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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 325 records · Page 18Linked to original sources

Plasma and urinary heart-type cytoplasmic fatty acid-binding protein in coronary occlusion and reperfusion induced myocardial injury model.

The leakage of heart-type cytoplasmic fatty acid-binding protein (H-FABPc) from injured myocardial cells has been reported. We have previously proposed that its plasma and urinary levels could be used as an early indicator of myocardial injury and also reflect the severity of myocardial injury. To confirm this hypothesis, the time course of changes of the plasma and urinary H-FABPc was investigated during myocardial injury induced by coronary artery occlusion and reperfusion in dogs. The plasma elimination kinetics and urinary excretion kinetics of H-FABPc were also analysed in dogs which were given a bolus injection of exogenous H-FABPc. The distribution of circulating H-FABPc was determined in mice by whole-body autoradiography using 125I-labelled H-FABPc. In myocardial injury model, plasma and urinary H-FABPc level showed rapid increase after reperfusion. The elimination kinetic study revealed that H-FABPc was mono-exponentially cleared from the circulation. The elimination rate constant (Ke) was 0.0275 +/- 0.0094/min (mean +/- S.D., n = 7) and the disappearance half-time (t1/2) was 27.5 +/- 8.4 min (mean +/- S.D., n = 7). Exogenous H-FABPc appeared in urine soon after administration, with the peak level being at 6.9 +/- 2.0 min (mean +/- S.D., n = 7). Whole-body autoradiography also demonstrated that 125I-H-FABPc accumulated rapidly in the kidneys. This study demonstrated that H-FABPc leaked rapidly from injured myocardium and rapidly appeared in plasma and urine. Infarct size was closely correlated with the calculated H-FABPc release (r = 0.89, r2 = 0.80, P < 0.01, n = 7) and with the amount of the urinary H-FABPc (r = 0.94, r2 = 0.88, P < 0.01, n = 7). These data suggest that measurement of the H-FABPc levels in plasma and urine might be useful for the early detection of myocardial injury and also for the assessment of infarct size.

Animals↗

Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse.

It has been considered that cortical malformation in the brain of the reeler mutant mouse is due to a defect in the process of neuroblast migration during development. We examined the process of Purkinje cell migration in the cerebellar primordium of the reeler mutant immunohistochemically and electron-microscopically, employing a specific marker for Purkinje cells and markers for radial glia. To facilitate the recognition of the homozygote of the reeler mutation (r1) at the embryonic stage, we introduced the chromosome carrying the autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross into the heterozygote of the reeler mutation, which is an autosomal recessive and located on the homologous chromosome. Using this double heterozygous strain (+/rl-Hm/+), the homozygote of rl can be selected from littermates by the normal appearance of the feet. Both the heterozygous rl embryos and non-carriers harbor the Hm locus and show the Hm phenotype as a deformity of the feet that can be recognized from the 15th day of gestation. In the cerebellar primordium of control mice, Purkinje cells migrated radially from the ventricular zone towards the cortex. In contrast, most of the migratory Purkinje cells remained in the intermediate zone, and their migration towards the cortex was obstructed in the cerebellum of the reeler mutant. A disorganized arrangement of both the processes and cell bodies of the radial glia was demonstrated in the cerebellar primordium of the reeler by labeling them with the antibody against tenascin, a neuron-glial adhesion molecule, and the monoclonal antibody 1D11, a marker for immature astroglia. Electron-microscopic observations revealed apposition of the migratory cells to the radially oriented glial processes in the intermediate zone of the control cerebellum. In contrast, the apposition of leading processes of the migratory neuroblasts to disorganized processes of the radial glia was observed in the intermediate zone of the reeler cerebellum. These findings suggest that the obstructed migration and disordered cortical alignment of Purkinje cells in the reeler cerebellum is due to dysgenesis and abnormal development of radial glia, resulting in disturbance of contact guidance in the process of Purkinje cell migration.

Animals↗

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) decrease in diastolic left ventricular function assessed by echocardiography.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are known to be associated with cardiomyopathy. Systolic and diastolic left ventricular functions were assessed by M-mode and Doppler echocardiography in four patients with MELAS and in 14 normal controls. The interventricular septal thickness and left ventricular posterior wall thickness were greater (11.0 +/- 1.6 mm vs. 5.8 +/- 0.7 mm and 11.0 +/- 2.2 mm vs. 5.9 +/- 0.8 mm) in patients with MELAS than in a control group. Parameters of systolic left ventricular functions (ejection fraction, shortening fraction, systolic time intervals, and mean Vcf) and left ventricular dimensions were not significantly different between the two groups. To assess the diastolic function, blood flow velocity across the mitral valve was measured by Doppler echocardiography and various indexes were obtained. In patients with MELAS, the impairment of diastolic left ventricular filling was demonstrated by decrease in the following indexes: peak flow velocity in the early passive filling period (E) (0.76 +/- 0.10 m/s vs. 0.94 +/- 0.09 m/s), integrated velocity for total E (10.2 +/- 1.3 vs. 13.0 +/- 0.9), the ratio of E and late atrial filling integrated velocities (1.72 +/- 0.06 vs. 2.49 +/- 0.29).

Adolescent↗

Expression of tenascin and BDNF during the migration and differentiation of grafted Purkinje and granule cells in the adult rat cerebellum.

It is believed that 'cell-adhesion molecules' and neurotrophic factors play important roles in the host-graft interactions during the reconstruction of injured brain by neural transplantation. In this study, we have examined the expression of such molecules and factors during the migration and differentiation of grafted Purkinje and granule cells in the adult rat cerebellum. Cerebellar primordium at the 14th gestational day (E14) was transplanted into adult rat cerebellum. Purkinje cells which had migrated from the grafted tissue into the host molecular layer were identified immunohistochemically with a specific marker, anti-spot 35 antibody, as well as by labeling them with bromodeoxyuridine (BrdU) during their final mitotic period. In the grafted site, transient expression of a neuron-glia cell adhesion molecule, tenascin, was detected immunohistochemically. This molecule was expressed transiently in the host tissue adjacent to the migratory Purkinje cells, as well as within the grafted tissue. Tenascin was not detected in intact host tissue apart from the grafted tissue. In the light of tenascin expression in the migratory process of Purkinje and granule cells during cerebellar development, the induction of this molecule in the host tissue might be involved in the migration of grafted Purkinje and granule cells. Furthermore, gene expression of brain-derived neurotrophic factor (BDNF) was found by in situ hybridization and the expression of NGF receptor was found immunohistochemically in the areas where grafted Purkinje and granule cells developed. These findings suggest the involvement of the neurotrophic factor in the growth and differentiation of the grafted cerebellar primordium.

Animals↗

Fate and behavior of genetically labeled cerebellar cells after transplantation into mouse cerebellum.

A foreign gene coding the bacterial enzyme, chloramphenicol acetyltransferase (CAT), was introduced into a primary culture of the mouse cerebellar primordium by a retrovirus vector which harbors the neomycin-resistant gene. Following selection of the gene-transferred cells based on neomycin resistance, most of the selected cells expressed the CAT gene product as well as a marker for astrocytes, glial fibrillary acidic protein (GFAP), when examined immunocytochemically. These cells were transplanted into the adult mouse cerebellum, and the surviving cells were examined immunohistochemically by marking them with anti-CAT antibody. The distribution of CAT-immunopositive cells coincided with that of GFAP-immunopositive cells observed in serial sections of grafted sites at 10 days after transplantation. Some of the transplanted CAT-immunopositive cells extended processes and exhibited the morphological appearance of fibrous astrocytes. Migration of the genetically labeled cells into the host molecular layer was also observed and the morphological plasticity of the differentiated primary cells was shown according to the grafted sites. These results indicate that stable marking of cells for grafting can be accomplished by retrovirus-mediated introduction of a foreign gene into the primary culture, and that the fate and behavior of the labeled donor cells can be analyzed immunohistochemically following transplantation into neural tissue.

Animals↗

Differential expression of c-fos mRNA in rat retinal cells: regulation by light/dark cycle.

The distribution and levels of c-fos expression in response to changes in the light/dark cycle were examined in rat retina by in situ hybridization histochemistry. Under a 12 hr light: 12 hr dark cycle (LD 12:12), c-fos mRNA levels in the inner nuclear layer and the ganglion cell layer increased transiently for 30 min immediately following the onset of the light period, whereas in the outer nuclear layer, c-fos mRNA expression was observed throughout the dark period. During a period of extended darkness following the dark period of LD 12:12, c-fos mRNA levels in the outer nuclear layer remained cyclic--low during the day and higher during the night--suggesting an endogenously generated rhythm. Furthermore, since a 30 min pulse of light during the dark period decreased c-fos expression in the outer nuclear layer, whereas a similar pulse of darkness during the light period resulted in an increase, environmental light/dark cues are also suggested to influence c-fos gene expression.

Animals↗

Haemodynamic and neurohumoral changes in spontaneously hypertensive rats with aortocaval fistulae.

1. Our aim was to evaluate the effects of an aortocaval fistula (1 mm) on cardiorenal haemodynamics, cardiac hypertrophy and neurohumoral factors in spontaneously hypertensive rats and to compare the results with those observed in Wistar rats at 2 weeks after fistulae placement. Sham-operated spontaneously hypertensive rats and Wistar rats served as controls. 2. Heart weight was significantly increased in spontaneously hypertensive rats (34%) and in Wistar rats (43%) at 2 weeks after fistula creation. Left ventricular systolic pressure and dp/dtmax. were significantly decreased (both P < 0.01) in spontaneously hypertensive rats with fistulae which had higher left ventricular end-diastolic pressure than Wistar rats with fistulae (P < 0.01). Signs of circulatory congestion (ascites, tachypnoea, prostration) were observed only in the overloaded spontaneously hypertensive rats (45%). Cardiac index was comparably increased in both fistulae groups due to an increase in stroke index, since heart rate was not increased. 3. Fistulae placement decreased renal blood flow and kidney weight, and increased blood urea nitrogen to a greater degree in spontaneously hypertensive rats (all P < 0.05); serum creatinine levels were unaltered. Plasma noradrenaline concentration was increased in spontaneously hypertensive rats with fistulae (P < 0.05), whereas plasma renin activity was not changed. 4. Thus, spontaneously hypertensive rats with fistulae developed overt haemodynamic signs of high-output heart failure with frequent ascites and dyspnoea, whereas most of these findings were milder or absent in Wistar rats. This model provides an opportunity to evaluate the pathophysiological and pharmacological responses in high-output heart failure.

Animals↗

Neurologic abnormalities in two dogs suspected Lyme disease.

A 2-year-old mongrel dog developed neurological signs following tick bite. These included astasia, persistent tonic convulsions and hyper-reflexia. Both serum IgG and IgM antibody titers against Borrelia burgdorferi were positive in enzyme-linked immunosorbent assay (ELISA). The neurological signs subsided after high-dose penicillin and streptomycin treatment. A strain of spirochetes (P427a) was isolated from the midgut of Ixodes persulcatus feeding on the dog. Morphological characteristic, immunological property and protein profile revealed that the isolate was B. burgdorferi. Similarly, a 2-year-old Labrador retriever dog developed neurological signs after tick bite and showed a positive IgG antibody titer against B. burgdorferi. Antibiotic treatment was effective also in this case. These findings suggest that neurological symptoms shown in both dogs were caused by infection with B. burgdorferi.

Animals↗

Effects of renal denervation on pressure-natriuresis in spontaneously hypertensive rats.

To investigate the role of renal sympathetic nerve activity (RSNA) under developing and established hypertension, renal function was studied in chronically renal-denervated and sham-operated male spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY) at 8 (early hypertensive) and 22 (established hypertensive) weeks of age. To further characterize the renal pressure-natriuresis-diuresis relationship in SHR, renal perfusion pressure (RPP) was reduced by aortic constriction to the level seen in age-matched WKY and the same studies were repeated. After denervation, urinary sodium excretion (UNaV), fractional excretion of sodium (FENa) and urine flow (UF) were increased in 8-week-old SHR (p < 0.01). With the exceptions of UNaV and FENa in denervated 8-week-old SHR, renal cortical blood flow, glomerular filtration rate, UF, UNaV and FENa decreased with the reduction of RPP in all of the SHR groups. These results suggest that RSNA significantly influences renal sodium and fluid handling, thus contributing to the shifting of the arterial pressure-renal sodium excretion curve to the right along the pressure axis and/or to an increase in the steepness of the relationship in 8-week-old SHR. There appeared to be a marked difference in renal sodium handling between 8- and 22-week-old SHR.

Animals↗

Hemodynamic and neurohumoral responses to exercise in patients with congestive heart failure.

Hemodynamic and neurohumoral responses to supine bicycle exercise were evaluated in 16 patients with congestive heart failure (New York Heart Association functional class II-III) and in 8 normal controls. We determined cardiac output by the dye-dilution method, and forearm hemodynamics by plethysmography. The patients had lower resting cardiac and stroke indexes (p < 0.05) than the normal controls. During exercise, the increase in the cardiac index due to an increase in heart rate, was less than that in the controls. Resting and exercise systemic vascular resistance indices were higher in the patients (p < 0.05). The patients had lower resting forearm blood flow and higher forearm vascular resistance (p < 0.05), and the increases during exercise were comparable in the 2 groups. However, forearm venous tone and venous pressure increased more in the patients (p < 0.05). Exercise duration was shorter in the patients (p < 0.01). Resting plasma angiotensin II and norepinephrine were similar in the 2 groups, but plasma 6-keto-prostaglandin F1 alpha and atrial natriuretic peptide were higher in the patients. During exercise, all of these neurohumoral parameters rose more in the patients than in the controls (p < 0.05). Thus, the patients exhibited impaired central and peripheral hemodynamics both at rest and during exercise. The excessive exercise responses of all of the neurohumoral factors suggest that both vasoconstrictor and vasodilator systems are activated in heart failure.

6-Ketoprostaglandin F1 alpha↗

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats.

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.

Adrenergic alpha-Antagonists↗

Limited adaptation in chronically hypertrophied hearts from aortic constricted rats: increased inhomogeneity in cross-sectional area of cardiomyocytes and intercapillary distance.

To study the sequential changes of myocardial structure in pressure-overloaded heart, rats were subjected to banding of ascending aorta at 8 weeks of age, and electron-microscopical morphometry was performed at weeks 1, 2, 4, 8, 16, and 24 postoperatively. Not only was the cross-sectional area of cardiomyocyte greater in banded rats but the degree of inhomogeneity increased in correspondence with development of hypertrophy. Intercapillary distance was significantly longer in banded rats than in controls. In banded rats, the distance around larger-than-normal cells (with a cross-sectional area exceeding 600 microns 2) was significantly longer than that around normal-sized cells (with a cross-sectional area under 600 microns 2) at 4, 16, and 24 weeks following surgery. Morphologically, intracellular capillaries were shown to develop; however, single or several necrotic cells were observed in 8- to 16-week banded rats and were attributed to acute ischemia. In 24-week banded rats, advanced interstitial fibrosis as well as collapsed intracellular capillaries were observed.

Acclimatization↗

Anatomical observations on cleavage line patterns of the skin in adult pigs.

In six pigs from 7 months to 3 years of age the cleavage line pattern of the skin was examined in the whole body by a thick metal probe with a sharp conical point. Directionality of the cleavage lines was determined from the relationship of the line of the long axis of each physical structure. The cleavage lines of adult pigs were compared with those of young pigs (Wakuri, 1967). The cleavage lines of the ear, neck, trunk, and free extremities of appendage were quite similar in adult and young pigs. Those of the buccal, interscapular and sacral regions, umbilicus and scrotum showed slight differences. The most noticeable directional variability in cleavage lines appeared in the masticatory region, arms and legs of adult pigs. Cleavage lines were found to be transverse in arrangement in the masticatory region, auricular root, neck, trunk, tail and legs. They showed an annular pattern around the preputial orifice and in the arms and anogenital region.

Animals↗

[Transurethral microwave thermotherapy for benign prostatic hyperplasia].

Transurethral microwave thermotherapy (TUMT) of prostate was administered to 10 patients with bladder outlet obstruction due to benign prostatic hyperplasia. The mean age of the patients was 74.4 years (range 63 to 85). The Prostatron device, which provides microwave heating of the prostate and conductive cooling of the urethra was used, and the prostate was heated with a calculated intraprostatic temperature of 45.5 degrees C for 55 minutes. No anesthesia was required for most of the patients. The clinical effects were evaluated at 4-6 weeks and 3 months after treatment. The symptomatic scores improved in the majority of patients. There was no significant change in prostate volume. The maximum flow rate and average flow rate were increased at 6 weeks and 3 months, but there was no significant change. The only side effects were transient hematuria and short-term obstruction secondary to urethral edema. In comparing TUMT with the transurethral resection of prostate (TUR-P), the maximum flow rate after TUMT was lower than that after TUR-P and the improvement of residual urine after TUMT was lower than that after TUR-P.

Aged↗

[Migration of donor Purkinje cells in the host adult rat cerebellum].

It is considered that cell adhesion molecules play important roles in the host-graft interaction during the reconstruction of the injured nervous system by neural transplantation. In this article, we report the expression of such molecules during the migration and differentiation of donor Purkinje cells in the adult rat cerebellum. Cerebellar primordium at the 14th day of gestation was transplanted into the adult rat cerebellum. Purkinje cells which had migrated from the grafted tissue into the host molecular layer were identified immunohistochemically with anti-spot 35 antibody, a specific marker for Purkinje cells in the cerebellum, as well as by labeling them with bromodeoxyuridine at their final mitotic period. In the grafted site, transient expression of a neuron-glia cell adhesion molecule, tenascin, was detected immunohistochemically. This molecule was expressed in the host tissue adjacent to the migratory Purkinje cells as well as within the donor immature tissue. Tenascin was not detected in the host tissue far distant from the grafted tissue. In considering the expression of tenascin in the migratory process of Purkinje cells during cerebellar development, this molecule induced in the host tissue may be involved in the migration of donor Purkinje cells.

Animals↗