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Biomedical subjects

S Nakajima

Publications and source records attributed to S Nakajima.

At least 19 recordsLinked to original sources
PubMed1992

A novel non-peptide endothelin antagonist isolated from bayberry, Myrica cerifera.

A potent non-peptide ET receptor antagonist, myriceron caffeoyl ester (50-235), was isolated from the bayberry, Myrica cerifera. This compound selectively antagonized specific binding of [125I]ET-1, but not of [125I]ET-3, to rat cardiac membranes, ET-1-induced increase in the intracellular free calcium concentration in Swiss 3T3 fibroblasts, and ET-1-induced contraction of rat aortic strips. Thus, 50-235 is the first non-peptide ET(A) receptor antagonist. This compound can be useful for studying the physiological role of endothelin and exploring its role in various diseases.

3T3 Cells↗
PubMed1992

Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis.

OBJECTIVE: To determine whether laboratory findings showing antibodies to hepatitis C virus (HCV) in patients with autoimmune hepatitis represent false-positive results and to identify possible explanations for true-positive results in these patients. DESIGN: Cross-sectional. SETTING: University-based hospital. PATIENTS: Fifty-two patients with non-A, non-B chronic hepatitis as a control group and 26 patients with classic chronic active autoimmune hepatitis. MEASUREMENTS: Comparison of the results of five kinds of assays of HCV antibodies and HCV RNA. MAIN RESULTS: Of 52 patients with non-A, non-B chronic hepatitis, HCV antibodies (anti-HCV) were detected in 42 patients (81%; 95% CI, 67% to 90%) by a first-generation enzyme-linked immunosorbent assay (ELISA-I), in 39 patients (75%) by Sp42 ELISA, in 37 patients (71%) by RIA-I, in 49 patients (94%) by ELISA-II, and in 48 patients (92%) by RIBA-II. We found HCV RNA in 47 patients (90%; CI, 79% to 97%). Of the 26 patients with autoimmune hepatitis, anti-HCV were detected in 23 patients (88%; CI, 70% to 98%) by ELISA-I, in 12 (46%) by both RIA-I and Sp42 ELISA, in 20 (77%) by ELISA-II, and in 9 (35%) by RIBA-II. However, HCV RNA was found in only five of these patients (19%; CI, 7% to 39%). None of our patients, including controls, had antibodies to superoxide dismutase. Of the 21 patients who had autoimmune hepatitis that was completely responsive to steroid therapy, 18 had anti-HCV by ELISA-I, but 13 of these patients had negative results by RIBA-II, and only two patients had HCV RNA. Of the five patients who did not respond to steroid treatment, all had anti-HCV by ELISA-I, four had negative results by RIBA-II, and three had HCV RNA. CONCLUSIONS: Testing for HCV antibodies in patients with autoimmune hepatitis frequently elicits positive results when the ELISA-I or ELISA-II tests are used. Most of these appear to represent false-positive results because HCV RNA is usually absent from the serum. Such false positivity may result from previous infection with HCV or from cross-reaction of an epitope of HCV. Other patients with apparent autoimmune hepatitis who fail to respond to corticosteroid therapy may actually have chronic hepatitis C (or other non-A, non-B hepatitis) infection.

Adult↗
PubMed1992

Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors.

CSF beta-glucuronidase, polyamines and carcinoembryonic antigen (CEA) were analyzed in 16 patients with meningeal carcinomatosis from solid tumor in systemic organs, 27 with benign brain lesions, 18 with primary brain tumors, 14 with metastatic brain tumors and 5 with leptomeningeal dissemination of other malignant diseases. Beta-glucuronidase levels in all cases of meningeal carcinomatosis, meningeal gliomatosis and meningeal lymphoma were higher than 100 micrograms/dl/hr; on the other hand, levels in all cases of benign brain lesions were below 100 micrograms/dl/hr. Levels of beta-glucuronidase and polyamines were not high in the cases with positive cytology after tumor resection. Polyamine levels were below 0.05 nmol/ml in all cases after resection of the metastatic brain tumor. Cystic fluid of malignant tumors showed high levels of beta-glucuronidase and polyamines. On the other hand, the levels of polyamines in the cystic fluid of benign tumor were low, although the levels of beta-glucuronidase were high. Some cases of meningeal carcinomatosis with high levels of serum CEA did not show high levels of CSF CEA. For metastatic brain tumors, the cases with intraparenchymal tumors, especially with dural attachment showed high levels of beta-glucuronidase and CEA preoperatively, but they returned to normal after surgery. In cases of meningeal carcinomatosis treated by intrathecal chemotherapy with methotrexate (MTX) and cytosine arabinoside (Ara-C), CSF beta-glucuronidase reflected the neurological status better than the cell count decreased rapidly following chemotherapy and beta-glucuronidase was considered as a useful CSF marker in cases of meningeal carcinomatosis to monitor the course of the disease. The same situation was observed in CSF CEA and CEA was also considered as a useful marker when CEA levels in CSF are higher than those in serum.

Antineoplastic Agents↗
PubMed1992

Diagnosis and treatment of patients with meningeal carcinomatosis.

The records of thirty-four patients with meningeal carcinomatosis treated at our hospital between 1984 and 1990 were reviewed. The sources, histologies, metastatic lesions outside the central nervous system, the history of the treatment of primary lesions and intraparenchymal of metastatic brain tumors and the period from the diagnosis of primary lesions and the treatment of intraparenchymal metastatic brain tumors to the diagnosis of meningeal carcinomatosis were investigated. Meningeal carcinomatosis was diagnosed and by neurological signs, CSF cytology, CT scan and MRI. Each patient was given a 5 mg single dose of methotrexate (MTX) alone or combined with 20 mg cytosine arabinoside (Ara-C) administered by intrathecal injection via an Ommaya reservoir and standard lumbar puncture with or without radiotherapy. Following intrathecal chemotherapy 22 of 29 patients showed symptomatic improvement of meningeal irritation and in 10 of 29 patients with cranial nerve impairment amelioration of symptoms was also observed. Moreover, CSF cytology became negative in 10 of 29 patients after a full course of intrathecal chemotherapy. Neurotoxicity Leukoencephalopathy, a neurotoxic effect of intrathecal chemotherapy was not observed in any of the patients. From these results, MTX in small doses is recommended for intrathecal chemotherapy of meningeal carcinomatosis to prevent neurotoxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Differential effects of scopolamine on working and reference memory depend upon level of training.

Controversy exists whether the cholinergic system in the brain is involved in working memory (WM) selectively or in both WM and reference memory (RM). Rats were trained to obtain food from four baited arms of an eight-arm radial maze. The remaining arms were never baited. Three types of errors were recorded: entry into unbaited arms (RM errors), reentry into baited arms (WM errors), and reentry into unbaited arms (WRM errors). There were no differences among three control conditions: methyl scopolamine, physiological saline, and uninjected. Scopolamine increased WM but not RM errors. When rats were trained to a higher criterion of learning, however, both WM and RM were impaired. It appears that when baseline error rate is sufficiently low RM errors under scopolamine become observable. The results suggest that the cholinergic system is involved in both WM and RM, and the selective involvement of WM is the result of insufficient training. The controversy in the literature over the involvement of the cholinergic system in WM and RM was addressed.

Animals↗
PubMed1992

Evaluation of vitamin D-binding protein and vitamin D metabolite loss in children on continuous ambulatory peritoneal dialysis.

We measured the serum concentration of vitamin D-binding protein (DBP) in children with chronic renal failure (CRF). We also evaluated the relationships between the peritoneal loss of vitamin D metabolites, DBP and albumin in nine children on continuous ambulatory peritoneal dialysis (CAPD). The serum levels of DBP in children with CRF were significantly higher than in normal children. The mean serum DBP level in CRF children undergoing CAPD was slightly lower than in CRF patients who were not on dialysis. In patients on CAPD, the peritoneal loss of 25-hydroxyvitamin D (25OHD) showed a significant positive correlation with the DBP concentration in the dialysate (r = 0.855, P less than 0.005). In contrast, the peritoneal loss of 1,25-dihydroxyvitamin D (1,25(OH)2D) showed a significant correlation with the loss of albumin in the dialysate (r = 0.779, P less than 0.01). The synthesis of 1,25(OH)2D3 is reduced in advanced renal failure, and the peritoneal losses of the active vitamin D sterols in patients on CAPD may aggravate this deficiency. We recommend that supplementation of active form of vitamin D, such as 1 alpha-hydroxyvitamin D3 or 1,25(OH)2D3, is important in CAPD patients, particularly those with elevated peritoneal loss of DBP and/or albumin.

Adolescent↗
PubMed1992

1,25-Dihydroxyvitamin D3 does not up-regulate vitamin D receptor messenger ribonucleic acid levels in hypophosphatemic mice.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) administration on duodenal vitamin D receptor (VDR) mRNA levels in hypophosphatemic (Hyp) mice, a murine homologue of human X-linked hypophosphatemic rickets, was examined. Basal levels of VDR mRNA in Hyp mice were similar to those of normal littermates and, in normal mice, VDR mRNA levels were up-regulated 1.8-2.7-fold after injection of 1 microgram/kg 1,25(OH)2D3. In contrast, no significant change in VDR mRNA was observed in Hyp mice treated with 1,25(OH)2D3. To determine the effect of phosphate repletion on VDR mRNA levels, high-phosphate diet was fed to Hyp mice. Although plasma phosphorus concentration was restored to normal, up-regulation of VDR mRNA was not recovered with phosphate supplementation. These results indicate that the vitamin D-resistance in Hyp mice is not caused by hypophosphatemia, per se, and may result from a fundamental molecular defect in vitamin D action at the intestine which could be related to ineffective up-regulation of VDR mRNA by 1,25(OH)2D3.

Animals↗
PubMed1992

Dissociated high-purity dopaminergic neuron cultures from the substantia nigra and the ventral tegmental area of the postnatal rat.

We have developed dissociated primary neuronal cultures obtained from the substantia nigra and from the ventral tegmental area of postnatal rats (two to three days old). After making brain slices, the regions of the substantia nigra and the ventral tegmental area were separately dissected. The removed fragments of brain tissue were dissociated and cultured on a glial feeder layer. Double immunocytochemical labeling for tyrosine hydroxylase and GABA on cultures grown for two to three weeks showed the presence of 42% dopaminergic and 39% GABAergic neurons in substantia nigra cultures, whereas in ventral tegmental area cultures there were 65% dopaminergic and 21% GABAergic neurons. The dopaminergic neurons were characterized by thick and straight primary processes dividing into several branches. Varicosities were found mainly on distal parts of the processes. In contrast, GABAergic neurons possessed highly branched thick and thin primary processes with intensive arborization and numerous varicosities. Co-existence of dopamine and cholecystokinin was found in about 70% of dopaminergic neurons from the substantia nigra and in about 35% of dopaminergic neurons from the ventral tegmental area. Physiological properties of these cultured dopaminergic neurons were investigated with the whole-cell version of the patch-clamp method. After each physiological experiment, immunocytochemical labeling confirmed that the cell was dopaminergic. Properties of single action potentials, with an action potential height of 92 mV and duration of 1.6 ms, were similar to those reported for dopaminergic neurons in brain slices. The neurons showed a high resting potential, and no spontaneous firing of action potentials. Constant current depolarizations elicited trains of action potentials. In the majority of cells, the train stopped firing within a few seconds, while in some cells it lasted indefinitely. When the cell was hyperpolarized, the voltage response started to decline slowly (sag), indicating the presence of hyperpolarization-activated currents (time-dependent inward rectification). These results show that by using our culture method it is possible to obtain separate dissociated cultures of the substantia nigra and the ventral tegmental area from newborn rats. Because they are rich in functional dopaminergic neurons, these cultures will be a useful tool for studying various properties of dopaminergic neurons.

Action Potentials↗
PubMed1992

Comparison of the HA genes of type B influenza viruses in herald waves and later epidemic seasons.

From January 1985 to May 1991, herald strains of influenza B virus were isolated in 1987 and 1989 in Japan. In both cases, influenza epidemics caused by the same type followed in the next winter season. The HA gene sequences of the influenza B viruses isolated in Japan from 1987-91, which covers two herald waves of influenza B viruses, were analysed and located on the phylogenetic tree for influenza B viruses after the B/Singapore/64 strain. Co-circulation of at least two evolutionary lineages of the HA genes existed for influenza B viruses in Japan during the period of this study. The herald viruses in one wave (1987) were genetically close to the winter isolates and were considered to be the parental viruses for the following influenza season, while in the other wave (1989) winter isolates belonged to another lineage on which one of the herald viruses was located, but they were genetically and antigenically different from the herald viruses.

Antigens, Viral↗
PubMed1992

Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat.

To examine the neurotoxic effects of domoic acid, an amnesic shellfish toxin, electroencephalographic and behavioural experiments were conducted on 38 rats. Injection of domoic acid (0.5-1.0 mg/kg intravenously, or 0.04-0.08 microgram intraventricularly) caused seizure discharges in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus. Learning of a radial maze task was severely impaired in naive rats after intraventricular injection of domoic acid (and diazepam, ip). In the animals previously trained on the maze task, domoic acid interfered with relearning of the same task. These effects appear similar to those of kainic acid and are analogous to the symptoms observed in humans who ingested mussels tainted with domoic acid.

Animals↗
PubMed1992

The mechanism of photosensitization in photodynamic therapy: chemiluminescence caused by photosensitization of porphyrins in saline containing human serum albumin.

Chemiluminescence (CL) caused by photosensitization of porphyrins in phosphate buffered saline (PBS) solution containing 3% human serum albumin (HSA) was observed for the first time. Irrespective of porphyrins concerned, CL shows a spectrum ranging from 380 to 520 nm with a peak near 450 nm and decays almost single-exponentially with a lifetime of about 15 s. The intensity of CL depends on concentrations of porphyrins and HSA in PBS solution. We have examined a number of porphyrins and observed CL for the compounds with triplet lifetimes longer than 0.1 ms. The appearance and quenching of CL by photosensitization of porphyrin-HSA systems indicate that type II reaction by singlet oxygen occurs significantly in photodynamic therapy resulting in hypoxic regions in environments surrounding the sensitizer.

Humans↗
PubMed1992

[Rapid diagnosis of influenza infection by PCR method--detection of influenza virus HA gene in throat swab].

We studied the detection of the HA gene of human influenza viruses in throat swabs obtained from the outbreaks of influenza in school children utilizing the polymerase chain reaction (PCR) method. Sensitivity and specificity of the PCR method was compared to conventional virus isolation using MDCK cells. Three pairs of primers for PCR in detecting the HA genes of AH1, AH3, and B influenza viruses showed both subtype and type specificity. The dilution experiments showed that influenza viruses, as few as 1.1-3.5 plaque-forming units per 50 microliters, were sufficient for the detection of HA genes by PCR method and the detection rate by PCR method was 2-3 fold higher than that by conventional method. Our results showed that the PCR method was a fast, sensitive and reliable method for the diagnosis of influenza infections.

Base Sequence↗