatory effects of GH and T4 restricted to the first 20 days of postnatal life.

We attempted to define the critical time period during early postnatal life when GH and T4 are essential for myelination. We administered bGH and T4 to Snell dwarf mice during the first and second 20 days after birth. Positive results were obtained only when hormones were given during the first 20 days of postnatal life. We observed a distinct increase in brain weight, DNA content, CNPase activity and a remarkably increased level of spontaneous locomotion activity with a diurnal periodicity. Morphological observations of brain sections stained for myelin basic protein (MBP) correlated the biochemical findings. The later administration of hormones was ineffective. Our interpretation is that the administration of exogenous hormones led to increased myelinogenesis through their stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit).

To determine whether GH has an independent action on cerebral development, we examined the central nervous system of the little mouse (lit), a promising model of isolated growth hormone deficiency. Our findings are (A); the weights of two parts of the lit brain were significantly less than those of the normal controls, 81.5% less for the cerebrum, and 81.6% for the cerebellum, (B): the total DNA content was reduced to approximately 80% in the cerebrum and 84% in the cerebellum compared to those of the normal controls, (C); the total RNA content was also reduced in the cerebrum and cerebellum, proportional to the reduction in DNA, (D); CNPase activity was reduced selectively in the cerebrum of the lit mouse (74.4% of the normal control), and (E); the lit mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. These results indicate that GH has independent actions on cerebral development, especially on glial cell proliferation as a precondition of myelin formation.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Abnormal neuronal growth in the little (lit) cerebrum.

Mice genetically deficient in growth hormone were compared with normal littermates for evidence of altered neuronal development. In the lit/lit motor cortex, area 6 of Caviness, cell number, stratification of neurons, and the proportionate layer widths were identical to those of the controls (lit/+). Examined by the Golgi-Cox method modified by Ramon-Moliner, however, the pyramidal neuron was found to have short primary dendrites with sparse branchings. This result was confirmed in sections stained for neuron-specific enolase. Therefore, we conclude that growth hormone has an independent action on neuronal development.

Animals↗

Nucleotide sequence of bacteriophage T4 uvsY gene.

We have determined the nucleotide sequence of a 1001-bp region comprising the uvsY gene of bacteriophage T4. An open reading frame of 420 base pairs was found to encode the uvsY gene product. The uvsY gene comprised a 140-amino acid protein with ATG (methionine) as the initiation codon, which is consistent with the molecular weight determined by SDS-polyacrylamide gel electrophoresis. The uvsY gene was oriented in the direction of the early genes and a sequence common to the middle promoter consensus was found in the 5'-upstream region.

Base Sequence↗

The effects of thyroxine and methimazole treatment on the synthesis of prostacyclin (PGI2) in the rat.

The effects of thyroxine (T4) and methimazole administration on plasma prostacyclin (PGI2) levels in vivo and on PGI2 release by aortic rings incubated in vitro were investigated in rats. Male rats were given single injection of T4 (200 micrograms/100 g body wt) ip every 24 h for either 3, 7 or 14 days for hyperthyroid rats. For hypothyroid rats, a group of rats were given methimazole (0.01 % in drinking water) for 14 days. PGI2 concentrations were determined in plasma and also in the medium in which aortic rings were incubated. PGI2 was measured as 6-keto-PGF1 alpha by RIA. Plasma PGI2 levels in T4-treated groups were found to be significantly higher than those of control animals. Aortic rings obtained from rats given single injection of T4 for 7 and 14 days showed significant increases in release of PGI2 into the incubation medium. In contrast, rats given methimazole for 14 days showed a significant decrease in the production of PGI2 by aortic rings without any significant changes in plasma levels. Direct addition of T4 into the incubation medium did not cause any significant changes in PGI2 release by aortic rings obtained from control rats. These results suggest the regulatory role of thyroid hormone in PGI2 synthesis in vivo.

6-Ketoprostaglandin F1 alpha↗

Biphasic modulation of spontaneous activities of entopeduncular neurons by systemic application of apomorphine in anesthetized cats.

The responses of entopeduncular neurons to apomorphine were investigated with extracellular recording methods in anesthetized cats. Apomorphine was applied intravenously in increasing doses, which cumulatively doubled with each addition (5-640 micrograms/kg). The spontaneous firing rates of entopeduncular neurons, which were inhibited by electrical stimulation of the caudate nucleus, increased when lower doses of apomorphine (5-20 micrograms/kg) were applied. However, higher doses (40-640 micrograms/kg) produced a dose-dependent decrease in the firing rate. The results suggest that there are direct and indirect effects of systemically administered apomorphine on entopeduncular neurons which may contribute to biphasic responses in the spontaneous discharge rate.

Action Potentials↗

New antiarrhythmic agents. N-aryl-8-pyrrolizidinealkanamides.

The synthesis and antiarrhythmic activity of N-aryl-8-pyrrolizidinealkanamides are described. The target compounds were evaluated for their ability to protect against chloroform-induced fibrillation in mice. Many of them were found to have antifibrillatory activity comparable to that of lidocaine; several are more potent than lidocaine. N-(2,6-Dimethylphenyl)-8-pyrrolizidineacetamide which was found to be more potent and less toxic (LD50) than lidocaine, also showed a long duration of action in dogs with ventricular arrhythmias after oral administration.

Animals↗

Immunoreactive myelin basic protein in tumor cells associated with carcinomatous neuropathy.

Tumors from two patients with carcinomatous neuropathy were studied with an immunohistochemical method using anti-myelin basic protein (anti-MBP) sera. In both cases, immunoreactive MBP was clearly demonstrated in some of the tumor cells, which were widely distributed either singly or, more often, in clusters. The staining intensity varied from cell to cell. An autoimmune mechanism to nervous elements has been suggested in the pathogenesis of carcinomatous neuropathy. MBP is known to be a highly specific and potent antigen that can induce allergic neuritis in animals. In one patient the progressively worsening neurologic condition rapidly improved after gastrectomy removed the carcinoma. It is possible that immunoreactive MBP in tumor cells may function as an "antigen" in the development of carcinomatous neuropathy.

ACTH Syndrome, Ectopic↗

The adreno-sympathetic system, the genetic predisposition to hypertension, and stress.

The blood pressure, heart rate, and plasma catecholamine (CA) response to standing and mental stresses were studied in 14 normotensive subjects with normotensive parents (PNT group), 14 normotensive subjects with hypertensive parent(s) (PHT group), and eight borderline hypertensive patients (BHT group). Mean basal plasma norepinephrine (NE) concentration in BHT group (302 +/- 94 pg/ml) and PHT group (289 +/- 167 pg/ml) were significantly higher than in PNT group (205 +/- 76 pg/ml). Significant differences in the mean basal plasma epinephrine (E) were found only between the PNT and BHT groups (22 +/- 12 vs 43 +/- 18 pg/ml, p less than 0.01). Both plasma NE and E increased significantly on standing in all groups. With mental stress, plasma E increased significantly, though plasma NE did not change significantly in all three groups. The mean changes in blood pressure, heart rate, and plasma CA in response to standing and mental stresses were not different in the three groups. However, a higher incidence (50%) of high blood pressure responders (greater than or equal to 20 mmHg in systolic blood pressure) to mental stress was found in the PHT group compared with PNT (14%) and BHT (12%). The high responders in the PHT group had significantly higher mean plasma E concentrations throughout the experiment. Also, their increases in plasma NE and E in response to mental stress were higher than those of the low responders. The results indicate that genetic predisposition to hypertension plays a significant role in determining plasma catecholamine levels and the responsiveness to stress, especially to mental stress.

Adolescent↗

Partial restoration of cerebral myelination of the congenitally hypothyroid mouse by parenteral or breast milk administration of thyroxine.

We attempted to define whether thyroid hormone can ameliorate the cerebral hypomyelination present in the congenitally hypothyroid (hyt) neonatal mouse, and to define the critical time period during early postnatal life when thyroxine (T4) is essential for myelin formation. We administered T4 to the hyt mouse by breast milk during the first 20 days of postnatal life, and through the diet during the second 20 days of postnatal life. Positive results were obtained only when hormone was given during the first 20 days of postnatal life. A distinct increase in cerebral 2',3'-cyclic nucleotide 3'-phosphohydrolase activity was noted, and brain sections stained for myelin basic protein correlated with the biochemical findings. The later administration of hormone through diet was ineffective.

Administration, Oral↗

Biochemical and immunobiological properties of lipopolysaccharide (LPS) from Bacteroides gingivalis and comparison with LPS from Escherichia coli.

Lipopolysaccharides (LPSs) were isolated from Bacteroides gingivalis and Escherichia coli by the phenol-water and butanol-water procedures. The phenol-water-extracted LPS from B. gingivalis 381 was composed of 46% carbohydrate, 23% hexosamine, 18% fatty acid, and 5% protein. The major component sugars of this preparation were glucose, glucosamine, rhamnose, galactose, galactosamine, and mannose, and their molecular ratio was 1:0.9:0.7:0.6:0.6:0.4, respectively. Neither heptose nor 2-keto-3-deoxyoctonate was detected. The butanol-water-extracted LPS from this strain was composed of 76% glucose, 7% fatty acid, and 13% protein, and it was associated with a number of polypeptides (13 to 56 kilodaltons). The main fatty acid of both LPS preparations was palmitic acid. It was found that biological activities of LPS from B. gingivalis were comparable to those of LPS from E. coli in terms of activation of the clotting enzyme of Limulus amebocyte lysate, mitogenicity, polyclonal B cell activation, and stimulation of interleukin 1 production in BALB/c mice. Furthermore, LPS-nonresponsive C3H/HeJ spleen cells were found to yield good mitogenic responses to both phenol-water-extracted LPS and butanol-water-extracted LPS from B. gingivalis or butanol-water-extracted LPS from E. coli. On the other hand, spleen cells from LPS-responsive C3H/HeN mice responded well to all these LPS preparations.

Amino Acids↗

Clonal growth and mesenchymal differentiation of PCC3/A/1 teratocarcinoma cells in serum-free medium.

Clonal culture of PCC3/A/1 teratocarcinoma stem cells in serum-free medium has been achieved with feeder layers. Under this culture condition, stem cells effectively differentiated into various types of somatic cells, in particular chondrocytes and adipocytes. Myotubes and neuron-like cells also appeared, but infrequently. Embryonic endoderm cells were rarely observed. There appeared to be two stages in the differentiation process; In the early stage, only fibroblastic cells were found with the undifferentiated stem cells. In the later stage, chondrocytes and adipocytes predominated. Chondro-adipocyte differentiation occurred only after fibroblastic cell differentiation, an indication that fibroblastic cells may have an important function in chondro-adipocyte differentiation. Thus, the serum-free culture of PCC3/A/1 cells provides a suitable system with which to study the cell lineages and regulatory mechanisms of chondro-adipocyte differentiation.

Adipose Tissue↗

A case of Cushing's syndrome associated with possible adrenomedullary hyperplasia.

A 57-year-old male, who had been suffered from hypertension and diabetes mellitus for 10 years, was admitted to the hospital because of thirst, lassitude and muscle wasting. On admission, his urinary excretion of 17-OHCS and plasma cortisol levels were elevated without diurnal variations. Plasma ACTH levels were found to be very low with repeated determinations. Dexamethasone suppression test, 2 mg 4 times a day orally for 2 days, showed no changes in plasma cortisol levels and only a mild reduction in urinary 17-OHCS excretion. Estimation of urinary catecholamines showed an increase only in norepinephrine. Abdominal computerized tomography and radionuclide scanning of adrenal glands with 131I-adosterol demonstrated a well-defined adrenal mass in the left side without apparent changes in the right side. 131I-metaiodobenzylguanidine scintigraphy was negative. At surgery, his left adrenal medulla was found to be hypertrophic in addition to the cortical tumor. The left adrenal gland was also removed. After surgery, excretion of urinary catecholamines fell to nearly the normal range and he was discharged without insulin and antihypertensive drugs. Microscopically, the cortical tumor is an adenoma consisting of lipid laden cells and eosinophilic compact cells. Medullary cells were distinctly hyperplastic in appearance and many of the cells were extensively vacuolated, suggesting an active functional status. The present report describes a patient with Cushing's syndrome who showed increased urinary catecholamine excretion due to the possible coexistence of adrenal medullary hyperplasia. As far as we know, this is the first case of Cushing's syndrome with this abnormality.

Adrenal Medulla↗