Biomedical subjects

Y Hamada

Publications and source records attributed to Y Hamada.

At least 253 records · Page 14Linked to original sources

PubMed1996

Laparoscopically assisted ileocecal resection for Crohn's disease associated with intestinal stenosis and ileovesical fistula.

We describe a 22-year-old man with Crohn's ileocolitis accompanied by intestinal stenosis and ileovesical fistula in whom laparoscopically-assisted surgery was successfully performed after thorough nutritional therapy. Laparoscopic procedures are characterized by minimal access and minimal invasion, features which can contribute to the early recovery of patients who undergo surgery. It is suggested that laparoscopic (or laparoscopically-assisted) surgery after strict nutritional therapy can be effective in the treatment of patients with Crohn's disease who have intestinal complications.

Adult↗

PubMed1996

A novel microsatellite polymorphism in the human OB gene: a highly polymorphic marker for linkage analysis.

The mouse ob gene and its human homologue OB have recently been cloned. The mutations in the ob gene are known to be associated with extreme obesity. The relationship between the human OB gene and disease, however, is largely unknown due to the lack of suitable markers within or adjacent to the OB gene. To obtain informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the human OB gene and identified a novel tetranucleotide repeat in the 3' flanking region. Fifteen alleles were detected in this marker with a heterozygosity of 0.85 and polymorphism information content of 0.83, indicating a highly informative nature of this marker. Two-point linkage mapping in two Centre Etude Polymorphisme Humaine (CEPH) reference families suggested that this marker is located in the interval between D7S514 and D7S530, the same interval where the OB gene is located (recombination fractions with D7S514 and D7S530 were 0.026 and 0.034, respectively). Although allele frequency distributions of this marker did not differ between 84 control subjects and 69 NIDDM patients, there was a tendency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 +/- 11.1 vs 60.8 +/- 10.3 kg, p = 0.05). The highly polymorphic nature of this marker and its location in the OB gene makes this marker useful for linkage studies of the OB gene with a number of phenotypes, such as obesity, non-insulin-dependent diabetes mellitus, hypertension and the insulin resistance syndrome.

Alleles↗

PubMed1996

Inducible nitric oxide synthase in uterine smooth muscle.

The expression of inducible nitric oxide synthase (iNOS) mRNA in rat uterus upon in vivo stimulation with lipopolysaccharide (LPS) was studied by reverse transcription and polymerase chain reaction. The injection of LPS induced an increase in mRNA levels of a macrophage-type iNOS. In unstimulated rats, low levels of iNOS mRNA was detected in the uterus and lungs, but absent or negligible in the kidneys and liver. NO was produced in the LPS-treated uterus by addition of 1 to 1000 microM L-arginine. The production of NO in uterine tissue that faces the outside of the body may provide a bacteriocidal protective function against microorganisms in physiological condition. However, NO produced in a large amounts by cytokine and LPS may play some pathological reaction during septic shock or infection.

Animals↗

PubMed1996

Roles of nitric oxide in compression injury of rat spinal cord.

Nitric oxide (NO) was measured directly after spinal cord injury (SCI) in rats by an ESR spin-trapping technique using Fe2+ and diethyldithiocarbamate (DETC). The levels of NO and lipid peroxides expressed as thiobarbituric acid reactive substances (TBARS) were increased by SCI in the injured region and the adjacent central region. Pretreatment with 30 mg/kg of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO synthase, accelerated increases of the TBARS level and myeloperoxidase (MPO) activity in the injured tissue and caused deterioration of hind limb motor function after SCI, suggesting that NO formation by constitutive NO synthase (c-NOS) has a protective effect against cellular damage resulting from ischemia-reperfusion after SCI. Though c-NOS mRNA expression was not altered after SCI, inducible NO synthase (i-NOS) mRNA expression increased to a maximum of 24 h after SCI with progress of motor dysfunction. Intravenous injection of L-NAME (0.1 mg/kg) 6, 24, 48, and 72 h after SCI reduced the motor disturbance. These results indicate that NO induced by i-NOS may be neurotoxic in the subacute phase after SCI.

Animals↗

PubMed1996

Sensory response properties of cortical neurons in the anterior ectosylvian sulcus of cats: intracellular recording and labeling.

Visual and auditory sensory responses of cortical neurons in the caudal half of the anterior ectosylvian sulcus (AES) of cats were examined under alpha-chloralose anesthesia, using intracellular recording and labeling techniques. Stable intracellular recordings were obtained from 155 neurons, and 141 neurons exhibited responses to sensory stimuli. Of 141 sensory neurons, 74 (52%) were bimodal neurons that responded to both visual and auditory stimuli, and 67 (48%) were unimodal showing sensory responses only to visual (25) or auditory stimulation (42). Forty-five neurons (35 pyramidal neurons, 5 non-pyramidal neurons, 5 not classified) responsive to sensory stimuli were labeled with biocytin. The percentage of bimodal neurons of the biocytin-labeled neurons was 40% (4/10) in layer II, 50% (10/20) in layer III-IV, 70% (7/10) in layer V and 60% (3/5) in layer VI. Thus the convergence of visual and auditory inputs on single neurons was most intense in layer V. Auditory response latencies were in a narrow range from 10 to 40 ms, whereas visual response latencies were in a wide range from 15 to 100 ms. Late visual responses (> 60 ms) were more commonly elicited in biomodal neurons than in visual unimodal neurons. Visual responses in layer II were all elicited over 40 ms, whereas early visual responses within 40 ms were observed in the other cortical layers. A subgroup of neurons (22/141) had a propensity to exhibit a burst discharge, a train of three to seven action potentials on a depolarizing envelope in response to sensory stimuli. Their specific distribution in cortical tissue was suggested by the result that six out of nine biocytin-labeled neurons (seven pyramidal neurons, two non-pyramidal neurons) showing burst discharges to sensory stimuli were observed in layer V. These results are considered to signify some aspects of intracortical organization related to the cross-modal integration of sensory inputs.

Animals↗

PubMed1996

Effect of a novel hypoglycemic agent, KAD-1229 on glucose metabolism and fructose-2,6-bisphosphate content in isolated hepatocytes of normal rats.

The effects of a novel hypoglycemic agent, calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate dihydrate (KAD-1229), which is a benzyl succinate derivative, on liver metabolism were investigated using isolated hepatocytes from normal rats. In the presence of 10 mM glucose, KAD-1229 increased the L-lactate production (41.1 +/- 0.9 versus 60.9 +/- 2.6 mumol of lactate/g of cells/30 min; P < 0.05) and inhibited gluconeogenesis in hepatocytes (0.94 +/- 0.02 versus 0.70 +/- 0.03 mumol of [2-14C]-pyruvate converted to glucose/g of cells/20 min; P < 0.05). These effects by KAD-1229 were accompanied by an increase in the cellular content of fructose-2,6-bisphosphate (F-2,6-P2), which is one of the important regulators of hepatic glucose metabolism, in a dose-dependent manner (0.05-2.5 mM). KAD-1229 also stimulated the oxidation of [2-14C]-pyruvate and [6-14C]-glucose in the tricarboxylic acid cycle (+18 and +31%, respectively), indicating that stimulation of tricarboxylic acid cycle activity and/or enhancement of the glycolytic flux rate had occurred. Moreover, KAD-1229 did not modify the activities of 6-phosphofructo 2-kinase or fructose-2,6-bisphosphatase, but increased significantly the accumulation of fructose 6-phosphate in hepatocytes. These results suggest that KAD-1229 has extrapancreatic effects on hepatic glucose metabolism, that its actions are mediated through the inhibition of fructose-1,6-bisphosphatase and stimulation of both the 6-phosphofructo 1-kinase reaction and tricarboxylic acid cycle activity by increasing the F-2,6-P2 content in hepatocytes, and that these multiple effects may account in part for the ability of KAD-1229 to reduce blood glucose levels in vivo.

Analysis of Variance↗

PubMed1996

Hemifacial degloving approach to tumours in the infratemporal and pterygopalatine fossae: a preliminary report.

A new approach to tumours in the infratemporal or pterygopalatine fossa is presented. Through a midline skin incision, one side of the face from the forehead to the neck is completely degloved. Zygomatic and mandibular osteotomies improve access. All mimic muscles and the facial nerve are included in the elevated flap. This approach provides a widely exposed field from the temporal fossa to the neck without damage to major vessels or nerves other than the supra- and infraorbital nerves. Direct access to tumours in the infratemporal or pterygopalatine fossa is facilitated, thus making tumour resection easier, safer and more reliable. Details of this approach are described.

Craniotomy↗

PubMed1996

Effect of dietary vitamin C on compression injury of the spinal cord in a rat mutant unable to synthesize ascorbic acid and its correlation with that of vitamin E.

The roles of vitamin C on secondary pathological changes after spinal cord injury were investigated by evaluating the effects of dietary vitamin C on experimental spinal cord injury in a mutant strain of Wistar rats unable to synthesize ascorbic acid (ODS rats). Two groups of ODS rats were given vitamin C-deficient or vitamin C-supplemented diet for 1 week before injury. Motor disturbance induced by spinal cord injury was found to be greater in the vitamin C-deficient group. Histologically, the area of bleeding in the spinal cord was also greater in the vitamin C-deficient group. The levels of ascorbic acid and alpha-tocopherol in the spinal cord tissue and serum decreased during and after compression injury of the spinal cord. The decrease of alpha-tocopherol was similar in the two groups. However, the decrease of ascorbic acid was greater in the vitamin C-supplemented group. These results indicated that their protective effects against spinal cord injury are through scavenging water-soluble free radicals by vitamin C and lipid-soluble by vitamin E, and the effects of these vitamins were suggested to be independent.

Animals↗

PubMed1996

Involvement of an intercellular adhesion molecule 1-dependent pathway in the pathogenesis of secondary changes after spinal cord injury in rats.

The intercellular adhesion molecule 1 (ICAM-1) plays an important role in immune responses by promoting infiltration of neutrophils into tissues; however, its implication in the secondary destructive pathomechanism after the initial mechanical injury to the spinal cord has not been clarified yet. This study was conducted to examine the role of ICAM-1 in this process after spinal cord injury (SCI) in rats. The expression of ICAM-1 mRNA was investigated by the reverse transcription-PCR method and the effect of monoclonal antibody (mAb) to ICAM-1 on SCI was evaluated by measuring various parameters. ICAM-1 mRNA expression correlated with the severity of injury and reached its maximum level 6 h after SCI. Intravenous injection of ICAM-1 mAb (1 mg/kg) 30 min after SCI reduced motor disturbance and enhanced recovery. Moreover, it significantly suppressed myeloperoxidase activity by 43.0% and spinal cord edema by 1.1% in the injured spinal cord tissue. The posttraumatic drop in spinal cord blood flow was also improved. These results suggest that ICAM-1 is deeply involved in the secondary self-destructive process after mechanical injury of the spinal cord and should be an effective target for developing a pharmacological treatment for SCI.

Animals↗

PubMed1996

Effects of lecithinized superoxide dismutase on rat spinal cord injury.

Although superoxide dismutase (SOD) has been reported to promote functional recovery in ischemic spinal cord injury, it presents many difficulties in practical use primarily due to its short half-life in vivo and low tissue affinity. In this study, we investigated the effects of a new type of SOD, a lecithinized superoxide dismutase (PC-SOD), on motor disturbances, spinal cord edema, levels of myeloperoxidase (MPO), and spinal cord blood flow (SCBF) after spinal cord injury (SCI) in rats. PC-SOD is reported to show a delayed plasma disappearance in vivo in rats and has a higher affinity for vascular endothelium cells, neutrophils, and other cells than unmodified SOD. PC-SOD (4000 units/kg), unmodified SOD (4000 units/kg), or vehicle was injected intravenously 30 min after SCI. Four hours after SCI, SOD activities in spinal cord tissue and plasma were significantly higher in the PC-SOD group than in the unmodified SOD group. In the PC-SOD-treated rats, motor function was significantly better than in the other 2 groups of rats. PC-SOD significantly suppressed MPO activity, an indicator of neutrophils infiltration, in the spinal cord, at 4, 8, and 24 h after SCI, and spinal cord edema at 24 h after SCI. Moreover, the decrease of SCBF after SCI was less marked in the PC-SOD group. The present results suggest that lecithinization can improve the drug delivery of SOD to the spinal cord and PC-SOD may be an alternative pharmacological treatment for SCI.

Animals↗

PubMed1996

Role of polyol pathway in nonenzymatic glycation.

In order to confirm the link between nonenzymatic glycation and the polyol pathway, we observed the effect of treatment with epalrestat (Ep), an aldose reductase inhibitor, on the concentration of advanced glycation end-products (AGEs) in erythrocytes from diabetic patients. We also examined the effect of the drug on erythrocyte fructose 3-phosphate (F3P), a novel metabolite that has been reported to relate to the polyol pathway, and ascertained the glycation capability of F3P and its possible breakdown product, 3-deoxyglucosone (3DG), by incubating the metabolites with bovine serum albumin (BSA). Incubation of BSA with F3P or 3DG resulted in a greater production of AGEs in comparison with the incubation with glucose or fructose. F3P was significantly increased in erythrocytes from diabetic patients compared with those from nondiabetic individuals and was lower in patients who had been treated with Ep than in those who were free from the compound. A treatment of patients with Ep for 1 month resulted in a significant decrease in F3P. Erythrocyte AGEs were significantly elevated in diabetic patients compared with nondiabetic individuals and tended to be lower in patients taking Ep than in those without Ep. Administration of Ep for 2 months decreased AGEs. These results show that the polyol pathway is likely to play a substantial role in the nonenzymatic glycation of proteins and the suppression of E3P as well as AGEs by an aldose reductase inhibitor may explain in part the preventive effect of the drug on diabetic complications.

Aldehyde Reductase↗

PubMed1996

Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid.

We have previously demonstrated that elemental diet (ED) induces decreased lymphocyte transport in intestinal lymph and significant changes in T cell subsets and the number of IgA-containing cells in gut-associated lymphoid tissues of rats. In order to examine whether the low fat content contributes to the induction of immunological changes in gut-associated lymphoid tissues, the effects of additional fatty acid in the ED were investigated. Rats were divided into four groups: elemental diet alone, elemental diet supplemented with 5% oleic acid (OA), elemental diet with 10% OA and conventional diet as a control. These diets were given at the same daily calorie intake for 4 weeks. The flow rate of intestinal lymph showed no significant difference between the four groups. However, lymphocyte flux as well as the percentage of CD3+ and CD4+ cells were significantly greater in the control and the 10% OA groups than in the ED and 5% OA groups. Intestinal lymph showed decreased concentrations of IgG and IgA in the ED group, whereas the addition of 10% OA significantly attenuated the decrease in these levels. In mesenteric lymph nodes, the CD4+/CD8+ ratio was significantly decreased in the ED group, but 10% OA reversed this change. Immunohistochemical analysis of the ileal mucosa showed that in the ED group the population of CD4+ cells was decreased, while the number of CD8+ cells was increased. Supplementation of OA to ED produced similar stepwise attenuation of the changes in lymphocyte subpopulations in the lamina propria, while the 10% OA group reached levels that were not statistically different from controls. In the elemental diet group, there was a significant decrease in immunoglobulin-containing cells of the IgA class in the lamina propria of the intestine. Similarly, the addition of OA induced dose-dependent recovery in the number of IgA-containing cells. These results suggest that a low dietary concentration of fat may be closely related to changes in lymphocyte transport in intestinal lymph and mucosal immunity of intestinal mucosa induced by the feeding of a long-term ED.

Animals↗

PubMed1996

Advanced glycosylation end-products and heat shock proteins accumulate in the basophilic degeneration of the myocardium and the corpora amylacea of the glia.

Using monospecific antibody for the advanced glycosylation end-products (AGEP), it was revealed that the AGEP localized in the basophilic degeneration of the myocardium and the corpora amylacea of the glia. The stability of the proteins that constitute those degenerative deposits suggests that they would be ideal substrates for non-enzymatic glycation, a process that occurs over a long time under a high glucose content, and ultimately results in the formation of the AGEP. Such deposits also exhibited evidence of stress reactions: the accumulation of HSP72, heme oxygenase-1 and ubiquitin. As recent studies have shown that AGEP-modified proteins aggregate and that they generate reactive oxygen intermediates, the accumulation of such heat shock proteins may reflect the oxidative stress concomitant with AGEP accumulation, and thereby promote their cellular dysfunction. Hereby, it is proposed that the age-related increase in the AGEP, that is, a fundamental aging process, is involved in the formation of the basophilic degeneration in the myocardium and the corpora amylacea of the glia.

Aged↗

PubMed1996

Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment.

The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 +/- 632 ng/ml) and C4a (1088 +/- 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 +/- 1045 ng/ml and 1494 +/- 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 +/- 177 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma beta-thromboglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.

Adult↗

PubMed1996

Optimal transport parameters of the inner medullary collecting duct in interaction between urine concentrating and urea excreting mechanisms: a computer simulation study.

Although the accumulation of urea in the renal medulla is essential for the formation of concentrated urine, it is also necessary for the kidney to excrete considerable amounts of urea into the urine as a waste product of protein degradation. Thus, the urine concentrating capacity is attained by the interaction with the efficiency of urea excretion. To seek the best condition for this phenomenon, we developed an objective function for evaluating urea excreting capacity relative to urine concentrating capacity by using a mathematical model consisting of components of the countercurrent multiplication system: the ascending thin limb, capillary network, and inner medullary collecting duct. The values of the objective functions were calculated as three-dimensional functions of transport parameters for the inner medullary collecting duct, including hydraulic conductivity, urea permeability, and reflection coefficient for urea. The results of the computer analysis revealed that the maximum value of the objective function was attained when values for transport parameters of the inner medullary collecting duct corresponded to those experimentally obtained values reported previously. We conclude that the maximum urine concentrating capacity is limited by the efficiency of urea excreting capacity of the kidney, and vice versa.

Biological Transport↗

PubMed1996

Effects of Actinomyces amphiphile on the fluidity of endothelial cells: a spin label study.

Actinomyces amphiphile (AcA) is an amphipathic molecule produced by Actinomyces viscosus that exhibits several biological activities. The effect of AcA on the fluidity and permeability of the plasma membrane in human umbilical vein endothelial cells was analyzed by a spin label method with 5- and 16-stearic acid nitroxide labels (SAL). These labels help to visualize the fluidity at the shallow (5-SAL) and deep (16-SAL) portions of the lipid bilayer. Cells were incubated with and without AcA (control) at 37 degrees C for 6 hours, and membrane fluidity was periodically measured. Another spin label, 4-(N, N-dimethyl-N-hexadecyl) ammonium-2, 2, 6, 6-tetramethyl-piperidine-1-oxyliodine (CAT-16), was also used to assess the physical state of the cell surface. The order parameter of 5-SAL was significantly lower in the cells incubated with AcA than in control cells after the six-hour incubation. The motion parameter of 16-SAL was significantly lower in AcA-treated cells than in controls after 4 and 6 hours of incubation. These findings indicated that the AcA increased the fluidity. There were no significant differences between the AcA-treated and control cells incubated for only 2 hours. In addition, there were no differences in CAT-16 measurements between AcA-treated and control cells. The release of endoplasmic lactate dehydrogenase (LDH) into the medium tended to increase in the AcA-treated vs. the control cells. LDH release increased in both a dose- and time-dependent manner, indicating that AcA increased the permeability of plasma membranes. These findings suggest that AcA alters the biophysical properties of the plasma membranes of endothelial cells, affecting membrane function.

Actinomyces viscosus↗

PubMed1996

Analysis of candidate genes for insulin resistance in essential hypertension.

To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of beta3 adrenergic receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension.

Case-Control Studies↗

PubMed1996

Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.

6-Ketoprostaglandin F1 alpha↗