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Biomedical subjects

G Watanabe

Publications and source records attributed to G Watanabe.

At least 181 records · Page 10Linked to original sources

Case report: rupture of a gastric varix in liver cirrhosis associated with glycogen storage disease type III.

Glycogen storage disease type III, or Cori's disease, is caused by a deficiency of amylo-1,6-glucosidase (debranching enzyme), which leads to the storage of an abnormal glycogen in the liver and in skeletal and heart muscle. Glycogen storage disease type III is usually characterized by hepatic symptoms, growth failure and myopathy. Even though liver cirrhosis is reported, portal hypertension is a rare complication of this disease. We describe the case of a glycogen storage disease type III patient who was diagnosed at 3 years of age and developed complications (liver cirrhosis and rupture of a gastric varix) at 31 years of age. We discuss the histological progression to cirrhosis of the liver and describe the liver enzyme profile at 3 and 31 years of age.

Adult↗

Thoracoscopic radiofrequency ablation of the myocardium.

Radiofrequency (RF) catheter ablation has been used for the treatment of ventricular tachycardia (VT), however, in some patients VT might result from subepicardial macroreentry that could be successfully terminated by epicardial approach. This study examined the feasibility of thoracoscopic RF ablation of myocardium from epicardium using a custom made electrode. In five mongrel dogs, the thoracoscope was introduced through the 7th intercostal space. A 500-KHz continuous wave RF energy was connected to a custom made multiple electrode probe. Under thoracoscopic guidance, the heart was exposed and the RF probe was introduced. RF ablation was performed on the nonvascular ventricular wall of the beating heart. The left ventricular free wall and right ventricular outflow tract were satisfactorily visualized and ablated. The total dose of RF energy ranged from 50 to 500 J, and the estimated volume of ablated lesions ranged from 41.0-799 mm3. There were significant correlations between the RF discharge output and the irradiated lesion volume (P < 0.01), and the depth of the lesions (P < 0.01). Grossly, after RF ablation the ventricular myocardium demonstrated a circular, well-demarcated area of thermal injury. Volume and depth of the lesion depended upon the total dose of delivered RF energy. Thoracoscopic RF ablation appears to be a minimally invasive and useful method for creating irradiated myocardial lesions from epicardial surface. This method could be technically feasible for the treatment of Vts for which endocardial RF ablation is ineffective.

Animals↗

Inhibin secretion in the stallion.

To examine the physiological role of inhibin in the stallion, a heterologous radioimmunoassay (RIA) based on a bovine RIA was validated and used to measure immunoreactive (ir)-inhibin concentrations in plasma and testicular homogenates. The bioactivity of equine testicular inhibin was also examined using an assay for suppression of FSH secretion from rat anterior pituitary cells. In addition, to identify the cell responsible for secreting testicular inhibin, the localisation of inhibin in the testis was investigated by an immunohistochemical method using a polyclonal antibody against (Tyr30)-porcine inhibin alpha(1-30) NH2. In the RIA, parallel dose response curves were obtained for the bovine inhibin standard and serial dilutions of stallion plasma and equine testicular homogenates. Parallel FSH inhibition curves were also observed for the bovine inhibin standard and serial dilutions of equine testicular homogenates in the bioassay. The inhibition of FSH secretion from rat pituitary cells by equine testicular homogenates was neutralised by an antiserum against bovine inhibin in vitro. Plasma concentrations of ir-inhibin, testosterone and oestradiol-17beta in stallions decreased abruptly after bilateral gonadectomy and FSH and LH concentrations in the plasma subsequently increased. Therefore, circulating inhibin in the stallion appeared to be largely of testicular origin. The histochemical results showed for the first time that strong immunopositive staining for inhibin occurred in the Leydig cells of the testes. Sertoli cells were also stained by the inhibin antibody but the reaction was weaker than that in Leydig cells. These results indicate clearly that both Leydig and Sertoli cells are potential sources of testicular inhibin in the stallion. A clear increase in plasma ir-inhibin concentrations was observed during the natural breeding season. Similar seasonal changes in the plasma concentrations of testicular steroid hormones and pituitary gonadotrophins occurred throughout the year. In conclusion, the testes appear to be the main source of inhibin, and testicular inhibin is secreted by Leydig and Sertoli cells in stallions. The positive correlations between plasma ir-inhibin and testicular activity during both the breeding and nonbreeding seasons indicate that plasma ir-inhibin is a useful indicator of reproductive activity in the stallion.

Animals↗

Inhibition of cyclin D1 kinase activity is associated with E2F-mediated inhibition of cyclin D1 promoter activity through E2F and Sp1.

Coordinated interactions between cyclin-dependent kinases (Cdks), their target "pocket proteins" (the retinoblastoma protein [pRB], p107, and p130), the pocket protein binding E2F-DP complexes, and the Cdk inhibitors regulate orderly cell cycle progression. The cyclin D1 gene encodes a regulatory subunit of the Cdk holoenzymes, which phosphorylate the tumor suppressor pRB, leading to the release of free E2F-1. Overexpression of E2F-1 can induce apoptosis and may either promote or inhibit cellular proliferation, depending upon the cell type. In these studies overexpression of E2F-1 inhibited cyclin D1-dependent kinase activity, cyclin D1 protein levels, and promoter activity. The DNA binding domain, the pRB pocket binding region, and the amino-terminal Sp1 binding domain of E2F-1 were required for full repression of cyclin D1. Overexpression of pRB activated the cyclin D1 promoter, and a dominant interfering pRB mutant was defective in cyclin D1 promoter activation. Two regions of the cyclin D1 promoter were required for full E2F-1-dependent repression. The region proximal to the transcription initiation site at -127 bound Sp1, Sp3, and Sp4, and the distal region at -143 bound E2F-4-DP-1-p107. In contrast with E2F-1, E2F-4 induced cyclin D1 promoter activity. Differential regulation of the cyclin D1 promoter by E2F-1 and E2F-4 suggests that E2Fs may serve distinguishable functions during cell cycle progression. Inhibition of cyclin D1 abundance by E2F-1 may contribute to an autoregulatory feedback loop to reduce pRB phosphorylation and E2F-1 levels in the cell.

3T3 Cells↗

Blockage of gonadotropin-induced first ovulation caused by thyroidectomy and its possible mechanisms in rats.

To determine the role of the thyroid gland on the ovarian functions during the initiation process of puberty, we examined the effects and its mechanisms of hypothyroidism on the first ovulation induced by equine chorionic gonadotropin (eCG) in immature female rats. Animals were thyroidectomized on day 22 and were injected with 5 IU of eCG on day 26 to induce the first ovulation on day 29. The number of antral follicles that secrete inhibin and the ovarian weight were significantly increased in thyroidectomized rats (Tx rats) 48 h after eCG treatment compared with those in non-Tx rats. However, thyroidectomy (Tx) significantly suppressed the rates of ovulating animals on day 29. The blockage of ovulation in Tx rats was recovered by administration of human chorionic gonadotropin or luteinizing hormone (LH)-releasing hormone (LHRH) on day 28. Inhibition of serum LH (not follicle-stimulating hormone) levels induced by Tx was almost restored to control levels by injection of LHRH. A significant increment in prolactin levels in Tx rats was also observed on day 28. The present data indicate that Tx before puberty in female rats causes the blockage of the first ovulation and that the inhibitory effects on ovulation are mainly due to the reduction in the preovulatory LH surge, which is partially mediated through an inhibition of LHRH action on the secretion of LH.

Animals↗

Relationship between calcium channel antagonists and nocturnal hypotension and autonomic imbalance in patients with a previous myocardial infarction.

The present study was conducted to evaluate the effect of calcium channel antagonists on diurnal changes in blood pressure and on autonomic function in 71 patients who were receiving a calcium channel antagonist because they had previously suffered a myocardial infarction. Ambulatory blood pressures and Holter ECGs were recorded simultaneously for 24 h. Autonomic function was assessed by heart rate variability. Nocturnal systolic pressure was > or = 90 mmHg in 63 patients (group I) and < 90 mmHg in 8 patients (group II). Significant day to night changes in high-frequency power (from 4.3 +/- 1.2 to 4.5 +/- 1.0/m2) as well as in the ratio of low-frequency power to high-frequency power (from 1.3 +/- 0.1 to 1.1 +/- 0.2) were observed in group I. whereas such changes were blunted in group II. When the calcium antagonist was discontinued or the dose was reduced in group II, the autonomic imbalance improved along with elevation of nocturnal systolic blood pressure. Thus, nocturnal blood pressure should be monitored when such drugs are administered for the treatment of ischemic heart disease to a patient with a previous myocardial infarction. If nocturnal hypotension occurs, the dose should be reduced or the drug should be discontinued.

Adult↗

Hormonal and cardiorenal responses to acute saline loading in mild congestive heart failure--the effect of angiotensin converting enzyme inhibition.

We investigated cardiorenal responses to acute saline loading in patients with mild congestive heart failure (CHF) with and without angiotensin-converting enzyme (ACE) inhibition. Saline loading (infusion of 250 ml of normal saline) was performed on 10 patients with mild CHF and 10 control subjects. Although saline loading reduced plasma renin activity and plasma angiotensin II to a similar extent in both groups, it increased cardiac output, renal blood flow, and the ratio of renal blood flow to cardiac output in the mild CHF group but not in the control group. After saline loading, urinary sodium excretion was higher in the control than in the mild CHF group. In the mild CHF group, saline loading was performed again after an ACE inhibitor (delapril) had been administered for 5 days. Although delapril increased cardiac output and renal blood flow under basal conditions, saline loading did not affect these variables. Delapril improved urinary sodium excretion after saline loading. Thus, the renin-angiotensin-aldosterone axis may contribute to cardiorenal hemodynamics and renal sodium handling in patients with mild CHF. This effect may attenuate the natriuretic response to acute saline loading, and administration of an ACE inhibitor improves this attenuation.

Adult↗

Effects of indomethacin on the selective release of follicle-stimulating hormone during the period of ovulation in the rat.

To determine whether indomethacin, a potent inhibitor of prostaglandins endoperoxide synthetase, affects the selective follicle-stimulating hormone (FSH) surge during the period of ovulation, the compound was administered intravenously (i.v.), concurrent with 10 IU human chorionic gonadotropin (hCG), to diestrous female rats at 16:00 hr. Indomethacin inhibited the number of ovulations in a dose-dependent manner, and treatment with 500 micrograms indomethacin reduced number of oocytes in the ampullae most effectively without enteric lesions. In the histological observation, oocytes that had began to mature were found not only in unruptured luteinized follicles but also in ovarian interstitium beneath ruptured luteinized follicle. Despite the inhibitory effects of indomethacin on ovulation, peri-ovulatory FSH and progesterone surges occurred in comparable levels and duration to vehicle-treated animals. These results indicate that indomethacin-induced inhibition of prostaglandin synthesis does not affect the selective release of FSH during the peri-ovulatory period.

Animals↗

Effects of thyroidectomy or thiouracil treatment on copulatory behavior in adult male rats.

Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal axis in hypothyroid male rats were investigated in the present study. Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory behavior test, intromission latencies in hypothyroid rats were significantly longer than those in euthyroid rats and ejaculation frequencies were reduced in hypothyroid male rats compared to control rats without reduction of plasma concentrations of testosterone. These changes in copulatory behavior in hypothyroid male rats were restored to control levels by administration of T4 (5 micrograms/rat). Hypothyroidism decreased adrenal weights, and basal and peak concentrations of corticosterone during diurnal variation, whereas it increased peak concentrations of ACTH in adult male rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male copulatory behavior.

Adrenal Glands↗

Influence of thiouracil-induced hypothyroidism on adrenal and gonadal functions in adult female rats.

The effect of hypothyroidism on adrenals and gonads in adult female rats was investigated throughout the estrous cycle. Hypothyroidism was induced by administration of 4-Methyl-2-Thiouracil (Thiouracil) in the drinking water. The weight of ovaries and adrenals, and the plasma levels of corticosterone decreased in hypothyroid rats as compared with euthyroid rats throughout the estrous cycle. Hypothyroidism resulted in decreased concentrations of plasma LH on the day of diestrus and proestrus, whereas the plasma concentrations of prolactin and progesterone increased as compared with euthyroid rats. The weight of uteri and plasma concentrations of estradiol decreased during the day of diestrus and proestrus in hypothyroid rats as compared with euthyroid rats. To further clarify the dysfunction of hypothalamo-hypophysial-adrenal axis in hypothyroid rats, animals were stressed by immobilization for 3 hr. In hypothyroid rats, a marked increase in plasma levels of ACTH in response to immobilization stress was observed compared to euthyroid control, whereas increases in plasma concentrations of corticosterone were much smaller in hypothyroid than euthyroid rats. These results clearly indicate that hypothyroidism causes both gonadal and adrenal disturbances in adult female rats. The increased concentrations of plasma progesterone may be due to hypersecretion of prolactin during the day of proestrus and estrus, which in turn result in disruption of the estrous cycle.

Adrenal Glands↗

Expression of inhibin alpha-subunit in horse testis.

Inhibin is believed to play roles in the pituitary secretion of FSH and in the paracrine regulation of testicular function. Although it has been generally accepted that inhibin is produced in Sertoli cells, there was a recent evidence for the localization of inhibin in Leydig cells of primates, rat and sheep. However, there is no report on the expression of inhibin in the adult horse testis. Therefore, using immunohistochemistry, western blotting and in situ hybridization techniques, the present study examined inhibin alpha-subunit (Ih-alpha) expression in the adult horse testis. For the detection of Ih-alpha protein, we used anti-porcine Ih-alpha antibody in immunohistochemistry and western blotting. Furthermore, digoxigenin-labeled complementary RNA probes were prepared to detect intracellular messenger RNA (mRNA) of Ih-alpha. Immunostainings for Ih-alpha were found not only in Leydig cells but also in Sertoli cells. The intensity in Leydig cells was stronger than in Sertoli cells. Immunoreactivities for Ih-alpha were found at approximately 46 kDa, 56 kDa and 90 kDa in the homogenates from testicular interstitial tissues. The bands at 56 kDa and 90 kDa agree with previous report, but not at 46 kDa. Signals for mRNA of Ih-alpha by in situ hybridization were detected in Leydig cells and in the basal region of seminiferous epithelium including Sertoli cells. These results suggest that Ih-alpha is expressed in Leydig cells and Sertoli cells of horse testis, and the expression level should be higher in Leydig cells than Sertoli cells.

Animals↗

Inhibition of ovarian follicular development associated with a decrease in luteinizing hormone levels during the estrous cycle of the rat.

To examine the importance of tonic LH secretion in ovarian follicular development, plasma concentrations of LH were lowered by administering antiserum to GnRH (GnRH AS). At 1100 h on metestrus or diestrus of the 4-day estrous cycle, rats were injected with GnRH AS, and blood samples were collected at 6 h intervals until 1100 h on the next metestrus. Separately, rats were injected with hCG after the administration of GnRH AS to examine the effect of lowered LH on the number of ovulatory follicles. Treatment with GnRH AS on either metestrus or diestrus lowered plasma concentrations of LH, inhibin, and estradiol. In contrast, the plasma concentrations of FSH increased after the GnRH AS treatment, probably due to a decrease in plasma levels of inhibin associated with suppression of ovarian follicular development. Administration of GnRH AS on metestrus noticeably reduced the number of ovulatory follicles in spite of the high FSH secretion. Such a reduction in the number of ovulatory follicles was blocked by replacing rat LH with ovine LH. These data indicate that tonic secretion of LH plays an important role in the regulation of follicular development during the estrous cycle of the rat.

Animals↗

Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion.

The relationship between hypothyroidism and disturbance of the hypothalamo-hypophysial-adrenal axis was investigated using adult male rats. Hypothyroidism was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Hypothyroidism decreased adrenal weights to 57% of controls and plasma concentrations of corticosterone to 48% of controls. The changes in the weight of adrenals recovered to control levels by administration of thyroxine. The pituitary responsiveness to corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) for ACTH release markedly increased in hypothyroid rats as compared with euthyroid rats. In vivo release of CRH and AVP in median eminence significantly increased in hypothyroid rats as compared with euthyroid rats. There were no significant differences in hypothalamic concentrations of CRH and AVP. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH mediated by increases in synthesis of CRH and AVP in the hypothalamus.

Adrenal Glands↗

[Efficacy of the MIDCAB doughnut: a new instrument for immobilization and hemostasis during MIDCAB].

A new instrument for the immobilization and hemostasis of an anastomotic site during off-pump bypass is described. The instrument called "MIDCAB doughnut" was used safely and accurately in 31 patients who underwent MIDCAB without CPB. In these, the instrument was applied in 44 anastomotic sites on the beating heart (30 left anterior descending, 7 right coronary, and 7 obtuse marginal arteries). It can make an operative field motionless and bloodless without distal snaring, because of air sucked fixation of an entire circuit of the anastomotic site. There was no operative and hospital deaths. Postoperative angiography revealed a 100% patency rate of the grafts. MIDCAB doughnut can improve a quality of the anastomosis during beating bypass surgery.

Cardiac Surgical Procedures↗

[Minimally invasive direct coronary artery bypass grafting (MIDCAB) for right and circumflex coronary artery systems].

BACKGROUND: Single-vessel coronary bypass grafting of the left internal thoracic artery (LITA) to the left anterior descending coronary artery (LAD) with mini-thoracotomy has been shown to produce excellent results with almost no mortality. However this procedure cannot be used in patients with double or triple vessel disease. METHODS: Between Aug. 96 and Dec. 97, 17 pts underwent minimally invasive direct coronary artery bypass (MIDCAB) to right (RCA) and circumflex coronary artery (CX). LITA and RITA were thoracicscopically harvested and the right gastroepiploic artery (RGEA), inferior epigastric artery, and radial artery were then harvested. A limited left thoracotomy in combination with limited anterior right thoracotomy (n = 3) or right lower parasternal incision extending to below the xiphoid process (n = 6) were made. The double MIDCAB as performed in 16 pts and triple in 1 pt. RESULTS: There was no operative death. At follow up, all pts are alive and well. The postoperative angiographic studies showed 30/31 grafts were patent. CONCLUSION: The utility of multi-vessel MIDCAB for the LAD, CX and RCA with in-site arterial grafts has been demonstrated in the present study. This less invasive surgical technique may become a viable option for the management of multi-vessel coronary artery disease.

Aged↗

Simultaneous determination of STR polymorphism and a new nucleotide substitution in its flanking region at the CD4 locus.

In the course of the investigation of a pentanucleotide repeat polymorphism at the human CD4 locus, a C-A transversion was found at the position corresponding to the 3' end of the original forward primer presented by Edwards et al. (1). In the present study, the simultaneous determination of the new sequence polymorphism and the pentanucleotide repeat polymorphism at the CD4 locus was attempted. To achieve this purpose, we adopted amplified product length polymorphism (APLP) analysis and designed some new allele-specific forward primers tagged with non-complementary nucleotides differing in length. A total of 646 DNA samples from peripheral blood of Japanese, Chinese and German populations were investigated. Although the C-A transversion was restricted to CD4*5, a new subtype allele with A and 5 repeats, designated CD4*5A, was observed at polymorphic frequencies in the three populations. The simultaneous genotyping by APLP analysis resulted in dramatically increased heterozygosity and discriminating power of the human CD4 locus.

Base Sequence↗