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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 487 records · Page 27Linked to original sources

[The effect of Japanese herbal medicine on MRSA carrier in neurosurgery].

Since the management of methicillin-resistant staphylococcus aureus (MRSA) carriers is not established, these patients are isolated individually, limited in activity, and delayed in rehabilitation. In this study, the effect of Japanese herbal medicine on MRSA carriers was examined. In the control group, MRSA carriers were isolated individually. In the treatment group, one of the Japanese herbal medicines "Juzentaihotou" or "Hotyuekkitou" was given in addition to isolating the patient. It was shown in cultures that Japanese herbal medicines had effectively changed MRSA carriers to negative. They also shortened the duration required to bring about the change of MRSA carriers to negative. As a result, the total number of MRSA carriers was reduced. These results suggested that Japanese herbal medicines may be useful for the management of MRSA carriers in neurosurgery.

Carrier State↗

Pathological appearance of the stomach after endoscopic mucosal resection for early gastric cancer.

BACKGROUND: The pathological findings of the resected stomach after endoscopic mucosal resection (EMR) for early gastric cancer were reviewed. EMR was indicated when a lesion consisting of well or moderately differentiated adenocarcinoma had a diameter of less than 2 cm. METHODS: Of 39 patients with early gastric cancer were treated with EMR between 1990 and 1995, 11 required additional surgery. RESULTS: Malignant tissue in the gastric wall was completely removed in four patients, while cancer cells remained in the mucosa adjacent to the scar in five and infiltrated into the submucosa in two. Most of these residual cancers were characterized by a lesion with a diameter exceeding 15 mm and by the location in the body or cardia of the stomach. Lymph node metastases were observed in one patient whose carcinoma invaded the deeper submucosal layer. Assessment of the depth of entire invasion from the endoscopically-resected specimen was correct for six of 11 patients. CONCLUSION: Gastric carcinomas to be resected by EMR should be smaller, especially if located in the body or cardia. Accurate diagnosis of the width and depth of invasion is indispensable before proceeding to EMR. Surgery may be the treatment of choice when there is submucosal invasion.

Aged↗

[CT-guided lung needle biopsy using a new supporting implement].

We contrived a new supporting implement to increase the hit rate of CT-guided needle biopsy (CTNB) for localized pulmonary lesions. Using this implement, twenty-two CTNB examinations for localized pulmonary lesions were performed. In 21 out of the 22 examinations (95%), the lesions were hit, and specimens appropriate for cytological or histological diagnosis were obtained. The course of needle insertion, which was difficult to define in the past, has become to be easier and more precise with this method. Using this new implement, CTNB is now applicable to smaller and deeper lesions.

Adult↗

[Idiopathic delayed puberty--female].

The developmental changes during puberty occur over a period of 3 to 5 years, usually between ages 9 and 14. The age of onset of puberty is influenced by genetic and environmental factors. Delayed puberty is a rare condition in girls, and a genetic problem or hypothalamic-pituitary-ovarian disorder can be suspected. In addition, anatomic abnormalities of the uterus and ovaries are rare but important factors to consider. The history and physical examination are useful in the diagnostic work-up. Pelvic examination and U.S. should be completed. Also, hormonal analysis should be recommended with diagnostic plan. Although, the possibility of rare diagnoses should always be kept in mind.

Adolescent↗

[A case of idiopathic orthostatic hypotension with selective involvement of postganglionic noradrenergic neurons].

A 44-year-old man had a 30-year history of orthostatic hypotension and diarrhea. One month before admission, he suddenly lost consciousness by defecation, and was hospitalized. He became alert within two days, but he could not sit up due to severe orthostatic hypotension. At that point, he was transferred to our hospital. On admission, talipes and microdactylia were noted. Neurological examination revealed brisk patellar tendon reflexes. Anhidrosis or impotence was not present. Analyses of blood and urine yielded normal results. Cardiological examination revealed no abnormality that could be responsible for the hypotension. MR images of the brain were also normal. However, single photon emission tomography revealed diffuse hypoperfusion of the brain. A head-up tilt (50 degrees) test induced a remarkable fall in systolic blood pressure from 149 (heart rate; 65/min) to 64 mmHg (83). Immersion of hand in ice-cold water failed to increase blood pressure. Heart rate variation and cystometry results, which represent the function of parasympathetic nerves, were normal. Warming of his body caused normal sweating. Intravenous injection of low doses of norepinephrine and methoxamine increased blood pressure while isoproterenol remarkably increased heart rate, suggesting that both alpha- and beta-receptors developed supersensitivity. Instillation of 5% cocaine and 5% tyramine into the conjunctival sac failed to cause pupillary dilation. Clinical findings and pharmacological challenge test results suggested that the main lesion of his autonomic nervous system was selectively confined to the postganglionic sympathetic nerves and noradrenergic (not cholinergic) neurons. The autonomic failure of our patient can be classified as idiopathic orthostatic hypotension. However, most patients with idiopathic orthostatic hypotension or pure autonomic failure complain of anhidrosis and impotence, which were not noted in our patient. These symptomatic differences may be the result of the highly selective involvement of noradrenergic neurons in the postganglionic sympathetic system in our patient.

Adult↗

[A case of complete remission of gastric endocrine cell carcinoma with multiple bone metastasis by combination chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation].

A 31-year-old man was admitted to our hospital complaining of epigastric discomfort and severe lumbago. An upper gastrointestinal endoscopy revealed several submucosallike tumors. Histologic examination of biopsy specimens confirmed the presence of endocrine cell carcinoma. Gallium scintigraphy and CT revealed multiple bone metastasis. He was treated with 6 cycles of combination chemotherapy consisting of CDDP, etoposide, CPA, EPI and VCR. Both gastric tumors and bone metastasis completely disappeared. After 7 cycles of the chemotherapy, he was treated with HDCT with PBSCT. There was no severe complication. This result suggested that the combination of conventional chemotherapy and HDCT with PBSCT was useful in cancer patients with poor prognoses, such as advanced gastric endocrine cell carcinoma.

Adult↗

Metabolism of epinastine, a histamine H1 receptor antagonist, in human liver microsomes in comparison with that of terfenadine.

Epinastine is a non-sedative second-generation antiallergic drug, like terfenadine. In the present study, the metabolism of epinastine in human liver microsomes was investigated and compared with that of terfenadine. Terfenadine was extensively metabolized to terfenadine acid with a Km value of 1.78 microM, a Vmax value of 173.8 pmol/min/mg and a metabolic clearance (Vmax/Km) of 103.9. Epinastine, in contrast, was poorly metabolized by microsomes from the same source with a high Km value of 232 microM. Metabolic clearance of epinastine was only 0.832, which was lower by three orders of magnitude than that of terfenadine. Studies with microsomes expressing recombinant cytochrome P450 (CYP) species revealed that the CYP isoforms responsible for epinastine metabolism are CYP3A4, 2D6 and (to a minor extent) 2B6. Epinastine and terfenadine had no effect on CYP1A2 (theophylline 1-demethylation), 2C8/9 (tolbutamide hydroxylation) or 2E1 (chlorzoxazone 6-hydroxylation) activity, but weakly inhibited CYP2D6 (debrisoquine 4-hydroxylation) activity. CYP3A4 (testosterone 6 beta-hydroxylation) activity was strongly inhibited by terfenadine with a Ki value of 25 microM, whereas epinastine had no effect at up to 100 microM. Thus, epinastine is very poorly metabolized compared to terfenadine in human liver microsomes and does not inhibit CYP3A4 activity in vitro, unlike terfenadine.

Aryl Hydrocarbon Hydroxylases↗

Distribution of free D-amino acids in tissues and body fluids of vertebrates.

Reports on the distribution, metabolism and origins of free D-amino acids in vertebrate tissues and body fluids are reviewed. The transient emergence of D-aspartic acid during the development of brain and peripheral organs or early stages of life is reported. D-Serine in brain is postulated to be a potentiator for the N-methyl-D-aspartate (NMDA) receptor. Some D-amino acid concentrations in human serum, such as D-Ser and D-Ala, are suggested to correlate with damage to renal function.

Alanine↗

Phencyclidine alters regional concentrations of neuropeptide Y and peptide YY in rat brain.

The psychotomimetic effects of Phencyclidine (PCP) often have a delayed onset and extend far from the time plasma drug levels reach their peak. PCP at a low dose is considered selective for actions on the N-methyl-D-aspartate-PCP receptor. We evaluated effects of PCP (2 and 10 mg/kg, IP) on regional content of neuropeptide Y (NPY)-like immunoreactivity (LI) and peptide YY (PYY)-LI, in the rat brain. Thirty minutes after administration of PCP, NPY-LI levels were significantly elevated in some limbic structures following both doses. A significant, widespread increase in NPY-LI levels was induced 2 hours after administration of the higher dose of PCP. On the contrary, NPY-LI was significantly decreased in a number of the regions 24 hours after PCP. The extent of reduction was less following the higher dose of PCP than following the lower dose. PCP did not cause a consistent effect on PYY-LI. The findings suggest that effects of PCP on brain NPY content might depend on the dose and the interval between administration of the drug and sacrifice.

Animals↗

Time course of impaired coronary flow reserve after reperfusion in patients with acute myocardial infarction.

To evaluate the time course of coronary flow reserve after reperfusion, 14 patients with a first anterior wall acute myocardial infarction who underwent successful coronary angioplasty within 6 hours after symptom onset were studied. After angioplasty, coronary flow reserve of the left anterior descending artery was measured with a coronary Doppler guidewire and intravenous dipyridamole (0.56 mg/kg over 4 minutes). Measurements were repeated at predischarge (16 +/- 3 days, n = 12) and at follow-up (6 +/- 3 months, n = 9). Patients with restenosis at the time of repeat catheterization were excluded. An additional 13 patients with normal angiograms served as reference patients. Coronary flow reserve was 1.33 +/- 0.29 after angioplasty. It increased to 1.88 +/- 0.36 at predischarge (p <0.01) and further to 2.34 +/- 0.38 at follow-up (p <0.01 vs after angioplasty and at predischarge, respectively). However, compared with reference patients (3.15 +/- 0.48), coronary flow reserve was significantly reduced in the infarct patients even at follow-up (p <0.01). In infarct patients, the infarct region wall motion was initially -3.86 +/- 0.67 SD/chord. It significantly improved to -2.07 +/- 1.04 SD/chord at predischarge (p <0.01) and to -1.67 +/- 1.43 SD/chord at follow-up (p <0.01). However, there was no significant relation between coronary flow reserve and region wall motion after angioplasty (r = 0.10), at predischarge (r = 0.35), and at follow-up (r = 0.28). Thus, coronary flow reserve is severely impaired early after reperfusion. Coronary flow reserve improves over 2 weeks, but the impairment persists at 6 months after acute myocardial infarction. The impairment of coronary flow reserve cannot be predicted by left ventricular function. Small sample size is a potential limitation of this study, and a larger study should be performed to confirm these findings.

Aged↗

Are there cholinergic and non-cholinergic paradoxical sleep-on neurones in the pons?

Using microiontophoresis on unanesthetized head-restrained cats, we have found two distinct groups of neurones exhibiting tonic discharge specific to paradoxical sleep (PS) (PS-on neurones) in the mesopontine tegmentum, which contains both cholinergic and non-cholinergic neurones. One group is characterized by a broad action potential, slow conduction velocity and an inhibitory response to a potent cholinergic agonist, carbachol, applied iontophoretically during PS. The other is characterized by a short action potential, fast conduction velocity and an excitatory response to applied carbachol. All PS-on neurones were excited by glutamate. The present findings demonstrate the existence of two types of PS-on neurones and suggest their cholinergic and noncholinergic neurochemical properties.

Animals↗

Time-course and reversibility of the hypoxia-induced alterations in cerebral vascularity and cerebral capillary glucose transporter density.

The adult rat adapts to prolonged moderate hypobaric hypoxia by polycythemia, increased brain vascularity, and increased density of the brain capillary glucose transporter (GLUT-1). We now report on the time-course and reversibility of these adaptive alterations. Adult male Wistar rats were subjected to hypobaric hypoxia at 0.5 atmosphere for periods of 4 days or 1, 2 or 3 weeks, and compared to normoxic littermate controls. Reversibility of the effects of hypoxia was studied in rats subjected to hypobaric hypoxia for 3 weeks and then allowed to recover at normobaric conditions for 3 additional weeks. Cerebral vascularity was studied in cross-sections of the cerebral cortex that were immunocytochemically stained with a GLUT-1 antibody. The density of GLUT-1 was determined in isolated cerebral microvessels by quantitative autoradiography of immunoblots. Blood hematocrit and cerebral microvascularity did not significantly increase after 4 days of hypoxia, but were significantly increased at 1, 2 and 3 weeks of hypoxia. Three weeks of normoxic recovery after 3 weeks of hypoxia reversed the polycythemia and cerebral hypervascularity. However, the density of GLUT-1 in isolated cerebral microvessels, which was significantly increased after 1 and 3 weeks of hypoxia, remained elevated after 3 weeks of normoxia.

Adaptation, Physiological↗

CD4 confers susceptibility to human immunodeficiency virus type 1 infection in a rat fibroblast cell line.

A new model system is delineated that will enable study of CD4 cofactors and gp120 binding proteins other than CD4. We have previously described a nontransformed rat fibroblast cell line that can efficiently produce HIV-1 upon transfection with an HIV-1 infectious clone, in contrast to other nonhuman mammalian cell lines tested. In the present study we analyzed the susceptibility to HIV-1 infection of Rat2 cells expressing the human CD4 protein. We have used the mammalian expression vector pKS286, in which HIV-1 LTR drives the expression of the CD4 gene. We show that the Rat2 cell line, expressing the human CD4 (Rat2/CD4), is susceptible to fusion with and infection by HIV-1. The virus produced by the Rat2/CD4 cells was infectious. CD4 expression in the Rat2/CD4 was down-regulated over time, similarly to HIV-1 expression in HIV-1-transfected Rat2 cells. Transfection of the Rat2/CD4 cells with a tat expression vector reestablished the CD4 expression on the surface of those cells, as expected. We conclude that the expression of a gp120 binding protein on the Rat2 cells' surface suffices to render the Rat2 cells susceptible to HIV-1 infection.

Animals↗

Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats.

We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde. Extravasation of Evans blue dye into airway tissues was used as an index of airway microvascular leakage. Leakage of dye in the trachea and main bronchi increased significantly in a concentration-dependent fashion after 10 min inhalation of formaldehyde (5-45 parts per million (ppm)). The airway response induced by 10 min inhalation of 15 ppm formaldehyde (trachea: 119.5 +/- 13.9 ng/mg, n = 7; main bronchi: 139.6 +/- 7.9 ng/mg, n = 7) was abolished by the administration of CP-99,994 (3 and 6 mg/kg i.v.), but not by the administration of HOE 140 (0.65 mg/kg i.v.) nor ketotifen (1 mg/kg i.v.). The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation. Activation of bradykinin receptors and mast cells did not appear to play an important role in this airway response.

Animals↗

Nicorandil suppressed ventricular arrhythmias in a canine model of myocardial ischaemia.

These experiments were designed to explore the possibility that a K+ channel opener which also donates nitric oxide to the myocardium (nicorandil) may modify ischaemia-induced ventricular arrhythmias in a large animal model. In mongrel dogs anaesthetised with chloralose-urethane and thoracotomised, a side branch of the left anterior descending artery was catheterised for the local intracoronary infusion of nicorandil (2.5 micrograms kg-1 min-1 for 20 min prior to coronary artery occlusion and then continuing throughout the 25 min occlusion period). In this dose, nicorandil had no haemodynamic effects, increased coronary blood flow by up to 16% and significantly reduced the severity of ischaemia-induced arrhythmias (e.g. from nearly 500 ventricular premature beats in the controls to 160 +/- 60 in the nicorandil group). There was a significant reduction in the number of episodes of ventricular tachycardia during the ischaemic period and a reduced incidence of ventricular fibrillation following reperfusion resulting in a 42% survival from the combined ischaemia-reperfusion insult (cf. 0% in the control; P < 0.05). The marked changes that occurred in ST-segment elevation (mapped with epicardial electrodes) and in the inhomogeneity of electrical activation within the ischaemic area in control dogs was markedly reduced in those dogs administered nicorandil. We conclude that the local intracoronary administration of nicorandil reduces the severity of both ischaemia and the life-threatening arrhythmias that result from an abrupt reduction in coronary blood flow in this canine model. Possible mechanisms include an increase in coronary blood flow, a reduction in the severity of myocardial ischaemia and an ability of the compound to "donate' nitric oxide to the ischaemic area.

Animals↗