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Biomedical subjects

T Hashizume

Publications and source records attributed to T Hashizume.

At least 19 recordsLinked to original sources

Bovine posterior pituitary extract stimulates prolactin release from the anterior pituitary gland in vitro and in vivo in cattle.

It has been reported that the posterior pituitary (PP) gland contains a potent, unknown prolactin (PRL)-releasing factor (PRF) in rats. PRFs are assumed to be produced in neurones located within the hypothalamus, and to be peptidergic in nature. However, little is known about PRFs in domestic animals. To characterize the PRF in the PP of domestic animals, the present study examined the PRL-releasing activity of an acidic extract from bovine PP (bPP) in vitro and in vivo in cattle. First, the PRL-releasing effect of bPP extract was compared with that of PRL-releasing peptide (PrRP), and thyrotropin-releasing hormone (TRH) from cultured bovine anterior pituitary cells. The extract significantly increased PRL concentrations in the culture medium, at doses of 0.002 and 0.02 eq./ml (one eq. is the PP extract from one animal), compared with the control (p < 0.05). PrRP failed to stimulate the release of PRL. TRH significantly increased PRL concentrations in the culture medium, at doses from 10(-9) to 10(-7) M, compared with the control (p < 0.05). The rate of increase in the PRL concentration, by 0.02 eq./ml bPP extract, was significantly greater than that in TRH (p < 0.05). Secondly, plasma PRL responses to the intravenous (i.v.) injection of bPP extract (0.5 eq./head), PrRP [3.59 mug/kg body weight (BW)], TRH (1 mug/kg BW), and a dopamine receptor antagonist (sulpiride, 0.1 mg/kg BW), were examined in calves. PrRP failed to stimulate PRL release; however, plasma PRL increased immediately following the injection of bPP extract, TRH and sulpiride. The PRL-releasing effect of i.v. injections of TRH and sulpiride was more potent than that of bPP extract. Finally, plasma PRL responses to the intra-hypothalamic injection of bPP extract were examined in calves. The intra-hypothalamic infusion (arcuate nucleus) of 0.0625 eq./head of bPP extract strongly stimulated PRL release in calves (p < 0.05). The present results show that PP contains a physiologically potent PRF in cattle.

Animals↗

[Benign metastasizing leiomyoma from uterine myoma; report of a case].

A case, 53-year-old female, of benign metastasizing leiomyoma was reported. The patient had undergone a hysterectomy for uterine myoma at the age of 40. The computed tomography (CT) scan film on health screening revealed 4 nodular lesions on right lung field and 2 nodular lesions on left lung field. Two tumors of the left side were resected under thoracoscopic surgery. Pathologically 2 lesions were consisted of benign spindle cells and diagnosed as benign metastasizing leiomyoma. Postoperative course was uneventful. Right lung nodules have been meticulously followed up.

Female↗

[An operative approach of extrapleural pneumonectomy].

We present a case of breast cancer with pleural metastasis and empyema treated with extrapleural pneumonectomy. We showed the some of technically important points for this operation. The careful preparation was needed to prevent hemorrhage from such as great vessels, bronchial arteries and intercostal arteries. Especially in this surgical procedure, we should select the best approach method to have enough surgical field for complete tumor resection. We suggest that we should make additional thoracotomy and skin incision immediately when we feel the surgical field is not wide enough during the operation. The extrapleural pneumonectomy is one of the most highly invasive operation in general thoracic surgery, so careful perioperative managements should be required.

Breast Neoplasms↗

Dopant-pair structures segregated on a hydrogen-terminated Si(100) surface.

Novel atomic structures on a H-terminated Si(100)-(2x1)-H surface were found using scanning tunneling microscopy (STM). The structures are distinguishable only from Si dimers in empty-state STM images. They were observed on arsenic- and phosphorus-doped substrates, but not on boron-doped substrates. Surface density of these structures was found to be proportional to the dopant density in the substrate. First-principles calculations clarify that they are consisting of dopant pairs that are segregated from the bulk material. Hydrogen atoms attached to the dopant pair are found to flip between two positions on the surface due to a quantum effect.

Journal Article↗

Construction of a linkage map and QTL analysis of horticultural traits for watermelon [Citrullus lanatus (THUNB.) MATSUM & NAKAI] using RAPD, RFLP and ISSR markers.

We have been constructing linkage maps for watermelon ( Citrullus lanatus) on the basis of random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), inter-simple sequence repeats (ISSRs) and isozymes using an F(2) population derived from a crossing between a cultivated inbred line (H-7; C. lanatus) and an African wild form (SA-1; C. lanatus). A total of 120 F(2) plants was used for construction of a linkage map using 477 RAPDs, 53 RFLPs, 23 ISSRs and one isozyme markers. Linkage analysis revealed that 554 loci could be mapped to 11 linkage groups that extended for 2,384 centimorgans (cM). While a BC(1) population [(H-7 x SA-1) x H-7] consisting of 60 individuals was grown and scored for quantitative traits. Another linkage map with a total length of 1,729 cM was constructed in the BC(1) using genetic markers found to segregate in the F(2) population. A QTL analysis was applied by means of interval mapping for locating such agronomic traits as hardness of rind, Brix of flesh juice, flesh color (red and yellow) and rind color. The relative order of markers in the BC(1) map was essentially the same as that on the linkage map in the F(2). A total of five QTLs for four agronomic traits was detected. The QTL for hardness of rind was mapped on group 4. The linkage group 8 contained the QTL for sugar content of the flesh as expressed in Brix of the juice. The QTL for red flesh color was detected on groups 2 and 8. The QTL for rind color mapped on the group 3. The present map and QTL analysis may provide a useful tool for breeders by introducing valuable wild watermelon genes to cultivars.

Chromosome Mapping↗

Effects of Ghrelin on growth hormone secretion from cultured adenohypophysial cells in pigs.

To clarify the direct effects of Ghrelin on growth hormone (GH) release from anterior pituitary (AP) cells in pigs, GH-releasing effects of human Ghrelin (hGhrelin) and rat Ghrelin (rGhrelin) on porcine AP cells were compared with GHRH in vitro. The AP cells were obtained from 6-month-old pigs and the cells (2 x 10(5) cells per well) were incubated for 2 h with the peptides after incubating in DMEM for 3 days. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses of 10(-8) and 10(-7)M (P < 0.05). The rates of increase in GH at 10(-8) and 10(-7)M of hGhrelin were 82.7 and 131.9%, while those with rGhrelin were 43.9 and 79.5%, respectively. GHRH significantly stimulated GH release from the cells at a dose as low as 10(-11)M (P < 0.05), and the response to GHRH was greater than that induced by Ghrelins. In time-course experiments, GHRH continued to increase GH concentrations in media until 120 min after incubation; however, those in media treated with hGhrelin reached a plateau 60 min after incubation, and the maximal value was approximately one third that obtained with GHRH. When hGhrelin (10(-8)M) and GHRH (10(-8)M) were added together, additive effects of both peptides on the release of GH were observed (P < 0.05). Somatostatin (SS, 10(-7)M) significantly blunted GH release induced by hGhrelin (10(-8)M) and GHRH (10(-8)M) (P < 0.05). In the presence of SS, additive effects of hGhrelin and GHRH on the release of GH were observed (P < 0.05). These results show that Ghrelin directly stimulates GH release from anterior pituitary cells in pigs; however, the GH-releasing effect is weaker than that of GHRH in vitro. The present results also show that Ghrelin interacts with GHRH and SS to in the release of GH from porcine adenohypophysial cells.

Animals↗

Insulin-like growth factor I enhances gonadotropin-releasing hormone-stimulated luteinizing hormone release from bovine anterior pituitary cells.

The role of insulin-like growth factor I (IGF-I) in the release of luteinizing hormone (LH) is unclear in ruminants. In the present study, the effects of IGF-I on the release of LH stimulated by gonadotropin-releasing hormone (GnRH) were examined in primary cultures of bovine anterior pituitary (AP) cells, and the interaction between estradiol-17beta (E(2)) and IGF-I was characterized. GnRH(100nM)-stimulated LH release from the cultured cells was increased (P<0.05) 12, 24 and 36h after addition of IGF-I (250ng/ml), with a maximum at 12h (48.4ng/ml media versus 35.4ng/ml media in controls). IGF-I at concentrations of 25, 250 and 500ng/ml increased the release by 18.7, 24.2 and 28.9%, respectively (P<0.05), when compared with controls (37.2ng/ml media). E(2) (10nM), IGF-I (250ng/ml) and combined treatment of E(2) plus IGF-I also induced significant increases in LH release (P<0.05). The amounts of LH release after treatment with E(2) alone was 37.3% greater than with IGF-I alone (39.0ng/ml media versus 28.4ng/ml media) (P<0.05). When E(2) and IGF-I were added together (45.6ng/ml media), the release of LH was significantly greater than with either E(2) alone or IGF-I alone (P<0.05). E(2) (10nM) significantly (P<0.05) increased the amount of GnRH bound to the cells by 51.6% when compared with controls, however, IGF-I (250ng/ml) failed to increase GnRH binding. These results show that IGF-I enhances GnRH-stimulated LH release without changing the number of GnRH receptors in cattle, and IGF-I interacts with E(2) to increase the response to GnRH.

Animals↗

Supraclavicular and axillary lymphadenopathy as the initial manifestation in Wegener's granulomatosis.

Wegener's granulomatosis (WG) is a systemic granulomatous vasculitis that typically affects the upper airways, lungs and kidneys. Lymphadenopathy is rare in patients with WG. Here, we present the first case of WG whose initial manifestation was superficial lymphadenopathy (i.e. supraclavicular and axillary lymphadenopathy). One year after the initial presentation, a mass appeared in the lung. Biopsy specimens obtained from supraclavicular lymph nodes and lung demonstrated granulomatous vasculitis. This patient was negative for classic antineutrophil cytoplasmic antibodies (c-ANCA). Treatment with glucocorticoids, cyclophosphamide and trimethoprim-sulfamethoxazole has induced complete remission.

Aged↗

[Chylothorax after video-assisted thoracic surgery].

A 27-year-old male was admitted to our hospital with an abnormal shadow on chest X-ray. Chest computed tomography (CT) showed a localized mediastinal tumor. Thoracoscopic resection of the tumor was performed and the pathological diagnosis was bronchogenic cyst. Chylothorax occurred on postoperative day 1. Low fat diet therapy was performed. The discharge of chyliform pleural effusion was stopped on postoperative day 10. Thoracic drainage tube was removed and the patient discharged from hospital on postoperative day 19. He has been well for 10 months since operation, with no recurrence of the tumor or chylothorax.

Adult↗

Atomic wire oxidation of H-terminated Si(100)-( 2x1): domino reaction via oxidation and H migration.

We studied oxidation at a dangling bond (DB) on the H-terminated Si(100) surface by the first-principles calculations. We found that oxidation easily occurs at the exposed DB on the H-terminated Si(100) surface. The dissociated O atoms are chemisorbed at a dimer bond and a back bond, resulting in adjacent H atom migration onto the DB. As a consequence of the alternate oxidation and subsequent H atom migration processes, the atomic wire oxidation is actually found to occur on the H-terminated Si(100) surface at low temperatures without desorbing H atoms, as observed in our scanning tunneling microscopy experiment.

Journal Article↗

cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine.

A cDNA encoding a novel human CYP4F enzyme (designated CYP4F12) was cloned by PCR from a human small intestine cDNA library. RT-PCR analysis demonstrated that CYP4F12 is expressed in human small intestine and liver. This cDNA contains an entire coding region of a 524-amino-acid protein that is 81.7, 78.3, and 78.2% identical to CYP4F2, CYP4F3, and CYP4F8, respectively. When expressed in Saccharomyces cerevisiae, the P450 catalyzes leukotriene B(4) omega-hydroxylation and arachidonic acid omega-hydroxylation, typical reactions of CYP4F isoforms. Their activity levels are, however, much lower than those of CYP4F2. Interestingly, CYP4F12 catalyzes the hydroxylation of the antihistamine ebastine with significantly higher catalytic activity relative to CYP4F2 (385 vs 5 pmol/min/nmol P450). These results indicate that CYP4F12 has a different profile of substrate specificity from other CYP4F isoforms, enzymes responsible for metabolizing endogenous autacoids, therefore suggesting that it may play an important role in xenobiotic biotransformation in the human small intestine.

Amino Acid Sequence↗

Plasma growth hormone (GH) responses after administration of the peptidergic GH secretagogue KP102 into the oral cavity, rumen, abomasum and duodenum in adult goats.

The study was performed to determine whether orally administered KP102 (also known as GHRP-2) stimulates GH release in adult goats, and how the orally administered KP102 passes through the digestive tract and stimulates GH release in ruminant animals. Five mg/kg body weight (BW) of KP102 dissolved in 9 ml of saline were administered into the oral cavity, rumen, omasum and duodenum of adult goats, and GH release after administration of KP102 was examined. The GH levels were significantly elevated at 20 min after administration of KP102 into the oral cavity, and plasma concentrations of GH remained significantly elevated until 60 min (P < 0.05). The GH levels after administration of KP102 into the abomasum were variable. However, the GH level tended to increase within 30 min after administration, and were significantly higher than those of controls after 120 to 150 min (P < 0.05). The GH levels after administration of KP102 into the duodenum were significantly elevated at 40 min after administration, and plasma concentrations of GH remained significantly elevated until 140 min (P < 0.05). The administration of KP102 into the rumen failed to stimulate GH release. The GH response curves (AUC) produced after administration of KP102 into the abomasum or duodenum were 2.2-fold greater than those for after administration into the oral cavity (P < 0.05). The oral administration of 5 mg/kg BW of KP102 in the powder state, not dissolved in 9 ml of saline, failed to stimulate GH release. These results suggested that orally administered KP102 dissolved in saline transiently stimulates GH release in adult goats, and this phenomenon might be due to small amounts of the peptides entering directly into the abomasum with liquid bypassing the rumen.

Abomasum↗

Dicationic dithiocarbamate carbapenems with anti-MRSA activity.

A new class of 1 beta-methylcarbapenems bearing a doubly quaternarized 1,4-diazabicyclooctane (DABCO) substituted dithiocarbamate moiety at the C-2 side chain was prepared, and the biological profiles of the compounds, including in vitro and in vivo anti-MRSA activity and DHP-I susceptibility, were evaluated to identify a carbapenem derivative that was superior to BO-3482 (1). As a result, we discovered a 1 beta-methyl-2-[4-(4-carbamoylmethyl-1,4-diazabicyclo[2,2,2]octanediium-1-yl)methyl-1,2,3,6-tetrahydropyridinylthiocarbonylthio]carbapenem, 14a showing greater than 2-fold better anti-MRSA activity in a mouse infection model and 3-fold better DHP-I susceptibility as compared with BO-3482 (1).

Animals↗

Mesangial proliferative glomerulonephritis with deposits of anti-nicotinic acetylcholine receptor antibody in a patient with myasthenia gravis.

A patient with myasthenia gravis developed nephrotic syndrome 3 years after thymectomy. The kidney biopsy specimen revealed mesangial proliferative glomerulonephritis with immune deposits. The glomerular mesangial cells and tubular epithelial cells were sensitive to alpha-bungarotoxin (alpha-BT), a ligand for nicotinic acetylcholine receptor (nAChR), and the binding was inhibited by native alpha-BT, as well as other nAChR ligands, nicotine and d-tubocurarine. In addition, FITC-alpha-BT-neuromuscular junction complexes could also bind to the mesangial cells, and preincubation with unlabeled nAChR inhibited the binding. These findings are consistent with the notion that both nAChR-like protein and anti-nAChR antibody are present in t he mesangial cells of the patient. Although the pathogenetic role of anti-nAChR antibody on the development of glomerulonephritis is unclear, the present observations provide an important insight into the autoimmune-mediated pathophysiological relationship between myasthenia gravis and mesangial proliferative glomerulonephritis.

Adult↗

Internalization rates of murine and ovine gonadotropin-releasing hormone receptors.

Rates of internalization of the murine GnRH receptor fused via its C-terminus to green fluorescent protein (GnRH-R-GFP) were examined in Chinese hamster ovary cells (CHO cells) and compared to those of native murine GnRH-R in a clonal murine gonadotroph cell line (LbetaT2 cells). The resulting rates of internalization of murine receptors were then compared with those of sheep GnRH-R in ovine gonadotrophs. Cells were incubated with radioiodinated [D-Ala6]GnRH on ice for 4 h to allow binding of the ligand to GnRH-R, then cells were warmed to 37 degrees C to permit internalization. Surface-bound radioligand began to decrease as soon as the cells were warmed and had decreased significantly within 20 min. A steady-state level of surface-bound radioligand was achieved after 60 min in both CHO cells and LbetaT2 cells (38% and 41%, respectively, of initial value; P < 0.05). Internalization of radioligand began immediately after warming the cells to 37 degrees C, and a significant proportion of surface ligand had been internalized by 20 min. A steady-state maximum of internalization was reached after 60 min in both CHO cells and LbetaT2 cells (29% and 28%, respectively, of total cell-associated ligand; P < 0.05). Changes in surface-bound radioligand and internalized radioligand in sheep pituitary cells were similar to those in CHO cells and LbetaT2 cells, but the amount of radioligand internalized after 60 min (40% of total cell-associated ligand) was 1.4 times higher than in CHO cells and LbetaT2 cells (P < 0.05). In a separate experiment, the effect of estradiol on the rate of internalization of GnRH-R in ovine pituitary cells was examined. Although treatment of ovine pituitary cells with estradiol approximately doubled the number of GnRH receptors, it did not alter either the rate or extent of receptor internalization. These results show that rates of internalization of recombinant murine GnRH-R-GFP in CHO cells and native murine and ovine GnRH-R in LbetaT2 cells and in sheep pituitary cells, respectively, are similar, but amounts of ovine GnRH-R internalized are greater than those for murine GnRH-R. Further, the rate of internalization of occupied receptor is similar in gonadotroph and nongonadotroph cells, and the addition of GFP to the C-terminus of the murine GnRH-R does not alter the rate of internalization.

Animals↗

Serum levels of vascular endothelial growth factor and cavity formation in active pulmonary tuberculosis.

BACKGROUND: In active pulmonary tuberculosis, certain cytokines have been postulated to be related to cavity formation, although the detailed mechanism of cavity formation is not yet known. OBJECTIVE: We examined the relationship between cavity formation in pulmonary tuberculosis and vascular endothelial growth factor (VEGF), which functions as an angiogenesis factor. METHODS: Forty-eight patients with active pulmonary tuberculosis were divided into two groups according to cavity formation as evaluated by chest high-resolution computed tomography. We evaluated serum VEGF levels by enzyme immunoassay. RESULTS: Group A (with cavities) was comprised of 22 patients and group B (without cavities) was comprised of 26 patients. The serum levels of VEGF were significantly higher in group B (58.733 +/- 21.612 pg/ml) than those in normal individuals (8.739 +/- 3.656 pg/ml) and in group A (13.053 +/- 8.670 pg/ml) (Mann-Whitney U test, p = 0.0149 and p = 0.0481, respectively). Serum levels of interleukin-8 and tumor necrosis factor-alpha were not significantly different between the two groups. CONCLUSION: These findings suggested that increased serum VEGF levels subdue cavity formation in active pulmonary tuberculosis.

Adolescent↗

Effects of antihypertensive agents on blood pressure during exercise.

The relationship between blood pressure (BP) and cardiovascular morbidity has been appreciated for many years. Casual BP may not be representative of the pressure at other times. It is recognized that BP during exercise may be a more accurate predictor than casual BP. There is, however, little information about the effects of antihypertensive drugs on the BP during exercise. This study was designed to investigate the effects of various antihypertensive agents on BP during exercise. Sixty-four patients (age, 49+/-10 years) with untreated essential hypertension (WHO I, II) were studied during a supine ergometric exercise regimen. A graded exercise test was started at a workload of 50 W, and the load was increased by 25 W every 3 min. The hemodynamic responses to exercise were evaluated by changes in systolic and diastolic BP (SBP, DBP) and heart rate (HR). Plasma norepinephrine (NE) levels were measured at rest and during submaximal exercise, and before and after 4 weeks of treatment with metoprolol (METO), doxazosin (DOXA), trichlormethiazide (TCTZ), nifedipine (NIFE), amlodipine (AMLO) and temocapril (TEMO) between left ventricular mass index (LVMI) and BP values at rest, during exercise, and during the recovery period after exercise were assessed by multiple regression analysis. The stepwise selection (forward conditional) method showed that LVMI was significantly associated with SBP during submaximal exercise and during the recovery period. All antihypertensive treatments decreased SBP and DBP (p<0.01) at rest. METO, AMLO and TEMO significantly lowered SBP (p<0.05) during exercise, whereas DOXA, TCTZ and NIFE induced no change in SBP. The exercise-induced increase of plasma NE was further enhanced by METO and NIFE but not by AMLO, DOXA, or TCTZ, and it was significantly suppressed by TEMO (p<0.01). These results suggest that BP during exercise is more highly associated with the progression of left ventricular hypertrophy (LVH) than is casual BP. Because antihypertensive agents differ in their effects on exercise hemodynamics, we recommend that hemodynamic factors during exercise be considered when selecting the optimal antihypertensive medication for highly active patients.

Adult↗

A novel cytochrome P450 enzyme responsible for the metabolism of ebastine in monkey small intestine.

Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. P450 MI-2 and P450 MI-3 showed the respective apparent molecular weights of 56,000 and 53,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The internal amino acid sequence of P450 MI-2 had high similarity with those of human CYP4F2, CYP4F3, and CYP4F8. The first 27 amino acid residues of P450 MI-3 were highly homologous with those of monkey CYP3A8 and human CYP3A4/5/7. Furthermore, P450 MI-2 and P450 MI-3 were recognized by anti-CYP4F and anti-CYP3A antibodies, respectively, in immunoblot analysis and catalyzed leukotriene B(4) omega-hydroxylation and testosterone 6beta-hydroxylation, which are known to be mediated by CYP4F and CYP3A, respectively. Although both enzymes had ebastine hydroxylation activity, the V(max) value of P450 MI-2 was much higher than that of P450 MI-3 (37.0 versus 0.406 nmol/min/nmol of P450), and the former K(M) (5.1 microM) was smaller than the latter K(M) (10 microM). Anti-CYP4F antibody inhibited the hydroxylation in small intestinal microsomes strongly (70%), but anti-CYP3A antibody did not. These results indicate that P450 MI-2 belongs to the CYP4F subfamily and is mainly responsible for hydroxylation of ebastine in monkey small intestinal microsomes. This suggests that the small intestinal CYP4F enzyme, P450 MI-2, can play an important role in the metabolism of drugs given orally.

Amino Acid Sequence↗