Biomedical subjects
Publications and source records attributed to M Machida.
The synthesis and anti-RSV (Rouse Sarcoma Virus) activity of HMCA, (+/-)-9-(2-hydroxymethyl-cyclopenthyl)-adenine, and its derivatives are described. It has been demonstrated that trans-HMCA has greater anti-RSV activity in tissue culture than cis-HMCA.
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The effects of various surfactants and protease inhibitors on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were examined in rats. No effects of bile salts and acids such as sodium glycocholate or taurocholic acid, amphoteric surfactants such as lauryldimethyl betaine, or anionic surfactants such as sodium lauryl sulfate on the absorption were found at a concentration of 1%. But non-ionic surfactants with hydrophile/lipophile balance (HLB) of 13 to 18 increased the total leukocyte numbers maximally by about 250% as a relative increase ratio to the control without surfactants. The increase in the plasma rhG-CSF concentration was obviously observed only in the presence of non-ionic surfactants, and in particular, the effects of Laureth-9 on the increase in total leukocyte numbers and plasma rhG-CSF concentration were maximal. In the presence of various kinds of protease inhibitors, the increasing effect of rhG-CSF on the total leukocyte numbers was not changed. Consequently, it is considered that the permeation of rhG-CSF through the nasal epithelium can be improved by non-ionic surfactants, but the effect of a protease inhibitor is smaller than that of the surfactant.
Familial hypertrophic cardiomyopathy (FHCM) is thought to be caused by missense mutations in cardiac beta-myosin heavy chain (beta-MHC) gene in 30-40% of affected Caucasian individuals. On the other hand, it has been reported that Japanese FHCM is closely linked to DNA marker PALB on chromosome 18q by linkage analysis. Therefore, in order to elucidate the etiological significance of missense mutations in beta-MHC gene in Japanese HCM patients, we have investigated the sequence variation in exon 3 to 25 of beta-MHC gene from 16 multiplex FHCM kindreds and 28 sporadic patients by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. In this study we demonstrated one missense mutation (codon741: GlyGGG-->ArgAGG) in only one kindred among 16 multiplex Japanese kindreds with FHCM. Two synonymous mutations (codon715: TryTAC-->TryTAT, codon 989: IleATT-->IleATC) are demonstrated in another kindred. The same mutation in codon 989 is also detected in one sporadic patient. Furthermore, we performed linkage study with two DNA markers (F13B on chromosome 1q, D11S916: AMF185yal on chromosome 11p-q) which are recently reported to be linked with FHCM. Three and four families showed statistically negative linkage with F13B and D11S916 (AMF185yal), respectively. These results suggest that several responsible genes for HCM may exist in Japanese and principal responsible gene for Japanese HCM is different from it for Caucasian HCM.
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Experimentally induced scoliosis was investigated in pinealectomized chickens using pathologic and neurophysiologic means. A total of 90 chickens were tested; 30 served as a normal control, 30 received an autografted pineal body in the intramuscular tissue of the trunk, and 30 underwent pinealectomy without autograft. Scoliosis developed in all pinealectomized chickens within 2 weeks, showing gradual progression during the next 5 or 6 weeks. At 3 months, the three-dimensional spinal deformity consisted of lateral curvature and vertebral body rotation, resulting in a prominent lordoscoliosis at the thoracic level. In contrast, scoliosis developed in only 10% of the autografted chickens. Histologic examination revealed no pathologic change in the brain in either the pinealectomized scoliosis group or in the autografted nonscoliosis group. Cortical potentials in the scoliosis group were delayed, thus suggesting conduction disturbance rostral to the brain stem. Although the relationship between the cause and effect is uncertain, these findings implicate neurotransmitters or neurohormonal systems in the pineal body as a major contributing factor in this type of experimental scoliosis.
The nucleotide sequence of the gene encoding chicken ribosomal protein L37a was determined. The gene was 2626 bp long and distributed in four exons and three introns. The transcription initiation site is located at a cytidine residue in a tract of 16 pyrimidines flanked by (G + C)-rich regions. Neither canonical TATA nor the CAAT box was found in the 5'-flanking region. The region from nucleotides -78 to -35 was shown to be important for promoter activity and also to be a binding site for nuclear proteins. This region contains two copies of the sequence [sequence: see text] that is common to many ribosomal protein genes of higher eukaryotes.
Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was approximately 2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5-10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.
Because the affinity of FK506 for red blood cells is strong, plasma FK506 levels vary depending upon the temperature at which plasma is separated from whole blood. This study was undertaken to investigate the effects on plasma FK506 of blood temperature at the time of separation and of its rewarming at 37 degrees C, using A) blood samples from rats administered with FK506 at 1 mg/kg for 7 days, and B) human blood samples added with FK506 at 1.0, 3.2 and 10 ng/ml in vitro. 1) Plasma FK506 levels of samples from rats were not affected by storage time, but samples separated at 20 degrees C were significantly lower in FK506 levels than those separated at 37 degrees C. Plasma FK506 level after rewarming blood at 37 degrees C was not significantly different from that of blood stored at 37 degrees C. 2) FK506 levels in human plasma, separated at 30 degrees C and 20 degrees C were 51% and 33%, respectively, of the corresponding value for plasma separated at 37 degrees C. But the level of plasma separated at 0 degrees C was 56%, which was higher than that at 20 degrees C. 3) Rewarming of human blood at 37 degrees C for 5 minutes allowed the plasma FK506 level to return to the initial level. FK506 levels of plasma separated without regard to temperature are less reliable and reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)
To elucidate the change with aging in prostatic morphology, 447 cases without acute diseases and prostate cancer of the first visit from January 1988 to December 1990 were examined by transrectal ultrasonography. Total weight of the prostate, area of maximum section, lateral and anteroposterior diameter on the maximum section and supero-inferior diameter were evaluated. The total weight of the prostate was not found to be correlated with aging. The total weight of the prostate showed a high variation with aging. Prostate growth with more than 30 g was greater in the fifties and increased gradually thereafter. Similar findings were observed for antero-posterior diameter on the maximum section and supero-inferior diameter. With aging, the total weight of the prostate in 20-30% of the patients showed an increase while in 30-40% of the patients, no increase. The total weight of the prostate increased in the fifties with subsequent gradual increase in the sixties. According to prostate shape, antero-posterior diameter on the maximum section and supero-inferior diameter was related to the weight of the prostate.
OBJECTIVES: The purposes of this report were to examine whether or not a positive bile acid breath test in cirrhotic patient was associated with bacterial overgrowth in the upper small intestine, to verify that these bacteria have deconjugation ability, and, in addition, to elucidate whether or not changes in the gastric pH are related to bacterial overgrowth. METHODS: Twenty-seven patients with liver cirrhosis were tested by breath analysis technique using glycine-1-14C-labeled glycocholate. Jejunal fluids were aspirated through a double-lumen tube with a rubber cover on the tip. Anaerobes and aerobes were isolated and identified. After culturing, we used thin layer chromatography to determine whether each bacteria had the ability to deconjugate bile salts. RESULTS: Expired breath samples from seven of 27 patients with liver cirrhosis showed a marked increase of 14CO2-specific activity. Bacterial overgrowth was found in the jejunal fluid of these patients. Administration of chloramphenicol to the seven patients reduced 14CO2 specific activity significantly. The majority of the species identified deconjugated bile acids. Seventeen healthy control subjects showed no increase in CO2 excretion, and 16 of the 17 had no bacteria isolated from jejunal fluid. The relationship between 14CO2 specific activity of expired breath samples and gastric pH was also tested in the cirrhotic patients. There was a relatively good correlation (n = 27, r = 0.87, p < 0.05) between 14CO2 activity and gastric pH. CONCLUSION: We conclude that some patients with liver cirrhosis have bacterial overgrowth in the proximal small intestine that contains species that can deconjugate bile salts, and that the bacterial overgrowth is probably associated with the shift to alkaline pH in gastric juice.
Magnetic coil stimulation applied to the spine excites the lumbosacral roots rather than the spinal cord itself. To evaluate the mechanism responsible for this phenomenon, the effects of volume conduction on the activation of neural elements were studied. In ten intact dogs compound muscle action potentials could be recorded in the soleus muscle only when the magnetic coil was placed over the cauda equina. After laminectomy and pediculotomy, compound muscle action potentials also could be elicited when the magnetic coil was placed over the spinal cord. These findings suggest that the bony structure surrounding the spinal cord interferes with the spread of magnetically induced eddy currents to the spinal cord.
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The role of aspartic acid 53 of human lysozyme (peptidoglycan N-acetylmuramoylhydrolase, EC 3.2.1.17) has been investigated by a site-directed mutagenesis. In order to clarify the importance of precise positioning of the negatively charged carboxylate group in the active site geometry, both the three-dimensional structure and the enzymatic function of glutamic acid 53 human lysozyme (Glu-53 human lysozyme) have been characterized in comparison with those of wild type enzyme. Glu-53 human lysozyme was crystallized and analysed by X-ray crystallography. No remarkable difference in the conformation of whole molecule except the side chain of 53rd residue was observed. In spite of full retention of the binding activities against either beta-1,4-linked trisaccharide of N-acetylglucosamine ((GlcNAc)3) or the corresponding hexasaccharide ((GlcNAc)6), the conversion of Asp-53 to Glu reduced the enzymatic activities against both bacterial cell substrate and p-nitrophenyl penta-N-acetyl-beta(1----4)-chitopentaoside (p-NO2-(GlcNAc)5) to a few percent of the activities of wild type enzyme. Calculation of electrostatic potential around the reaction center predicted that no significant change in pKa of Glu-35 was caused by the mutation. These results indicate that the precise positioning of the negatively charged carboxylate in the geometry of reaction center is essential for the rate enhancement in the catalytic action of lysozyme, and suggest that Asp-53 of human lysozyme participates in the catalytic action not simply in an electrostatical manner but partly in a nucleophilical manner.
In order to study the structure-activity relationships of 2',3'-dideoxypurine nucleosides as potential anti-retroviral agents, various purine derivatives have been synthesized and tested against rous sarcoma virus (RSV) in chick embryo fibroblast (CEF) cells, and against human immunodeficiency virus (HIV) in human CD4+ T cells (ATH8). Some of the new purine derivatives found to be significant antiretroviral activities. And the correlations of activity between anti-RSV and anti-HIV have shown fairly good values so far.
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In 20 patients with cervical spine or cord lesions, we examined motor evoked potentials (MEPs) by transcranially applied magnetic stimulation to the motor cortex. We used a large-diameter (12 cm) coil to induce equal current in both left and right hemispheres. The MEPs were recorded simultaneously from multiple muscles covering the C5 to C8 myotome distribution bilaterally. The MEP abnormalities correlated well with clinical muscle weakness in 15 patients. In two patients, MEP revealed abnormalities in muscles of normal strength. Three patients with sensory but without motor deficit had normal MEPs. We conclude that magnetic stimulation is a useful adjunct in confirming and objectifying motor weakness, and in localizing the level of dysfunction in cervical spine lesions.
The interaction of lidocaine hydrochloride or lidocaine ester derivatives with lecithin vesicles was investigated by proton magnetic resonance (1H-NMR) spectroscopy. Signal broadening of drug indicated the incorporation of the drug into the vesicle membrane. Positively charged nitrogen of lidocaine hydrochloride interacted with polar part of the lecithin vesicles. On the other hand, lidocaine ester derivatives indicated interaction with lecithin vesicles not only by positive charge of nitrogen but also by electrostatic effect of ester carbonyl group. This may be related with the prolonged duration of lidocaine ester derivatives.