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Biomedical subjects

R Hayashi

Publications and source records attributed to R Hayashi.

At least 91 records · Page 5Linked to original sources

Effects of high pressure on lipids and biomembranes for understanding high-pressure-induced biological phenomena.

This review covers high pressure effects on lipids, lipid bilayers, and biochemical observations recently found in the field of high-pressure bioscience and biotechnology including deep-sea microbiology and food science. To explain these phenomena in a unified model, recent studies of physical and chemical properties of artificial membranes and natural membranes are summarized. On the basis of this newly described knowledge, high pressure effects on biochemical events are considered at the molecular level and concluded that high pressure induces decreases in biomembrane fluidity and phase transitions that result in breakage of the membrane, and finally, leads to the destruction of bilayer membrane accompanied by denaturation of membrane-associated proteins.

Animals↗

Glucose transporter 2 concentrations in hyper- and hypothyroid rat livers.

The deterioration of glucose metabolism frequently observed in hyperthyroidism may be due in part to increased gluconeogenesis in the liver and glucose efflux through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a facilitative glucose transporter localized to the liver and pancreas, may play a role in this distorted glucose metabolism. We examined changes in the levels of GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased in hyperthyroid rats and were not decreased in hypothyroid rats compared with euthyroid rats. The same results were obtained with a densitometric assay. These findings suggest that changes in the liver GLUT 2 concentration may contribute to abnormal glucose metabolism in thyroid disorders.

Animals↗

Motor unit discharge pattern in soleus muscles associated with rapid body sway.

Motor unit discharge (MUD) patterns of the soleus muscles associated with rapid forward body sway were studied in relation to displacement of the center of foot pressure (CFP) and to angular changes in the position of the ankle joint. Subjects were instructed to shift the CFP from a relaxed bending posture (N) to a leaning posture half of maximally forward (1/2F) by swaying their bodies, pivoting at the ankles as rapidly and accurately as possible following an auditory signal. Ten motor units recorded from 5 subjects were studied. During body sway accompanied by elongation of the soleus muscle, a stereotyped serial motor unit discharge pattern was observed: cessation of unit discharge (acceleration phase), and then resumption of unit discharge (deceleration and stop phase). The rate of MUD during the deceleration and stop phase was higher than that when subjects held their bodies during holding his body at N or 1/2F. A strong positive correlation was observed between the timing of the resumption of MUD and both the CFP changes and the angular changes in the position of the ankle joint. These results strongly suggest that peripheral inputs are important for control of both the timing of the resumption and the frequency of MUD in the performance of a rapid body sway.

Adult↗

[Antiangiogenic and antitumor effect of BPHA, an orally-active matrix metalloproteinase inhibitor, in in vivo murine and human tumor model].

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.

Animals↗

Rotatory motion of a cemented acetabular component caused by aseptic loosening and dissociation of the polyethylene liner: a case report.

A 63-year-old woman without rheumatoid arthritis who had undergone cemented total hip arthroplasty developed coxalgia 1 year later. Radiography showed a clear zone at the cement-implant interface and rotatory motion of the acetabular component, so revision surgery was performed 4.5 years after the first operation. Aseptic loosening was noted and 7 spacers outside the acetabular component were broken and buried under the cement mantle. We consider that the rotatory motion may be caused by circumferential loosening of the acetabular component stemming from incomplete implant fixation and also dissociation of the ultra-high-molecular weight polyethylene (UHMWPE) liner from the metal base plate.

Acetabulum↗

The central role of CD4(+) T cells in the antitumor immune response.

The induction of optimal systemic antitumor immunity involves the priming of both CD4(+) and CD8(+) T cells specific for tumor-associated antigens. The role of CD4(+) T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8(+) cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4(+) T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4(+) T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.

Animals↗

Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats.

Sorbitol accumulation plays an important role in diabetic complications involving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the effects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic hyperthyroid (thyroxine-injected) rats (DM+HT). The sorbitol (Sor) concentrations in the kidney, liver and sciatic nerve (2.53+/-0.74, 0.97+/-0.16 and 24.0+/-5.1 nmol/mg protein, respectively) of the DM rats were significantly higher than those (1.48+/-0.31, 0.58+/-0.13 and 3. 1+/-0.6 nmol/mg protein) of the control rats. The Sor concentrations in the kidney and sciatic nerve of the DM+HT rats (1.26+/-0.29 and 9. 40+/-1.2 nmol/mg protein) were significantly lower than those in the DM rats. These values were reduced in the liver, unchanged in the kidney, and increased in the sciatic nerve from the hyperthyroid rats without diabetes. Thyroid hormone reduced the aldose reductase (AR) activities in the kidney, liver and sciatic nerve of the DM rats, and similarly reduced AR in the kidney and liver, but not in the sciatic nerve, of the non-diabetic rats. The sorbitol dehydrogenase (SDH) activities were decreased by thyroid hormone in the kidney and liver but not the sciatic nerve of DM rats. In the non-diabetic rats, this enzyme activity was decreased in liver, but not in kidney or sciatic nerve. A positive correlation between the Sor concentration and AR activity was observed in the kidney and liver but not in the sciatic nerve from control, DM and DM+HT rats. A negative correlation was observed between the Sor concentration and SDH activities in the same organs. These data suggest that thyroid hormone affects the sorbitol pathway, but the detailed mechanism whereby this hormone reduces the sorbitol content (especially in diabetic rats) remains to be clarified.

Aldehyde Reductase↗

A physical map of Arabidopsis thaliana chromosome 3 represented by two contigs of CIC YAC, P1, TAC and BAC clones.

We have constructed a physical map of Arabidopsis thaliana chromosome 3 by ordering the clones from CIC YAC, P1, TAC and BAC libraries using the sequences of a variety of genetic and EST markers and terminal sequences of clones. The markers used were 112 DNA markers, 145 YAC end sequences, and 156 end sequences of P1, TAC and BAC clones. The entire genome of chromosome 3, except for the centromeric and telomeric regions, was covered by two large contigs, 13.6 Mb and 9.2 Mb long. This physical map will facilitate map-based cloning experiments as well as genome sequencing of chromosome 3. The map and end sequence information are available on the KAOS (Kazusa Arabidopsis data Opening Site) web site at http://www.kazusa.or.jp/arabi/.

Arabidopsis↗

Transglutaminase activity in serum and cerebrospinal fluid in sporadic amyotrophic lateral sclerosis: a possible use as an indicator of extent of the motor neuron loss.

The activity of transglutaminase (TGase), a marker enzyme for tissue degeneration, was examined in serum and cerebrospinal fluid (CSF) obtained from patients with sporadic amyotrophic lateral sclerosis (SALS), and compared to those from patients without SALS. When the serum TGase activity values from SALS patients were compared against the 'ALS-scale', which is used for clinical evaluation of the progression of ALS, the TGase activity values were higher at the initial stage of the disease than in non-ALS subjects, whereas they became extremely low at the late stage of ALS. The TGase activity in the CSF taken at later than middle stage from ALS patients with definite clinical motor dysfunctions was significantly lower than in that from non-ALS subjects. We have previously demonstrated marked reduction of tissue TGase activity in all regions of spinal cord tissue transections from ALS patients, not only in ventral but also lateral and dorsal regions, relative to that in non-ALS patients. These results suggest that some TGase may be leaked out of the spinal cord tissue into the CSF and then into the blood-stream during the progression of ALS, and the enzymic activity finally becomes depleted at the terminal stages of the disease when most of the spinal motor neuronal perikarya have been destroyed.

Aged↗

Influence of diabetes during pregnancy on gestational age-specific newborn weight among US black and US white infants.

This study examined the impact of maternal diabetes on birth weight for gestational age patterns of all term black infants and white infants in the United States using data derived from the 1990-1991 US Live Birth File of the National Center for Health Statistics. Infants of both black mothers and white mothers exhibited the expected fetal overgrowth associated with maternal diabetes. However, the increase in birth weight was much greater in infants of black than white diabetic mothers in comparison with their nondiabetic counterparts, as measured by the discrepancy in birth weight between infants of diabetic and nondiabetic mothers at each gestational week, the incidence of large for gestational age, high birth weight, small for gestational age, and low birth weight. After adjustment for maternal hypertension, prenatal care use, and sociodemographic factors, the disparity in mean birth weight associated with diabetes was 211.67 g in black infants and 115.74 g in white infants. The adjusted odds ratios of birth weight > or = 4,000 g were 2.98 (95% confidence interval 2.89-3.12) for black infants and 1.83 (95% confidence interval 1.78-1.89) for white infants. Given the potential risks for mothers and infants consequent to maternal diabetes and fetal hyperinsulinemia, further investigation of the prevalence, characteristics, and outcomes of diabetes during pregnancy among black mothers and infants is warranted.

Adult↗

A new concept and technique for reconstruction of the lower pharyngeal space using the free jejunal graft.

OBJECTIVE: To report on a new concept and simple operative procedure to conform the diameter of the oral end of free jejunal grafts to that of pharyngeal defects for reconstruction of the lower pharyngeal space. DESIGN AND METHODS: A preliminary study showed that the jejunum is supplied by a highly vascular network and that longitudinal paramesenteric incisions can be made without disturbing the blood supply of the jejunum. We then developed the following operative procedure. The position of the highest point of the pharyngeal defect and the site of the recipient vessels are determined. The free jejunal graft is positioned with its mesentery in correspondence with the location of the recipient vessels. The position of a longitudinal incision 180 degrees to the highest point of the defect is then determined. After the oral border of the jejunum is opened with scissors, a pharyngojejunal end-to-end anastomosis is performed. PATIENTS: Eighteen patients with defects of the lower pharyngeal space after cancer treatment. RESULTS: We transferred jejunal grafts in 18 patients using this operative procedure. In 7 of these patients, paramesenteric incisions were made. The lengths of the incisions ranged from 2 to 8 cm. Transfer was successful in all 18 patients. Postoperative leakage occurred in 1 patient in whom an antimesenteric incision had been made; however, a fistula did not develop. CONCLUSIONS: Our method allows defects of the lower pharyngeal space to be reconstructed with end-to-end anastomosis of free jejunal grafts regardless of the location of the defect or of recipient vessels. This method is simple and appropriate for correcting large pharyngeal defects.

Adult↗

Reduction of activity, but no decrease in concentration, of erythrocyte Cu,Zn-superoxide dismutase by hyperglycaemia in diabetic patients.

Cu,Zn-superoxide dismutase(SOD) activity in erythrocytes is affected by various diseases, including diabetes mellitus (DM). We investigated changes in the Cu,Zn-SOD activity compared to changes in the Cu,Zn-SOD concentration in erythrocytes obtained from patients with Type 2 (non-insulin-dependent) diabetes mellitus. Cu,Zn-SOD activity in erythrocytes was significantly lower in Type 2 DM patients than in healthy non-diabetic subjects. The activity correlated negatively with HbA1c, but not with other indicators of metabolic control, such as fasting blood glucose or plasma cholesterol or triglyceride. However, there was no statistically significant difference in erythrocyte concentration of Cu,Zn-SOD between diabetic and control samples. Concentration did not correlate with enzymatic activity or HbA1c. These findings indicate that the inactivation of Cu,Zn-SOD activity in erythrocytes of Type 2 DM patients by hyperglycaemia may be slow, because there is a negative correlation between the enzyme activities and HbA1c levels, but not fasting blood glucose levels. This is consistent with glycosylation of the active site of Cu,Zn-SOD, without any effect of hyperglycaemia on the concentration of Cu,Zn-SOD.

Adult↗

Mexiletine in the treatment of spasmodic torticollis.

We studied the clinical efficacy of mexiletine, a derivative oral form of lidocaine, for treatment of spasmodic torticollis. One of the nine subjects of this study was previously reported. Before starting oral mexiletine, normal saline was first injected intravenously as placebo control; lidocaine infusion then followed and clinical evaluation was provided by dystonia rating scale scores, videotape recordings, and surface electromyographic recording. In all patients, lidocaine injection resulted in a decrease of dystonic muscle contractions within 5 minutes and the effect lasted approximately 1 hour. With gradual increase of mexiletine dose, similar clinical improvement was obtained with oral doses ranging from 450-1200 mg/day for more than 6 months. Side effects in six of nine patients included upper gastrointestinal symptoms, dizziness, ataxia, and dysarthria. These were tolerable or medically manageable; only one patient required a small reduction in mexiletine dose. Strong positive correlation was found between serum and cerebrospinal fluid (CSF) mexiletine concentrations with a CSF/serum ratio of 0.6 (r = 0.96, p = 0.0005) suggesting its effective penetrance into the central nervous system. We suggest that oral mexiletine therapy may be a safe and effective treatment for spasmodic torticollis.

Administration, Oral↗

Afferent feedback in the triphasic EMG pattern of leg muscles associated with rapid body sway.

Electromyographic (EMG) patterns of leg muscles associated with rapid body sway were studied in relation to displacement of the center of foot pressure (CFP). Standing subjects were instructed to shift the CFP by swaying their bodies, pivoting at the ankle as rapidly and accurately as possible after an auditory signal. CFP position was designated as N when the subject maintained a relaxed bending posture and as F when a maximally forward-leaning posture was maintained. A serial, stereotyped triphasic EMG pattern was observed in the rapid shift of CFP from N to F: cessation of EMG activity in the gastrocnemius (GC) muscle was followed by a burst in the tibialis anterior (TA) muscle (acceleration phase), and then resumed discharge occurred in the GC muscle with cessation of activity in the TA muscle (deceleration and stop). When the subject shifted the CFP from N to F to different degrees, the duration and amount of EMG activity in the TA muscle during acceleration and the GC muscle in deceleration were proportionate to the amount of CFP displacement associated with forward body sway. To determine the functional roles of sensory inputs from the foot on the triphasic EMG pattern, body sway was studied under the condition of sensory block in the feet induced by ischemia from tourniquets placed bilaterally just above the ankle joints. The triphasic EMG pattern persisted during ischemia. The time of GC cessation and the onset of TA burst at acceleration remained unchanged, but the times of TA cessation and resumption of GC discharge at deceleration were altered during ischemia. Moreover, subjects were unable to stop at F and eventually fell. These results indicate that both amount and duration of EMG activity associated with rapid body sway are functions of the amount of CFP displacement. Somatic sensation from the feet is important for control of burst and cessation timing and duration in leg muscle activity.

Adult↗

Microorganism inactivation using high-pressure generation in sealed vessels under sub-zero temperature.

In order to test the possibility of utilizing high pressure in bioscience and biotechnology, a simple method for high-pressure generation and its use for microbial inactivation have been studied. When a pressure vessel was filled with water, sealed tightly and cooled to sub-zero temperatures, high pressure was generated in the vessel. The pressure generation was 60 MPa at -5 degrees C, 103 MPa at -10 degrees C, and 140 MPa at -15 degrees C, -20 degrees C, and -22 degrees C. The high pressure generated inactivated microorganisms effectively: yeasts (Saccharomyces cerevisiae and Zygosaccharomyces rouxii), bacteria (Lactobacillus brevis and Eschericia coli), and fungi (Aspergillus niger and Aspergillus oryzae) were completely inactivated when stored in sealed vessels -20 degrees C for 24 h. However, Staphylococcus aureus was only partly inactivated under the same conditions. This method opens up a new application of high pressure for storing, transporting, and sterilizing of foods and biological materials.

Bacteria↗

Leukoencephalopathy induced by chemotherapy with tegafur, a 5-fluorouracil derivative.

We report an autopsy case of a 64 year-old Japanese man diagnosed as having leukoencephalopathy caused by tegafur, a 5-fluorouracil derivative, and review seven previous cases, mostly reported in Japan. In the present case, tegafur had been orally administered for the shortest period of 3 weeks in pre- and postoperative cancer chemotherapy. He died 2 years later after having made a slight recovery from a prolonged akinetic mute state. Unlike similar cases previously reported, the degeneration of the white matter was most prominent in the temporal lobes. Histologically, the severely involved white matter showed nearly complete myelin and axonal loss with a proliferation of hypertrophic astrocytes. In the less severely involved areas, such as in the frontal white matter where myelin was relatively well preserved, numerous activated microglial cells and a small number of T lymphocytes were identified immunohistochemically. The cerebral cortex, cerebellum and brain stem were well preserved, which is consistent with the previous reports. Literature review revealed that the histopathological features of the lesions reported in human cases are quite different from those reported in animal experiments.

Antimetabolites, Antineoplastic↗

Neuroleptic malignant syndrome during haloperidol treatment in a cancer patient. A case report.

A case of neuroleptic malignant syndrome (NMS) in a 64-year-old man with cancer of the soft palate is reported. During haloperidol treatment for delirium, the patient showed consciousness disturbance with extrapyramidal signs. With discontinuation of haloperidol and replacement by dantrolene and bromocriptine, the patient recovered completely. Although major tranquilizers are widely used in clinical oncology to manage symptoms, NMS has been rarely reported in cancer patients, presumably because of lack of awareness. Early recognition of NMS and prompt treatment may improve the potentially fatal outcome.

Antipsychotic Agents↗

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves' disease (GD).

We investigated the effect of T cell-dependent B cell activation on the surface expression and release of the soluble forms of CD8 and CD23 by peripheral blood mononuclear cells (PBMC) obtained from patients with GD, versus patients with Hashimoto's thyroiditis, and normal controls. Incubating the PBMC with anti-CD40 MoAbs and IL-4 increased the soluble CD23 levels in cells from all three groups. An increase in the number of CD23+ cells was observed in the PBMC from the patients with GD, but not in PBMC from Hashimoto's thyroiditis or controls. Less soluble CD8 was released from anti-CD40 antibody and IL-4-stimulated PBMC obtained from patients with GD relative to those from the controls. In addition, the number of CD8+ cells was significantly reduced in stimulated PBMC from the GD patients relative to those from controls. Incubation of PBMC with anti-CD40 antibody plus IL-4 did not affect the proportions of CD4+, CD20+, Fas+ CD4+, and Fas+ CD8+ cells. The addition of T3 to cultured PBMC from controls did not reproduce the changes in CD23+ and CD8+ cells noted in the samples froin GD patients. Thus, T cell-dependent B cell activation, mediated by a CD40 pathway, may reduce the number of CD8+ cells, causing exacerbation of GD.

Adult↗