Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 73 records · Page 4Linked to original sources

PubMed2001

Potential role of the anterior spinal artery in preventing propagation of thrombus in a therapeutically occluded vertebral artery: angiographic studies before and after endovascular treatment.

Therapeutic occlusion of the vertebral artery (VA) is one of the treatments for unclippable aneurysms and other lesions, although controversy still surrounds the appropriate site for occlusion to attain selective thrombosis of the lesion while avoiding ischaemic complications. The lower two-thirds of the lateral medulla are supplied by perforating branches of both the VA and the posterior inferior cerebellar artery (PICA). However, in patients without a PICA or in whom the origin of the PICA is low (at or below the foramen magnum), the VA is usually the only source of perforating vessels. We retrospectively studied the results of VA occlusion on such anatomically high-risk patients, and propose a safer procedure. Five high-risk patients underwent therapeutic occlusion of the VA for dissecting aneurysms or arteriovenous fistula. A lateral medullary syndrome developed due to propagation of thrombus after the procedure in two patients in whom angiography did not demonstrate the anterior spinal artery (ASA) within the stump of the VA. Ischaemic signs did not develop in the other three patients, in whom the ASA was visible, and retrograde flow was observed proximal to the origin of the ASA. This suggests that the ASA may play a role in preventing propagation of thrombus in the VA distal to the site of occlusion and supply blood to its perforating arteries in high-risk patients. Angiographic assessment of the ASA may be useful for predicting the likelihood of the lateral medullary syndrome developing with therapeutic occlusion of the VA in patients without a PICA or with one whose origin is low.

Adult↗

PubMed2001

Green fluorescent protein-transgenic rat: a tool for organ transplantation research.

The purpose of this study is to evaluate green fluorescent protein (GFP) transgenic rats for use as a tool for organ transplantation research. The GFP gene construct was designed to express ubiquitously. By flow cytometry, the cells obtained from the bone marrow, spleen, and peripheral blood of the GFP transgenic rats consisted of 77, 91, and 75% GFP-positive cells, respectively. To examine cell migration of GFP-positive cells after organ transplantation, pancreas graft with or without spleen transplantation, heart graft with or without lung transplantation, auxiliary liver and small bowel transplantation were also performed from GFP transgenic rat to LEW (RT1(1)) rats under a 2-week course of 0.64 mg/kg tacrolimus administration. GFP-positive donor cells were detected in the fully allogenic LEW rats after organ transplantation. These results showed that GFP transgenic rat is a useful tool for organ transplantation research such as cell migration study after organ transplantation without donor cell staining.

Animals↗

PubMed2001

A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice.

Tuberous sclerosis (TS) is characterized by the development of hamartomas in various organs and is caused by a germ-line mutation in either TSC1 or TSC2 tumor suppressor genes. From the symptomatic resemblance among TS patients, involvement of TSC1 and TSC2 products in a common pathway has been suggested. Here, to analyze the function of the Tsc1 product, we established a line of Tsc1 (TSC1 homologue) knockout mouse by gene targeting. Heterozygous Tsc1 mutant (Tsc1(+/-)) mice developed renal and extra-renal tumors such as hepatic hemangiomas. In these tumors, loss of wild-type Tsc1 allele was observed. Homozygous Tsc1 mutants died around embryonic days 10.5-11.5, frequently associated with neural tube unclosure. As a whole, phenotypes of Tsc1 knockout mice resembled those of Tsc2 knockout mice previously reported, suggesting that the presumptive common pathway for Tsc1 and Tsc2 products may also exist in mice. Notably, however, development of renal tumors in Tsc1(+/-) mice was apparently slower than that in Tsc2(+/-) mice. The Tsc1 knockout mouse described here will be a useful model to elucidate the function of Tsc1 and Tsc2 products as well as pathogenesis of TS.

Animals↗

PubMed2001

Association between cadmium concentration in rice and mortality in the Jinzu River basin, Japan.

A follow-up survey on 2101 inhabitants (1566 men, 535 women), who participated in a 1967 health survey and had resided in their present rural community since birth was conducted to determine the influence of environmental cadmium exposure on the mortality of the general population in the Jinzu River basin. The survey was conducted over 6128 days from August 1, 1967 to May 10, 1984. The rural communities were divided into two groups, one with a cadmium concentration in rice of < 0.30 ppm and the other > or = 0.30 ppm. The influence of cadmium concentration in rice on mortality was analyzed using SMRs and a Cox's proportional hazards model. In both sexes, SMRs tended to be greater in the > or = 0.3 ppm group as compared to < 0.3 ppm group. The Cox hazard ratios for males and females in the > or = 0.30 ppm group, to those in the < 0.30 ppm group, were 1.42 and 1.10, respectively (significant in the men). Since the mean cadmium concentration in rice in each rural community was closely related to the development of renal injury, in regions with high cadmium concentrations in rice, the development of renal injury induced by cadmium is believed to be the factor underlying the increased mortality observed.

Adult↗

PubMed2001

Seizure outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy.

OBJECTIVE: To describe the clinical, genetic and MR characteristics of patients with familial mesial temporal lobe epilepsy (MTLE). DESIGN/METHODS: The familial occurrence of MTLE was identified by a systematic search of family history of seizures in patients followed in the authors' epilepsy clinic. All probands and, whenever possible, other affected family members underwent EEG and MR investigations. RESULTS: Twenty-two unrelated families with at least two individuals with MTLE were identified by clinical and EEG findings. Ninety-eight individuals with history of seizures were evaluated. Sixty-eight patients fulfilled the diagnostic criteria for MTLE. MRI was performed in 84 patients, and showed hippocampal atrophy with increased T2 signal in 48 (57%). The distribution of hippocampal atrophy according to the seizure outcome groups was 6 of 13 patients (46%) with seizure remission, 16 of 31 (51%) with good seizure control under medication, and all 16 patients with refractory MTLE. Hippocampal atrophy was found also in patients that did not fulfill the criteria for MTLE: 3 of 10 (30%) patients with febrile seizure alone, 6 of 10 (60%) patients with recurrent generalized tonic-clonic seizures, and 1 of 4 (25%) patients with a single partial seizure. CONCLUSION: Familial MTLE is a clinically heterogeneous syndrome. Hippocampal atrophy was observed in 57% of patients, including those with benign course or seizure remission, indicating that the relationship between hippocampal atrophy and severity of epilepsy might be more complex than previously suspected. In addition, these findings indicate the presence of a strong genetic component determining the development of mesial temporal sclerosis in these families.

Adolescent↗

PubMed2001

Orthotopic intestinal transplantation using the cuff method in rats: a histopathological evaluation of the anastomosis.

Segmental small intestine transplantation (SIT) in rats, using a cuff technique, has achieved a high success rate. However, there have been few reports on the influence of the foreign body reaction to polyethylene cuff on vessel anastomoses and graft after SIT. This study involves the histopathological examination of the site of cuff anastomosis and grafts in the short- and long-term survival of segmental SIT. The data obtained from the suture anastomosis model also served as a control. One week after heterotopic segmental SIT using the cuff technique, orthotopic continuations were carried out in syngeneic combination. Twenty-five of 30 rats surviving >200 days (83.3%) were examined for vessel anastomosis. All arterial anastomoses were patent, but the portovenous anastomoses in 10 grafts (33%) were totally occluded and were associated with the formation of collateral vessels. Histopathological examination demonstrated good patency of the artery and vein anastomotic site in the short term, but granulation, fibrosis, and neovascularization at the anastomosis site surrounding the cuffs in the long-surviving group. However, the grafts appeared to be intact, with normal features of the villi. On the contrary, the site of the sutured anastomosis in the long-survival rats showed no inflammatory reaction. Although a polyethylene cuff caused foreign body reaction, the graft blood supplies were maintained by collateral vessels. Considering the low mortality and high success rate, polyethylene cuff is good for short-term study and an alternative method for long-term SIT experiments.

Anastomosis, Surgical↗

PubMed2001

Simplified method of heterotopic rat heart transplantation using the cuff technique: application to sublethal dose protocol of methotrexate on allograft survival.

Rodent heterotopic heart transplantation (HHT) models have been developed for the study of transplantation immunology. Most of these transplantations are performed by hand-suture techniques, requiring several months of training. We describe a modified technique of rat HHT in the neck, using a cuff method that can be mastered by beginners within a few weeks. Our main modification of the rat HHT in the neck is that the right superior vena cava of the graft is chosen as an outflow duct, while the pulmonary artery has been taken as an effluent drainage in the ordinary HHT models. The aorta of the donor is anastomosed with the carotid artery of the recipient. Donation can be completed within 5 min and vascular connections in the recipient done within 3 min, resulting in a minimum of ischemia time. Using this minimum surgical intervention model, we tested the immunosuppressive effect of a sublethal dose of methotrexate (MTX), which has been widely used in cancer therapy. Our results showed that high doses of MTX severely suppressed the recipient bone marrow, but prolonged heart allografts for more than 365 days after HHT. In conclusion, the new model simplified the rat HHT procedure and made it possible for the beginner of rodent transplantation to master this skill within a few weeks. Using this minimized intervention technique, we found that the high doses of MTX can significantly prolong the survival of fully mismatched DA heart graft in PVG/c recipient.

Animals↗

PubMed2001

Rat auxiliary liver transplantation without portal vein reconstruction: comparison with the portal vein-arterialized model.

Auxiliary liver transplantation (ALT) has been reintroduced in clinical cases recently and is now believed to be a viable alternative to orthotopic liver transplantation. To provide a simple rat ALT model for studying the physiological and immunological aspects of the ALT graft, a new ALT was performed, and the comparison between this new model and the portal arterialized one that was reported by other investigators was carried out. At first, we confirmed that liver could tolerate the deprivation of its portal flow well, using a portosystemic shunted rat model. The new rat ALT model, in which the ALT graft obtained its blood inflow only from the hepatic artery, was then performed. Our results demonstrated that 50% of the hepatic artery-alone ALT graft showed almost normal structure histologically at 1 month after grafting, with bile secretion preserved. By contrast, only 8% 1-month graft survival was noted in the portal arterialized group, and all grafts stopped bile secretion 1 week after operation. In conclusion, with arterial blood supply alone, the ALT graft survived and demonstrated normal bile secretion function for more than 1 month. Portal vein arterialization is not an appropriate way to establish the graft's blood supply if no pressure adjustment measures were taken in advance.

Animals↗

PubMed2001

A retrospective study on the relation between renal dysfunction and cadmium concentration in rice in individual hamlets in the Jinzu River basin, Toyama Prefecture, Japan.

Using as an index of exposure the Cd concentration in rice and as an index of health effect the urinary abnormality rate (proteinuria, glycosuria, and proteinuria with glycosuria) in the most systematic and extensive health screening examination conducted in 1967 and 1968 in the Jinzu River basin, Japan (a total of 13,183 subjects), we investigated whether a dose-response relationship exists between the two indices. For subjects that lived in the same hamlet since birth, with low Cd concentrations in rice it was confirmed that renal dysfunction does not develop unless the length of residence is prolonged, whereas with high Cd concentrations in rice renal dysfunction develops even when the length of residence is short. For subjects that lived in the same hamlet for over 30 years and that were aged over 50 years, the urinary abnormality rate in individual hamlets showed significant increases with increases in the mean Cd concentration in rice, demonstrating that a dose-response relationship existed. The allowable values of Cd concentration in rice were estimated to be in the range of 0.05-0.20 ppm, representing values lower than the 0.4 ppm provisionally adopted by the Japanese government.

Adult↗

PubMed2001

Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes.

OBJECTIVE: Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium has never been reported. The goal of this study is to examine MIF in the myocardium. METHODS AND RESULTS: MIF protein and mRNA levels were assayed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Increased MIF concentrations were detected in the sera of patients with acute myocardial infarction (AMI). In cultured rat cardiac myocytes, significant amounts of MIF were produced in response to hypoxia and hydrogen peroxide (H(2)O(2)), but not to angiotensin II, endothelin-1, interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha). H(2)O(2)-induced MIF production increased in a time- and dose-dependent manner and was completely abolished in the presence of catalase. H(2)O(2) also induced MIF mRNA expression. The H(2)O(2)-induced MIF production was completely inhibited by the protein kinase C (PKC) inhibitor GF109203X, partially inhibited by the tyrosine kinase inhibitor herbimycin A, and uninhibited by calcium chelation or phorbol ester-sensitive PKC down-regulation. This suggests that H(2)O(2)-induced MIF production is mediated by an atypical PKC isoform. DNA microarray analysis revealed that 52 genes were preferentially expressed in response to MIF. Of these, the MIF-induced expression of both glutathione S-transferase (GST) and lipopolysaccharide-induced CXC chemokine (LIX) mRNAs was confirmed using RT-PCR analysis. CONCLUSION: The present results suggest that MIF is expressed by the myocardium in response to redox stress and may play a role in the pathogenesis of myocardial ischemia.

Analysis of Variance↗

PubMed2001

Alcohol consumption and blood pressure in Japanese men.

In a study of Japanese men, a nonlinear association of alcohol consumption and blood pressure was not observed. This cross-sectional study was conducted to clarify the effect of infrequent or light alcohol consumption on blood pressure in normotensive Japanese men. The subjects were 2,179 male workers ranging in age from 40 to 54 years. Drinking habits were represented by three indices: episodic alcohol consumption, frequency of drinking, and monthly alcohol consumption. Seven items were analyzed as covariates: age, body mass index, salt intake, physical activity, and levels of gamma-glutamyl transpeptidase, uric acid, and plasma glucose. The association between drinking habits and blood pressure was evaluated by using analysis of covariance. Both episodic alcohol consumption and frequency of drinking were significantly associated with blood pressure in subjects aged 45 to 54 years. In those aged 40 to 44 years, there was a significant association between frequency of drinking and diastolic blood pressure. Significant associations of monthly alcohol consumption with blood pressure in every age group also were found. In subjects aged 45 to 54 years, linear associations between episodic alcohol consumption, frequency of drinking, monthly alcohol consumption, and adjusted blood pressure were observed. In those aged 40 to 44 years, nonlinear associations of monthly alcohol consumption and frequency of drinking with adjusted blood pressure were observed, and threshold effects of 540 ml of alcohol per month and a frequency of 1 to 12 days per month were found. In conclusion, habitual alcohol consumption increases blood pressure linearly in normotensive workers aged 45 to 54 years, although light consumption does not affect blood pressure in those aged 40 to 44 years.

Adult↗

PubMed2001

High-dose tacrolimus and lengthy survival of the combined rat pancreas/spleen graft in a high-responder combination.

Pancreas grafts do not survive for lengthy periods, especially in a high-responder rat combination. Recent data indicated that a combined spleen/pancreas graft protects against acute graft rejection and induces donor-specific tolerance. In this study, we performed a combination spleen/pancreas transplantation using high-dose tacrolimus in a high-responder rat combination of DA (RT1a) to LEW (RT1) and induced permanent survival in the few recipient rats. In these recipients, there was no difference in the mixed lymphocyte reaction (MLR) of the recipients when compared with that of the naive LEW splenic cells, but MLR inhibition by the serum from the recipients was significantly decreased. We also performed immunoblotting and detected a protein that has an affinity for the anti-DA class antibody. This protein may be an anti-idiotypic antibody and contribute to donor- and tissue-specific tolerance.

Animals↗

PubMed2001

Megastigmane glycosides and an acylated triterpenoid from Eriobotrya japonica.

Two new megastigmane glycosides, eriojaposides A (1) and B (2), and a new acylated triterpenoid (3) were isolated along with nine known compounds from a leaf extract of Eriobotrya japonica. The structures of 1--3 were characterized as (6R,9R)-3-oxo-alpha-ionyl-9-O-beta-xylopyranosyl-(1' '-->6')-beta-glucopyranoside, (6R,9R)-3-oxo-alpha-ionyl-9-O-alpha-rhamnopyranosyl-(1' '-->6')-beta-glucopyranoside, and 3 alpha-trans-feruloyloxy-2 alpha-hydroxyurs-12-en-28-oic acid, respectively, on the basis of spectral and chemical evidence.

Asia↗

PubMed2001

Three types of polymorphisms in exon 14 in porcine Mx1 gene.

Much is known about the antiviral activity of Mx proteins in species such as mouse and human. In the mouse, loss of resistability to influenza virus has been shown to be due to specific polymorphisms in the Mx gene. This gene is therefore an interesting candidate gene for disease resistance in farm animals. The porcine Mx1 gene has already been identified and characterized based on its homology with mouse Mx1; however, until now no evidence of polymorphisms in the porcine gene has been reported. In this study, we have found two new polymorphisms in exon 14 of porcine Mx1 by DNA sequencing and confirmed their presence in different breeds, using polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) with NarI and NaeI restriction enzymes. On the basis of the deduced amino acid sequence, one allele contains a deletion that may result in a frameshift to yield several amino acid substitutions and extension of the carboxyl terminal region of Mx1 protein. The deletion allele, Mx1c, was found to be segregating in Landrace, Berkshire, Duroc, Hampshire, and Yucatan miniature pig. A second point mutation, Mx1b, was detected in Meishan and two Vietnamese native pig breeds. All other breeds tested were fixed for the Mx1a allele that is identical to the sequence reported previously. It will be interesting to determine if the Mx1c deletion is associated with variation in resistance to the myxovirus family in the pig.

Amino Acid Sequence↗

PubMed2001

Gene gun-mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model: successful treatment of oral melanoma and distant skin lesion.

Malignant melanoma involving the oral cavity has a highly metastatic potential. Curative surgery is required to resect extensive oral tissues and often results in dysfunction as well as a severe cosmetic deformity in patients with the disease. An alternative technology for the local and sustained delivery of cytokines for cancer immunotherapy has been shown to induce tumor regression, suppression of metastasis, and development of systemic antitumor immunity. However, local immunization of the oral cavity has not previously been studied. In this study, we examined the efficacy of particle-mediated oral gene transfer on luciferase and green fluorescent protein production. The results showed that these proteins were more significantly expressed in oral mucosa than the skin, stomach, liver, and muscle. Using an established oral melanoma model in hamsters, particle-mediated oral gene gun therapy with interleukin (IL) 12 cDNA was then conducted. The results indicated that direct bombardment of mouse IL-12 cDNA suppressed tumor formation and improved the survival rate. The skin tumor model created by inoculation of melanoma cells was also significantly inhibited by the oral bombardment of IL-12 cDNA coupled with an irradiated melanoma vaccine administrated to the oral mucosa, compared to treatment with a percutaneous vaccine. IL-12 gene gun therapy, combined with an oral mucosal vaccine, induced interferon-gamma mRNA expression in the host spleen for a long time. These results suggest that immunization of oral mucosa may induce systemic antitumor immunity more efficiently than immunization of the skin and that oral mucosa may be one of the most suitable tissues for cancer gene therapy by means of particle-mediated gene transfer.

Animals↗

PubMed2001

Alcohol consumption and blood pressure change: 5-year follow-up study of the association in normotensive workers.

This study endeavours to clarify the effect of alcohol consumption on changes in the blood pressure of Japanese men. The subjects, who were followed from 1990 to 1995, were 2189 male normotensive steelworkers aged from 40 to 54 years in 1990. Drinking habits were represented by two variables: average daily baseline alcohol consumption, and change in alcohol consumption during the observation period, both derived from self-report questionnaires and interviews. Nine other items were analysed as covariates: systolic and diastolic blood pressure, age, body mass index (BMI), salt intake, physical activity, and levels of gamma glutamyl transpeptidase (GTP), uric acid and plasma glucose in 1990. The association between drinking habits and blood pressure was evaluated using ANCOVA. Subjects who had initiated antihypertensive therapy by 1995 were excluded from this dataset. The results of analysis disclosed that both daily alcohol consumption and its change were significantly associated with changes in systolic and diastolic blood pressure during the observation period. J-shaped associations of daily alcohol consumption with adjusted changes in systolic and diastolic blood pressure were found. Positive associations were observed between changes in alcohol consumption and adjusted changes in systolic and diastolic blood pressure. In conclusion, daily alcohol consumption was associated non-linearly with changes in blood pressure and with a threshold effect at 18 ml of ethanol per day in these middle-aged Japanese workers. In addition, increasing alcohol consumption was associated with blood pressure elevation, and decreasing consumption was associated with suppression of blood pressure elevation.

Adult↗

PubMed2001

Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage.

AIMS: To examine diurnal variation in biliary excretion of flomoxef. METHODS: Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. RESULTS: Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. CONCLUSIONS: These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.

Bile↗

PubMed2001

Genetic relationship amongst the major non-coding regions of mitochondrial DNAs in wild boars and several breeds of domesticated pigs.

We completed phylogenetic analysis of the major non-coding region of the mitochondrial DNA (mtDNA) from 159 animals of eight Euro-American and six East Asian domesticated pig breeds and 164 Japanese and five European wild boars. A total of 62 mtDNA haplotypes were detected. Alignment of these regions revealed nucleotide variations (including gaps) at 73 positions, including 58 sites with transition nucleotide substitutions, and two transversion substitutions. Phylogenetic analysis of the sequences could not organize domestic pig breeds into discrete clusters. In addition, many of the haplotypes found in members of diverged clustering groups were found primarily in Euro-American pig breeds, indicating extensive introgression of Asian domestic pigs into European breeds. Furthermore, phylogenetic analysis allocated the DNA sequences of non-coding regions into two different groups, and the deepest branchpoint of this porcine phylogeny corresponded to 86 000-136 000 years before present. This time of divergence would predate the historical period when the pig is thought to have been domesticated from the wild boar.

Animals↗