Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 289 records · Page 16Linked to original sources

PubMed1999

Results of surgical treatment of lung cancer in octogenarians.

The treatment of potentially resectable lung cancer in octogenarians has become a frequent clinical problem, due to the increasing number of elderly people maintaining an active daily life. In the present study, we reviewed the clinical records of patients to evaluate the results of the surgical treatment of lung cancer in octogenarians. From 1992 to 1995, 18 patients aged 80 years or older (octogenarians) with primary lung cancer underwent surgical resections including: three (16.7%) sleeve lobectomies, nine (50.0%) lobectomies, one (5.5%) segmentectomy, and five (27.8%) partial resections. The postoperative complication rate was 50% in octogenarians; however, no fatal complications were observed. The 5-year survival rate was 42.6%, which was similar to that obtained in younger patients. Based on our findings, the surgical treatment of lung cancer can thus be performed in selected octogenarians without increasing either morbidity or mortality, while also obtaining long-term survival.

Adolescent↗

PubMed1999

Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats.

Wistar rats were fed a fish oil-deficient diet through three generations. The young (five-week-old) male rats of the third generation were randomly divided into two groups. Over 10 weeks, one group was perorally administered docosahexaenoic acid dissolved in 5% gum Arabic solution at 300 mg/kg/day; the other group received a similar volume of vehicle alone. Five weeks after starting the administration, the rats were tested for learning ability related to two types of memory, reference memory and working memory, with the partially (four of eight) baited eight-arm radial maze. Reference memory is information that should be retained until the next trial. Working memory is information that disappears in a short time. Entries into unbaited arms and repeated entries into visited arms were defined as reference memory errors and working memory errors, respectively. Docosahexaenoic acid administration over 10 weeks significantly reduced the number of reference memory errors, without affecting the number of working memory errors, and significantly increased the docosahexaenoic acid content and the docosahexaenoic acid/arachidonic acid ratio in both the hippocampus and the cerebral cortex. In addition, the ratio demonstrated a significantly negative correlation with the number of reference memory errors. These results suggest that chronic administration of docosahexaenoic acid is conducive to the improvement of reference memory-related learning ability, and that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus or the cerebral cortex, or both, may be an indicator of learning ability.

Animals↗

PubMed1999

Effect of aging on plasma membrane fluidity of rat aortic endothelial cells.

To assess age-related changes in the physical properties of vascular endothelial cell (EC) plasma membranes, we measured membrane fluidity with 1,6-diphenyl-1,3,5-hexatriene (DPH), 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene, and 10-(1-pyrene)dodecanoic acid, and investigated the parameters affecting membrane fluidity of endothelial cells (ECs) cultured from the thoracic aortas of young (5-week-old) and aged (100-week-old) rats. Plasma membrane fluidity of aged rat ECs was significantly lower than that of young rat ECs, as assessed by increased 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization and by decreased pyrene excimer formation, although 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene did not demonstrate a change in membrane fluidity with aging. Compared with those in young rat ECs, cholesterol concentrations in aged rat ECs were significantly higher, whereas phospholipid concentrations were unchanged; consequently, the cholesterol/phospholipid molar ratio was significantly higher in aged rat ECs. Lipid peroxide levels measured with thiobarbituric acid reactive substances were significantly higher in EC plasma membranes of aged rats. These results indicate that age-related increases in cholesterol and lipid peroxide in vascular EC plasma membranes reduce membrane fluidity.

Aging↗

PubMed1999

Preparation and biological properties of biotinylated PhTX derivatives.

We report the synthesis of several highly functionalized biotinylated philanthotoxin (PhTX) analogues (7, 8, 10, 13-16) designed on the basis of earlier structure-activity relationship studies. Despite the extensive modifications, the binding to nicotinic acetylcholine receptor (nAChR) is in the low micromolar range according to an inhibition assay using 3H-thienylcyclohexyl-piperidine (TCP). A patch clamp functional assay gave comparable results. Compounds exemplified by 16, which consists of a biotinylated ligand linked to a bifunctional photoaffinity probe (BPP), represent a new type of probe which should find use in photo-crosslinking studies of ligand receptor interactions.

Animals↗

PubMed1999

Maitotoxin-induced calcium influx in erythrocyte ghosts and rat glioma C6 cells, and blockade by gangliosides and other membrane lipids.

Maitotoxin (MTX) at 0.3 nM elicited a 10-20-fold increase in the level of Ca(2+) influx in rat glioma C6 cells. At higher doses (3-30 nM), MTX induced marked Ca(2+) influx in human erythrocyte ghosts when monitored with the fluorescent dye Fura-2. Although the ghosts were not as susceptible to MTX as intact erythrocytes or other cell lines, Fura-2 experiments under various conditions suggested that the MTX-induced entry of ions into the ghosts was mediated by a mechanism similar to that reported for cells or tissues. These ghosts are the simplest system known to be sensitive to MTX and thus may be suitable for research on the direct action of MTX. Gangliosides GM1 and GM3, glycosphingolipids which have a sialic acid residue, strongly inhibited MTX-induced Ca(2+) influx in C6 cells, while the inhibitory action by asialo-GM1, which lacks a sialic acid residue, was somewhat weaker. Their inhibitory potencies were in the following order: GM1 (IC(50) approximately 2 microM) > GM3 (IC(50) approximately 5 microM) > asialo-GM1 (IC(50) approximately 20 microM). GM1 (3 microM) completely blocked MTX (30 nM)-induced Ca(2+) influx in human erythrocyte ghosts. When C6 cells were pretreated with tunicamycin, an antibiotic which inhibits N-linked glycosylation, or concanavalin A, a lectin which exhibits a high affinity for cell-surface oligosaccharides, MTX-induced Ca(2+) influx was significantly potentiated. This suggests that removal of oligosaccharides from the cell surface by tunicamycin or capping of sugar chains on plasma membranes by concanavalin A can potentiate the action of MTX.

Animals↗

PubMed1999

A novel cytokine-inducing glycolipid isolated from the lipoteichoic acid fraction of Enterococcus hirae ATCC 9790: a fundamental structure of the hydrophilic part.

Previously, we showed that quantitatively minor several glycolipids totaling only less than 5% of the lipoteichoic acid (LTA) fraction from Enterococcus hirae ATCC 9790 possessed cytokine-inducing activity, whereas the major component (over 90%) did not [Suda et al. (1995) FEMS Immun Med Microbiol 12:97-112]. The major inactive component was shown to have the chemical structure as was proposed for the LTA by Fischer [Hashimoto et al. (1997) J Biochem 121:779-86], suggesting that so-called LTA is not a cytokine-inducing component in the Gram-positive bacteria. In the present paper, the structure of the hydrophilic part of one of the cytokine-inducing glycolipid tentatively named GL4 is elucidated. GL4 was first subjected to hydrolysis with aqueous HF to give a polysaccharide and a mixture of low molecular weight products. The polysaccharide was composed mainly of highly branching mannan as concluded from NMR and MS analyses of its acetolysis products. The low molecular weight products consisted of phosphate and glycerol, suggesting the presence of a poly(glycerophosphate) structure in the original GL4. From these observations, the hydrophilic part of GL4 was shown to consist of mannose-rich polysaccharide and poly(glycerophosphate), the latter being bound to the former by a phosphodiester linkage.

Carbohydrate Sequence↗

PubMed1999

Leukotriene (LT)-receptor antagonist is more effective in asthmatic patients with a low baseline ratio of urinary LTE4 to 2,3-dinor-6-keto-prostaglandin (PG)F1alpha.

BACKGROUND: To test the hypothesis that urinary levels of arachidonic acid metabolites may be a predicting factor of the effects of pranlukast, a selective leukotriene (LT) antagonist, on chronic adult asthma, we investigated the relationship between its clinical efficacy and urinary eicosanoid levels. METHODS: An open, multicenter trial was conducted involving 38 stable moderate and severe asthmatic patients (mean percent predicted FEV1 was 71%). All patients received pranlukast (225 mg twice daily) for 4 weeks after a 2-week run-in period. Urinary levels of LTE4, 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha, and creatinine were measured in 3-h urine collected on day 1 of the treatment. The responder was defined by an improvement of asthma symptom scores and peak expiratory flow rate (PEFR). RESULTS: One patient was excluded because of an adverse effect, nausea. Thirteen out of 37 subjects were responders and 24 were nonresponders. There were no significant differences in patients' backgrounds and urinary arachidonate levels between the two groups. The urinary LTE4 to 2,3-dinor-6-keto-PGF1alpha ratio in the responder was significantly lower (P=0.01) than that in the nonresponder. In all patients, a significant inverse correlation was revealed between the baseline urinary LTE4/2,3-dinor-6-keto-PGF1alpha ratio and the improvement of PEFR in the morning (r=-0.43, P=0.007). CONCLUSIONS: These data suggested that the urinary ratio of LTE4 to 2,3-dinor-6-keto-PGF1alpha might be one of the predictive markers of the clinical efficacy of this LT-receptor antagonist in asthmatic subjects.

Adult↗

PubMed1999

The differential effects of aspirin on platelets, leucocytes and vascular endothelium in an in vivo model of thrombus formation.

Unanswered questions remain with regard to the therapeutic use of aspirin and the selective inhibition of thromboxane A2 and prostacyclin in platelets and endothelial cells. In the present study, the effects of aspirin on platelets and endothelial cells in vivo were examined using a helium-neon (He-Ne) laser-induced thrombosis model. Single intravenous injections of aspirin at concentrations of more than 0.5 mg/kg body weight mediated a dose dependent inhibition of thrombus formation in arterioles but not in venules. This antithrombotic effect was optimum after 15 min and declined after 90 min. Potent antithrombotic activity in arterioles was manifest at doses of 2.5 mg/kg to 50 mg/kg, and initial inhibition of thrombogenesis in vivo was most pronounced at high doses. Oral aspirin also inhibited thrombus formation in arterioles but not in venules, although the antithrombotic effects were delayed and prolonged. Maximum inhibition of ex vivo, collagen induced platelet aggregation by aspirin was observed approximately 180 min after intravenous injection. The results demonstrated that, although aspirin might have differential effects on platelets and endothelial cells, potent antithrombotic activity was manifest in arterioles at all concentrations. The findings suggest that the concept of the aspirin dilemma might be ignored for therapeutic purposes in many clinical circumstances. The antithrombotic effects of aspirin were unchanged in granulocyte-depleted animals, indicating that leucocyte-related mechanisms including neutrophil superoxide anion production did not modulate the potency of aspirin in this model.

Animals↗

PubMed1999

Selective effects of lomerizine, a novel diphenylmethylpiperazine Ca2+ channel blocker, on cerebral blood flow in rats and dogs.

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter). 2. Lomerizine (1.25-10 mg/kg, p.o.) dose-dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR). 3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., time at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 x 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks. 4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30-120 min after its administration. 5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose-dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min. 6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in conditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.

Animals↗

PubMed1999

Prevalence of TT virus before and after blood transfusion in patients with chronic liver disease treated surgically for hepatocellular carcinoma.

BACKGROUND: To examine the prevalence of TT virus (TTV) before and after blood transfusion, we retrospectively examined serum samples obtained from 55 patients who received blood transfusions before, during and after resection of hepatocellular carcinoma. METHODS: TT virus DNA was extracted from serum samples and detected by nested polymerase chain reaction. Before transfusion, seven (12.7%) were positive for TTV. Patients were transfused whole blood or separated blood components (fresh frozen plasma, platelet and/or red blood cells), the total amount of transfused fresh frozen plasma ranging from 12 to 271 (median 38) units. RESULTS: Seven (14.6%) of the 48 TTV-negative patients became positive for TTV-DNA 1 month after transfusion. Only one of the seven patients, who was already positive for HCV-RNA, exhibited elevation of alanine aminotransferase. Five of the newly infected seven patients become negative for TTV during a 2 year follow up. CONCLUSIONS: Our findings suggest that the proportion of patients with TTV was relatively high in this sample, and that the prevalence of TTV transmission by blood components was also relatively high (14.6%). Although TTV persisted for more than 6 months in some patients, infection was not noticeable during the course of chronic liver disease.

Carcinoma, Hepatocellular↗

PubMed1999

Antioxidative effects of docosahexaenoic acid in the cerebrum versus cerebellum and brainstem of aged hypercholesterolemic rats.

Female Wistar rats (100 weeks old) were divided into two groups; one group was fed a high-cholesterol diet (HC) and the other a high-cholesterol diet plus docosahexaenoic acid (HC-fed DHA rats). Fatty acid concentrations in brain tissues were analyzed by gas chromatography. In the HC-fed DHA rats, brain catalase (CAT), GSH, and glutathione peroxidase (GPx) increased in the cerebrum but not in the brainstem or cerebellum. The rate of increase was 23.0% for CAT, 24.5% for GSH, and 26.3% for GPx compared with that in the HC animals (p < 0.05). In the cerebrum of the HC-fed DHA rats, CAT and GPx increased, with an increase in the ratio of DHA to arachidonic acid. The cerebrum, unlike the other areas of the brain, seems to be more sensitive to DHA in stimulating CAT and GPx. We suggest that DHA plays an important role in inducing an antioxidative defense against active oxygen by enhancing the cerebral activities of CAT, GPx, and GSH.

Aging↗

PubMed1999

p53 overexpression and mutation in endometrial carcinoma: inverted relation with estrogen and progesterone receptor status.

Overexpression and mutation of p53 in 46 primary endometrial carcinomas were determined comparatively with the status for estrogen receptor (ER) and progesterone receptor (PR). Immunohistochemically p53 overexpression was found in 9 of 46 cases (20%), while eight kinds of mutations in that gene were detected in 7 of 46 endometrial carcinomas (15%), using polymerase chain reaction single-strand conformation polymorphism and subsequently direct sequencing method. Six of nine cases with p53 overexpression showed p53 mutation. All eight mutations showed single substitutions, and three cases in exon 4, one in exon 5, two in exon 6, and two in exon 7 were found. The cases with the p53 overexpression were significantly inversely related to that of ER or PR staining. Most endometrial carcinoma with p53 overexpression and/or mutation had a relatively poor prognosis and showed no reactivities of ER or PR.

Adult↗

PubMed1999

The effect of combination therapy with interferon and cryofiltration on mesangial proliferative glomerulonephritis originating from mixed cryoglobulinemia in chronic hepatitis C virus infection.

Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-alpha injection with corticosteroids. Interferon-alpha was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.

Aged↗

PubMed1999

Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy.

The purpose of this study was to evaluate the role of nitric oxide in the vasodilative effect of dehydroepiandrosterone sulphate (DHEA-S) in term pregnant women. Circulating nitrite, nitrate and oestradiol concentrations were measured on 10 normal full-term pregnant women before (-30 min) and after (10, 30, 60, 90 and 120 min) administration of a 200 mg i.v. dose of DHEA-S dissolved in 20 ml of 5% dextrose (DHEA-S group). Ten normal full-term pregnant women received 20 ml of 5% dextrose as controls (control group). Maternal blood pressure and heart rate were also recorded. The median oestradiol concentration increased significantly after the infusion in DHEA-S group (P < 0.001), whereas there was no significant change in plasma oestradiol in the control group. In the DHEA-S group, plasma circulating nitrate and nitrite increased significantly at 10 and 30 min after DHEA-S administration respectively (P < 0.05). In the control group, there was no change in plasma nitric oxide (NO) metabolites. No change was found in heart rate or mean arterial blood pressure in the control or DHEA-S groups. These results suggest there may be a link between increased NO and increased oestrogen after DHEA-S injection but their peak values did not coincide. Both may be associated with vasodilation in term pregnant women.

Blood Pressure↗

PubMed1999

The hypotensive effect of docosahexaenoic acid is associated with the enhanced release of ATP from the caudal artery of aged rats.

Fish oils have been shown to lower blood pressure in hypertensive subjects. To determine the mechanism of this hypotensive effect, we examined the effects of docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP, AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats (100 wk) were fed a high cholesterol diet and were administered intragastrically ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA group) or vehicle alone (control group). Compared with the controls, rats supplemented with DHA had significantly greater (10.1%) DHA concentrations in the caudal arteries. This was associated with more total (n-3) arterial fatty acids, a greater unsaturation index of arterial fatty acids, 43.9% lower plasma noradrenaline levels and the repression of the elevation in blood pressure observed with advancing age. The amount of purines released, both spontaneously and in response to noradrenaline, from arterial segments of DHA-supplemented rats was significantly higher than that released from tissues of control rats. Regression analysis revealed significant negative relationships between the total amount of purines released from the artery and the systolic (SBP) and diastolic (DBP) blood pressures. These results suggest that in aged rats, supplementation with DHA alters the membrane fatty acid composition as well as the amount of ATP released from vascular endothelial cells and decreases plasma noradrenaline, and that these factors may ameliorate the rise in blood pressure normally associated with advancing age.

Adenosine Triphosphate↗

PubMed1999

Renal-protective effect of non-depressor dose of cicletanine in streptozotocin diabetic rats.

OBJECTIVE: To assess the renal benefits of cicletanine (CIC) in diabetic rats with renal impairment. METHODS: Hemi-nephrectomized streptozotocin-diabetic Wistar-Kyoto Izmo rats (WKYIzm) (10 weeks old) were randomly assigned to receive vehicle or a low or high dose of CIC (30 or 100 mg/kg per day, orally) for 12 weeks. RESULTS: The blood pressure was raised slightly but not significantly in this model. An anti-hypertensive effect of CIC was not significantly observed. However, the sub-depressor doses of CIC significantly and dose-dependently decreased urinary albumin excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. CIC treatment significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. CIC did not affect urinary and blood glucose concentrations at either dose. CONCLUSIONS: These results suggest that CIC has a renal-protective action, which is not related to improvement of diabetes or of high blood pressure in this model. The action might be due to the reduction of intraglomerular capillary pressure, although the mechanism remains to be further investigated.

Animals↗

PubMed1999

Susceptibility of TT virus to interferon therapy.

TT virus (TTV) is a newly identified single-stranded DNA virus. We retrospectively analysed serum samples from sixteen patients, infected with both hepatitis C virus (HCV) and TTV, and who had been treated with interferon. An elevated serum alanine aminotransferase level after interferon was associated with persistence of HCV (abnormal in five of seven patients with persistence of HCV compared with normal in all nine patients who showed eradication of HCV) irrespective of persistence of TTV. Comparison of partial viral DNA nucleotide sequences and phylogenetic analysis showed that viral strains that had a high identity to the prototype virus were more resistant to interferon than those showing low nucleotide sequence identity. Although we observed no liver cell injury caused by persistent TTV infection, the mechanism(s) of TTV resistance to interferon should be further investigated for a better understanding of viral diseases and establishment of therapy.

Alanine Transaminase↗

PubMed1999

Organization of the canine calicivirus genome from the RNA polymerase gene to the poly(A) tail.

In recent years a wealth of data has become available about the caliciviruses that infect humans, as well as those which infect a range of animal species, notably cats, rabbits, pigs and marine animals. However, in the two decades since the earliest reports of calicivirus infection in dogs, very little has become known about the epidemiology, pathogenicity and molecular biology of the caliciviruses that may infect canines. In 1990, a canine calicivirus (CaCV) was isolated from a 2-month-old diarrhoeic domestic dog in Japan. This virus, which can be grown in cultured cells of canine origin, has the classic 'Star of David' morphology of caliciviruses, and the one major structural protein was shown to be immunogenic in dogs. In this study, a 3.8 kb region of the genome of this CaCV isolate from the RNA polymerase gene to the 3' poly(A) tail was cloned and sequenced, and phylogenetic analysis was undertaken in order to establish the relationship of CaCV to other animal and human caliciviruses. This CaCV isolate had a nucleotide sequence, genomic organization and phylogenetic position closest to, but clearly distinct from, both feline calicivirus and San Miguel sea lion virus isolates. These findings suggest that CaCV represents a new clade of animal caliciviruses, presumably as a member of the recently proposed new genus Vesivirus.

Animals↗