Biomedical subjects
Publications and source records attributed to N Murayama.
A novel immunosuppressant, Fr.5-B, has been isolated from the debris of Bacillus stearothermophilus UK563 autolysate. Fr.5-B suppressed mouse mixed leukocyte reaction at doses ranging from 10(-4) to 1 microgram/ml, but not proliferation stimulated by concanavalin A and lipopolysaccharide.
Thirty-one patients with intervertebral disc prolapse (IDP) underwent urodynamic study before surgical operation. The lesion was located between C4 and T10 in 14, T11 and L2 in 2 and L2 and S1 in 15 patients. Preoperative urinary symptoms were obstructive in 11 (36%), irritative in 5 (16%) and both obstructive and irritative in 5 (16%) patients, and the remaining 19 patients (32%) had no symptoms. Preoperative urodynamic abnormalities were noted in 23 cases (74%): abnormal urinary uroflow in 6 of 14 cases (43%), residual urine of more than 30 ml in 9 of 31 cases (29%), abnormal cystometrogram and/or external sphincter EMG in 16 of 31 cases (52%). These urodynamic abnormalities were closely correlated with perineal hyposensitivity. Voiding function was re-examined in 22 patients after operation: improved in 14 (64%), unchanged in 1 (4%), worsened in 2 (9%) and normal in 5 (23%) before and after operation. Therefore the above results could indicate that the presence of perineal hyposensitivity should be suspected to have voiding dysfunction in patients with IDP. Orthopedic surgery may improve voiding dysfunction in the majority of patients.
The expression of myeloid antigens has been extensively examined using two-color analysis in 43 children with B-lineage acute lymphoblastic leukemia (ALL). On pre-culture cells, CD33 expression was frequently observed in CD19+, CD10- B-precursor ALL, and CD14 was expressed only on the cells from B-precursor ALL expressing CD19, CD10 and CD20, and B-ALL. After 2 or 3 days of culture without TPA, CD13 emerged on the cells from 21 of 29 patients irrespective of the presence or the absence of fetal calf serum in the culture. Of four patients with CD10+ B-precursor ALL, which showed no expression of CD13 after culture, two had T-cell associated antigens. Whereas the addition of TPA to the culture enhanced the expression of CD13 on the cells from acute non-lymphocytic leukemia (ANLL), TPA reduced the expression of this antigen on B-precursor cells. These findings suggest that the regulatory mechanism of CD13 expression may be different between B-precursor ALL and ANLL. Co-culture with cycloheximide mostly abrogated the induction of CD13, suggesting that CD13 expression was mainly dependent on de novo protein synthesis.
American Bullfrogs, Rana catesbiana, immobilized with suxamethonium chloride (20 mg/kg b. w., i. p.), were used. By stimulating the glossopharyngeal (IX) nerve, reflex activities, composed of early (10-20 ms in latency) and late (greater than 20 ms) components, were evoked in both protoractor branch (P. br.) and retractor branch (R. br.) of the ipsilateral hypoglossal (XII) nerve. Contralateral IXth nerve stimulation increased the reflex activities of both components in the P. br. elicited ipsilaterally by the homonymous nerve. Whereas, it increased the reflex activities of the early component in the R. br. but, decreased that of the late component. On the other hand, stimulation of P. br. in the contralateral XIIth nerve increased the activities of both components in the P. br. and those of the late component in the R. br., but did not affect the activities of the early component in the R. br. The time course of these effects was similar to that by contralateral IXth nerve stimulation. The present findings strongly suggest the existence of afferent fibers in the XIIth nerve.
The topographic analysis of supratentorial brain tumors must answer the following questions: location of the tumor, its extension, its being infiltrative or well localized and especially the relationships with the main functional areas such as the speech areas, the sensori-motor area, and the visuel areas. Also the topographic analysis may help to approach the diagnosis of nature. The neuroradiological procedures include the CT, the angiography and especially the MRI in sagittal and coronal sections, with gadolinium enhancement. The anatomical accuracy is obtained using the bicommissural plane and superimposition techniques according to the Talairach's Atlas and anatomical sections and MRI superimposition with angiography. 3D volumic reconstruction is of considerable contribution for the topographic analysis of a cerebral tumor.
Brain metastases are frequent, accounting for 20% of all brain tumours. The most common primary tumours responsible for brain metastases are lung cancer in man and breast cancer in women. Most metastases are located at the grey matter-white matter junction, in junctional vascular territories and in the rolandic region. Although non-specific, MRI is the most sensitive neuroradiological method for the lesions, especially when accompanied by gadolinium injection. MRI must absolutely be performed before surgical treatment, as gadolinium might detect other metastatic lesions or show metastatic tumours so small that they were not visible at computerized tomography (CT).
Ependymoma is a rare tumour developed from ependymal cells and belonging to the group of neuroglial tumours. It may be located in any part of the central nervous system, but shows a preference for the ventricular cavities. Neuroradiology is not specific. CT shows a frequently large, calcified and cystic lesion of varied density and strongly contrast-enhanced. The signal emitted at MRI is often heterogeneous. Treatment consists of surgery combined with radiotherapy. Prognosis is poor owing to the difficulty of surgical excision and to the possibility of CSF grafts.
Suppression of two major phenobarbital-inducible cytochrome P-450s, P450IIB1 and P450IIB2, by thyroid hormone was studied and compared with growth hormone (GH)-induced suppression in rats in vivo and hepatocytes in primary culture in vitro. Treatment of adult male rats with 50 micrograms/kg triiodothyronine (T3) reduced the constitutively expressed amounts of P450IIB1 (up to 1 pmol/mg of protein) and P450IIB2 (2-5 pmol/mg of protein) to 42% and 3% of their levels in nontreated controls. Thyroidectomy increased the hepatic contents of P450IIB2 (to levels of 50-80 pmol/mg of protein) and, to a lesser extent, P450IIB1 (1-5 pmol/mg of protein) in male and female rats. Supplement of T3 to thyroidectomized rats reversed the increased contents to levels similar to those observed in normal rats. Hypophysectomy also increased both P450IIB1 and P450IIB2 protein, and their levels in both sexes were similar to that of P450IIB2 in thyroidectomized rats. Treatment of hypophysectomized rats with T3 as well as human GH suppressed hepatic contents of P450IIB1 and P450IIB2. In a hepatocyte culture including 2 mM phenobarbital, T3 and GH suppressed both P450IIB1 and P450IIB2. Other thyroid hormone derivatives, including thyroxine, D-T3, and reversed T3, also showed suppressive effects, in parallel with the potencies for their stimulatory action that have been reported. These results indicate that thyroid hormone may suppress both P450IIB1 and P450IIB2 by a direct effect on the liver, but not by an indirect effect through the modulation of pituitary GH synthesis. The high susceptibility of hepatic P450IIB2 to thyroid hormone-induced suppression also indicates that constitutive and phenobarbital-induced levels of P450IIB2 are suppressively regulated preferentially by thyroid hormone, in contrast to the high susceptibility to GH of P450IIB1 in rat liver. In addition, a difference in the suppressive mechanisms of thyroid hormone and GH was suggested by the difference in susceptibility to cycloheximide.
In vitro metabolism of trichloroethylene (TRI) and trichloroethanol (TCE) was investigated using liver microsomes from control and ethanol-, phenobarbital (PB)-, and 3-methylcholanthrene (MC)-treated rats. At least three forms of enzymes were involved in TRI metabolism. One was a low-Km type normally existing in microsomes from control rats. The ethanol-inducible enzyme was found to be catalytically identical to this low-Km isozyme. Another was a high-Km type which was induced exclusively by PB, and a third was an MC-inducible isozyme with a Km value between those of ethanol- and PB-inducible isozymes. Although MC treatment did not affect the rate of TRI metabolism in vitro, both ethanol and PB treatment markedly enhanced the metabolism. Ethanol-induced enhancement was different from PB-induced enhancement in that ethanol enhanced the metabolism predominantly at low substrate concentrations, whereas PB did so at high concentrations. In addition, TRI metabolism with enzymes from ethanol-treated rats was inhibited by the substrate itself at high concentrations. MC treatment of rats had little or no influence on the rate of TCE metabolism in vitro, whereas both ethanol and PB enhanced the microsomal conversion of TCE to chloral hydrate. As in the case of TRI metabolism, ethanol induced a microsomal TCE-metabolizing enzyme of low Km, whereas PB preferentially induced an enzyme of high Km.
While applying natural stimulation to the entire oral cavity, we recorded responses from 489 neurons (400 mechanoreceptive, 84 taste and 5 cold neurons) in the insular cortex of urethane-anesthetized rats. Intermingled with the mechanoreceptive neurons was a major group of taste neurons located in the granular or dysgranular insular area at levels of 2.55-1.20 mm anterior to the bed nucleus of the anterior commissure as stereotaxically located. Most of the taste neurons were also sensitive to mechanical stimulation of the oral and/or perioral tissue.
We previously reported a simple and rapid method for HLA-DQA genotyping by digestion of polymerase chain reaction-amplified DQA genes with allele-specific restriction endonucleases. Here we report the application of this method to DP genotyping. The second exon of the HLA-DPB genes was selectively amplified from genomic DNAs of 72 HLA-D homozygous B-cell lines by the polymerase chain reaction method. Amplified DNAs were digested with ApaI, SacI, BstUI, FokI, and RsaI, which can recognize allelic sequence variations in the polymorphic segments of the DPB second exon and then subjected to electrophoresis in polyacrylamide gels. Sixteen different polymorphic patterns of the restriction fragments were found, and twelve were identical to patterns predicted from the known DNA sequences correlating with each HLA-DPw specificity defined by cellular typing. The other four patterns were distinct from those of the known DPw specificities, suggesting the presence of novel DP alleles. This polymerase chain reaction-restriction fragment length polymorphism method provides a simple and rapid technique for accurate definition of HLA-DP types at the nucleotide level, replacing the technically demanding method of primed lymphocyte typing.
Stereoselective 4'-hydroxylations of R-(-)-mephenytoin and S-(+)-mephenytoin and 3'-hydroxylation of R-(-)-hexobarbital and S-(+)-hexobarbital were determined in liver microsomes of 14 Japanese subjects who were extensive metabolizers of mephenytoin and in five Japanese subjects who were poor metabolizers of mephenytoin. Content of P-450 human-2 assessed by Western blots was correlated to microsomal S-(+)-mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' alpha-hydroxylation, and S-(+)-hexobarbital 3' beta-hydroxylation, and was less correlated to R-(-)mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' beta-hydroxylation, and S-(+)-hexobarbital 3' alpha-hydroxylation. Antibodies raised against P-450 human-2 inhibited microsomal S-(+)-mephenytoin 4'-hydroxylation efficiently but was less efficient on R-(-)-mephenytoin 4'-hydroxylation in extensive metabolizers and on 4'-hydroxylation of mephenytoin enantiomers in poor metabolizers. The antibodies also inhibited R-(-)-hexobarbital 3' alpha-hydroxylation and S-(+)-hexobarbital 3' beta-hydroxylation but did not effectively inhibit the hydroxylation of the two other optical isomers of hexobarbital in extensive metabolizers and of four stereoisomers in poor metabolizers. These findings indicate the close relationship between polymorphic mephenytoin 4'-hydroxylation and two stereospecific hexobarbital hydroxylations, and they suggest that P-450 human-2 is a typical S-(+)-mephenytoin 4'-hydroxylase and a major hexobarbital 3'-hydroxylase in the livers of extensive metabolizers. The findings were further supported by the experiments that used P-450 human-2 complementary dexoyribonucleic acid-derived protein in yeast microsomes.
The effects of thyroid hormone and growth hormone on microsomal testosterone 7 alpha-hydroxylase, P-450a, were studied to understand the interaction of these hormone-mediated regulations in rats. In Western blots using anti-P-450a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 micrograms per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-450a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 micrograms/kg of T3 and of hGH-infused hypophysectomized rat with 50 micrograms/kg of T3.(ABSTRACT TRUNCATED AT 250 WORDS)
The mechanism of the alteration in carcinogenic arylamine-activating capacities in livers bearing pre-neoplastic (or hyperplastic) nodules induced by the Solt-Farber protocol was investigated in relation to the changes in hepatic cytochrome P-450 isozymes. In the Salmonella mutagenesis test, the numbers of revertants induced with 2-amino-3-methylimidazo[4,5-f]quinoline and 2-aminofluorene were significantly lower in the presence of microsomes of nodule-bearing livers than of control livers. A similar tendency was also observed with another heterocyclic arylamine, 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole. In Western blots using specific antibodies against 5 different forms of cytochrome P-450, hepatic contents of P-450-male (a main constitutive form) and P-450b (a main phenobarbital-inducible form) were decreased in the livers with hyperplastic nodules to 63% and 35% of the corresponding controls, while no significant decrease was observed in the contents of P-448-H (a main 3-methylcholanthrene-inducible form), P-450(6 beta-1) (testosterone 6 beta-hydroxylase) and P-450e (a phenobarbital-inducible form). In accordance with the reduction in P-450-male, capacities for microsomal 16 alpha- and 2 alpha-hydroxylations, but not 6 beta-hydroxylation, of testosterone were decreased in the livers with hyperplastic nodules. Although P-448-H has higher capacities for the activation of arylamines than does P-450-male, the hepatic content of P-450-male is more than ten-fold higher than that of P-448-H in both normal and nodule-bearing livers. These results indicate that the selective decrease in hepatic content of P-450-male is likely to be a main cause of the decrease in arylamine metabolic activating capacities in livers with hyperplastic nodules.
Angiotensin-converting enzyme (ACE) inhibitors were excised from the molecule of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of baker's yeast by heating at 120 degrees C in 1 M AcOH-20 mM HCl. Three inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the yeast ACE inhibitors, YG-3, was GAPDH peptide 79-89 (Pro-Ala-Asn-Leu-Pro-Trp-Gly-Ser-Ser-Asn-Val, IC50:18 microM), and contained the sequence homologous to vertebrate ACE inhibitors (GAPDH peptides 79-86 or 81-88). Other inhibitors, YG-1 (Gly-His-Lys-Ile-Ala-Thr-Phe-Gln-Glu-Arg, IC50: 0.4 microM) and YG-2 (Gly-Lys-Lys-Ile-Ala-Thr-Tyr-Gln-Glu-Arg, IC50: 2 microM), corresponded to amino acid residues 68-77 in two different forms of yeast GAPDH, respectively. Their sequences were quite different from those of the venom peptide family. YG-1 was the most potent ACE inhibitor among yeast and vertebrate GAPDH peptides excised by acid-limited proteolysis. Thus, yeast GAPDH seems to be an excellent source of naturally occurring ACE inhibitors.
Four cases of primary pneumatosis cystoides intestinalis (PCI) were studied in relation to occupational trichloroethylene (TRI) exposure. Three of the patients were exposed to TRI in the process of washing or polishing of camera lenses. The maximum concentration of TRI in the work environment of two PCI patients often exceeded 50 ppm, though the geometric mean concentrations were below this value. Monitoring of TRI exposure by measuring urinary TRI metabolites suggested that the third patient had been working in the environment with an 8-h time weighted average TRI concentration exceeding 50 ppm. Scrutiny of 19 PCI cases thus far collected by us revealed that i) three groups of patients (7 in total) were working in the same factories, ii) most of the PCI patients were workers in small-scale factories having poor working conditions, and iii) occupational TRI exposure is probably responsible for the development of primary PCI.
Neurourological studies were performed on 37 patients with cervical spondylotic myelopathy. Micturitional history revealed that 30 patients (81%) had voiding symptoms: obstructive in 14, irritative in 5, and both symptoms in 11. Urodynamic studies revealed that 9 of 20 had abnormal uroflowmetrogram, 17 of 37 had residual urine, 14 of 37 had detrusor hyperreflexia, and 6 of 37 had detrusor-sphincter dyssynergia. There were no statistical differences in lower extremity neurological signs in patients with or without residual urine.
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