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Biomedical subjects

H Yonekawa

Publications and source records attributed to H Yonekawa.

At least 91 records · Page 5Linked to original sources
PubMed1991

Transgenic mice susceptible to poliovirus.

Poliovirus-sensitive transgenic mice were produced by introducing the human gene encoding cellular receptors for poliovirus into the mouse genome. Expression of the receptor mRNAs in tissues of the transgenic mice was analyzed by using RNA blot hybridization and the polymerase chain reaction. The human gene is expressed in many tissues of the transgenic mice just as in tissues of humans. The transgenic mice are susceptible to all three poliovirus serotypes, and the mice inoculated with poliovirus show clinical symptoms similar to those observed in humans and monkeys. Rabbit antipoliovirus serum detects the antigens mainly in motor neurons in the anterior horn of the spinal cord and in nerve cells in the medulla oblongata and pons of the paralyzed transgenic mice. Therefore, cell types sensitive to poliovirus in the central nervous system of the transgenic mice appear to be identical to those of humans and monkeys. Furthermore, many more doses of oral poliovirus vaccine strains than of the virulent strains are required to cause paralysis in the transgenic mice. This may reflect the observation that the virulent strain multiplies more efficiently in the central nervous system than the attenuated strain. Thus, the transgenic mice may become an excellent new animal model to study molecular mechanisms of pathogenesis of poliovirus and to assess oral poliovirus vaccines.

Animals↗
PubMed1991

Gene responsible for deficient activity of the beta subunit of C8, the eighth component of complement, is located on mouse chromosome 4.

Sera from 73 strains of mice were tested for hemolytic activity through the classical and the alternative pathways (CP and AP) in a single radial hemolysis assay. Sera from 16 out of 45 laboratory inbred strains had no lytic activity, and Ouchterlony analysis with anti-C5 serum showed them to be C5-deficient. Sera from 2 out of 28 strains derived from wild mice also had no lytic activity, but the C5 molecule was detectable in both. The hemolytic activity of sera from these strains can be restored by the addition of partially purified human C8 or human serum deficient in C8 alpha-gamma, leading us to conclude that strains M.MOL-MSM (MSM) and Mae are deficient in the beta subunit of C8. Typing of (DBA/2J X MSM)F1 hybrids and of progeny of a backcross to MSM showed that this C8 deficiency is controlled by a single recessive gene, designated C8b; the allele with hemolytic activity is C8b1; and the allele with no activity C8b0. Because of synteny homologies in mouse and human, we looked for and found close linkage between C8b and Pgm-2. Typing of recombinant mice for Mup-1 mapped the C8b locus 2.3 centimorgans (cM) telomeric to Pgm-2 on mouse chromosome 4.

Animals↗
PubMed1991

Genetic control of the expression of two biological activities of an antitumor polysaccharide, lentinan.

In order to make clear whether the expression of biological activities and antitumor polysaccharides are under genetic control, the responses of mice to lentinan, a beta-1,6;1,3-glucan, in the induction of several acute phase proteins (APPs) and T-cell-mediated vascular dilation and hemorrhage (VDH) were investigated. Twenty inbred strains of mice were divided into two groups according to their phenotypes in the induction of APPs when they were administered lentinan i.p. at a dose of 10 mg/kg; sensitive strains showed a marked increase in levels of APPs and resistant strains showed as low a level of APPs as non-treated control mice. No sex-related differences and no relation with H-2 halotypes were found in the responses. Only low-level responses were observed in F1 hybrid mice obtained by crosses between a sensitive and a resistant strain, indicating that the low APP response to lentinan is dominant. The N2 progeny between the F1 and a high responder segregated into high and low responders at a ratio of almost 1:1. These results suggest that a single major gene on an autosome is responsible for the induction of APPs. The induction of VDH also depended on the strains of mice. However, the strain distribution pattern of the VDH phenotype was distinct from that of the APP phenotype, indicating that the VDH-controlling gene was different from the APP-controlling gene. Further analyses with F1 hybrid and backcross progeny mice suggested that the high VDH response was dominant, and that the phenotype was determined by a single major gene.

Acute-Phase Proteins↗
PubMed1991

Nucleotide sequences important for translation initiation of enterovirus RNA.

An infectious cDNA clone was constructed from the genome of coxsackievirus B1 strain. A number of RNA transcripts that have mutations in the 5' noncoding region were synthesized in vitro from the modified cDNA clones and examined for their abilities to act as mRNAs in a cell-free translation system prepared from HeLa S3 cells. RNAs that lack nucleotide sequences at positions 568 to 726 and 565 to 726 were found to be less efficient and inactive mRNAs, respectively. To understand the biological significance of this region of RNA, small deletions and point mutations were introduced in the nucleotide sequence between positions 538 and 601. Except for a nucleotide substitution at 592 (U----C) within the 7-base conserved sequence, mutations introduced in the sequence downstream of position 568 did not affect much, if any, of the ability of RNA to act as mRNA. Except for a point mutation at 558 (C----U), mutations upstream of position 567 appeared to inactivate the mRNA. In the upstream region, a sequence consisting of 21 nucleotides at positions 546 to 566 is perfectly conserved in the 5' noncoding regions of enterovirus and rhinovirus genomes. These results suggest that the 7-base conserved sequence functions to maintain the efficiency of translation initiation and that the nucleotide sequence upstream of position 567, including the 21-base conserved sequence, plays essential roles in translation initiation. A deletion mutant whose genome lacks the nucleotide sequence at positions 568 to 726 showed a small-plaque phenotype and less virulence against suckling mice than the wild-type virus. Thus, reduction of the efficiency of translation initiation may result in the construction of enteroviruses with the lower-virulence phenotype.

Animals↗
PubMed1991

Data compression: effect on diagnostic accuracy in digital chest radiography.

High-resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store. Data compression techniques are being developed to address this problem, but significant image deterioration can occur at high compression ratios. In this study, the authors evaluated a form of adaptive block cosine transform coding, a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality. To determine the effect of data compression on diagnostic accuracy, observer tests were performed with 60 digitized chest radiographs (2,048 x 2,048 matrix, 1,024 shades of gray) containing subtle examples of pneumothorax, interstitial infiltrate, nodules, and bone lesions. Radiographs with no compression, with 25:1 compression, and with 50:1 compression ratios were presented in randomized order to 12 radiologists. The results suggest that, with this compression scheme, compression ratios as high as 25:1 may be acceptable for primary diagnosis in chest radiology.

Humans↗
PubMed1990

Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein.

MTF, a murine minor histocompatibility antigen, is maternally inherited and thought to be encoded by a mitochondrial gene. We sequenced the entire mitochondrial genomes from three strains that differ in MTF Mtf beta, Mtf gamma, and Mtf delta) and compared the sequences with the known, Mtf alpha, mitochondrial DNA sequence. We found only one site where all four genomes differed, affecting amino acid residue 6 of ND1, a subunit of NADH dehydrogenase. Incubation of non-Mtf alpha target cells with synthetic peptide ND1 alpha 1-17 (the first 17 amino acid of the ND1 protein of Mtf alpha mice) rendered them susceptible to lysis by MTF alpha-specific cytotoxic T cells (CTLs). Similarly, non-Mtf beta target cells were lysed by MTF beta-specific CTLs after incubation with the allelic form ND1 beta 1-17. Thus, Mtf is attributable to allelic variation at a single residue of the ND1 protein. Cells can therefore display peptides derived from mitochondrially encoded proteins, and such peptides can be histocompatibility antigens.

Amino Acid Sequence↗
PubMed1990

Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclear-coded subunits of complexes involved in the oxidative phosphorylation.

Using mouse cell lines 5P and 5PEr (ethidium bromide-resistant derivative of 5P), we examined the influence of blocking expression of mitochondrial-gene products with ethidium bromide on the expression and assemblies of nuclear-coded subunits of the complexes involved in the oxidative phosphorylation. The results suggest that in the absence of mitochondrial-coded products, the expressions of subunit VIc of complex IV and beta-subunit of F1-ATPase are not affected, but that most nuclear-coded subunits other than alpha- and beta-subunits of F1-ATPase cannot be assembled nor inserted into the inner membrane.

Actins↗
PubMed1989

Nuclear but not mitochondrial genome involvement in 3-methylcholanthrene-induced expression of tumorigenicity in mouse somatic cells.

The involvement of heritable modifications of mitochondrial DNA (mtDNA) in chemical carcinogenesis was examined by studies on the effects on tumorigenicity of interchange of mtDNA between 3-methylcholanthrene (MCA)-induced mouse tumor cells and nontumorigenic mouse cells by the cytoplast-to-cell fusion technique. The difference in propagating abilities of two types of mouse mtDNA, type 1 mtDNA of B10mtJ strain and type 2 mtDNA of C57BL/10 strain, was applied successfully for complete replacement of the host cell mtDNA by cytoplasmically transmitted mtDNA. Tumorigenicity was assayed in nude mice by inoculating 5 x 10(6) cells s.c. into the backs of the mice. The results showed that tumorigenicity was not induced in nontumorigenic cells by replacement of their mtDNA by that from MCA-induced tumor cells. Moreover, the tumorigenicity of MCA-induced tumor cells was still expressed when their mtDNA was replaced by that from normal cells with a limited life span. These observations suggest that, even if MCA treatment causes heritable modifications of mtDNA, modified mtDNA cannot induce chemical carcinogenesis and that modifications of nuclear DNA alone are sufficient for the expression of tumorigenicity.

Animals↗
PubMed1989

Effects of bovine serum albumin and recirculation rate on the uptake of propranolol by rat perfused lung.

Lungs isolated from 7-week-old rats were perfused with pH 7.4, oxygenated Krebs-Ringer bicarbonate buffer solution containing 2.5 micrograms mL-1 of propranolol and 3 to 5% BSA at the recirculation rate of 4 to 16 mL min-1, at 37 degrees C for 60 min. The extent of propranolol metabolism after 60 min was less than 2.3% of the initial load under any in-vitro perfusion condition. Therefore, the amount disappearing from the perfusion medium was considered as being predominantly that taken up by tissue. Under all experimental conditions, perfusate drug level declined bi-exponentially with time. Apparent in-vitro pulmonary clearance of propranolol was not affected by the increase of BSA level from 3 to 5%. When the perfusate BSA level was fixed at 3%, the lowest recirculation rate (4 mL min-1) yielded the smallest clearance (about 0.15 mL min-1 g-1) but almost constant clearance value (about 0.40 mL min-1 g-1) was obtained at the rate ranging from 8 to 16 mL min-1. The tissue to medium concentration ratio of propranolol, after the perfusion with 3 to 5% BSA at the rate of 8 to 16 mL min-1, was approximately 35, whereas that with 3% BSA at 4 mL min-1 was reduced to about 20. The findings suggest evidence for flow-dependent in-vitro pulmonary clearance of propranolol.

Animals↗
PubMed1989

Specific age-dependence in capacity-limited uptake of propranolol by isolated rat lung.

To investigate the effect of age on the pulmonary uptake of propranolol, minced tissue (0.4 g) of lungs isolated from 3- to 104-week-old rats was incubated with the drug (1 to 500 micrograms mL-1) prepared in oxygenated, pH 7.4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA for 60 min at 37 degrees C. In any age-group the metabolism of propranolol was not significant (i.e. less than 0.6% of any initial load) under the present in-vitro conditions. The extent of uptake after the incubation with 2.5 micrograms mL-1 of the drug was largest in the 7 weeks (i.e. 82% of the initial load) and relatively small in the 3(64%), 24(61%), 52(51%) and 104(48%) week old rats. Similar, specific age-dependence was observed in the tissue-to-medium concentration ratio of the drug. In any age-group, the initial uptake rate obtained in the first 5 min of the incubation was found to be a combination of apparently linear transport and saturable (capacity-limited) processes. There was a marked, specific age-dependence in the capacity-limited uptake rate. Although Km' value was almost equivalent in any age-group (i.e. 24.4 to 25.4 micrograms mL-1), Vmax exhibited a specific age-dependence by yielding the highest value in 7 weeks (0.726 +/- 0.101 mg g-1 min-1) and relatively low values in 3 (0.501 +/- 0.082 mg g-1 min-1), 52 (0.410 +/- 0.088 mg-1 g-1 min-1) and 104 (0.397 +/- 0.074 mg g-1 min-1) weeks.

Aging↗
PubMed1989

Effects of metabolic inhibitors and incubation temperature on the saturable uptake of propranolol by isolated rat lung tissue.

The effects of several metabolic inhibitors (50 microM) on the initial uptake rate of propranolol (0.5 to 500 micrograms mL-1) by the minced lungs (0.4 g) isolated from 7-week-old rats has been investigated in oxygenated, pH 7.4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA at 37 degrees C for 5 min. The effect of the incubation temperature was also examined. Metabolism of propranolol was almost insignificant (i.e. less than 1.3% of the initial load). The overall initial uptake rate was considered to be a combination of apparent linear transport and saturable processes. For the control uptake rate, the linear transport rate constant was 1.26 +/- 0.16 g-1 mL-1 min-1, while Vmax and Km' of the capacity limited uptake process were estimated as 0.727 +/- 0.074 mg g-1 min-1 and 24.8 +/- 2.71 micrograms mL-1, respectively. No metabolic inhibitor tested had an effect on the linear transport rate of propranolol but 2,4-dinitrophenol and potassium cyanide inhibited saturable uptake rate (i.e. Vmax) of propranolol significantly (P less than 0.01) while ouabain, phloridine and iodoacetic acid did not do so significantly. Reduction of the incubation temperature to 15 degrees C decreased and at 25 degrees C tended to decrease, both linear transport and saturable uptake rates.

Animals↗
PubMed1989

[A case of resected metastatic adrenal carcinoma from gastric cancer].

A case of a metastatic adrenal carcinoma is presented. A 67-year-old female underwent total gastrectomy for an adenocarcinoma of the stomach before 52 months. A mass was indicated at the left supra-renal region by computed tomography. The mass was successfully resected by an upper abdominal para-aortic lymph node dissection. Histologically, the mass was confirmed as a metastatic adrenal carcinoma with a lymph node metastasis from the gastric cancer. Metastatic adrenal carcinomas and local lymph node dissections for treating metastatic carcinomas are discussed.

Adenocarcinoma, Papillary↗
PubMed1989

[Lipid metabolism after operation for esophageal cancer].

In order to clarify the abnormal lipid metabolism after resection of esophageal cancer, we measured serum cholesterol, HDL cholesterol, triglyceride phospholipid, free fatty acid, lipoprotein and apoprotein in 38 patients with esophageal cancer before and up to 4 weeks after operation. Patients were divided into three groups; group A consisted of 26 patients whose postoperative course was uneventful, group B, 12 patients who suffered from post-operative complications and group C, 15 control patients who underwent gastrectomy for cancer of the stomach. The conclusions were; 1) After operation, remarkable decrease was observed in many lipids and proteins which were synthesized mainly in the liver. This was more prominent in groups A and B than in group C. There was no difference between group A and B up to 2 weeks, however, after that recovery was slow in group B. 2) This decrease in serum lipids and proteins may be explained by the postoperative liver dysfunction which mimics acute hepatitis, and by abnormal increase in their consumption. 3) In group B, preoperative serum cholesterol, HDL cholesterol and albumin had been significantly lower than those in group A, and cholinesterase, apoAI and apoAII had also tended to be lower.

Blood Proteins↗
PubMed1988

A clinical study of Reinke's edema.

A clinical study of 76 cases with Reinke's edema who underwent endolaryngeal microsurgery was carried out, and the postoperative results were evaluated. The patients were classified into three types: Type I, II, and III according to the severity of the disease as determined by laryngeal appearance. Postoperative changes in subjective symptoms were assessed and sound spectrographic and perceptual evaluations of voices were carried out before and after surgery in 38 cases. The majority of the patients were over 40 years of age for both sexes and most of the elderly patients were female. In Type III patients, the incidence was higher among females. All the patients complained of hoarseness and nine cases of Type III complained of dyspnea. Most of them had been chronically affected for over one year and showed a bilateral pathology. Smoking appeared to be the most dominant etiologic factor, while aging and a long history of vocal abuse also seemed to be causative factors. Improvement in subjective symptoms was found in almost all the patients treated with the squeezing technique proposed by the author's group. Improvement in voice quality was observed in acoustic evaluations. Among Type III females, it was often the case that the voice fundamental frequency was very low before surgery, while it increased markedly after surgery. In general, the voice after surgery showed less fluctuation in both pitch period and amplitude, as well as a smaller amount of noise components compared to that recorded before surgery. As measured by perceptual judgement, voice quality was found to be more improved in females than in males.

Adult↗
PubMed1988

Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA.

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction-site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.

Animals↗
PubMed1988

Propranolol uptake with high capacity by rat perfused lung.

Lung isolated from 7-week-old rats was perfused with pH 7.4 Krebs-Ringer bicarbonate buffer solution (35 mL) containing 1 to 100 micrograms mL-1 of propranolol and 3% BSA at the recirculation rate of 8 mL min-1. Almost parallel bi-exponential drug concentration-time curves were obtained at the initial load lower than 10 micrograms mL-1, whereas relatively slow, mono-exponential decline was found after perfusion at 100 micrograms mL-1. Pharmacokinetic analysis for the perfusate propranolol concentration-time curves when loaded at 1 to 10 micrograms mL-1 yielded almost comparable values for the pulmonary perfusion clearance (0.387 +/- 0.092 to 0.486 +/- 0.095 mL min-1 g-1). In contrast, this parameter was significantly reduced at 100 micrograms mL-1 (0.113 +/- 0.042 mL min-1 g-1). The present findings suggest a trend towards saturation kinetics in the in-vitro pulmonary clearance of propranolol.

Animals↗