[Clinical evaluation of presystolic murmurs and sounds recorded on phonocardiogram].
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Biomedical subjects
Publications and source records attributed to T Kosaka.
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The distribution of Ca2+-binding protein, parvalbumin (PV), containing neurons and their colocalization with glutamic acid decarboxylase (GAD) were studied in the rat hippocampus and dentate gyrus using immunohistochemistry. PV immunoreactive (PV-I) perikarya were concentrated in the granule cell layer and hilus in the dentate gyrus and in the stratum pyramidale and stratum oriens in the CA3 and CA1 regions of the hippocampus. They were rare in the molecular layer of the dentate gyrus, in the stratum radiatum and in the stratum lacunosum-moleculare of the hippocampus. PV-I axon terminals were restricted to the granule cell layer, the stratum pyramidale and the immediately adjoining zones of these layers. Almost all PV-I neurons were also GAD immunoreactive (GAD-I), whereas only about 20% of GAD-I neurons also contained PV. The percentages of GAD-I neurons which were also immunoreactive for PV were dependent on the layer in which they were found; i.e. 40-50% in the stratum pyramidale, 20-30% in the dentate granule cell layer and in the stratum oriens of the CA3 and CA1 regions, 15-20% in the hilus and in the stratum lucidum of CA3 region and only 1-4% in the dentate molecular layer and in the stratum radiatum and the stratum lacunosum-moleculare of the CA3 and CA1 regions. PV-I neurons are a particular subpopulation of GABAergic neurons in the hippocampal formation. Based on their morphology and laminar distribution, they probably include basket cells and axo-axonic cells.
Fast spiking cells in the CA1 region of the rat hippocampus were revealed as gamma-aminobutyric acid (GABA)ergic non-pyramidal cells containing the calcium-binding protein parvalbumin by intracellular injection of Lucifer yellow in vitro in combination with postembedding parvalbumin immunohistochemistry.
The effects of the unilateral olfactory naris closure were studied immunohistochemically in the main olfactory bulb of adult rats. In the olfactory deprived bulbs, the tyrosine hydroxylase-immunoreactive elements in the glomeruli and the juxtaglomerular region decreased drastically, whereas the glutamate decarboxylase-immunoreactive elements in these regions showed no appreciable changes, indicating the differential effects of olfactory deprivation on catecholaminergic and GABAergic traits in spite of their coexistence in some neurons in these regions.
The organization of the GABAergic system in the rat main olfactory bulb was investigated immunohistochemically using antisera against glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), parvalbumin (PV) and methionin-enkephalin-Arg6-Gly7-Leu8 (ENK). Some GABAergic neurons were shown to contain TH immunoreactivity in the glomerular layer, PV immunoreactivity in the external plexiform layer and ENK-like immunoreactivity in the granule cell layer, indicating the stratified organization of the GABAergic subsystems.
The possibility of the colocalization of a Ca2+-binding protein, parvalbumin (PV), with peptides, cholecystokinin (CCK) and somatostatin (SS), all of which are known to be contained gamma-aminobutyric acidergic neurons in the cerebral cortex, was tested in the rat visual cortex by means of immunohistochemistry using the adjacent section technique. No PV immunoreactive (PV-I) neurons showed CCK-like immunoreactivity, and almost none (932 out of 934 PV-I neurons examined) showed SS-like immunoreactivity. These observations suggest that the GABAergic system of the cerebral cortex may consist of some distinct subsystems with different chemical and presumably physiological characteristics.
Postnatal development of catecholaminergic and gamma-aminobutyric acid (GABA)-ergic neurons in the periglomerular region of the rat main olfactory bulb was studied immunohistochemically using antisera against tyrosine hydroxylase (TH), glutamic acid decarboxylase and GABA. TH-like immunoreactive neurons almost always contained GABA-like immunoreactivity in the first postnatal week, but about 10% of them did not contain GABA-like immunoreactivity in older animals.
The coexistence of immunoreactivities for tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD) and/or gamma-aminobutyric acid (GABA) was revealed in various brain regions in colchicine-injected and untreated rats, using the peroxidase-antiperoxidase method. Consecutive 40 micron thick Vibratome sections were incubated in different antisera and those cells which were bisected by the plane of sectioning so as to be included at the paired surfaces of two adjacent sections were identified. The coexistence of the immunoreactivities for TH and GAD or GABA in the same cell could thus be determined by observing the immunoreactivity of the two halves of the cell incubated in two different antisera. In the olfactory bulb, retina, diencephalon, mesencephalic central grey and cerebral cortex, many TH-like immunoreactive neurons also showed GAD-like or GABA-like immunoreactivity, whereas in the substantia nigra, ventral tegmental area and locus ceruleus none of TH-like immunoreactive neurons showed either GAD-like or GABA-like immunoreactivity. In the olfactory bulb, retina and cerebral cortex, the majority of the TH-like immunoreactive neurons were also GAD-like or GABA-like immunoreactive. In the diencephalon of colchicine-injected rats, at least one-third of the TH-like immunoreactive neurons were GAD-like immunoreactive. Using serial 0.5 micron thick plastic-embedded sections, it was shown that immunoreactivities for three antigens, GAD, GABA and TH could occur in the same neurons in the olfactory bulb. These observations indicate the possible coexistence of two classical transmitters. GABA and catecholamine, in various brain regions of the rat.
Using specific antisera against the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in combination with the peroxidase-antiperoxidase method and/or the avidin-biotin complex method, we have found a new group of TH immunoreactive (TH-I) neurons in the rat cerebral cortex. Numerous TH-I cells were observed all over the isocortex, that is, frontal, temporal, parietal and occipital regions, and in some parts of the allocortex such as the anterior cingulate cortex, the retrosplenial cortex and anterior part of the insular cortex. In contrast, they were rare in the perirhinal cortex, posterior part of the insular cortex, piriform cortex, entorhinal cortex and hippocampal formation. TH-I cells were situated throughout all cortical layers, but were most concentrated in layer II/III. Although TH-I cells were heterogeneous in shape, the majority were bipolar. All TH-I cells so far examined appeared to be of the nonpyramidal type. The majority of these intrinsic TH-I neurons also contained the GABA-like immunoreactivity and thus could be regarded as a subpopulation of cortical GABAergic neurons.
The effects of 711389-S (0.1-10 mumol.litre-1) on membrane potentials and currents of rabbit sinoatrial node preparations were studied using a conventional double microelectrode voltage-clamp method. The agent 711389-S decreased the heart rate, the maximum rate of depolarisation, and the amplitude of the action potential and increased the action potential duration in a dose dependent manner. The slope of the diastolic depolarisation was also reduced. Of the current systems of sinoatrial node, 711389-S depressed the slow inward current (Isi), the potassium outward current (IK), and the hyperpolarisation activated current (Ih) dose dependently. The kinetics of IK were not altered significantly by the drug. It is concluded that 711389-S does not have an effect on a single current system but that the drug exerts a depressant effect on the electrical activity of the sinoatrial node.
A simple method is described for evaluating the potencies of catecholamines on the slow response of myocardium. Catecholamines depolarize guinea pig ventricular muscle cells exposed to the high K+ (27 mmol/l) Tyrode's solution containing 0.2 mmol/l Ba through an increase in slow channel conductance. Higher concentrations of catecholamines in addition induce spontaneous action potentials. This model was used to estimate and compare catecholamine potencies on myocardium. Catecholamine concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as basis for comparison. The order of potency obtained by means of this new method was: l-isoproterenol greater than l-adrenaline greater than or equal to dl-noradrenaline greater than or equal to dobutamine greater than or equal to dopamine. This is similar to the order reported with other methods.
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Differences in the secretion of pregnane compounds by ovaries with cystic follicles of rats exposed to constant light (light-induced oestrous rats) and by ovaries with normal follicles of early pro-oestrous rats were studied. Some rats were injected iv with 2 micrograms of LH to stimulate the secretion of steroids 30 min before their blood was sampled. The injection greatly increased the secretion of progesterone by both kinds of ovaries. The secretion of 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one also increased in normal rats, but not in the polycystic ovaries of light-induced oestrous rats, which suggested that the 5 alpha-reductase activity was low. The pre-ovulatory LH surge is absent in light-induced oestrous rats, so a classic approach was taken to circumvent the probable deficit in the cyclic release of LH; we gave multiple injections of 10 micrograms of LH. Five such injections were given at intervals of 4 days, and ovarian venous blood was collected 4 days after the last injection. Cystic follicles in the ovaries of rats disappeared when the injections of LH were given every 4 days. The production of 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one from the ovaries of such rats was significantly higher (P less than 0.01) than in controls given multiple injections of saline. These results suggest that the low 5 alpha-reductase activity in polycystic ovaries of light-induced oestrous rats may be due to the absence of an LH surge from the pituitary gland.
A case of limb-girdle muscular dystrophy with cardiomegaly, electrocardiographic abnormalities, and paroxysmal ventricular tachycardia was described. Some of the interesting electrocardiographic features were discussed, and the importance of serial electrocardiograms for the detection of cardiac involvement is emphasized, since acute disturbances in cardiac rhythm may indicate that the patient is in immediate danger of sudden death.
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The nuclear DNA content of paraffin-embedded materials was measured by microfluorometry in 108 colorectal (59 colon and 49 rectal) cancers and 29 metastatic liver tumors from the colorectum. The classification of the nuclear DNA distribution is as follows: Low ploidy, 10% greater than over 4C; intermediate ploidy, 10% less than or equal to over 4C and 10% greater than over 6C; high ploidy, 10% less than or equal to over 6C. In primary lesions, thirty-one (29%) were found to contain cells with high ploidy. The ploidy pattern was not related to pathological stage. However, in curatively resected cases, only 24% of patients with high ploidy survived 10 years. This 10 year-survival rate was significantly lower as compared with 80% and 88% of patients with intermediate and low ploidy, respectively (p less than 0.05). In non-curatively resected cases, no patients with high ploidy survived 2 years, although 21% and 67% of patients with intermediate and low ploidy survived, respectively. In metastatic liver lesions, eleven materials (42%) were found to contain cells with high ploidy. Prognosis of patients with high ploidy was worse than that with intermediate and low ploidy (p less than 0.05). These observations suggest that the nuclear DNA distribution in colorectal cancers may be an important prognostic factor, independent of pathological stage.
Cardiac metastases have been reported increasingly partly because of the longevity of cancer patients, but its antemortem diagnosis is frequently missed. This is due to the nonspecific clinical manifestations or relative lack of characteristic signs which are masked by the underlying disease. This is a report of a 42-year-old man diagnosed as having a metastatic cardiac tumor by echocardiography, six months after operation for squamous cell carcinoma of the gall bladder. Echocardiography revealed abnormal structures in the regions of the posterior and lateral walls of the left ventricle and interventricular septum, suggesting metastatic tumors. The cytological findings of a fine-needle aspiration biopsy specimen were squamous cell carcinoma. The patient died of cardiac failure eight months after the echocardiographic diagnosis. At autopsy, the abnormal structures in the heart were identified as cardiac metastatic tumors from gall bladder cancer. Reports of cardiac metastasis of gall bladder cancer is very rare (0-3%). The myocardial metastasis may have a more serious prognostic importance than the primary neoplasm itself; thus, its definite diagnosis is mandatory.
Effect of 1-[3-isobutoxy-2-(benzylphenyl) amino]propyl pyrrolidine hydrochloride (bepridil), a new antianginal agent, on membrane potentials and membrane currents of sinoatrial node cells of rabbits was examined using conventional microelectrode and double microelectrode voltage clamp methods. Bepridil at a concentration of 10 mumol/l caused an increase in spontaneous cycle length, and a decrease in maximum rate of rise of the action potential and action potential amplitude. The rate of diastolic depolarization (phase 4) was also decreased by the drug. In the voltage clamp experiment, bepridil reduced both the slow inward current (Isi) and the hyperpolarization activated current (Ih), and increased the recovery time constant of Isi, whereas the time-dependent potassium current (IK) was not altered significantly. The major effect, however, was the reduction of Isi. These electrophysiological findings suggest that bepridil has a depressant effect on the electrical activity of sinoatrial node mainly by mediating the depression of slow channel.