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Biomedical subjects

K Sugiyama

Publications and source records attributed to K Sugiyama.

At least 19 recordsLinked to original sources

Identification of nociceptive neurons in the medial thalamus: morphological studies of nociceptive neurons with intracellular injection of horseradish peroxidase.

Somatosensory neurons including nociceptive ones in the medial thalamus have been studied extracellularly, and are classified into three types: nociceptive-specific, wide dynamic range, and tap neurons. However, the morphological characteristics of these three neurons have not yet been clarified. We studied the morphological characteristics of the neurons by iontophoretic injection of HRP into single neurons in 32 cats. Nine wide dynamic range neurons and two tap neurons were electrophysiologically identified and successfully stained with HRP in and around the parafascicular and subparafascicular nuclei, and in the mediodorsal nucleus. All nine wide dynamic range neurons had fewer dendrites which formed scanter tufts, whereas the two tap neurons had many more dendrites which formed denser tufts: i.e. wide dynamic range neurons were of the isodendritic type, and the tap neurons were of the allodendritic type, according to Ramón-Moliner's classification. The axons of the two tap neurons ran antero-laterally whereas those of wide dynamic range neurons ran in many directions. These morphological differences suggest that tap neurons may have more specialized and fixed functions than wide dynamic range neurons.

Animals

Two forms of the low-affinity Fc receptor for IgE differentially mediate endocytosis and phagocytosis: identification of the critical cytoplasmic domains.

We have previously identified two species of the low-affinity human Fc receptor for IgE, Fc epsilon RIIa and Fc epsilon RIIb, which differ only in a short stretch of amino acids at the N-terminal cytoplasmic end. Their differential expressions on B cells and monocytes suggest that Fc epsilon RIIa and Fc epsilon RIIb are involved in B-cell function and IgE-mediated immunity, respectively. Here we show that Fc epsilon RII-mediated endocytosis is observed only in Fc epsilon RIIa-expressing cells, whereas IgE-dependent phagocytosis is observed only in Fc epsilon RIIb-expressing cells, demonstrating the functional difference between Fc epsilon RIIa and Fc epsilon RIIb. Furthermore, site-directed mutagenesis revealed that the tyrosine residue in the Fc epsilon RIIa-specific region is important for endocytosis, and the Asn-Pro residues in the Fc epsilon RIIb-specific region are required for phagocytosis. These findings suggest that endocytosis and phagocytosis are functionally separable phenomena involving distinct amino acid residues.

Amino Acid Sequence

Halothane-induced hyperpolarization and depression of postsynaptic potentials of guinea pig thalamic neurons in vitro.

Intralaminar thalamic nuclei have been considered to be a component of the non-specific sensory system which is involved in physiological functions related to consciousness and pain sensation. The effect of halothane on membrane potentials and synaptic properties of neurons of the parafascicular (Pf) nucleus in guinea pig brain slices was investigated using intracellular recording methods. Halothane at concentrations of 0.4-1.0 mM, which are in the range of clinical concentrations, produced hyperpolarizations of 2-8 mV in approximately 50% of the cells. The halothane-induced hyperpolarization was nullified at a membrane potential close to the K+ equilibrium potential. The amplitude of the hyperpolarization was dependent on the external K+ concentration, and was decreased by either Ba2+, or 4-aminopyridine, or intracellular injection of Cs+. All these results indicate that the hyperpolarization was due to an increase in K+ conductance. Halothane at clinical concentrations depressed both excitatory and inhibitory postsynaptic potentials in a concentration-dependent manner. On the other hand hyperpolarizing responses to exogenous gamma-aminobutyric acid (GABA) in the presence of bicuculline were suppressed by halothane, but depolarizing responses to L-glutamate were not altered. The results indicate that the depressant action of the anesthetic on the excitatory postsynaptic potential (EPSP) may occur presynaptically, whereas the blocking action on the inhibitory postsynaptic potential (IPSP) may occur postsynaptically.

Animals

Effect of intracarotid infusion of etoposide with angiotensin II-induced hypertension on the blood-brain barrier and the brain tissue.

This study investigated the effects of the intracarotid infusion of etoposide in combination with angiotensin II (AT II)-induced hypertension on the blood-brain barrier (BBB) and brain tissue in rats. Eighty rats were divided into five groups: Group 1, intravenous infusion of AT II to increase arterial blood pressure; Group 2, intracarotid infusion of etoposide at 22.5 mg/m2 for 10 minutes; Group 3, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes; Group 4, intracarotid infusion of etoposide at 75.0 mg/m2 for 20 minutes; Group 5, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes with AT II-induced hypertension. Evans blue staining of the brain was used as a monitor of BBB disruption. Mean arterial blood pressure over the experimental period in Group 1 increased from 86.3 +/- 1.3 mmHg (mean +/- SEM) to 139.0 +/- 2.4 mmHg, and Group 5 from 85.9 +/- 1.8 mmHg to 137.3 +/- 2.4 mmHg. None of the animals in Group 1 and 2 showed any obvious neurological change, while all the animals in Group 3, 4 and 5 exhibited diminished activity as their sole neurological change throughout the course of the experiment. Slight evidence of BBB disruption was seen in only 25% of the animals in Group 1. Significant BBB disruption was found in the animals in Group 2, 3, 4 and 5. No histological change was observed in any animal in Group 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Penetration of etoposide into human malignant brain tumors after intravenous and oral administration.

Penetration of etoposide into the cerebrospinal fluid, brain tumor, and brain tissue after intravenous administration was investigated in patients presenting with malignant brain tumors. A relatively low dose (55-65 mg/m2) was used to compare intravenous with oral administration. High-performance liquid chromatography with fluorescence detection was used to evaluate drug levels. Plasma and cerebrospinal fluid levels of etoposide after oral administration (50-150 mg/day) were also studied so as to determine the adequate oral dose for the treatment of malignant brain tumors. The peak plasma concentration after intravenous administration ranged from 7.01 to 10.47 micrograms/ml, varying in proportion to the injected dose, whereas that after oral administration was lower, namely, 1.44-4.99 micrograms/ml, and was unstable when the oral dose was 150 mg daily. The peak cerebrospinal fluid level following either intravenous or oral administration was much lower than the plasma concentration and was influenced by the peak plasma level and the sampling site. The etoposide concentration in cerebrospinal fluid taken from the subarachnoid space and ventricle of patients displaying no tumor invasion and of those presenting with meningeal carcinomatosis and in cerebrospinal fluid taken from the dead space after tumor resection was 0.7% +/- 0.5%, 3.4% +/- 1.0%, and 7.2% +/- 8.5%, respectively, of the plasma concentration. Serial oral administration did not result in the accumulation of etoposide in cerebrospinal fluid. The tumor concentration (1.04-4.80 micrograms/g) was 14.0% +/- 2.9% of the plasma level after intravenous administration, was related to the injected dose, and was approximately twice the concentration detected in the brain tissue. Therefore, a relatively low dose of etoposide injected intravenously penetrates the brain tumor at an efficacious concentration. Our results indicate than an oral dose of 100 mg etoposide be given for malignant brain tumors, as limited penetration of the drug into the intracranial region was observed.

Administration, Oral

Treatment of small hepatocellular carcinoma.

Of the 692 patients with hepatocellular carcinoma (HCC) who were admitted to our hospital between 1976 and 1990, 60 (8.8%) had small HCC with a maximal diameter of below 2 cm. The outcome of these 60 cases was analyzed after they had been divided into 4 groups based on the therapeutic method used: operation group (17 cases), percutaneous ethanol injection therapy (PEIT) group (20 cases), transcatheter arterial embolization (TAE) group (13 cases), and oral anticancer drug therapy (per os) group (10 cases). The 1-, 2-, 3-, 4-, and 5-year survival values obtained for the operation group (100%, 87.5%, 87.5%, 87.5%, and 87.5%, respectively) were significantly higher than those found for the per os group (P < 0.01). The best therapeutic results were achieved in the operation group. Although the follow-up period for the PEIT group was short, the 2-year survival of this group was nearly equal to that of the operation group. Whereas the duration of survival tended to increase in inverse proportion to the severity of the underlying liver cirrhosis, the survival values did not differ between solitary and multiple tumors or among the different histological grades of HCC. In this series, 20 patients died; 9 deaths (45.0%) were due to progressive disease and 3 deaths (15.0%) were attributed to hepatic failure. Because the operation group included many patients who displayed relatively good liver function, we cannot rule out the possibility that their excellent outcome may have been associated with this background factor. Therefore, further prospective investigation is necessary to compare the efficacy of various therapies in patient groups with a homogeneous background.

Aged

Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency.

The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0-inaffinity) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1%, Group II, 21.6%, Group III, 12.8%). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.

Angiotensin-Converting Enzyme Inhibitors

Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases.

To better understand the metastatic behavior of pulmonary adenocarcinoma, we studied the differences in carbohydrate antigens between primary tumors and their metastases using three monoclonal antibodies (FH-2 defining Lewis [Le]x, AH-6 defining Le(y), and FH-6 defining sialyl Le(x-i)) on 56 autopsy cases (including 15 cases in which primary tumors were surgically resected) and 116 cases of surgically resected pulmonary adenocarcinoma. Metastatic lesions were divided into two groups according to the route of metastasis: group 1 comprised lymphatic metastases, such as lymph node and contralateral lung metastases, and group 2 comprised hematogenous metastases, such as extrathoracic spread. Both primary tumors and metastatic lesions with well-differentiated glandular patterns showed higher positive rates for Le(y) than the poorly differentiated lesions. Such a difference in the antigen expression in relation to tumor differentiation was barely demonstrated for Le(x) and sialyl Le(x-i). Discordance in antigen expression between primary and metastatic lesions (ie, positive primary tumors with negative metastatic lesions and negative primary tumors with positive metastatic lesions) was observed in the following order of frequency: extrathoracic metastatic lesion, contralateral lung, mediastinal lymph node (N2), and ipsilateral peribronchial and hilar (N1) lymph nodes. This study revealed increased biologic diversity of pulmonary adenocarcinoma in cell surface antigens following tumor progression, especially in extrathoracic metastasis.

Adenocarcinoma

Ganglioglioma of the optic pathway. A case report.

A case of ganglioglioma of the optic pathway associated with congenital exophthalmos and strabismus is presented. Since the tumor extended from the right optic nerve to the right geniculate body, it was diagnosed as an optic glioma before operation. However, optic nerve biopsy showed that the lesion was a ganglioglioma. Although a literature review yielded two previous cases of ganglioglioma of the optic pathway, this is the first case in which the tumor involved the whole optic pathway.

Adolescent

Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: report of six cases and review of the literature.

The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment.

Adolescent

Intracranial metastasis from a spinal cord primitive neuroectodermal tumor: case report.

A patient with intracranial seeding from a spinal cord primitive neuroectodermal tumor with ependymal differentiation is presented. The first and second stages of intracranial dissemination were well controlled by a combination of irradiation and chemotherapy. The authors review previously published cases and discuss the possible mechanism of seeding from the spinal cord to the intracranial region.

Adolescent

Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion.

To investigate the mechanism of oral carbohydrate-stimulated secretion of the two most potent incretin candidates, gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1), we studied the changes in the plasma levels of these peptides in five healthy men after sucrose ingestion with or without pretreatment with an alpha-D-glucosidase inhibitor (AO-128). After sucrose ingestion, plasma levels of GIP peaked at 15 min and remained high up to 120 min. Plasma levels of GLP-1 NT measured with antiserum R1043 (N-terminal specific) tended to decrease gradually and those of GLP-1 CT measured with antiserum R2337 (C-terminal specific) increased. Therefore, estimated plasma levels of tGLP-1 increased markedly within 30 min, then declined slightly over the next 60 min. After treatment with AO-128 (0.6 mg/day) for 1 week, increases in plasma glucose and insulin levels were attenuated and the increase in plasma GIP levels was diminished, while the increase in tGLP-1 levels was sustained much longer. It is concluded that GIP secretion is stimulated by glucose absorption and tGLP-1 secretion by the presence of sucrose in the gut.

Adult

Influences of cyclooxygenase inhibitors on the cataleptic behavior induced by haloperidol in mice.

Haloperidol administered intraperitoneally, and prostaglandin F2 alpha (PGF2 alpha) and PGE2 intraventricularly induced dose-dependent cataleptic behavior in mice. The cataleptic behavior induced by haloperidol was inhibited dose-dependently by oral pretreatment with aspirin and indomethacin, inhibitors of PGs synthetase. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole 3 acetic acid (5-HIAA) were elevated by haloperidol, although dopamine (DA) and 5-hydroxytryptamine (5-HT) levels did not change. The increase of DOPAC level in striatum induced by haloperidol was significantly suppressed by aspirin, but not in brain stem. The alteration of DOPAC level by aspirin correlated with the behavioral response. These results suggest that central prostaglandin synthesis may participate in the development of cataleptic behavior, which might also involve alteration of brain catecholaminergic activity.

3,4-Dihydroxyphenylacetic Acid

Presence of amelanotic melanocytes within the outer root sheath in senile white hair.

In order to determine whether amelanotic melanocytes are present in senile white hair, we attempted to detect tyrosinase mRNA and its protein using in situ hybridization and immunohistochemical staining. Specifically stained cells containing tyrosinase mRNA or its protein were detected by each technique in 7/23 (30.4%) or 4/14 (28.6%) senile white hairs, respectively. These cells were located in the outer root sheath between the hair-bulb and the infundibulum. Silver staining was used to determine whether melanin was present within the outer root sheath of the senile white hair. Because none of the 21 white hairs tested showed specific staining within the outer root sheath, the absence of melanin was confirmed. Thus our results suggest the presence of amelanotic melanocytes within the outer root sheath of senile white hair.

Adult

HLA profiles of multiple sclerosis in Hokkaido, the northernmost island of Japan.

We studied HLA haplotypes in 43 consecutive clinically definite MS patients in Hokkaido. The patients were classified into Group A, 12 patients with acute transverse myelopathy (ATM) during the course of illness, and Group B, 31 without ATM. We found an association with HLA-DQw7 in Group A, and with DR4 and DRw8 in Group B. The frequency of DQw7 and DR4 were significantly different between Groups A and B. This study may indicate the different genetic backgrounds between the groups. DRw8 and DRw52 antigens were significantly more common in MS than in controls. Our result is inconsistent with previous Japanese studies, and ethnic variation might be considered as a possible cause of the contradiction.

Adult

[Comparison of submaximal front crawl and breast stroke swimming in relation to energy expenditure].

The purpose of this study was to compare the energy expenditure during submaximal front crawl (Fr) and breast stroke (Br) swimming. Six male college swimmers performed submaximal and maximal exercise tests in both styles in a swimming flume. In submaximal exercise tests, they swam at the following given velocities for 5 min, Br: 0.3, 0.5 and 0.7 m/sec; Fr: 0.3, 0.5, 0.7 and 0.9 m/sec. In maximal exercise tests, following submaximal swimming at 0.9 m/sec in Br and 1.1 m/sec in Fr, swimming velocity was increased progressively by 0.1 m/sec every 1 min until the subjects reached to voluntary exhaustion. VO2max obtained from the maximal swimming tests in Br and Fr were 4.27 and 4.18 l/min, respectively. And there was no significant difference between these two values. VO2 during Br and Fr swimming at four and five submaximal velocities were 1.06, 1.30, 1.79, 2.65 l/min and 1.17, 1.34, 1.63, 2.04, 3.05 l/min, respectively. And, it was found that VO2 at 0.3 and 0.9 m/sec were significantly different (p < 0.05 and p < 0.01) between Fr and Br. VO2 in both styles curvilinearly increased with swimming velocity, and these relationships were well fitted for the regression equation of the second order (Br: y = 3.84625x2 - 1.95914x + 1.310463,r2 = 0.999 (p < 0.05), Fr: y = 3.233446x2 - 2.28136x + 1.611524, r2 = 0.979 (p < 0.05)). It was calculated that the two curves crossed at a point on 0.49 m/sec, and that VO2 at this point was 1.27 l/min. This value equivalented to 30.4% VO2max in Br and 29.7% VO2max in Fr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Systemic lupus erythematosus with sensorineural hearing loss and improvement after plasmapheresis using the double filtration method.

A 32-year-old female was diagnosed as having systemic lupus erythematosus based on her laboratory tests. In 1985 she began to complain of hearing difficulty. Her hearing ability deteriorated to the extent that her audiogram revealed a hearing loss of 90 db to 110 db in both ears in September 1989. She received two series of plasmapheresis treatments using the double filtration method. After two series of plasmapheresis treatments, her hearing improved dramatically. This improvement suggests that circulating immune complexes and anti-phospholipid antibodies might play a pathological role in the hearing impairment in SLE patient.

Adult