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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 181 records · Page 10Linked to original sources
PubMed1999

Diacylglycerol kinase in the central nervous system--molecular heterogeneity and gene expression.

Diacylglycerol (DAG) is one of the important second messengers, which serves as an activator of protein kinase C (PKC). DAG kinase (DGK) phosphorylates DAG to generate phosphatidic acid, thus DGK is considered to be a regulator of PKC activity through attenuation of DAG. Recent studies have revealed molecular structures of several DGK isozymes from mammalian species, and showed that most of the isozymes are expressed in the brain in various amounts. We have cloned four DGK isozyme cDNAs from rat brain library (DGK alpha, -beta, -gamma, and -zeta) (previously also designated DGK-I, -II, -III, and -IV, respectively) and examined their mRNA expressions in rat brain by in situ hybridization histochemistry. Interestingly, it is revealed that the mRNA for each isozyme is expressed in a distinct pattern in the brain; DGK alpha is expressed in oligodendrocytes, glial cells that form myelin; DGK beta in neurons of the caudate-putamen; DGK gamma predominantly in the cerebellar Purkinje cells; and DGK zeta in the cerebellar and cerebral cortices. Molecular diversity and distinct expression patterns of DGK isozymes suggest a physiological importance for the enzyme in brain function. Furthermore, functional implications of these DGK isozymes are briefly discussed.

Animals↗
PubMed1999

Myocardial expression of endothelin-2 is altered reciprocally to that of endothelin-1 during ischemia of cardiomyocytes in vitro and during heart failure in vivo.

We and other groups have reported that endothelin (ET)-1 expression in the heart is altered in the setting of heart diseases. We have also reported that myocardial ET-1 is involved in the progression of heart failure, and that an ET receptor antagonist improves long-term survival in heart failure (Nature 384: 353-355, 1996). However, the role of myocardial ET-2 in disease states are not known. To characterize the role of ET-2, we used a) the failing hearts of rats with heart failure caused by myocardial infarction, and b) primary cultured cardiomyocytes subjected to hypoxia. In the failing heart in vivo, ET-1 mRNA increased by 390% compared with that in the non-failing heart, while ET-2 mRNA drastically decreased by 88%. Thus, gene expression of ET-1 and ET-2 was reciprocally altered in the failing heart in vivo. In in vitro studies, reciprocal alterations in ET-1 and ET-2 gene expression were also observed in isolated primary cultured cardiomyocytes, subjected to hypoxia. Specifically, acute hypoxic stress induced a significant increase (360% of the basal level) in ET-2 mRNA expression compared with that in normoxic cells, whereas it decreased ET-1 mRNA expression by 62% in primary cultured cardiomyocytes. Although these two crucial conditions, i.e., heart failure in vivo and acute hypoxic stress in vitro, are pathophysiologically distinct from each other, reciprocal alteration of ET-1 and ET-2 gene expression was observed in both cases. To further investigate the regulatory mechanism of the altered gene expression, luciferase analysis was performed using primary cultured cardiomyocytes. ET-2 promoter, which is the 5'-flanking region of preproET-2 gene (5'ET-2), showed a marked increase in luciferase activity during acute hypoxia. In contrast, the luciferase activity of 5'ET-1 (ET-1 promoter) did not change in response to hypoxic stress. The present study suggests that there are transcriptionally distinct regulatory mechanisms for ET-1 and ET-2 expression in cardiomyocytes, and therefore this study may provide a new aspect of cardiac ET system that not only ET-1 but also ET-2 can be participated in the pathophysiological conditions.

Animals↗
PubMed1999

Vertebral arteriovenous fistula that developed in the same place as a previous ruptured aneurysm: a case report.

BACKGROUND: Aneurysms of the extracranial vertebral artery (VA) and vertebral arteriovenous fistulas (VAVFs) are relatively rare diseases. The most frequent cause of both diseases is trauma. Atraumatic lesions are less common. Presented here is a case of atraumatic AVF of the extracranial VA that developed in the same location as a previous ruptured aneurysm of the ipsilateral VA that was originally treated by proximal occlusion 11 years earlier. METHODS: A 40-year-old woman presented with a massive hematoma in the upper posterior neck region caused by the rupture of an extracranial VA aneurysm. Proximal occlusion of the VA was performed by use of a detachable balloon. She enjoyed good health for 11 years, then she noticed a pulsatile bruit. Angiograms revealed an AVF between the left VA that was fed by collateral circulation and the paravertebral venous plexus. Incidentally found were soft tissue masses in the left retroauricular and the right suboccipital regions. Also, skull X-ray films showed multiple bony defects. Biopsy of the subcutaneous mass was performed in the hope of obtaining clues as to which pathological processes had weakened the artery. RESULTS: As direct transarterial access to the fistula was out of the question, the fistulous compartment of the paravertebral venous plexus was tightly packed with multiple platinum coils effected by the transfemoral approach. A histological examination of the specimen revealed features of a neurofibroma, and a diagnosis of neurofibromatosis Type 1 was established. CONCLUSIONS: In this case, transvenous embolization of the VAVF was successfully performed. The fragility of the arterial wall, related to neurofibromatosis Type 1, was considered to contribute to the development of the aneurysm and AVF.

Adult↗
PubMed1999

Preparation of poly(ethylene glycol)-polystyrene block copolymers using photochemistry of dithiocarbamate as a reduced cell-adhesive coating material.

This article reports a novel preparation method of poly(ethylene glycol) (PEG)-polystyrene (PST) amphiphilic block copolymers with well-defined block lengths by using photopolymerization of an iniferter, benzyl N,N-diethyldithiocarbamate. PEG macroiniferters, which were prepared by end-capping of PEG monomethyl ethers with benzyl N,N-diethyldithiocarbamate group at one end, were irradiated with UV light in the presence of styrene (ST). NMR analyses showed that the PST block was chain-extended from the PEG block, resulting in the preparation of PEG-PST block copolymers. The number-average molecular weights of the copolymers increased almost linearly with irradiation time, light intensity, and concentration of ST. The polydispersities of the copolymers remained relatively small throughout the reaction (Mw/Mn approximately 1.3). The composition of two PEG-PST block copolymers thus obtained was as follows: PEG (Mn; 1.9 x 10(3) gmol(-1))-PST (3.0 x 10(3) gmol(-1)) and PEG (4.9 x 10(3) gmol(-1))-PST (2.6 x 10(3) gmol(-1)). These copolymers were coated onto a poly(ethylene terephthalate) film surface. X-ray photoelectron spectroscopy analyses and water wettability measurements showed that the PST block was enriched at the outermost layer as cast in air, whereas upon immersion into water, the PEG block was oriented toward water. Enhanced wettability was observed for the diblock copolymer with a higher PEG content. Significantly reduced cell adhesion was observed on both the coated surfaces. Thus, the PEG-PST block copolymer may function as a cell adhesion-resistant coating which reduced cell-substrate interaction.

Animals↗
PubMed1999

Heart failure and endothelin receptor antagonists.

Cardiac myocytes and vascular endothelial cells produce endothelin-1, which increases the contractility of cardiac muscles and of vascular smooth muscles. Endothelin-1 also exerts long-term effects, such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. In heart failure, the production of endothelin-1 is markedly increased in the failing heart. Here, evidence that an endothelin receptor antagonist is a useful new drug for the treatment of heart failure is discussed. Long-term treatment with an endothelin receptor antagonist greatly improves the survival rate of animals (rat, hamster, etc.) with chronic heart failure. This beneficial effect is accompanied by amelioration of left ventricular dysfunction. The myocardial endothelin system appears to be a novel and important target for therapeutic intervention in heart failure.

Animals↗
PubMed1999

Structure, tissue distribution, and pharmacological characterization of Xenopus orexins.

We isolated the Xenopus gene encoding prepro-orexin to predict the structures of orexins in submammalian chordates. Putative mature Xenopus orexin-A and -B are highly similar to each mammalian counterpart. Especially, the C-terminal 10 residues were highly conserved among these species and isopeptides. Immunohistochemical examination of Xenopus brain revealed that orexin-containing neurons were highly specifically localized in the ventral hypothalamic nucleus. A rich network of immunoreactive fibers was found in various regions of the Xenopus brain. The distribution was similar to that of mammalian orexins. Xenopus orexin-A and -B specifically bind and activate human orexin receptors expressed in Chinese hamster ovary cells. Of interest, Xenopus orexin-B had several-fold higher affinity to human OX2R compared with human orexins. These results suggest that Xenopus orexin-B might be a useful pharmacological tool as an OX2R selective high-affinity agonist.

Amino Acid Sequence↗
PubMed1999

Triplet repeat polymorphism in the MICA gene in HLA-B27 positive and negative caucasian patients with ankylosing spondylitis.

Previously, we reported a triplet repeat polymorphism in the transmembrane region within the MICA gene closely linked to HLA-B in a limited number of B27-positive Caucasian patients with ankylosing spondylitis (AS) (N = 48). In this study, we enrolled much more patients including some negative for B27, 162 AS subjects consisting of 140 B27-positive, and 22 B27-negative patients. The microsatellite allele consisting of 4 repetitions of (GCT/AGC) (A4 allele) was present at a significantly higher phenotype frequency in the patient group than in the ethnically matched control group (Pc < 0.000001). However, the frequency of the A4 allele was not significantly higher in the B27-positive and B27-negative patient groups, as compared to the B27-positive and B27-negative control groups, respectively. The higher phenotype frequency of the A4 allele in the patient group was supposed to be due to a strong linkage disequilibrium between the MICA and HLA-B genes. Thus, the possibility that the MICA gene is involved in the pathogenesis of AS can be excluded, supporting the hypothesis of a primary association of AS with HLA-B27.

Case-Control Studies↗
PubMed1999

Bis-N-nitroso-caged nitric oxides: photochemistry and biological performance test by rat aorta vasorelaxation.

Three new caged nitric oxides (NOs)-BNN3, BNN5Na, and BNN5M were tested for biological use. BNNs have a strong ultraviolet (UV) absorption band (lambda(max): 300 nm, epsilon: 13.5 mM(-1) cm (-1)) extended to 420 nm and produce NO upon irradiation with 300-360 nm light in quantum yields about 2. A photoexcited BNN molecule yields two NOs with time constants of less than 10 ns for phase 1 and less than 20 micros for phase 2 at 37 degrees C, suggesting usefulness of BNNs for measuring in vivo and in vitro fast NO reactions. Upon irradiating with UV light, caged nitric oxides-loaded rat aortic strips maintained in a state of active tonic contraction effectively relaxed ( < 3 microM BNN5M loading solution concentration). BNN3 is incorporated in the lipid membrane. BNN5Na, insoluble in organic solvents but water soluble, localizes in the water phase. BNN5M, is muscle-cell-permeable and hydrolysed to BNN5Na to remain in cytosol. BNNs were thermally stable and demonstrated no observable toxicity.

Animals↗
PubMed1999

HLA class I and II typing of the patients with Behçet's disease in Saudi Arabia.

Thirteen Saudi Arabian patients with Behçet's disease (BD) were typed for HLA-A and -B alleles by the conventional serologic typing and for HLA-DRB1, -DQB1 and -DPB1 alleles by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. As a result, the phenotype frequency of the B51 antigen was significantly increased in the patient group as compared to the ethnically matched control group (76.9% in patients vs. 22.20% in controls), but no significant difference was observed in HLA-A, -DRB1, -DQB1 or -DPB1 alleles between the patients and controls, as previously observed in Japanese BD. Further, by HLA-B51 allelic genotyping performed by the polymerase chain reaction-sequence specific primers (PCR-SSP) method, all of the B51-positive patients and controls were found to carry one particular allele, B*5101, except one patient with B*5108.

Behcet Syndrome↗
PubMed1999

Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization.

A number of consistent clinical observations provide direction for the hypothesis that pathological sensitization of neuronal systems may be an important factor for relapse or the onset of stimulant-induced psychosis (eg, methamphetamine or amphetamine psychosis, cocaine psychosis and phencyclidine psychosis) and schizophrenia. First, psychotic symptoms can be produced in normal subjects by stimulants. Secondly, a large portion of schizophrenic patients exhibit exacerbation of psychotic symptoms in response to stimulants at doses which would not be psychotogenic in normal subjects. Lastly, the ability of stress to precipitate the onset and relapse of schizophrenia is well documented. In this regard, acute responses to stimulants provide useful information for relapse prediction of schizophrenia and substance abuse. This paper addresses the nature and role of pathological sensitization in relapse of stimulant- and phencyclidine-induced psychosis and schizophrenia, and its relation to pathophysiology of schizophrenia.

Animals↗
PubMed1999

Effects of prone and supine position on sleep characteristics in preterm infants.

The purpose of this study was to address the influence of sleep position on sleep characteristics in preterm infants. We studied 16 infants at a mean post-conceptional age of 36.5 weeks. Infants were successfully recorded with videopolysomnograph in the supine and prone position. Between the two positions, there were no significant differences in percentage of active sleep and quiet sleep (QS), the occurrence of arousal, and the incidence of apnea. The first QS after the feeding was longer in the prone position. The sleep position could affect sleep characteristics but not respiratory characteristics in preterm infants.

Arousal↗
PubMed1999

Pharmaceutical evaluation of multipurpose excipients for direct compressed tablet manufacture: comparisons of the capabilities of multipurpose excipients with those in general use.

Recently, a novel type of multipurpose excipient (MPE) with high binding characteristics and high fluidity has been developed. In this study, the capabilities of MPEs (Ludipress and Microcelac) were compared with those of excipients in general use. Also, the effects on powder and tableting characteristics of the physical properties and contents of active ingredients were examined in tablets prepared with these MPEs by the direct compression method. Multipurpose excipients mixed with adjuvants such as fillers, binders, lubricants, disintegrants, and the like show superior fluidity and compressibility. Tablets containing very small amounts of highly active ingredients with little dispersion were prepared. However, with increases in active ingredient content, each of the physical properties was affected strongly by the properties of the active ingredient. Tablets with appropriate hardness and disintegration characteristics could be prepared by mixing of different types of MPEs.

Chemistry, Pharmaceutical↗
PubMed1999

The critical region for Behçet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping.

The HLA-B51 allele is known to be associated with Behçet disease. Recently, we found a higher risk for Behçet disease in the MICA gene, 46 kb centromeric of HLA-B, by investigation of GCT repetitive polymorphism within exon 5 of MICA. The pathogenic gene causing Behçet disease, however, has remained uncertain. Here, eight polymorphic microsatellite markers, distributed over a 900-kb region surrounding the HLA-B locus, were subjected to association analysis for Behçet disease. Statistical studies of associated alleles detected on each microsatellite locus showed that the pathogenic gene for Behçet disease is most likely found within a 46-kb segment between the MICA and HLA-B genes. The results of this mapping study, and the results of an earlier study of ours, suggest that MICA is a strong candidate gene for the development of Behçet disease.

Behcet Syndrome↗
PubMed1999

Phase I study of cisplatin and docetaxel plus mitomycin C in patients with metastatic non-small cell lung cancer.

BACKGROUND: Docetaxel, cisplatin and mitomycin C are some of the active drugs used in the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose of the three drugs in combination for such patients. METHODS: Chemotherapy-native patients with metastatic NSCLC were enrolled in this study. The doses of docetaxel and cisplatin were fixed at 60 and 80 mg/m2, respectively. It was planned to increase the dose of mitomycin C from 4 to 6 and 8 mg/m2. All drugs were administered on day 1 and repeated every 3-4 weeks. RESULTS: All six patients received 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin, three of them with 4 mg/m2 of mitomycin C (level 1) and the other three with 6 mg/m2 of mitomycin C (level 2). Two of the three level 2 patients experienced dose-limiting toxicities (DLTs) in first cycle: febrile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was concluded to be 60 mg/m2 for docetaxel, 80 mg/m2 for cisplatin and 6 mg/m2 for mitomycin C. Evaluation of the data from all of the cycles, however, showed that four of the six patients experienced DLTs. CONCLUSIONS: The addition of mitomycin C to docetaxel and cisplatin resulted in relatively high toxicities. It was impossible to use a high enough dose of mitomycin C to improve the survival of NSCLC patients. We therefore concluded that further evaluation of this combination is unwarranted.

Aged↗
PubMed1999

Effect of nebulized morphine in cancer patients with dyspnea: a pilot study.

BACKGROUND: It is known that opioids may decrease subjective dyspnea. The recent finding that opioid binding sites are present in the peripheral bronchus supports the possibility of a local action of opioids. However, the clinical benefit of nebulized morphine is controversial. The purpose of this study was to confirm the feasibility of nebulized morphine and to evaluate its clinical benefits. PATIENTS AND METHODS: Fifteen cancer patients with dyspnea in the Thoracic Oncology Division and Palliative Care Unit in the National Cancer Center Hospital East were given 20 mg of morphine hydrochloride dissolved in 5 ml of normal saline through an ultranebulizer. The subjective effects were evaluated using a visual analog scale (VAS) immediately before and 60 min after inhalation. Respiratory rate (RR), hemoglobin oxygen saturation (SpO2) and blood pressure also were measured twice at these two time points. A questionnaire about adverse reactions was included. RESULTS: No major adverse reactions such as respiratory depression, sleepiness, nausea or vomiting were observed. VAS was significantly decreased after nebulization (p = 0.005) without any significant change in RR or SpO2. In eight of 15 patients, dyspnea was improved as measured by a decrease in VAS of more than 10%. This correlated with the desire of the patients to continue its use. CONCLUSION: Our preliminary data confirmed the feasibility of nebulized morphine and suggested its possible clinical benefit for dyspneic patients. A randomized controlled study is warranted to exclude a placebo effect and to compare the clinical benefits of nebulized morphine with those of other methods of treatment.

Adult↗
PubMed1999

Epidemiology of altered intestinal permeability to lactulose and mannitol in Guatemalan infants.

BACKGROUND: Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low-income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition. METHODS: Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5-hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas-liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations. RESULTS: The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non-breast-feeding. Children with serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01). CONCLUSION: Age, feeding practices, low weight-for-age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.

Aging↗