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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 361 records · Page 20Linked to original sources
PubMed1998

Gamma-mangostin, a novel type of 5-hydroxytryptamine 2A receptor antagonist.

Gamma-mangostin, purified from the fruit hull of the medicinal plant Garcinia mangostana caused a parallel rightwards shift of the concentration/response curve for the contraction elicited by 5-hydroxytryptamine (5-HT) in the rabbit aorta (pA2 = 8.2) without affecting the contractile responses to KCl, phenylephrine (alpha1) or histamine (H1). The perfusion pressure response of rat coronary artery to 5-HT (5-HT2A) was reduced concentration dependently by gamma-mangostin (IC50 = 0.32 microM). 5-HT amplified, ADP-induced aggregation of rabbit platelets (5-HT2A) was inhibited by gamma-mangostin (IC50 = 0.29 microM), whereas that induced by thrombin was not affected, nor did gamma-mangostin affect 5-HT-induced contraction of the guinea-pig ileum (5-HT3)in the presence of 5-HT1, 5-HT2 and 5-HT4 receptor antagonists. Furthermore, 5-HT-induced contraction of the rat fundus (5-HT2B) and 5-HT-induced relaxation of the rabbit aorta in the presence of ketanserin (5-HT1) and carbachol-induced contraction of the guinea-pig ileum (muscarinic M3) were not affected by gamma-mangostin (5 microM). Gamma-mangostin inhibited [3H]spiperone binding to cultured rat aortic myocytes (IC50 = 3.5 nM). The Kd for [3H]spiperone binding was increased by gamma-mangostin (3 nM) from 11.7 to 27.4 nM without affecting Bmax. These results suggest that gamma-mangostin is a novel competitive antagonist, free from a nitrogen atom, for the 5-HT2A receptors in vascular smooth muscles and platelets.

Animals↗
PubMed1998

On the pattern of polymorphisms at major histocompatibility complex loci.

The pattern of polymorphisms at major histocompatibility complex loci was studied by computer simulations and by DNA sequence analysis. Two types of selection, overdominance plus short-term selection and maternal-fetal incompatibility, were simulated for a gene family with intra- and interlocus gene conversion. Both types of selection were found to be consistent with the observed patterns of polymorphisms. It was also found that the more interlocus conversion occurs, the higher the divergence becomes at both nonsynonymous and synonymous sites. The ratio of nonsynonymous-to-synonymous divergence among alleles decreases as the interlocus conversion rate increases. These results agree with the interpretation that the rate of interlocus conversion is lower in human genes than in genes of other nonprimate mammals. This is because, in the latter, synonymous divergence at the ARS (antigen recognition site) is often higher than that at the non-ARS, whereas in the former, this is not so. Also, the ratio of nonsynonymous to synonymous substitutions at the ARS tends to be higher in human genes than in other mammalian genes. The main difference between overdominance plus short-term selection and maternal-fetal interaction is that the number of alleles and heterozygosity per locus are higher in the latter than in the former under the presumed selection intensities. However, the average divergence among alleles tends to be lower in the latter than in the former under similar conditions.

Animals↗
PubMed1998

Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene.

We investigated the XLRS1 gene in Japanese patients with retinoschisis (RS). All exons of the XLRS1 gene were sequenced in 14 males, including a pair of monozygotic twins, from 11 individual families with RS and five of their mothers who are asymptomatic but diagnosed as carriers. Six kinds of missense mutations and a nonsense mutation, including six novel mutations, were detected in all 14 patients and carriers. Mutations in the XLRS1 gene are also responsible for RS in non-Caucasian patients. Most Japanese RS cases are caused by an XLRS1 gene defect. A novel mutation, Glu72Lys, was found in four families, suggesting a common mutation in the Japanese population. Clinical features of RS patients with both the Glu72Lys and Pro193Leu mutations indicate that a genotype-phenotype correlation is not recognized in RS.

Eye Diseases, Hereditary↗
PubMed1998

Comparison of cytotoxic effects of bisphosphonates in vitro and in vivo.

We compared the cytotoxic effects of alendronate (ALN) and incadronate (YM175) on isolated rabbit osteoclasts in vitro and on rats in vivo. In the in vitro experiment, each bisphosphonate was added to the culture of isolated osteoclasts at the final concentration of 3 x 10(-5), 3 x 10(-4), or 3 x 10(-3) M, and the amount of creatine phosphokinase (CPK) released into the medium was taken as an index of cytotoxicity at 5, 10, and 24 hours after the treatment. Also viability of osteoclasts, measured in terms of trypan blue exclusion, was assessed at 24 hours after the treatment. In YM175-treated groups, CPK activity in the medium increased in a concentration-dependent manner with time, and phase-contrast microscopic observation revealed damaged cell membranes and nuclear deterioration in YM175-treated osteoclasts. As a result, the viability of the osteoclasts was decreased at the concentrations of 3 x 10(-4) and 3 x 10(-3) M. However, in the ALN-treated groups, neither CPK activity nor viability of isolated osteoclasts changed significantly compared with control levels even at 3 x 10(-3) M for up to 24 hours. In the in vivo experiment, each bisphosphonate was administered separately to normal rats (7 weeks old, Sprague-Dawley) by intravenous injection at 1, 5, or 25 nmol/kg. Two days after the injection, the animals were euthanized, and the plasma Ca concentration and total CPK activity were measured. In YM175-injected rats, the CPK activity increased at 25 mmol/kg, and a slight decrease in the plasma Ca level was seen at this dose. In contrast, in ALN-injected rats, CPK activity did not increase even at 5 or 25 mmol/kg, and the plasma Ca level did decrease significantly compared with controls. Isozyme analysis revealed that, not only was CPK activity increased in the BB type in YM175-injected rats, it was also increased in the MB and MM types. In conclusion, alendronate, unlike YM175, does not have any cytotoxic effects on osteoclasts either in vitro or in vivo.

Alendronate↗
PubMed1998

Alendronate inhibits osteopontin expression enhanced by parathyroid hormone-related peptide (PTHrP) in the rat kidney.

It has been reported that osteopontin (OPN) plays an important role during urolithiasis as well as bone formation. Generation of stones in the urinary tract may be associated with osteoporosis and bisphosphonates are potent inhibitors of bone resorption, being used with effect in the management of bone disease. We therefore investigated the relationship between alendronate, a bisphosphonate derivative, and OPN expression in the kidney. Alendronate was administered to rats made hypercalcemic by treatment with parathyroid hormone-related peptide (PTHrP). The renal expression of OPN was then evaluated at both protein and mRNA levels. OPN expression was enhanced in the distal tubular cells of hypercalcemic rats and was decreased by alendronate. The observed inhibition of OPN expression suggests an ability of alendronate and other bisphosphonates to act as inhibitors of stone formation in the urinary tract.

Alendronate↗
PubMed1998

Structure and function correlations at the imprinted mouse Snrpn locus.

The human SNRPN gene maps within Chromosome (Chr) 15q11-q13, the region responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS). As one of several 15q11-q13 transcripts expressed from the paternal allele-only, SNRPN is a candidate gene to explain at least some of the PWS phenotype in human and in genetic mouse models. The promoter and first exon of the SNRPN gene also correspond to an imprinting center element responsible for resetting of the maternal to paternal imprints within 15q11-q13 during spermatogenesis. Through characterization of the imprinted murine Snrpn locus in mouse Chr 7C, we have found that the gene structure is very similar to the human, with ten conserved exons spanning 22 kb, the last seven of which are tightly clustered. The promoter of Snrpn is differentially methylated in ES cells and adult tissues, supporting a role for DNA methylation at this site in somatic establishment and/or maintenance of Snrpn imprinting. The first intron of the mouse and human genes contains structurally conserved G-rich clustered repeats which may play a role in establishing DNA methylation patterns associated with imprinting of this gene. On the basis of the conserved structural and imprinted features of the human SNRPN and mouse Snrpn genes, we suggest that imprinting mechanisms are conserved between human and mouse.

Angelman Syndrome↗
PubMed1998

Calcium channel current facilitation in porcine adrenal chromaffin cells.

The mechanisms of depolarizing-prepulse-induced facilitation of Ca2+ channel current were investigated in a study of porcine chromaffin cells. The Ba2+ current evoked by a pulse to 0 mV was increased by a strong depolarizing prepulse (conditioning pulse), termed "facilitation". This facilitation increased with an increase in either the duration or the voltage of the conditioning pulse, and decreased with an increase in the interpulse interval. For example, the Ba2+ current was increased to 1.14 times the control (facilitation ratio) by a 150-ms conditioning pulse to +100 mV followed by a 10-ms interpulse interval. Forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) and Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) did not affect the facilitation of the Ba2+ current, suggesting that a cAMP-dependent mechanism is not involved. Intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) decreased the Ba2+ current to 0.59 times the control and GDP beta S increased it to 1.19. However, neither GTP gamma S nor guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) changed the amplitude of the Ba2+ current that was facilitated by the conditioning pulse. Thus, GTP gamma S increased the facilitation ratio to 2.05 and GDP beta S decreased it to 1.05. Furthermore, the facilitation of the Ba2+ current was abolished by omega-conotoxin GVIA but not by either omega-agatoxin IVA or nifedipine. These results suggest that, in porcine chromaffin cells, there is a omega-conotoxin GVIA-sensitive N-type Ca2+ channel that is under the inhibitory control of a G protein, which can be relieved by a conditioning pulse.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes mellitus.

UNLABELLED: Coronary artery disease (CAD) is a major cause of death in patients with insulin-dependent diabetes mellitus. Qualitative changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) are thought to be important for evaluating the risk for CAD. In the present study, we evaluated LDL particle size (LDL-size) by 2%-16% gradient gel electrophoresis, along with conventional lipids and apolipoproteins, in 23 children with IDDM (10 males and 13 females) and 27 nondiabetic controls (12 males and 15 females). The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. Plasma levels of triglyceride were significantly lower in diabetic children than in controls. Plasma apoA-I and apoA-II levels in female diabetic children were significantly higher and lower than those in controls respectively. Plasma levels of HDL-cholesterol and the ratio of apoA-I to apoA-II were significantly higher in diabetic children than in controls. Other lipid and apolipoprotein parameters in diabetic children were similar to those in controls. LDL-size in diabetic children was significantly greater than that in controls. FERHDL, which reflects the particle size distribution of HDL, was significantly lower in diabetic children than in controls, which suggests that diabetic children had larger HDL particles. CONCLUSION: The qualitative and quantitative changes in LDL and HDL in diabetic children are similar to those associated with a reduced risk for CAD. Intensive insulin therapy in children may help preventing coronary heart disease in adulthood.

Adolescent↗
PubMed1998

Limb salvage and survival rates among elderly patients with advanced limb ischemia.

The purpose of this study was to clarify the incidence of limb salvage and patient survival rates among elderly patients with advanced leg ischemia. We reviewed the records of 159 patients treated for advanced ischemia over a 15-year period at Aichi Medical University, 74 of whom were aged over 75 years and 85, between 65 and 74 years. There was a collective total of 186 limbs; 82 in the older group and 104 in the younger group. The older group had a greater proportion of women, and a higher incidence of coronary heart disease, pulmonary dysfunction, and acute onset of advanced ischemia than the younger group. Limb salvage was achieved in 73% of the affected limbs in the older group and in 92% of the limbs in the younger group. The poor limb salvage rate in the older group was mainly related to the high initial amputation rate. Early recognition of the sentinel ischemic signs before the ischemia is essential, especially in the elderly. Timely revascularization should be attempted whenever possible, and it should not be abandoned simply because the patient is deemed too old. The 1-, 3-, and 5-year survival rates in the older group were 59%, 28%, and 23%, respectively, which were markedly poorer than the expected survival rates of the age- and sex-matched Japanese population at 1, 3, and 5 years, which were 93%, 79%, and 65%, respectively. Thus, advanced limb ischemia carries a poor prognosis to the point of being life-threatening, and further continuous systemic management with the collaboration of physicians and surgeons must be provided even after the patient has left the hospital.

Aged↗
PubMed1998

Angiogenesis in poorly differentiated medullary carcinoma of the stomach.

We studied the role of angiogenesis in patients with medullary type poorly differentiated adenocarcinoma (MTPDA) of the stomach. Immunohistochemical analyses were conducted using antibodies against factor VIII (endothelial cells), vascular endothelial growth factor (VEGF) and its receptors (KDR andflt-1), and basic fibroblast growth factor (bFGF) and its receptors (bek andflg). Archival specimens of MTPDA (n=22) and non-MTPDA (n=47) were studied. The expression of VEGF and bFGF, the vessel count, and positivity of KDR on endothelium were all significantly higher in MTPDA than in non-MTPDA. The vessel count correlated with the VEGF expression in MTPDA. The vessel count and VEGF expression increased with the increasing stage of disease in MTPDA but not in non-MTPDA. The expression of bFGF and its receptors did not correlate with the vessel count and stage of disease in either type. These findings thus suggest that the biological behavior of medullary type poorly differentiated adenocarcinoma of the stomach is angiogenesis-dependent. The correlation of the VEGF expression and its endothelial receptors with the vessel count and the stage of disease thus suggests that VEGF is a factor responsible for the induction of angiogenesis in this type.

Adult↗
PubMed1998

Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development: a possible role in bile duct morphogenesis.

BACKGROUND/AIMS: Cell adhesion molecules play an important role in the morphogenesis of developing organs. However, little is known about their expression during intrahepatic bile duct development. METHODS: We immunohistochemically investigated the expression of E-cadherin (E-Cad), alpha-catenin (A-Cat) and beta-catenin (B-Cat) during human intrahepatic bile duct development, using 31 fetal livers of various gestational ages. The developmental stages of bile ducts were classified into the ductal plate, migrating biliary cells (remodeling stage), and immature bile ducts (remodeled stage). RESULTS: E-Cad was broadly and strongly expressed in the ductal plate with a cytoplasmic pattern, heterogeneously and weakly expressed in the migrating biliary cells with a cytoplasmic pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. A-Cat was broadly and strongly expressed in the ductal plate with a membrane pattern, broadly and moderately expressed in the migrating biliary cells with a membranous pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. In contrast, expression of B-Cat was weak or slight in the ductal plate, but B-Cat was expressed broadly and strongly with a membranous pattern in migrating biliary cells and in immature bile ducts. Immature hepatocytes rarely expressed E-Cad and A-Cat, but expressed B-Cat with a membranous pattern throughout development. CONCLUSIONS: These results suggest that E-Cad, A-Cat and B-Cat are involved in the normal developmental morphogenesis of human intrahepatic bile ducts.

Bile Ducts, Intrahepatic↗
PubMed1998

Comparison of children and coronary heart disease patients with low high density lipoprotein cholesterol levels.

Low plasma high density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary heart disease (CHD) in adults. In the field of pediatrics, subjects with low plasma HDL-C are often found among obese or dyslipidemic children. However, it is not clear whether low HDL-C in children should be considered a risk factor for CHD. The purpose of this study was to evaluate the risk for CHD in children with low HDL-C by comparing their lipid and apolipoprotein levels and physicochemical characteristics of their HDL with those of age-matched children with normal HDL-C and CHD patients with low HDL-C. Plasma lipids and apolipoproteins were measured in 206 dyslipidemic children (dyslipidemic), 65 obese children (obese), 93 CHD patients with low HDL-C (< 40 mg/dl) and 128 children with normal HDL-C (controls). To evaluate the physicochemical characteristics of HDL, molar and fractional esterification rates of cholesterol in plasma (MER(plasma) and FER(plasma)) and HDL (MER(HDL) and FER(HDL)) were determined in 128 children with normal HDL-C, 71 dyslipidemic, 33 obese and 93 CHD who allowed second blood samples to be taken. Compared to controls, children with low HDL-C showed atherogenic profiles of lipid and apolipoprotein levels and physicochemical characteristics of HDL (lower apo A-I, lower ratio of apo A-I to apo B and higher FER(HDL)). Therefore, the differences in lipid and apolipoprotein profiles between children with low HDL-C and CHD patients with low HDL-C were examined next. The two groups of subjects based on the HDL-C level (Group I: < 30 mg/dl, Group II 30 < or = HDL-C < 40 mg/dl) were studied. Compared to CHD, Group I children showed less atherogenic apolipoprotein profiles (lower apo B and higher ratio of apo A-I to apo B). Similar findings were also found in Group II children, but the differences were less prominent than those in Group I children. FER(HDL) in children with low HDL-C were similar to those in CHD. These findings suggest that the physicochemical characteristics of HDL in children with low HDL-C are similar to those in CHD, but the abnormalities of apo B-containing lipoproteins are milder than those in CHD patients. Thus, if further changes in the nature of apo B-containing lipoproteins could be prevented, children with low HDL-C might not become high risk for CHD in later life.

Adolescent↗
PubMed1998

Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers.

To better understand the vascular activity of hemoglobin-based (Hb-based) oxygen carriers, the endothelial permeability characteristics of Hb derivatives having various molecular masses were defined by using monolayers of bovine endothelial cells cultured on microporous membranes. The endothelial permeability of unmodified bovine Hb was almost twice that of bovine serum albumin. Intramolecularly cross-linked human Hb showed slightly but significantly reduced permeability as compared with unmodified bovine Hb. Polyethyleneglycol modification or haptoglobin binding to Hb further reduced the permeability. These properties were intensified in conditions in which the endothelial barrier function was reduced by pretreatment with either interleukin-6 (100 ng/mL, 21 hours) or lipopolysaccharide (1 microg/mL, 10 hours). In contrast, there was little permeability of liposome-encapsulated Hb, and it was almost unaffected by the pretreatments. These data provide the first information that Hb derivatives with smaller molecular masses show larger transendothelial flux. Because Hb is a potent scavenger of endothelium-derived relaxing factor (EDRF), our observations support the idea that smaller Hb-based acellular oxygen carriers are potent vasoconstrictors as a result of abluminal EDRF scavenging.

Animals↗
PubMed1998

Practical synthesis of androgen: the efficient transformation of 17-oxo group to 17 alpha-hydroxy group.

The present report describes the improved transformation of the 17-oxo group in 3 beta-acetoxy-5 alpha-androstan-17-one to a 17 alpha-hydroxy group. A mixture of 17 alpha-acetoxy and 16-ene compounds, which are usually produced by the standard synthetic route, were treated with peracetic acid (epoxidation of the 16-ene compound) and then sodium borohydride-sodium hydroxide (reduction-hydrolysis) to give the desired 17 alpha-hydroxy compound in much better yield than that in previous reports. Recrystallization of the crude product with cyclohexane-methanol gave the pure compound in 54% yield (total yield from starting ketone).

Androgens↗
PubMed1998

MR angiographic source images for depicting surgical topography of anterior communicating artery aneurysm.

BACKGROUND: This study evaluated the usefulness of magnetic resonance (MR) angiography on preoperative depiction of surgical topography around anterior communicating artery aneurysms. METHODS: Twenty cases of anterior communicating artery aneurysms, nine ruptured and 11 unruptured, were included. MR angiographic source images and projection images were obtained by three-dimensional (3D) time-of-flight techniques. Conventional angiography was performed by femoral artery catheterization. By comparing the topography based on these angiograms to that confirmed during surgery, we evaluated the information provided by MR angiography that was beneficial during surgery. RESULTS: MR angiographic source images could visualize cerebral and nerve tissues around the aneurysms in all 20 cases. In five cases, the source images provided additional useful information to that from conventional angiography. It included visualization of aneurysmal domes in the gyrus rectus in two cases and aneurysmal adhesion to the optic nerve or chiasma in three cases. These findings were considered to have contributed to successful aneurysmal surgery. The remaining 15 cases, however, had such typ ical anatomy around the aneurysm that clipping was conventionally performed without additional information from the source images. CONCLUSIONS: MR angiographic source images have a distinguishing feature in defining neural tissue-vascular relationships and can significantly improve preoperative depiction of surgical topography. They would be useful only when there are still questions after careful reading of conventional angiography.

Humans↗
PubMed1998

Magnetic resonance angiographic source images for depicting topography and surgical planning for middle cerebral artery aneurysms: technique application.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) angiographic source images for determining the feasibility of M1 segment control via the distal approach in pterional craniotomy for middle cerebral artery (MCA) aneurysms. METHODS: MR angiographic source and conventional angiographic source images were obtained in 40 patients with MCA aneurysms. Each aneurysm was treated surgically using a pterional craniotomy. We initially approached the aneurysm distally. When this was judged inappropriate, the approach was altered to proximally. We compared the topography based on these angiograms to that confirmed during surgery. RESULTS: MR angiographic source images visualized the aneurysm, the M1 and M2 segments of the MCA, the insula, and the frontal and temporal opercula in all 40 patients. In 22 (55%) of them, the distal portion of the M1 segment was recognized from the posterolateral perspective between the aneurysmal neck and the insular surface. These aneurysms were successfully clipped via the distal approach after definite proximal control of the MCA was obtained. CONCLUSIONS: It was concluded that MR angiographic source images have a distinguishing feature in defining cerebral tissue-vascular relationships and that they are useful in the surgical planning for MCA aneurysms.

Feasibility Studies↗
PubMed1998

Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report.

BACKGROUND: Fluorescein has been used in the field of neurosurgery; however, fluorescein enhancement or contrast proved to be inadequate because of a lack of appropriate light sources or filters. A new operative microscope system, in which the microscope itself is equipped with excitation and barrier filters, and the application of this system to surgery for malignant glioma are reported. METHODS: BP 450-490, a glass interference filter used as the excitation filter for the light source optical system, and a Kodak Wratten No. 12 filter used as the barrier filter for the microscope optical system, were incorporated in the operative microscope. A switching apparatus was devised so that filters could be inserted instantly when fluorescence was to be observed. Ten cases in which the location of malignant glioma was enhanced by computed tomography (CT) or magnetic resonance imaging (MRI) were selected for this study. After incision of the dura mater, 8 mg/Kg body weight of fluorescein Na was injected intravenously. Tumor removal was begun some 20 min after the injection with the aid of this newly developed fluorescein operative microscope system. RESULTS: Fluorescence enhancement and contrast were remarkable when this system was used. It enabled surgical maneuvering while viewing the fluorescent image of objects. The boundaries between the tumor areas enhanced by CT or MRI and the surrounding brain could be clearly distinguished in the fluorescent image; the tumor was totally removed, except for deep lesions, without any neurological deterioration. When the tumor was relatively hard, the area surrounding the tumor was aspirated with a cavitron ultrasonic surgical aspirator; as a result, the tumor could be removed en bloc; otherwise, the fluorescent tumor was removed piece by piece. CONCLUSIONS: This system provides adequate fluorescent enhancement and contrast and is useful for observing intravenously injected fluorescein during an operation. Though long-term follow-up of such cases is needed, the conditions of our patients immediately after surgery for malignant glioma were satisfactory. These results suggest that our fluorescein operative microscope system is highly effective in surgery for malignant glioma.

Adult↗