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Biomedical subjects

K Kawano

Publications and source records attributed to K Kawano.

At least 235 records · Page 13Linked to original sources

Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen.

Previous studies have indicated that corticostriatal glutamatergic pathways are implicated in the regulation of neuroleptic catalepsy. To obtain a better understanding of the way in which dopamine (DA) and glutamate interact within the caudate-putamen (CP) in the development of catalepsy, we investigated the regional distribution within the rat CP of the cataleptogenic effect of haloperidol and its antagonism by D(-)-2-amino-5-phosphonopentanoic acid (D(-)AP5), a selective antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. Bilateral injections of haloperidol (3 micrograms/side) into the rostral ventromedial (VM) CP induced potent catalepsy with a short latency after the injection. In contrast, only a weak cataleptic response, of slower onset, was observed after haloperidol injections into the rostral ventrolateral (VL), rostral dorsomedial (DM), or rostral dorsolateral (DL) CP, or into the nucleus accumbens. D(-)AP5 (5 micrograms/side) injected bilaterally into the dorsorostral CP (DM and DL) strongly inhibited the catalepsy induced by systemic haloperidol (1 mg/kg, i.p.), and this effect lasted longer when the drug was injected into the DM than when it was injected into the DL. D(-)AP5 did not affect haloperidol-induced catalepsy when injected into the ventrorostral (VM and VL) or intermediate dorsal CP. D(-)AP5 injected into the DM, the region most sensitive to the anticataleptic effect of the drug, had no effect on basal levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, or on the modification of these levels by haloperidol in either the DM or VM. These findings suggest that, while the catalepsy resulting from DA receptor blockade by haloperidol originates mainly from the VM, the expression of this phenomenon depends on an intact glutamatergic transmission within the dorsorostral CP. In the development of neuroleptic catalepsy, the mesencephalostriatal DAergic and corticostriatal glutamatergic pathways seem to be functionally linked through an indirect, rather than a direct, interaction.

2-Amino-5-phosphonovalerate↗

Unusual generation of hydroxyl radicals in hepatic copper-metallothionein of LEC (Long-Evans cinnamon) rats in the presence of hydrogen peroxide.

A mutant strain of LEC rats (Long-Evans rats with a cinnamon-like coat color) develop spontaneous hepatic injury associated with severe jaundice about 4 months after birth. Recently, we obtained evidence which shows an unusual accumulation of copper (Cu) in the liver of LEC rats, followed by the finding of copper-metallothionein (Cu-MT) induction. To know the mechanism for the development of hepatitis in LEC rats, in relation to induced Cu-MT, we examined whether the generation of active oxygen species is observed. When the Cu-MT was treated with H2O2, which is formed by dismutation of superoxide anion radicals or NADPH oxidases in living systems, strong ESR signals due to Cu(II) state appeared when measured at 77K. On the same system, ESR signals due to the spin trapped hydroxyl radicals were observed at room temperature when DMPO (5,5-dimethyl-pyrroline-1-oxide) was used as a spin-trapping agent. The present results suggested that Cu-MT of LEC rat has an important pathogenic role by generating hydroxyl radicals, when hydrogen peroxide is produced in cells or tissues.

Animals↗

Structure-function relationships of tachyplesins and their analogues.

Haemocytes of the horseshoe crab (Limulus) contain a new family of arthropodous peptide antibiotics, termed the tachyplesin family. These cationic peptides are composed of 17-18 amino acid residues with a C-terminal arginine alpha-amide. Tachyplesin I takes on a fairly rigid conformation constrained by two disulphide bridges and adopts a conformation consisting of an antiparallel beta-sheet connected by a beta-turn. Isopeptides of tachyplesin I with amino acid replacements, tachyplesins II and III, and polyphemusins I and II have also been found in the haemocytes of the South-East Asian species and Limulus polyphemus. These peptides are present in abundance in the small granules of the haemocytes and inhibit strongly the growth of not only Gram-negative and Gram-positive bacteria but also fungi such as Candida albicans. Tachyplesin exists in the prepro form consisting of 77 residues; this precursor is probably processed by intracellular proteases and an amidation enzyme before incorporation into the small granules of the haemocytes. We examined the mode of action of tachyplesin I on biomembranes, comparing it with that of gramicidin S. Tachyplesin caused an efflux of K+ from Staphylococcus aureus and Escherichia coli cells similar to that caused by gramicidin S. Another antimicrobial substance, anti-LPS factor, has been isolated from haemocytes.

Amino Acid Sequence↗

31P NMR assessment of orthotopic liver rejection in a rat model.

31P NMR spectroscopy was used serially to study rejecting (ACl-->LEW) and nonrejecting (ACl-->ACl) orthotopic liver transplants in rats. Recipients were evaluated on post-transplant days 1, 3, 5, 7, 9, and 11. The relative changes in phosphomonoester (PME), inorganic phosphate (Pi), high-energy phosphates and pH were studied. The earliest significant difference between the rejecting and nonrejecting groups was a decrease in the alpha-NTP peak area on Day 5. This was followed by significant decreases in beta-NTP and pH, and increases in PME and Pi on Day 7. High-resolution 31P NMR spectra of perchloric acid extracts demonstrated the PME increase to be due mainly to elevated phosphoethanolamine. Using the parameter (Pi + PME)/(alpha + beta + gamma-NTP), rejecting livers were distinguished from nonrejecting livers at a moderate stage of rejection.

Animals↗

Detection of the human cytomegalovirus gene in placental chronic villitis by polymerase chain reaction.

Placental chronic villitis was observed in 44 cases (2.12%) of 2,073 histologically examined placentas. Infiltrating lymphocytes in chronic villitis were determined by immunohistochemistry to be predominantly helper/inducer T cells. Detection of the cytomegalovirus (CMV) gene was performed on paraffin-embedded sections by polymerase chain reaction (PCR) using two different primers (CMV immediate early gene and CMV late antigen gp 64). Both CMV immediate early gene and late antigen gp 64 gene were detected in one case. Cytomegalovirus late antigen gp 64 gene was observed in only three cases. Among these four cases, the cytomegalic inclusion body was observed only in a single case with light microscopic examination. In two cases generalized CMV infection was manifested during the early infantile period and the patient died of the disease. The other two cases were asymptomatic. Our data suggest that approximately 9% of the cases of chronic villitis are caused by CMV infection, and most of them are difficult to detect morphologically. Detection of CMV gene by PCR using primers, especially late antigen gp 64 gene, is very useful for assessing the cause of placental chronic villitis.

Antigens, Viral↗

Information representation by Purkinje cells in the cerebellum during ocular following responses.

A quantitative analysis of simple spike activity of Purkinje cells (P-cells) in the cerebellum of awake monkeys suggested their possible contribution in motor control. Simple spike activities of ventral parafloccular P-cells were recorded during short-latency ocular following responses. The relationship between the firing frequency of these P-cells and the simultaneously recorded eye movements during ocular following was analyzed by using a linear time-series regression method. The result suggests that ventral parafloccular P-cells contribute to the dynamic (velocity and acceleration) rather than the static (position) control of eye movements.

Animals↗

OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain.

The characteristic features of OLETF rats are: (1) late onset of hyperglycemia (after 18 weeks of age); (2) a chronic course of disease; (3) mild obesity; (4) clinical onset of diabetes mellitus (DM) mostly in males; (5) hereditary trait: (a) multiple recessive genes are involved in the induction of DM; (b) rat MHC, RT1 has no diabetogenic effect; (c) control strain, LETO appears to share some of diabetogenic genes with OLETF rats; (d) female OLETF rats also carry diabetogenic genes; and (e) one of the diabetogenic genes, designated as odb-1, is transmitted linked with the X-chromosome of OLETF rats, however testosterone is an important factor involved in developing diabetes; (6) the changes of pancreatic islets can be classified into three stages: (1) an early stage (at less than 9 weeks of age) mild lymphocyte infiltration; (2) a hyperplastic stage (10-40 weeks of age); hyperplastic change and fibrosis in or around islets; (3) a final stage (at more than 40 weeks of age) showing atrophy of islets; (7) diabetic nephropathy; (a) diffuse glomerulosclerosis; (b) nodular lesion (thickening of basement membranes, mesangial proliferation, fibrin cap). These clinical and pathologic features of disease in OLETF rats resemble those of human NIDDM.

Animals↗

Usefulness of magnetic resonance imaging for detecting intrasubstance tear and/or degeneration of lateral discoid meniscus.

In order to determine the usefulness of magnetic resonance imaging (MRI) for detection of intrasubstance tears or degeneration of the lateral discoid meniscus, we compared findings obtained with MRI with those of histological examination. Sixty-four symptomatic lateral discoid menisci were studied using MRI before surgical treatment. Of these, 18 (28%) met the criteria that MRI signals did not extend to the surface and that no visible tears were observable at arthroscopy. Findings of intrameniscal regions of high signal intensity and flattening in shape on MR images were found to represent intrasubstance tears or degeneration not detected at arthroscopy. Our findings thus demonstrate that MRI is more sensitive than arthroscopy in the detection of intrasubstance pathologies of the lateral discoid menisci.

Adolescent↗

Lysozyme requires fluctuation of the active site for the manifestation of activity.

Mutations around His15 which lie far away from the active site, stimulated glycol chitin activity of lysozyme at physiological temperature. Del-Arg14His15 lysozyme, a mutant lysozyme whose Arg14 and His15 were deleted together, and has the highest activity among these mutant lysozymes, had a similar binding ability to a trimer of N-acetyl-glucosamine, a substrate analogue, relative to native lysozyme. This suggests that the increased activity was due to an increased kcat in the catalysis reaction. The H-D exchange rate of the N-1 proton in the Trp63 which is located in the active site cleft, was enhanced in the Del-Arg14His15 lysozyme, while 2-D proton NMR analysis revealed no conformational change around Trp63. We conclude that some sort of fluctuation at the active site might be required for the manifestation of activity. This theory is supported by the finding that the Del-Arg14His15 lysozyme showed a shift in temperature dependency of activity to lower temperatures compared with that of native lysozyme.

Acetylglucosamine↗

Comparative study of staphylococcal flora on the skin surface of atopic dermatitis patients and healthy subjects.

Bacterial samples were obtained from the facial and forearm skin of atopic dermatitis (AD) patients and healthy subjects in humid summer weather. Staphylococcus (Staph) species bacteria were selectively sampled by a plate-contact technique using mannitol salt medium-coated film. Staph species were isolated from the film after the number of colonies was counted, and the species were determined by the API-Staph system and coagulase test. Large numbers of S. aureus were isolated in the samples from the facial skin of patients with severe dermatitis, as previously reported. The number of S. aureus colonies in the samples from the forearm skin of the patients was significantly greater than from the healthy subjects; the mean and standard deviation of colony forming units per 10 cm2, expressed as log10 value, were 1.64 +/- 0.96 for patients and 0.02 +/- 0.07 for healthy subjects (p < 0.01). One hundred and seventeen strains were isolated, and their sensitivities to ten antibiotics were tested. Ten of the strains were resistant to some antibiotics; all of these were isolated from patients. Penicillin type antibiotics had weak effects, but cephem type had strong effects. The number of S. aureus colonies isolated in this study was compared with the number isolated during the winter, in our previous study, in order to identify seasonal variations. The only significant seasonal difference was on the forearm skin of the AD patients, which had significantly more S. aureus colonies (p < 0.01) in this study. There were no significant seasonal differences in S. aureus numbers on the facial skin of patients or healthy subjects.

Adolescent↗

Efficacy of prostacyclin analogue (OP-2507) in viable hepatic grafts from pigs with non-beating hearts.

We investigated whether the stable prostacyclin analogue (OP-2507; OP) would ameliorate warm ischemia-related injury of the liver graft under conditions of a nonbeating heart. Thirty-six mongrel pigs were arranged into 3 groups of 6 pairs. Group 1 pigs underwent orthotopic liver transplantation from heart-beating donors (HBD). In group 2, animals received liver grafts from nonheart-beating donors (NHBD), defined as 30 min of cardiac arrest. Group 3 pigs received grafts from NHBD, but the donor had been pretreated with OP by intraportal infusion (2 microg/kg x min for 30 min immediately before the induction of cardiac arrest). The grafts were preserved at 4 degrees C in Euro-Collins solution in which OP was dissolved at 200 microg/l. Five-day survival rates after transplantation improved significantly in OP-treated animals (3/6, for group 3), compared with 0/6 for group 2 (P < 0.05, generalized Wilcoxon test). Five of 6 animals survived more than 5 days in the HBD group (group 1). Although the serum transaminase activities and bile production did not differ in the early phase of recirculation among the groups, there was a significant improvement in the hepatic microcirculatory environment in the surviving groups (groups 1 and 3). Analysis of arterial prostanoid levels showed a substantial suppression of PGE2 release by OP treatment following reperfusion. Our data indicate that a stable prostacyclin analogue can be clinically useful for expanding the donor pool by improving the quality of the liver graft.

Animals↗

Immunodepressants ameliorate normothermic ischemia injury to the rat liver by down-regulating tumor necrosis factor, not by alleviation of lipid peroxidative injury.

Mechanisms by which immunodepressants (Cyclosporine, CsA; FK 506, FK; Azanthioprine, AZA) ameliorate warm ischemic injury of the liver were examined. Female Sprague-Dawley rats were subjected to 60-min of normothermic liver ischemia. Animals were assigned to one of four groups: group I, control with vehicle treatment; groups II, III, and IV, treatment with CsA (10 mg/kg), FK (1 mg/kg), and AZA (1 mg/kg), respectively. The immunosuppressive agents were given per os for 4 consecutive days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activities of tumor necrosis factor-alpha (TNF), plasma levels of phosphatidylcholine hydroperoxide (PCOOH) as a lipid peroxide, and serum alanine aminotransferase (ALT) were investigated in blood samples collected from the suprahepatic vena cava. A 7-day survival period was significantly higher in the immunosuppressed animals. Serum TNF levels were elevated and peaked at 3 h following reperfusion. When, the peak values were compared, the animals given immunodepressants had significantly lower levels of TNF (217.0 +/- 40.6 pg/ml for group I, 67.6 +/- 13.7 for group II, 87.9 +/- 28.3 for group III and 89.1 +/- 19.9 for group IV; Mean +/- SEM). Plasma PCOOH levels were also elevated following reperfusion, but with no statistical difference among the groups. Our data suggest that immunodepressants ameliorate warm ischemia/reperfusion injury through modulation of TNF production and not through a diminution of lipid peroxidative injury.

Alanine Transaminase↗

[A study on wounds caused by cats as basic materials of cat scratch disease].

Between October, 1992 and March, 1993, the incidence of bite or scratch by the cat, was surveyed by questionnaire in 1,619 peoples who were veterinarians, veterinary technicians, students and the general population (male 652, female 967). The wound rate by cat: Veterinarians, veterinary technicians, students of veterinary college, students of veterinary technician school were significantly higher than the general population. Incidence of bite or scratch in the cat owner were significantly higher than the non cat owner, and the incidence of wounds in cat owners was more than 90%. Most injuries for veterinarians were of the occupational nature. Their injuries clearly differed from those of the other groups. In our survey 33 cases were suspected to have CSD; 19 of 102 veterinarians, 4 of 45 veterinary technicians, 2 of 517 students of veterinary college, 1 of 400 students of veterinary technicians, 7 of 555 in the general population. Of the seven cases suspected for CSD among the general population, four were proven to have cat-scratches, suggesting that injuries can be prevented by clipping the cat's nails at home. However, most of the injuries suffered by veterinarians are caused by bites, prevention poses a more serious problem. It is therefore important to educate people in all fields to fully understand sanitation and zoonosis including CSD, and teach them to handle their pets appropriately.

Adolescent↗

Neural activity in cortical area MST of alert monkey during ocular following responses.

1. We studied response properties of neurons in the superior temporal sulcus (STS) of behaving monkeys that discharged during brief, sudden movements of a large-field visual stimulus, eliciting ocular following. Most neurons responded to movements of a large-field visual stimulus with directional selectivity, preferring high stimulus speeds. Neurons were mostly recorded in the medial superior temporal area (MST) (187/250) and the middle temporal area (MT) (57/250). Further response properties were studied in the MST neurons. 2. Response latencies were measured when a large-field random dot pattern was moved in the preferred direction and preferred speed for each neuron. Eighty percent (120/150) of the neurons were activated < 50 ms after the onset of the stimulus motion. In most cases (89%, 134/150), increased firing rates started before the eye movements, with 59% (88/150) starting > 10 ms before the eye movements. 3. The relationship between the latency of neuronal responses and that of eye movements was studied in 59 neurons by changing the stimulus speed systematically (10-160 degrees/s). The latencies of both neuronal and ocular responses decreased as stimulus speed increased. As a result, the time difference between the response latencies for neuronal and ocular responses varied little with changes in stimulus speed. 4. Blurring of the random dot pattern, by interposing a sheet of ground glass, increased the latency of both neuronal responses and eye movements. 5. With the use of a check pattern instead of random dots, both neuronal and ocular responses began to decrease rapidly when the temporal frequency of the visual stimulus exceeded 20 Hz. At 40 Hz the neurons showed a distinctive burst-and-pause firing pattern, and the eye movements showed signs of oscillation. 6. The response properties of the MST neurons during ocular following were similar to those of the dorsolateral pontine nucleus (DLPN) neurons, reported previously. Our results indicate that the MST neurons may provide visual information to the DLPN neurons and may play a role in eliciting ocular following. 7. Responses during smooth-pursuit eye movement were studied in 55 MST neurons. Each of these neurons responded to the moving large-field visual stimulus, which elicited ocular following, and 40 of these neurons were activated during smooth pursuit in the dark. Response latencies during smooth pursuit were long in those neurons having different directional preferences during smooth pursuit and ocular following but were short for those having the same directional preferences during smooth pursuit and ocular following.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Evidence that FK506 alleviates ischemia/reperfusion injury to the rat liver: in vivo demonstration for suppression of TNF-a production in response to endotoxemia.

The mechanism by which FK506 (FK) prevents hepatic injury induced by ischemia/reperfusion was studied. Adult Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were divided into two groups: group I, controls, saline vehicle treatment; group II, FK treatment. FK (1 mg/kg/day, p.o.) was given for 4 consecutive days prior to inducing ischemia. In addition to a survival study, plasma levels of endotoxin and serum activities of tumor necrosis factor-alpha (TNF) and aspartate aminotransferase (AST) were assessed in the blood collected from suprahepatic vena cava. Results showed: (1) FK therapy significantly improved 7-day survival (80.0%) compared with nontreated animals (50.0%, p < 0.05); (2) both TNF and endotoxin were elevated following reperfusion, reaching maximum values at 3 h after reperfusion (217.0 +/- 40.6 and 280.5 +/- 31.4 pg/ml, respectively, in the control; mean +/- SEM), and (3) serum activities of TNF and AST following reperfusion were substantially suppressed with FK treatment, whereas FK did not reduce the rise in endotoxin. These findings suggest that suppression of TNF production in response to endotoxemia might account at least in part for the protective effect of FK against ischemia-induced hepatic injury.

Animals↗

Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers.

BACKGROUND: Alcohol has been reported to be an important factor that modulates the development and prognosis of chronic viral hepatitis; however, little is known about interaction of alcohol intake and chronic hepatitis C. The aim of this study was to examine whether alcohol drinking affects the effectiveness of interferon (IFN) therapy for chronic hepatitis C. METHODS: Thirty-nine patients with chronic hepatitis C were divided into three groups on the basis of the amount of alcohol intake before IFN therapy: group I (n = 15), non-drinkers; group II (n = 14), less than 70 g/day; and group III (n = 10), more than 70 g/day of ethanol intake for at least 10 years. The IFN (total dose, 330 +/- 206 MU) was administered daily for 2 weeks and then intermittently. Drinkers stayed abstinent for at least 1 month before, during, and after IFN therapy. The sustained responder was defined as the patient who showed normal alanine aminotransferase (ALAT) levels continuously for more than 6 months after the therapy. The liver histology (HAI score) and serum hepatitis C virus (HCV) RNA were also examined before and after the therapy. RESULTS: There was no significant difference among the three groups in the level of ALAT before IFN therapy, age, total dose of IFN, and liver histology. The rates of sustained responders in groups I, II, and III were 53.3%, 42.9%, and 0%, respectively, resulting in a significantly lower rate in group III than in groups I (p < 0.01) and II (p < 0.01). The serum HCV-RNA turned negative after the therapy in 58.3%, 20.0%, and 12.5% of groups I, II, and III, respectively, leading to a significantly lower rate of disappearance of HCV-RNA in group III than in group I (p < 0.05). CONCLUSION: The IFN therapy for chronic hepatitis C was less effective in heavy drinkers than in non-drinkers.

Alanine Transaminase↗