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Biomedical subjects

M Kihara

Publications and source records attributed to M Kihara.

At least 199 records · Page 11Linked to original sources

[Activities and isozymes of adenosine deaminase and lactate dehydrogenase in tuberculous pleural effusion with special reference to the presence of mycobacterium tuberculosis].

We have previously shown that tuberculous pleurisy possesses a high level of adenosine deaminase (ADA) which is predominantly composed of ADA2. In this paper, we report the cases of tuberculous pleural effusion which contained mainly ADA1. In these cases, mycobacterium tuberculosis was positive by smear examination and/or culture and granulocytes were found to be major components. Analysis of lactate dehydrogenase (LDH) revealed that its activity was high and LDH5 occupied about 50% of total activity. In the tubercle bacillus negative cases, lymphocytes were the main components and the levels of LDH containing mostly LDH3 were low. It was assumed that the difference in LDH activity and isozyme pattern is due to the differential presence of leukocytes in pleurisy i.e., granulocytes and lymphocytes in tubercle bacillus positive and negative pleurisy, respectively. In conclusion, tuberculous pleural effusions can be divided into two groups on the basis of ADA and LDH activities and isozymes which may reflect the presence of mycobacterium tuberculosis.

Adenosine Deaminase↗

[Adenosine and adenosine receptors in the kidney].

In the kidney, adenosine plays important regulatory roles, including renal blood flow, glomerular filtration rate, renin secretion, tubuloglomerular feedback, tubular reabsorption of sodium and water, sympathetic neurotransmitter release, and erythropoietin secretion. These functions are mediated through adenosine 1 (A1)-receptors and adenosine 2 (A2)-receptors. These receptors couple to the inhibition and stimulation of adenylate cyclase, through Gi and Gs proteins, respectively. A variety of other effecter systems have been reported to be coupled to A1 receptors, including phospholipase C, phospholipase A2 and potassium, as well as Ca++ channels. Recently, A1 receptors, A2 receptors and novel A2 receptor have been cloned, sequenced and expressed. In association with the development of selective adenosine analogues, we are now ready to take up problems at the biochemical and molecular biological levels.

Adenosine↗

[Diseases of the autonomic nervous system. General aspect of symptomatology].

The human internal environment is regulated by the autonomic nervous system (ANS), endocrine glands and neuropeptides as well as the integrated activity of these three systems. The ANS is divided into thoraco-lumbar (sympathetic) and cranio-sacral (parasympathetic) divisions. They comprise two neurons: pre- and post-ganglionic fibers. The limbic system and hypothalamus are known to regulate the peripheral ANS through descending pathways in the brain stem and spinal cord. Cardinal semiologies of the ANS disorders are classified as follows: cardiovascular (orthostatic hypotension, a variety of syncopes, postprandial hypotension, Raynaud's phenomenon), pupillomotor (paralytic mydriasis, Adie's tonic pupil, Horner's syndrome), urodynamic (urinary retention and incontinence), and sexual (impotence, hyper- and hyposexuality).

Animals↗

The effect of aging on endoneurial blood flow, hyperemic response and oxygen-free radicals in rat sciatic nerve.

Electrophysiologic abnormalities and reduced energy metabolic rate develop in aging nerves. We investigated the effects of aging on nerve blood flow (NBF) in Fischer rats aged 2, 12, 24 and 30 months. NBF regressed negatively with increasing age and this decline was associated with an increase in nerve vascular resistance. Twenty minutes of nerve stimulation resulted in an increase in blood flow by about 50% in adult animals and did not decline with increasing age. As indices of oxygen free radical activity, we measured conjugated dienes, hydroperoxides, and norepinephrine from 2 to 30 months. There was a gradual decline with increasing age of all indices. We conclude that NGF declines with aging due to reduced microvascular caliber. These vessels retain their hyperemic response and oxygen free radical activity is less with increasing age.

Aging↗

Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals.

Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg.kg-1.day-1), group II received STZ plus AG (50 mg.kg-1.day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

Action Potentials↗

Neurilemoma of the retroperitoneum.

A case is presented in which suprarenal neurilemoma was associated with paroxysmal attacks of hypertension, headache and sweating with elevated plasma and urinary catecholamines. Pheochromocytoma was excluded using an overnight clonidine suppression test. Ultrasonography, computed tomography and magnetic resonance imaging, which showed cystic mass with a pedicle continuing to the widened intervertebral foramen, were helpful for the preoperative diagnosis of retroperitoneal neurilemoma. The excised tumor was revealed to be benign neurilemoma and contain detectable levels of adrenaline, noradrenaline and dopamine. The relationships between tumor catecholamines and clinical manifestations will be discussed.

Aged↗

Ipsilateral but not contralateral blockade of excitatory amino acid receptors in the caudal ventrolateral medulla inhibits aortic baroreceptor reflex in rats.

The caudal ventrolateral medulla (CVLM) contains vasodepressor neurons which, when activated, decrease vasomotor tone. To investigate whether excitatory amino acid receptors in the CVLM of the rat are involved in mediation of the aortic baroreceptor reflex, we microinjected amino acid antagonists unilaterally into the CVLM and examined their effects on the depressor response to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anaesthetized with urethane, paralyzed and artificially ventilated. To block reflex vagal effects, methylatropine (1 mg/kg) was given intravenously. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the CVLM markedly inhibited the depressor response to aortic nerve stimulation, while both injections produced a similar small increase in basal blood pressure. Muscimol (1 ng), a GABA receptor agonist, injected ipsilaterally into the CVLM partly inhibited the baroreflex response, while it produced a moderate increase in basal blood pressure. 2-Amino-5-phosphonovalerate (APV) (10 ng), a N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801 (30 ng), a NMDA receptor channel blocker, partly inhibited the baroreflex response. MK-801 (30 ng) injected into the CVLM reduced the depressor response to the NMDA receptor agonist NMDA (0.3 ng) but not to the quisqualate receptor agonist quisqualate (0.1 ng) and the kainate receptor agonist kainate (0.1 ng), while kynurenate (227 ng) inhibited the depressor response to all three excitatory amino acid receptor agonists. These findings provide further evidence for the presence of excitatory amino acid receptors involved in mediating the aortic baroreceptor reflex in the rat CVLM.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

Unilateral blockade of excitatory amino acid receptors in the nucleus tractus solitarii produces an inhibition of baroreflexes in rats.

Excitatory amino acid receptors and L-glutamate in the nucleus tractus solitarii (NTS) may be involved in the regulation of baroreceptor reflexes. To evaluate this hypothesis, we microinjected amino acid antagonists unilaterally into the rat NTS, and examined their effects on cardiovascular responses to electrical stimulation of the aortic nerve and on depressor responses to excitatory amino acid agonists microinjected into the NTS. Male Wistar rats were anesthesized with urethane, paralyzed, and artificially ventilated. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the NTS, markedly inhibited the depressor response to aortic nerve stimulation. L-Glutamate diethylester (GDEE, 3 micrograms), another excitatory amino acid antagonist, injected ipsilaterally into the NTS, also markedly inhibited both reflex depressor and bradycardic responses. MK-801 (30 ng), an N-methyl-D-aspartate (NMDA) receptor channel blocker, slightly inhibited the baroreflex responses, while Joro spider toxin JSTX-3 (17 ng), a glutamate receptor antagonist, did not affect them. Kynurenate (227 ng) and GDEE (3 micrograms) markedly inhibited the depressor response to the NMDA receptor agonist NMDA (0.3 ng), the quisqualate receptor agonist quisqualate (0.1 ng), the kainate receptor agonist kainate (0.1 ng), and L-glutamate (10 ng), microinjected into the NTS, while MK-801 (30 ng) reduced only the depressor response to NMDA (0.3 ng), and JSTX-3 (17 ng) reduced only the depressor response to kainate (0.1 ng). These findings provide evidence for the presence of excitatory amino acid receptors involved in mediating the aortic baroreceptor reflex in the rat NTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The assessment of sudomotor dysfunction in multiple system atrophy.

We studied sudomotor function in 21 patients with multiple system atrophy and in 11 age-matched controls. The extent and severity of the sudomotor deficit was assessed using the quantitative thermoregulatory sweat test. Central sudomotor function was studied by measuring sweating in response to raising body heat and administering thyrotropin-releasing hormone. Postganglionic sudomotor function was studied using the sudomotor axon reflex test evoked by nicotine. We conclude that in multiple system atrophy, thermoregulatory sudomotor dysfunction was more severe in the lower extremities. Heat stimulation increased the frequency of sweat expulsion and sweat rate on the forearm in moderate multiple system atrophy to a similar degree as controls but failed to do so on the thigh. Thyrotropin-releasing hormone enhanced sweating in moderate multiple system atrophy and controls. Results of the sudomotor axon reflex test indicate that in multiple system atrophy there is postganglionic sudomotor dysfunction which may be due to transsynaptic changes. These results suggest that the main lesion responsible for sudomotor dysfunction in multiple system atrophy is within the intermediolateral column cells of the spinal cord.

Adult↗

Endoneurial blood flow in rat sciatic nerve during development.

1. Endoneurial blood flow (EBF) in the sciatic nerve of rats aged 2-12 weeks was studied using microelectrode H2 polarography. 2. EBF is highest in 2-week-old rats and progressively declines during development. Mean arterial pressure (MAP) is low at 2 weeks of age, gradually increases through the next 4 weeks, and is relatively constant thereafter. The decrease in EBF, in spite of an increase in MAP, occurs because the endoneurial vascular resistance is increasing faster than the MAP. 3. The higher EBF in younger rats is not due to the smaller diameter of their nerves. Sural and tibial nerves of 12-week-old rats, with diameters comparable to that of the sciatic nerve of a 3-week-old rat, have EBFs similar to that of the sciatic nerve of a 12-week-old rat. 4. There was no compelling evidence of autoregulation of EBF in 3-week-old rats over a MAP range from -40 to +30 mmHg of the normal value. 5. The increase of nerve vascular resistance with maturation is probably due to a decrease in capillary density and, to a lesser extent, to an increase in plasma viscosity and haematocrit. 6. The higher EBF in immature rats is likely to be a developmentally adaptive mechanism which permits greater blood-nerve exchange of material to accommodate the greater metabolic needs of rapidly elongating and myelinating axons and proliferating Schwann cells.

Aging↗

[A case of Enterococcus faecalis brain abscess in a patient with suprapharyngeal cancer].

A 55-year-old male was admitted to our hospital for the treatment of suspected brain abscess on March 18, 1989. The brain CT scan showed low density area with ring enhancement. After admission, both cefminox 2 g/day and clindamycin 500 mg/day were administered intravenously. On March 29, 1989, the patient developed cerebral herniation suddenly. Therefore emergency burr hole operation was done. Many gram-positive cocci were observed on gram-staining of the aspirated pus. Moreover neutrophils with phagocytosed gram-positive cocci were also observed. Culture of aspirated pus revealed colonies of gram-positive cocci which were subsequently identified as E. faecalis. Same species of bacteria were also isolated from fistula of right mastoid. From both findings of brain CT scan and data of MICs of E. faecalis, it may be suggested that direct infection developed from right mastoiditis to intracranial space. We experienced a severe case who developed cerebral herniation because of brain abscess due to E. faecalis which is an infrequent pathogen of brain abscess.

Brain Abscess↗

Effects of intravenous infusions of angiotensin II on muscle sympathetic nerve activity in humans.

The effect of angiotensin II (ANG II) on the sympathetic outflow was examined in normal humans. The mean arterial pressure and muscle sympathetic nerve activity (MSNA) were measured before and during intravenous infusions of phenylephrine (0.5 and 1.0 micrograms.kg-1.min-1) or ANG II (5, 10, and 20 ng.kg-1.min-1) for 15 min at 30-min intervals. The baroreflex slope for the relationship between the increases in mean arterial pressure and the reductions in MSNA was significantly less acute during the infusions of ANG II than during the infusions of phenylephrine. When nitroprusside was infused simultaneously to maintain central venous pressure at the basal level, MSNA significantly increased during the infusions of ANG II (5 ng.kg-1.min-1 for 15 min) but not during the infusions of phenylephrine (1.0 micrograms.kg-1.min-1 for 15 min), with accompanying attenuation of the elevation in arterial pressure induced by these pressor agents. These findings suggest that ANG II stimulates the sympathetic outflow without mediating baroreceptor reflexes in humans.

Adult↗

Immunocytochemical localization of glutamate containing neurons in the ventrolateral medulla oblongata and the nucleus tractus solitarius of the rat.

Using antisera raised against excitatory neurotransmitter glutamate fixed to carrier proteins and purified by affinity chromatography, localization of glutamate in the ventrolateral medulla oblongata and the nucleus tractus solitarius of the rat was studied. Within the rostral portion of the ventrolateral medulla, glutamate-like immunoreactive neurons were found in the lateral wing of the raphe magnus and in the region of the paragigantocellular reticular nucleus. In the caudal portion of the ventrolateral medulla, glutamate-positive neurons were clustered within the nucleus reticularis lateralis and a lesser number of stained neurons were scattered in the region around this nucleus. Glutamate-immunoreactive neurons were found in the nucleus tractus solitarius at the level of the area postrema. They were densely distributed especially in the medial subdivision of the nucleus whereas other subdivisions contained considerable glutamate positive cells. These results provide immunohistochemical evidence for the presence of glutamate-containing neurons in the ventrolateral medulla oblongata and the nucleus tractus solitarius of the rat.

Animals↗

Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat.

Neuropeptide Y (NPY), neurotensin, arginine vasopressin (AVP), angiotensin II (ANG II), atrial natriuretic peptide (ANP) and calcitonin gene-related peptide (CGRP) have been suggested as putative neurotransmitters in the nucleus tractus solitarii (NTS) where baro- and chemoreceptor afferents terminate. To investigate modulation of the aortic baroreceptor reflex by neuropeptides, we microinjected these neuropeptides into the medial area of the rat NTS and examined their effects on the depressor and bradycardic responses to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. NPY (3 ng) and neurotensin (0.3 ng) injected into the NTS caused a decrease in blood pressure and/or heart rate, and facilitated the depressor and bradycardic responses to aortic nerve stimulation. AVP (3 ng) produced an increase in blood pressure and heart rate, and inhibited the responses to aortic nerve stimulation, whereas d(CH2)5Tyr(Me)AVP(100 ng), a V1 vasopressin receptor antagonist, did not affect the basal cardiovascular parameters and the baroreflex responses. ANG II (0.3 and 3 ng) caused a decrease in blood pressure and heart rate whereas at 0.3 ng it did not affect the baroreflex responses. ANP (3 ng) and CGRP (3 ng) did not affect the basal blood pressure and heart rate, and the responses to aortic nerve stimulation. These findings indicate that NPY, neurotensin and AVP microinjected into the rats NTS can modify the aortic baroreceptor reflex. Some of these neuropeptides may play a role in modulation of the aortic baroreceptor reflex within the NTS.

Angiotensin II↗

Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices. Effects of inhibitors of aspartate aminotransferase and GABA transaminase.

The effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and gamma-acetylenic GABA and gabaculine, both gamma-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2(+)-dependent stimulus-evoked release of endogenous aspartate. AOAA (10(-4) and 10(-3) M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 x 10(-5) M), gamma-acetylenic GABA (10(-4) M) and gabaculine (10(-5) M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced a decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata.

4-Aminobutyrate Transaminase↗

Resolution, absolute stereochemistry, and enantioselectivity of 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol.

Racemic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) was found to be an effective potentiator of the contractile response of norepinephrine (NE) on rat anococcygeus muscle. This paper describes the resolution of racemic PI-OH by an HPLC method to give the optically pure enantiomers (+)-1 and (-)-1. The absolute configuration of (+)-1 was R as determined by CD analysis and by single-crystal X-ray diffractometric analysis of the methiodide 6 derived from (+)-1. Examination of the effects of the enantiomers to potentiate the contraction of the rat anococcygeus muscle by NE showed a high degree of enantioselectivity. The NE potentiation was found to reside exclusively in (R)-(+)-1; the activity ratio being 21 at 3 x 10(-6) M, whereas (S)-(-)-1 did not show any potentiating and inhibiting activity.

Animals↗

Regulation of rat nerve blood flow: role of epineurial alpha-receptors.

1. Transperineurial arterioles connect the extrinsic (epineurial) and the intrinsic (endoneurial) microvasculatures. Our goal was to determine whether the extrinsic system regulated nerve blood flow locally and whether subperineurial and centrifascicular endoneurial nerve blood flows were regulated differentially. 2. The local application of noradrenaline resulted in a dose-dependent reduction of nerve blood flow in subjacent endoneurium. Asymptotes of 78.8 and 76.3% vasoconstriction were recorded for subperineurial and centrifascicular endoneurial nerve blood flow, respectively, indicating near-complete closure of capillaries. 3. Near-identical concentrations required to generate 50% vasoconstriction (EC50) and asymptotes are suggestive of the fact that the two areas are not differentially regulated. 4. Local vasoconstriction cannot be due to a systemic effect of noradrenaline since a significant decrease in nerve blood flow occurs despite undetectable increases in plasma noradrenaline and mean blood pressure, or decrease in contralateral sciatic nerve blood flow. 5. There are small and statistically non-significant reductions of the compound muscle action potential and conduction velocity in the sciatic-tibial nerve following nerve ischaemia. 6. These findings suggest that epineurial arterioles control regional nerve blood flow and are primarily responsible for its regulation in subjacent endoneurial tissue.

Animals↗

Isolated human growth hormone deficiency due to the hGH-I gene deletion with (type IA) and without (the Israeli-type) hGH antibody formation during hGH therapy.

Three Japanese patients with isolated growth hormone deficiency from two different families were shown to be homozygous for deletion of the structural gene for human growth hormone (hGH-I gene). These three patients had the same restriction fragment length polymorphism haplotypes. In patient No. 1, the growth rate initially responded well to pituitary human growth hormone, but growth rapidly ceased concomitantly with the development of high levels of anti-hGH antibodies. He again responded well to recombinant methionyl hGH and recombinant hGH without the methionine residue, even though having high hGH antibodies. Two siblings (Patients No. 2 and 3) showed a rather good response to pituitary hGH treatment without hGH antibodies ever being detected (the Israeli-type). hGH-I gene deletions may not necessarily result in hGH antibody formation. Heterogeneity has been observed in isolated hGH deficiency due to hGH-I gene deletion. hGH-I gene analysis should not be limited to patients with hGH antibody formation and subnormal growth responses to hGH therapy.

Adolescent↗