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Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 685 records · Page 38Linked to original sources

Postsynaptic density visualized by whole mount electron microscopy.

Detergent-unextractable structures of synaptic plasma membrane of rat cerebrum were observed by whole mount electron microscopy. The globular structures were identified as postsynaptic densities (PSDs) from several criteria and appeared to consist of folded strings, to which a number of other molecules might be attached. Some of the globular structures were attached with subsynaptic webs. The structures contained a number of finely striated small strips (10-20 nm wide, 60-100 nm long), parts of which were peeled off from PSD cytoskeletal base by N-lauroyl sarcosinate.

Animals↗

Origin of short-latency somatosensory evoked potentials to median nerve stimulation in the cat. Comparison of the recording montages and effect of laminectomy.

Short-latency somatosensory evoked potentials were recorded from 23 cats with the frontal-neck, scalp-ear and scalp-noncephalic reference montages. In the frontal-neck recordings, four or five components (n9, n11, n13a, n13b and n14) were identified, whereas three components (p15, p18 and p20) were recorded in the scalp-ear leads. The noncephalic reference recordings had four to six components (p9, p10, p11, p13a, p13b and p14). The origin of these components was investigated by recording direct from the attributed generators and examining the effects of lesions. The suggested generators are as follows: n9, p9 and p10-peripheral nerve; n11, p11-dorsal column; n13a-segmental dorsal horn; p13a-spinocerebellar tract; n13b and p13b-cuneate nucleus and caudal part of the medial lemniscus; n14, p14 and p15-rostral part of the medial lemniscus; p18-thalamocortical radiation; p20-primary somatosensory cortex. Components with similar latencies such as n13a and p13a in the frontal-neck and noncephalic reference recordings had different generators. In the noncephalic reference recordings, the axially orientated dipoles, including the potential produced by the spinocerebellar tract (p13a) were clearly detectable, but the transversely orientated dipole of the segmental dorsal horn (n13a) was indistinct. The frontal-neck montage was distorted by the frontal 'reference' electrode active for part of the axially ascending volleys (p13a in some cats and p14), but could pick up the near-field potentials in the segmental dorsal horn (n13a). Desynchronized volleys in fibre tracts such as the spinothalamic tract did not contribute significantly to the potentials recorded from the skin, whereas the synaptic potential in the cuneate nucleus was shown to have a steep onset and open-field distribution with its dipole orientated in part axially, and was recorded in the noncephalic reference montage. The p9 and p11 positivities fused after laminectomy, suggesting that conductance change at the root entry to the bony spinal canal separates these components in the noncephalic reference recording.

Anesthesia↗

Mutagenic activation of biliary metabolites of benzo(a)pyrene by beta-glucuronidase-positive bacteria in human faeces.

Human faeces hydrolysed synthetic beta-D-glucuronides of both p-nitrophenol and phenolphthalein. The origin of this activity in faeces was localised in the bacterial pellet fraction after centrifugation. Ninety-seven bacterial strains with beta-glucuronidase activity isolated from fresh human faeces were identified as species of Bacteroides, Peptostreptococcus, Fusobacterium, Propionibacterium, Clostridium, Eubacterium and Bifidobacterium. They were classified into two groups according to their activity against two synthetic beta-D-glucuronides. One group hydrolysed p-nitrophenyl glucuronide and phenolphthalein glucuronide to the same extent and the other hydrolysed p-nitrophenyl glucuronide much more strongly than phenolphthalein glucuronide. The bile of rats given benzo(a)pyrene by mouth was tested for mutagenicity in the presence and absence of cell-free extracts of human faeces and bacteria. Extracts of beta-glucuronidase-positive bacteria increased the mutagenicity of metabolites of benzo(a)pyrene, as did faecal extracts, but extracts of beta-glucuronidase-negative bacteria did not. D-Saccharic acid-1,4-lactone inhibited the increase in mutagenicity produced by the faecal extracts and extracts of beta-glucuronidase-positive bacteria except for Peptostreptococcus strains 204 and 952. These results indicate that some intestinal bacteria have beta-glucuronidases heterogenous in substrate specificity and that they may be involved in mutagenicity of benzo(a)pyrene in the intestinal tract.

Adult↗

Characterization of Ca2+/calmodulin-dependent protein kinase associated with rat cerebral synaptic junction: substrate specificity and effect of autophosphorylation.

The Ca2+/calmodulin (CaM)-dependent protein kinase associated with rat cerebral synaptic junction (SJ) was characterized, using the SJ fraction as the enzyme preparation, to clarify the functional significance of the enzyme in situ. The protein kinase was greatly activated in the presence of micromolar concentrations of both Ca2+ and calmodulin (EC50 for Ca2+, 1.0 microM; that for CaM, 100 nM). The Km for ATP was 150 microM. SJ proteins were phosphorylated without a lag time, and the phosphorylation reached its maximum within 2-10 min at 25 degrees C. The endogenous substrates consisted of four major (160K, 120K, 60K, and 51K Mr) and 10 minor proteins. Compared with the endogenous substrate phosphorylation, the phosphorylation of exogenously added proteins (myosin light chains from chicken muscle, casein, arginine-rich histone, microtubule-associated protein-2, tau-protein, and tubulin) was weak, although they are expected to be good substrates for the soluble form of the Ca2+/CaM-dependent protein kinase. Autophosphorylation of the enzyme in SJ inhibited its activity and did not alter the subcellular distribution of the enzyme.

Adenosine Triphosphate↗

Prostate growth factor in the extracts of benign prostatic hypertrophy. Partial purification and physicochemical characterization.

The biochemical and physicochemical properties of prostate growth factor (PGF) in the extracts of benign prostatic hypertrophy (BPH) were investigated. The PGF activity stimulating the proliferations of fibroblasts (mouse 3T3 and human BUD-8 cells) was detected predominantly in BPH prostate, and also in normal human prostates and well-differentiated adenocarcinoma prostates. No significant correlation between PGF contents and BPH tissue weight or histological differences (fibromuscular or glandular type) was detected. Gel filtration and isoelectric focusing indicated that partially purified factor(s) by ion exchange column chromatography had a multimolecular form comprising three active components (80,000, 43,000 and 10,000 daltons) and acidic isoelectric points (pH 4.0, 4.3, and 6.0). The activity was susceptible to heat treatment at 80 degrees C for 10 min, and to trypsin, but the factor was devoid of esteropeptidase activity. Subcellular fractionation located the entire activity in cytosol fraction.

Adenocarcinoma↗

Effects of ACNU and radiotherapy on malignant glioma.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Adolescent↗

[Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy in the treatment of intracranial malignant germ cell tumors--a preliminary report of a phase II study--The Japanese Intracranial Germ Cell Tumor Study Group].

Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy was undertaken in 30 patients with primary intracranial malignant germ cell tumors in 11 neurosurgical clinics. The response rate of 17 evaluable patients with nonrecurrent tumors was 64.7% (eight CR and three PR), and that in eight patients with recurrent tumors was 50% (two CR and two PR). The one-year and two-year survival rates were 76.2% and 67.7%, respectively, which are better than the treatment results by radiation therapy alone, i.e., 69.8% and 46.5%. These findings suggest that PVB therapy is effective for intracranial malignant germ cell tumors.

Adult↗

[Clinical studies of cefoperazone in neurosurgery].

A multicenter trial consisting of 164 institutions through out Japan, has been conducted to study the transfer of cefoperazone (CPZ) into the cerebrospinal fluid (CSF), and the clinical effectiveness of CPZ as a therapeutic or prophylactic agent in neurosurgery. The levels of CPZ in serum and CSF were determined in 96 patients. After initial dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum level of CPZ after 1 hour was 124.5 +/- 6.6 micrograms/ml (Mean +/- S.E.), and even after 6 hours, it maintained as high as 47.8 +/- 16.6 micrograms/ml. The peak CPZ levels in CSF in patients with normal or minimal impairment in blood-CSF-barrier (BCB) (group I) and in those of localized impairment in BCB (group II) were 1.0 +/- 0.5 micrograms/ml at 2 hours and 3.0 +/- 1.8 micrograms/ml at 3 hours, respectively. The highest CSF level was seen in patients with meningitis (group III) and showed 5.0 +/- 2.4 micrograms/ml at 6 hours. After multiple dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum kinetics of CPZ were not significantly different from those obtained after initial dose. However, the CPZ levels in CSF were higher than those observed after initial dose in all 3 groups and were higher than MIC75 against relevant pathogens for meningitis such as Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. Moreover, in group III peak level of CPZ in CSF exceeded the MIC75 against Pseudomonas aeruginosa which is also frequently isolated from patients with meningitis in neurosurgery. As a therapeutic agent CPZ administered as sole agent was effective in 42 out of 55 cases (76.4%) in meningitis, in 78 out of 116 cases (67.2%) in pneumonia and in 36 out of 47 cases (76.6%) in urinary tract infection (UTI). Its efficacy rate against all infections treated was 72.2% (184/255). Regarding CPZ's prophylactic use, 39 out of 514 cases (7.6%) were judged as having or possibly having infections as follows; meningitis (13/514, 2.5%), pneumonia (15/514, 2.9%), UTI (2/514, 0.4%). In prophylactic use of CPZ, the incidence rates of postoperative meningitis and other central nervous system (CNS) infection following ventricular drainage and supratentorial craniotomy for aneurysm were higher than those observed in other types of operation, 12.0% (3/25) and 6.2% (8/130), respectively. Also, regarding prophylactic use of CPZ, the organisms isolated by culture from 13 cases of postoperative CNS infections included 2 strains of Staphylococcus sp., 1 strain of Serratia sp. and 3 strains of other Gram-negative bacteria (GNB).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Investigation of HLA in patients with glioma].

HLA was studied in 35 patients with gliomas (20 anaplastic gliomas, 11 astrocytomas, 2 ependymomas, 2 oligodendrogliomas) and 38 volunteers who served as controls, by using the microdroplet lymphocyte cytotoxicity test. Phenotype frequency (PF), gene frequency (GF) and relative risk (RR) of each HLA antigen were studied statistically with the chi 2-test, where corrected P (CP) less than 0.05 was considered significant. Concerning HLA-B antigens, either Bw 61 or Bw 62 was found in 45.7% of the patients and the both in 14.3%. HLA-Bw 61 had a tendency to increase in the patients (PF = 0.46, GF = 0.27, RR = 7.16, chi 2 = 9.64, P less than 0.002, CP less than 0.064). Contrary to HLA-B antigens, HLA-DRw 6 was absent in the patient (chi 2 = 8.3379, P less than 0.004, CP less than 0.04). No relation between HLA and histological types was found. HLA has its genetic locus on the short brachium of the 6th chromosome and complement C2, C4, properdin, etc are considered to link HLA. Immunoregulatory genes (Ir genes), immunosuppressive genes (Is genes), disease susceptibility genes and disease resistant genes are also considered to link HLA, especially HLA-B, D loci. Although diseases are multifactorial, according to our report, the incidence of HLA-Bw 61 is higher, while that of HLA-DRw 6 is lower in patients with glioma. These phenomena seem very interesting considering the previous evidence that HLA has a close relation between disease susceptibility and immunological competence.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

[Morphological changes of the thymus and spleen with acute experimental allergic encephalomyelitis (EAE) in Lewis rats].

Nervous and immune systems are thought to have an important role in host defence mechanism. Recent reports have suggested the presence of common antigens between nervous and immune systems. In this paper, we described the interactions between nervous and immune systems observed in an acute EAE model of Lewis rats. Seventeen Lewis rats were immunized by homogenized brain tissue in complete Freund adjuvant. Acute EAE rats were developed in 10 rats, all of which died within 25 days after the immunization. The thymus of these rats showed marked atrophy and histological examination revealed severe de generation of the lymphocytes and infiltration of macrophage showing phagocytosis in the thymus. The weight of spleen was also decreased, but no remarkable changes were observed microscopically except slight reduction of the white pulp. The fact that the immune reactions was induced not only in the nervous system but also in the thymus of EAE animals may suggest the possibility of common antigen between oligodendroglia and lymphocytes. This also suggest the close interaction between nervous system and immune system. However, the reactions of the thymus and spleen were different in this experiment, and further studies are necessary to evaluate the mechanism of these immune reactions.

Animals↗