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Biomedical subjects

H Mizuma

Publications and source records attributed to H Mizuma.

At least 19 recordsLinked to original sources

Microsphere embolism-induced elevation of nerve growth factor level and appearance of nerve growth factor immunoreactivity in activated T-lymphocytes in the rat brain.

Changes in nerve growth factor (NGF) level and type of cells producing NGF were investigated in the rat brain after sustained cerebral embolism. The NGF level was determined by a two-site enzyme immunoassay specific for NGF. The cerebral cortex, striatum, and hippocampus of the embolized hemisphere maximally contained 2.4-, 2.4-, and 1.7-times higher NGF levels than the corresponding regions of the nonembolized hemisphere. A significant increase was transiently observed for 1 week in the cerebral cortex and striatum, whereas the increase was longer lasting, at least of 4 weeks' duration, in the hippocampus. To examine the localization of NGF-like immunoreactivity (NGF-LI), we used a newly developed anti-NGF peptide antiserum that specifically recognized a 30-kDa molecule(s) in the hippocampal extracts or in NGF cDNA-transfected cells, suggesting that the antibody predominantly reacted with the putative NGF precursor protein(s). NGF-LI, which was localized in neurons of the normal or non-embolized hemisphere, was reduced, and on the embolized side new signals emerged in small non-neuronal cells having a round shape. These included cells with common leukocyte antigen CD45 and T-lymphocyte antigen CD3, which did not appear in the normal or non-embolized hemisphere. NGF-LI and CD3 were colocalized in a substantial number of the cells, suggesting that some activated T-lymphocytes produce NGF for neuronal regeneration after sustained cerebral embolism.

Animals↗

Hepatic insulin clearance increases after weight loss in obese children and adolescents.

BACKGROUND: Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population. METHODS: We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention. RESULTS: All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss. CONCLUSIONS: Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.

Adolescent↗

Pretranslational regulation of rhythmic type II iodothyronine deiodinase expression by beta-adrenergic mechanism in the rat pineal gland.

It has been demonstrated that type II iodothyronine deiodinase is present in rat pineal gland, and the deiodinase activity markedly increases during the hours of darkness, primarily through beta-adrenergic mechanism. We have studied the relationship between pineal type II iodothyronine deiodinase messenger RNA (mRNA) and the deiodinase activity to elucidate the mechanisms involved in the nocturnal rise in pineal deiodinase activity. Northern analysis has demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland, and the mRNA markedly increases during the hours of darkness. The nocturnal increase in pineal type II iodothyronine deiodinase activity is preceded by the increase in its mRNA. Daytime isoproterenol administration resulted in a rapid increase in pineal type II iodothyronine deiodinase mRNA followed by the increase in deiodinase activity. Propranolol treatment, bilateral superior cervical ganglionectomy, or constant light exposure significantly suppressed the nocturnal rise in type II iodothyronine deiodinase mRNA as well as the deiodinase activity. Moreover, isoproterenol or (Bu)2AMP stimulated type II iodothyronine deiodinase mRNA and the deiodinase activity in cultured rat pineal glands. These results suggest that the rhythmic change in pineal type II iodothyronine deiodinase activity is regulated at least in part at the pretranslational level by a beta-adrenergic mechanism transmitted through superior cervical ganglia.

Adrenergic beta-Agonists↗

Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells.

T4, which is a major secretory product of the thyroid gland, needs to be converted to T3 by iodothyronine deiodinase to exert its biological activity. After the molecular cloning of human type II iodothyronine deiodinase (DII) complementary DNA, DII expression was unexpectedly detected in human skeletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscle cells and studied the mechanisms involved in the regulation of DII expression in those cells. All of the characteristics of the deiodinating activity in cultured human skeletal muscle cells were compatible with those of DII. Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)2cAMP, forskolin, or beta-adrenergic agonists and were negatively regulated by thyroid hormones in cultured human skeletal muscle cells. Although interleukin-1beta and interleukin-6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-alpha decreased DII expression in those cells in a dose-dependent manner. These data have demonstrated, for the first time, that DII activity and DII mRNA are present in cultured human skeletal muscle cells, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid hormones and tumor necrosis factor-alpha.

Adrenergic beta-Agonists↗

Primary culture of cells from hyperfunctioning thyroid adenoma with an activating mutation of G alphas.

We analyzed cultured cells from hyperfunctioning thyroid adenoma and its surrounding thyroid tissue from a Japanese woman and determined the nucleotide sequences of genes encoding the alpha subunit of the stimulatory G-protein 1 (G alphas) and thyrotropin (TSH) receptor in its tumor tissue. Primary culture of cells from hyperfunctioning thyroid adenoma and its surrounding thyroid tissue revealed that cAMP production was constitutively activated while intracellular Ca2+ concentration was suppressed both at the basal level and in the response to TSH stimulation in the cells from tumor tissue compared with those from non-tumor tissue. Nucleotide sequence analysis demonstrated the somatic missense mutation at codon 201 (CGT(Arg)-CAT(His)) of G alphas gene in tumor tissue but not in its surrounding tissue. No mutation was observed in the transmembrane region of TSH receptor. These results suggest that cAMP regulatory cascade is constitutively activated while phospholipase C-Ca2+ signaling cascade is suppressed in hyperfunctioning thyroid adenoma with an activating mutation of G alphas gene in the present case.

Adenoma↗

Northern analysis of type II iodothyronine deiodinase mRNA in rat Harderian gland.

It has been known that type II iodothyronine deiodinase activity is present in rat Harderian gland and the activity is significantly increased by isoproterenol administration. We have performed Northern analyses to study whether the transcript for type II iodothyronine deiodinase is expressed in rat Harderian gland and whether the isoproterenol stimulation of type II iodothyronine deiodinase activity in rat Harderian gland is due to the change in its mRNA level. Northern analyses have demonstrated that type II iodothyronine deiodinase mRNA, approximately 7.5 kb in size, is expressed in rat Harderian gland, and the mRNA levels as well as the deiodinase activities are greater in hypothyroid rats than those in euthyroid rats. Type II iodothyronine deiodinase mRNA levels and the deiodinase activities in Harderian gland were increased by isoproterenol administration, and the increase in the mRNA levels preceded that in the deiodinase activities. These results indicate that 7.5 kb transcript for type II iodothyronine deiodinase is expressed in rat Harderian gland and beta-adrenergic stimulation of type II iodothyronine deiodinase activity is due at least in part to the increase in its mRNA level.

Actins↗

Efficacy of L-846 in patients with insomnia: evaluation by polysomnography.

The effects of L-846, an ultra-short-acting pyrazolopyrimidine hypnotic, on sleep were studied in nine insomniacs and two neurotic patients with insomnia. The patients were randomly assigned to receive 5 mg (n=6) or 10 mg (n=5) L-846. The study schedule comprised of one adaptation night, two baseline nights, three drug nights, and two withdrawal nights. Sleep latency and slow wave sleep (SWS) latency was largely shortened and %SWS increased in the early phase of sleep. No clear evidence of rebound insomnia was noted.

Acetamides↗

Wrist activity rhythm and sleep diary of delayed sleep phase syndrome.

Wrist activity rhythm and sleep diary data in a case of delayed sleep phase syndrome were investigated. The sleep self-estimation was nearly compatible with the activity levels of the actigraph. The actigraphic data were also analyzed. The subject's most fixed period of activity was 24.31 h, and acrophase (time of day) that fixed the data to a 24 h period was 03.25 h. The subject has had reversed night and day sleep patterns for more than 7 years. It was very difficult to advance the sleep phase when the delayed phase has been continuous long-term under the state of poor social cues.

Activity Cycles↗

[Therapeutic outline of sleep disorders].

The more sleep disorders become chronic, the more they become resistible for the treatments. Therefore, it is most important that physicians establish the good relationship with patients and correctly diagnose and treat patients who have acute or transient sleep complaints. Physicians can improve patients' quality of life by evaluation of disease, supportive psychotherapy which include Morita therapy and behavior therapy, sleep hygine advice, and appropriate medications. In all patients, it is necessary for physicians to be aware of the physical, psychological and pharmacological factors, social aspects, and environmental factors of patients, because all these factors play an important role in appearance of sleep disorders.

Anti-Anxiety Agents↗

Expression and nocturnal increase of type II iodothyronine deiodinase mRNA in rat pineal gland.

It has been demonstrated that thyroxine deiodinating activity is present in rat pineal gland, and its activity increases significantly during the night time. We have studied whether mRNA for type II iodothyronine deiodinase is expressed in rat pineal gland and whether the nocturnal rise of pineal T4 deiodinating activity is due to the change in type II iodothyronine deiodinase mRNA level. Reverse transcription-polymerase chain reaction amplification and Northern blot analyses have demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland and its mRNA level increases markedly at midnight. These results suggest that the nocturnal rise in pineal T4 deiodinating activity is due to the change in type II iodothyronine deiodinase mRNA level.

Animals↗

Excessive twitch movements in rapid eye movement sleep with daytime sleepiness.

A man who showed excessive twitch movement, such as fragmentary myoclonus (FM) and periodic movements in sleep (PMS) predominantly during REM sleep, is reported. He complained of excessive daytime sleepiness (EDS). After examination, his twitch movements were shown not to accompany narcolepsy, and his EDS were considered to originate from nocturnal sleep disturbance caused by FM and PMS.

Adult↗

Treatment of sleep apnea with a new separated type of dental appliance (mandibular advancing positioner).

We investigated a new separated type of dental appliance (mandibular advancing positioner: MAP) that is mobile and allows free adjustment of mandibular advancement. In 8 adult male patients with sleep apnea syndrome (SAS), the mean apnea index (AI) decreased from 31.1 to 4.2, and the mean apnea hypopnea index (AHI) decreased from 44.2 to 11.7. The distance of mandibular advancement using the Flankfort horizontal plane as a standard ranged in the 8 SAS patients from 1.8 to 5.0 mm by lateral cephalograms. A high positive correlation was observed between the distance of mandibular advancement and the rate of improvement in AI (R2 = 0.878), or the rate of AHI (R2 = 0.861), showing a higher improvement rate with more marked mandibular advancement.

Adult↗

Sex and age differences in soluble guanylate cyclase activity in human platelets.

Soluble guanylate cyclase is a key enzyme of nitric oxide (NO)-related intracellular signal transduction in platelets. In the present study, we investigated the effects of sex and age on the enzyme activity in human platelets. Soluble guanylate cyclase activity was determined by generation of cyclic GMP in platelet cytosol. No significant differences in the basal activity of soluble guanylate cyclase were observed between in men and women, and between in young and old subjects. However, soluble guanylate cyclase activity in response to sodium nitroprusside, an exogenous NO donor, was higher in young men than in young and old women. Furthermore, the enzyme activity was lower in old than in young men, but there were no differences in female platelets between from young and old subjects. The present data suggest that NO-related signal transduction system in the platelet is affected by sex and age, which, to certain extent, contributes to different sensitivity of human platelets.

Adult↗

The bioactive peptide cyclo(His-Pro) may be absorbed following ingestion of nutritional supplements that contain it.

OBJECTIVE: Food contains a number of peptides with potential bioactivity. We previously found ng/mliter to mcg/mliter quantities of cyclo(His-Pro)-like immunoreactivity in a number of foods and nutritional supplements. A number of activities have been attributed to cyclo(His-Pro) (CHP), including appetite inhibition and inhibition of insulin secretion in vitro. We wondered whether the cyclo(His-Pro)-like immunoreactivity present in nutritional supplements might be absorbed and, if so, whether parameters of insulin secretion would be altered. METHODS: After performing a pilot study which suggested some common nutritional supplements contain CHP, a follow-up study was done to confirm and expand the findings of the pilot study. Eight fasting volunteers ingested approximately 250 mL of a CHP-containing supplement one day, and then an equienergetic CHP-free supplement the next. RESULTS: Blood drawn for CHP, insulin, glucose, and C-peptide a number of times on both days revealed that when volunteers ingested CHP-containing supplements, CHP levels at 120 minutes were significantly higher than baseline (7.69 +/- 0.50 pmol/mL vs. 9.18 +/- 0.48 pmol/mL; p = 0.011 in the CHP group and 7.90 +/- 0.85 pmol/mL vs. 7.22 +/- 0.73 pmol/mL, p > 0.3 in the CHP-free group) and significantly higher than levels achieved when they drank CHP-free supplements. Levels of glucose, insulin, and C-peptide were not different in the two groups. CONCLUSION: CHP in nutritional supplements may be absorbed when ingested orally and does not grossly affect glucose or parameters of insulin secretion.

Absorption↗

Diagnostic use of daytime polysomnography versus nocturnal polysomnography in sleep apnea syndrome.

The usefulness of daytime polysomnography (DPSG) in the diagnosis of sleep apnea syndrome (SAS) is examined. Diagnostic use was investigated by conducting DPSG of two different time periods (Group M, 11.00-14.00 h, and Group A, 15.00-18.00 h). The subjects were 30 patients (28 men and two women; mean age, 54.0 years). Nocturnal polysomnography (NPSG) and DPSG were investigated by comparing indices of sleep, apnea index (AI) and arterial oxygen saturation (SaO2). There was no significant difference among these indices but there was a significant positive correlation between NPSG and DPSG in all variables related to sleep apnea. Moreover, there was no significant difference in the frequency of each type of apnea between NPSG and DPSG in either group. These findings suggest that DPSG is useful not only in diagnosing SAS but in evaluating its severity.

Adult↗

Discrete characteristics of antibodies raised against thyrotropin receptor-related peptides whose sequences are not conserved in the luteinizing hormone/chorionic gonadotropin receptor.

In order to identify the specific regions in the human TSH receptor for TSAb and thyroid stimulation-blocking antibody (TSBAb), we produced rabbit antibodies raised against several peptides of the extracellular domain of the human TSH receptor, where sequences are not conserved in the LH/CG receptor, and measured the TSAb activity and TSBAb activity of those antibodies using Chinese hamster ovary cells expressing human TSH receptors. Only antisera from rabbits that were immunized with a peptide of amino acid 32-56, including the small insertion near the N-terminal end of the extracellular domain, showed apparent TSAb activities and have been shown to be significantly precipitated by IgG of patients with Graves' disease. TSAb activity positively correlated with the antibody titers against the peptide in those rabbits. In contrast, antisera from rabbits immunized with a peptide of amino acid 352-378, including a part of the large insertion near the C-terminal end of the extracellular domain, showed the obvious TSBAb activities. TSBAb activity also positively correlated with the degree of antibody titers against the peptide in those rabbits. Moreover, this peptide was significantly immunoprecipitated by the IgG from hypothyroid patients who had TSBAb, and the immunoprecipitation of this peptide positively correlated with TSBAb activities. These results suggest that the epitope responsible for TSAb is quite different from that for TSBAb in the extracellular domain of the human TSH receptor.

Amino Acid Sequence↗

A paradoxical elevation of brain cyclo(His-Pro) levels in hyperphagic obese Zucker rats.

Several studies suggest a role for endogenous cyclo(His-Pro) or CHP in appetite regulation. In the present study, we have examined the regional brain distribution of CHP in hyperphagic obese Zucker rats and their lean littermates. The data show a significant elevation in the levels of CHP in many brain regions, including hypothalamus of the obese rat. Within the hypothalamus, the lateral hypothalamic (LH) nucleus of obese rats had significantly higher levels of CHP when compared to that of the lean littermates. Administration of dehydroepiandrosterone, a steroid hormone known to decrease food intake and body weight gain, to obese rats led to decrease in the levels of CHP in the LH. These data further suggest a role for the endogenous CHP in attenuating food intake.

Animals↗

Biology of enterostatin. II. Development of enzyme-linked immunosorbentassay (ELISA) for enterostatin (Val-Pro-Asp-Pro-Arg), the procolipase activation peptide.

Enterostatins belong to a family of pentapeptides (e.g., Val-Pro-Asp-Pro-Arg in pig, horse, dog, and rat; Ala-Pro-Gly-Pro-Arg in human and chicken; and Val-Pro-Gly-Pro-Arg in rat) derived from the amino-terminus of procolipase after the action of trypsin. Pharmacologic studies with Val-Pro-Asp-Pro-Arg have suggested a role for this peptide in appetite regulation and pancreatic insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible due to the lack of a suitable method for enterostatin assay. To this end, we raised a highly specific antibody and developed an enzyme-linked immunosorbent assay for Val-Pro-Asp-Pro-Arg. Using the newly developed assay we have shown the presence of Val-Pro-Asp-Pro-Arg-like immunoreactivity (2455 +/- 440 pmol/g) in the rat brain.

Amino Acid Sequence↗