Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 289 records · Page 16Linked to original sources

PubMed1995

Golgi retention mechanism of beta-1,4-galactosyltransferase. Membrane-spanning domain-dependent homodimerization and association with alpha- and beta-tubulins.

Recent studies on proteins residing in the Golgi complex revealed that the membrane-spanning domain of these proteins are largely responsible for their retention in the Golgi complex. We show here that beta-1,4-galactosyltransferase (GT) forms homodimers and large oligomers in vivo, and the formation of the homodimers is dependent on cysteine and histidine residues within the transmembrane domain. Double mutations of these residues, Cys29-->Ser and His32-->Leu, abolish homodimerization and simultaneously reduce the Golgi retention. Co-immunoprecipitation of GT and various GT chimeras with anti-GT and anti-reporter molecule antibodies revealed that large aggregates of GT are associated with alpha- and beta-tubulins and also with other cellular proteins. This association between tubulins and GT suggests a supportive role of the cytoskeleton in the Golgi retention mechanism.

Amino Acid Sequence↗

PubMed1995

Effect of Thrombin Inhibition on Patients with Peripheral Arterial Obstructive Disease: A Multicenter Clinical Trial of Argatroban.

Background: Enhanced thrombin generation has been found in patients with peripheral arterial obstructive disease (PAOD). The objective of this study is to investigate the effect of thrombin inhibition in PAOD patients. Methods: Argatroban (20 mg/day) was infused intravenously over 2 hours for 14-68 days in 27 patients with chronic PAOD of the lower extremities. Plasma thrombin-antithrombin III complex (TAT) levels and clinical signs were assessed. Results: TAT levels before argatroban therapy were significantly higher in the PAOD patients than in age- and gender-matched controls. In the PAOD patients, TAT levels increased stepwise in the presence of rest pain classified as Fontain III and IV. To assess the effect of thrombin inhibition, we divided the patients into a high-TAT group (pretreatment TAT level >/=5 ng/ml, n = 12) and a low-TAT group (pretreatment TAT level <5 ng/ml, n = 15). In the high-TAT group, TAT levels were suppressed in 8 of 12 patients after the administration of argatroban, along with improvement of their clinical symptoms and a decrease in the size of ischemic skin ulcers, indicating that argatroban clearly inhibited thrombin generation in vivo. Even in the low-TAT group, argatroban improved the clinical signs and symptoms, and also reduced the size of ischemic skin ulcers although TAT levels remained within the low range (<5 ng/ml) in 13 of the 15 patients, indicating that PAOD signs and/or symptoms may be related to small amounts of thrombin generated locally at the sites of atherothrombotic stenotic lesion. Conclusions: These results suggest that thrombin generation was enhanced in PAOD and that the amount was related to disease severity. Thrombin inhibition by argatroban may break this vicious cycle and lead to clinical improvement in PAOD.

Journal Article↗

PubMed1995

Ruptured aneurysm associated with arachnoid cyst: intracystic hematoma without subarachnoid hemorrhage.

BACKGROUND: It is well-known that arachnoid cysts of the middle fossa are associated often with chronic subdural hematomas and/or intracystic hemorrhages. However, reports of an arachnoid cyst associated with an aneurysm are rare. CASE DESCRIPTION: A 45-year-old man was admitted with headache due to intracystic hemorrhage in the sylvian fissure, associated with a saccular aneurysm at the bifurcation of the internal carotid artery. The aneurysm ruptured into the arachnoid cyst, without causing a subarachnoid hemorrhage. Subsequently, the neck of the aneurysm was clipped successfully. The patient's postoperative course was uneventful, and there was no vasospasm. CONCLUSIONS: This is the first reported case of an intracystic hematoma due to a ruptured aneurysm. We discuss the possible etiology of the association between the aneurysm and the arachnoid cyst, and the formation mechanism for the intracystic hematoma that did not result in a subarachnoid hemorrhage.

Arachnoid Cysts↗

PubMed1995

Alteration of prejunctional alpha 2-adrenergic autoinhibition in DOCA-salt hypertension.

The possible involvement of prejunctional alpha 2-adrenergic autoinhibition in hypertension is still controversial. The aim of this study was to determine the functional integrity of this regulatory mechanism in conscious DOCA-salt hypertensive rats, a model characterized by an increased sympathetic tone and reactivity. Basal and hemorrhage-induced increases in catecholamine and immunoreactive neuropeptide Y (NPY) levels were compared between control and yohimbine (alpha 2-adrenergic receptor antagonist) pretreated normotensive and DOCA-salt hypertensive rats. DOCA-salt hypertensive rats had higher basal norepinephrine levels (NE), as well as increased NE and epinephrine (EPI) responses to a 15-mL/kg hemorrhage as compared to control normotensive rats. In normotensive animals, yohimbine (0.5 mg/kg, intravenous [iv]) doubled plasma NE, EPI, and NPY levels in basal conditions and in response to the hemorrhage. In contrast, the same treatment had smaller or no effect on basal NE levels and on the hemorrhage-induced responses in DOCA-salt hypertensive rats, although basal EPI levels were increased in this group. These results therefore suggest a decreased function of the prejunctional alpha 2-adrenergic autoinhibitory mechanism at the level of sympathetic nerve terminals and adrenal medulla during sympathetic hyperactivity in DOCA-salt hypertension. This dysfunction could in part explain the hyperactivity and hyperreactivity of the sympathetic nervous system observed in this model, and thus contribute to the elevation of blood pressure in DOCA-salt hypertension.

Adrenal Medulla↗

PubMed1995

Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen.

We report 10 cases of glomerulonephritis following methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome were an abrupt or insidious onset of rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA infection. The renal histologic findings showed a variety of types of proliferative glomerulonephritis with varying degrees of crescent formation; immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3. Laboratory findings showed polyclonal increases of serum IgA and IgG, with high levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and DR+CD8+T cells were observed in the peripheral circulation, with a high frequency of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and toxic shock syndrome toxin (TSST)-1, all of which are known to act as superantigens. From the above observations, we speculate that post-MRSA glomerulonephritis may be induced by superantigens causing production of high levels of cytokines, and polyclonal activation of IgG and IgA. The formation of ICs containing IgA and IgG in the circulation result in development of glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play an important role in the pathogenesis of this unique syndrome of nephritis and vasculitis.

Adult↗

PubMed1995

Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy.

An in vivo receptor binding technique was used to evaluate the binding profiles of typical and atypical antipsychotic drugs to striatal dopamine-D2 and frontal serotonin-5-HT2 receptors in a rat brain using more specific ligands than those previously employed. [3H]-YM-09151-2 or [3H]-ketanserin was injected into the tail vein 10 minutes after administration of test drugs. One hour after the ligand injection, radioactivities in the striatum, frontal cortex, and cerebellum were counted to obtain receptor occupancies by the test drugs. Higher ratios of potency in occupying 5-HT2 versus D2 receptors were found for clozapine, RMI-81512, and tiospirone compared to haloperiodol and pimozide. Zotepine, mosapramine, and clocapramine produced ratios that fall between these two groups. Chlorpromazine was exceptional as a typical antispychotic by these criteria. Relatively strong antagonism of 5-HT2 receptors by atypical antipsychotics was confirmed by this in vivo measure of receptor binding using more selective ligands than those used in previous studies.

Animals↗

PubMed1995

Effect of KCl concentration on gating properties of calcium release channels in sarcoplasmic reticulum vesicles.

The effect of KCl concentration on the gating properties of the Ca2+ release channel in sarcoplasmic reticulum vesicles was studied through measurement of the permeation of choline and glucose by means of the light scattering method. The calcium concentration which activates the channel at micromolar range was shifted to higher concentration in the presence of KCl. This phenomenon can be explained by competition between Ca2+ and K+ at the Ca(2+)-binding sites. Five millimolar caffeine increased the apparent affinity of Ca2+ about 10 times but the effect of caffeine was not modified by K+. Inhibition of the channel by millimolar Ca2+ was also competed with by K+. These effects of K+ were not duplicated by choline, suggesting that the binding of choline to these sites is weak. Blocking of the channel by ruthenium red and Mg2+ was also competed with by K+, but blocking by procaine or tetracaine was not. After the opening of the channel by ryanodine, higher concentrations of these blockers were required to close the channel, and further, in the presence of K+ much higher concentrations of blockers were required. These results suggest that these drugs do not block the channel by plugging the pore directly but do so by regulating the gate, and that the Ca2+ release channel has many binding sites for activators and inhibitor to the gate.

Animals↗

PubMed1995

A novel proteinase, glucagon-degrading enzyme, secreted by a human pancreatic cancer cell line, HPC-YO.

Sixty-four kinds of cell lines were examined as to their ability to degrade glucagon using conditioned-media obtained from their protein-free cultures. Two human tumor cell lines were shown to produce this activity, and the cell line, HPC-YO, established from a human pancreatic carcinoma was shown to produce the highest level of activity. The glucagon-degrading enzyme (GDE) was purified from HPC-YO conditioned-medium by a combination of ion-exchange, gel filtration, and hydroxylapatite column chromatographies. The purified GDE also degraded vasoactive intestinal polypeptide (VIP) and secretin, however, it did not cleave EGF, gastrin, insulin, somatostatin, substance P, neurotensin, or growth hormone. The molecular weight of GDE is 83,000, as determined on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of GDE was blocked, and the five partial amino acid sequences obtained on lysyl-endopeptidase digestion were determined to be N-L-T-E-E-Y-D-V-S-D-G-E-I-E-L-L-Y-E-K, V-E-T-Y-Y-D-L-L-F-E-K, L-Y-W-F-L-D-E-A-K, S-N-S-T-S-Y-V-K, and Y-Y-A-S-T-S-Y-D-D-T-Y-K. The same or homologous amino acid sequences have not been found in known proteins, demonstrating that GDE is a novel peptidase that degrades the secretin family: glucagon, VIP, and secretin.

Amino Acid Sequence↗

PubMed1995

Abnormal photic driving responses in never-medicated schizophrenia patients.

The present study was conducted to compare electroencephalogram (EEG) driving responses to 10 hertz photic stimulation in 14 drug-naive schizophrenia patients and 16 sex- and age-matched control subjects. The amplitude of photic driving responses (PDRs) recorded from the occipital region was significantly lower in schizophrenia patients than in controls. In eight schizophrenia patients (vs. none in the control group) the PDR amplitudes recorded at the frontal region were higher than those at the occipital region, and frontal to occipital PDR ratios were significantly larger in schizophrenia subjects than in controls. Quantitative analysis of the resting EEG showed that the patients also had a significantly lower amplitude for the alpha frequency band. These findings suggest that the PDRs of schizophrenia patients are abnormal in their amplitude and distribution.

Adult↗

PubMed1995

Enhancing effect of platelet-derived growth factors on migration of corneal endothelial cells.

To investigate the role of platelet-derived growth factor (PDGF) in corneal wound healing, we examined the effect of human natural PDGF, recombinant PDGF-BB, and PDGF-AA on the migration of rabbit corneal endothelial cells. In a modified Boyden chamber in fetal bovine serum-free conditions, natural PDGF and PDGF-BB, at a concentration of 1-3 or 10 ng/ml, enhanced the migration of endothelial cells, whereas at a higher concentration (10 or 30 ng/ml), this enhanced migration was suppressed; the optimal concentration range for enhancing migration was 3-10 ng/ml. PDGF-AA did not enhance the migration. Natural PDGF and PDGF-BB activity was found for up to 6 h after the beginning of culture, and was completely blocked by anti-PDGF neutralizing antibodies. A checkerboard assay demonstrated that PDGF-BB had a chemotactic effect on the corneal endothelial cell migration. These results suggest that natural PDGF and PDGF-BB, but not PDGF-AA, are involved in corneal wound healing by stimulating the migration of corneal endothelial cells.

Animals↗

PubMed1995

Novel after-loading interstitial photodynamic therapy of canine transmissible sarcoma with photofrin II and excimer dye laser.

Novel after-loading interstitial photodynamic therapy was performed in a canine transmissible sarcoma (CTS) model, utilizing photofrin II and an excimer dye laser. First, photofrin II was injected intravenously at a dose of 5 mg/kg, then 48 h later, laser-proof plastic tubing was inserted into the CTS, followed by photoradiation of the tumor from the inside. The mean diameter of tumor necrosis rapidly increased in parallel with increase in total irradiation energy below 240 J/cm; the mean diameter of tumor necrosis was 20.7 mm at an energy of 120 J/cm, and 24.5 mm at 240 J/cm. Beyond 240 J/cm, the diameter gradually increased to 26 mm at 960 J/cm. As a side effect, cutaneous tissue showed a deep open ulcer at 240 J/cm, a shallow open ulcer at 180 J/cm, and a scar healing at 120 J/cm. The thermal effect of laser light is considered negligible below 480 J/cm.

Animals↗

PubMed1995

Role of nitric oxide in the control of blood pressure in young and adult spontaneously hypertensive rats.

1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nomega-nitro-L-arginine methyl ester (L-NAME) were investigated in anaesthetized and ganglion-blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age-matched normotensive Wistar-Kyoto (WKY) rats. 2. SNP produced a dose-dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains. 3. L-NAME caused dose-dependent pressor responses in both strains. The sensitivity and the maximal response to L-NAME in SHR were significantly greater than those in age-matched WKY (P< 0.05 or 0.01; t-test, 13 d.f. in both ages). However, there were no significant differences in the responses between ages in each strain. 4. Acute reduction of BP induced by 7-O-ethylfangchinoline did not affect the responses to SNP and L-NAME in the adult SHR. 5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.

Aging↗

PubMed1995

Spinal tract degeneration confined to the bilateral posterior columns in malnutrition: report of an autopsy.

An autopsy case of malnutrition with spinal tract degeneration confined to the bilateral posterior columns is reported. The patient had schizophrenia in adolescence, and suffered from aplastic anemia in late middle age. Subsequently, he took little food due to delusions for 18 months until his death. He had malnutrition resulting in severe hypoproteinemia. He developed gait disturbance, loss of deep tendon reflexes and paresthesia of limbs. Neuropathological examination disclosed tract degeneration confined to the bilateral spinal posterior columns, in addition to the findings of aplastic anemia and hypoxic encephalopathy in the cerebrum. The myelin and axons were severely affected throughout the spinal cord; status spongiosus with many fatty-laden macrophages was seen in these lesions. Neurons in the posterior column nuclei were intact, while the dorsal roots and their ganglia were moderately affected. The unusual distribution and extension of the degeneration of the bilateral posterior columns in the poor nutritional state is discussed.

Anemia, Aplastic↗

PubMed1995

Antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses in Creutzfeldt--Jakob disease (Heidenhain type): a case study.

In a patient with Creutzfeldt-Jakob disease (Heidenhain type), which was characterized by the initial onset of visual symptoms and proved by autopsy, there was an antagonizing correlation between spontaneously-induced periodic synchronous discharges and photically induced giant evoked responses. In addition, the two electroencephalogram features appeared and disappeared in parallel with each other during the clinical course of the illness.

Aged↗

PubMed1995

Role of the capsular polysaccharide-like serotype-specific antigen in resistance of Actinobacillus actinomycetemcomitans to phagocytosis by human polymorphonuclear leukocytes.

Serotype b-specific polysaccharide antigen (SPA) of Actinobacillus actinomycetemcomitans Y4 consists of D-fucose and L-rhamnose. To clarify the role of SPA in phagocytosis of the organism by human polymorphonuclear leukocytes (PMNs), monoclonal antibodies (MAbs) against SPA and SPA-defective mutants, which were constructed by inserting the transposon Tn916 into strain Y4, were used in a chemiluminescence (CL) assay and a phagocytic killing assay. The CL responses of human PMNs to strain Y4 were very low, and the organism was not killed by PMNs. In contrast, SPA-defective mutants induced strong CL responses. The addition of immunoglobulin G MAbs against Y4 SPA enhanced significantly both the CL responses to strain Y4 and the killing of the organism in the presence of complement. The CL responses to SPA-defective mutants were little affected by the addition of these MAbs. We conclude that SPA of A. actinomycetemcomitans plays an important role in the resistance to host defenses by PMNs.

Adult↗

PubMed1995

Inhibition by BMS 186295, a selective nonpeptide AT1 antagonist, of adrenal catecholamine release induced by angiotensin II in the dog in vivo.

The aim of the present study was to investigate whether a novel nonpeptide AT1 selective antagonist, BMS 186295 (BMS), can antagonize adrenal catecholamine release induced by local administration of angiotensin II (AII) in anesthetized dogs. Plasma catecholamine concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. AII was locally administered to the left adrenal gland in the absence and presence of BMS. In the first group (n = 7), local infusion (0.5 mL/min, 1 min) of AII (0.001-1.0 micrograms/mL) resulted in a significant dose-dependent increase in the basal secretion of adrenal catecholamines. Aortic catecholamine levels and mean aortic pressure remained unchanged at all doses tested. In the second group (control, n = 10), four repeated infusions (at intervals of 15 min) of AII at 0.1 micrograms/mL resulted in significant increases of adrenal catecholamine secretion compared with the baseline. In the third group receiving BMS given locally to the gland (n = 8), the basal adrenal catecholamine secretion was not significantly altered by BMS itself at any dose tested. However, the net catecholamine response to AII (0.1 micrograms/mL) was significantly and dose dependently attenuated by approximately 40, 60, and 80% in the presence of BMS at doses of 0.1, 1.0, and 10 micrograms/mL, respectively, compared with the control group. The study indicates that BMS dose dependently blocks AII-induced catecholamine secretion in the dog adrenal gland in vivo.

Adrenal Glands↗

PubMed1995

Hepatic denervation reduces adrenal catecholamine secretion during insulin-induced hypoglycemia.

The present study was designed to investigate the functional implication of hepatic afferent nerves in controlling adrenal medullary counterregulatory response to insulin-induced hypoglycemia in anesthetized dogs subjected to an acute surgical denervation of the liver. Aortic glucose concentration decreased similarly in the groups of dogs with hepatic denervation (n = 8) and sham denervation (n = 8) reaching a glucose nadir 30 min after insulin injection (0.15 IU/kg i.v.) from a control value of 89.46 +/- 3.15 and 88.91 +/- 2.86 mg/dl to 52.92 +/- 3.27 and 48.80 +/- 4.18 mg/dl (P < 0.05), respectively. The catecholamine output from the adrenal glands in the sham group significantly increased (P < 0.05), reaching a maximum level 45 min after insulin injection from a control value for epinephrine of 86.35 +/- 26.65 ng/min and for norepinephrine of 32.14 +/- 11.68 ng/min to 659.03 +/- 269.39 and 181.21 +/- 63.03 ng/min, respectively. By contrast, however, adrenal catecholamine output increased only slightly in the hepatic-denervated group during insulin-induced hypoglycemia, from 148.37 +/- 95.29 and 52.06 +/- 28.05 ng/min to 210.49 +/- 96.09 and 79.61 +/- 26.11 ng/min for epinephrine and norepinephrine, respectively, the difference being statistically nonsignificant compared with the corresponding preinjection control value. The maximum net response of adrenal epinephrine and norepinephrine output observed in dogs with hepatic denervation was significantly attenuated by approximately 90 and 82% of the values obtained from the sham group, respectively. In a separate series of experiments, aortic immunoreactive insulin and glucagon concentrations were measured and found to be similar between hepatic-denervated and sham-denervated groups after insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1995

Correlation between neural release of VIP and adrenomedullary catecholamine secretion in vivo.

The aim of the present study was to determine whether vasoactive intestinal peptide (VIP) can be released along with catecholamines from the adrenal gland in response to direct splanchnic nerve stimulation in anesthetized dogs. An attempt was made to verify whether VIP was released mainly from chromaffin cells or from the splanchnic nerve terminals. The first group received a supramaximal stimulation (12 V) given on the left splanchnic nerve at three successive frequencies of 0.2, 2, and 20 Hz. The second group received increasing doses of 1,1-dimethyl-4-phenylpiperazinium (DMPP) locally infused into the denervated left adrenal gland. In response to nerve stimulation, adrenal venous catecholamine concentration significantly increased in a frequency-dependent manner, whereas VIP-like immunoreactive substance (VIP-ir) reached a significant level only at the highest frequency. The multiple linear regression analyses revealed that the net increases in adrenal venous catecholamine concentrations were strongly correlated with combined variables of VIP-ir concentration and frequencies, indicating r = 0.915 and 0.949 (n = 42, P < 0.0001) for epinephrine and norepinephrine concentrations, respectively. In response to local DMPP infusion, adrenal venous catecholamines increased in a dose-dependent manner, whereas VIP-ir remained unchanged. The results indicate that VIP-ir is released along with catecholamines from the dog adrenal gland in response to direct splanchnic nerve stimulation in vivo. The study also suggests that VIP is mainly released from splanchnic nerve endings.

Adrenal Medulla↗