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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 811 records · Page 45Linked to original sources

[A clinical investigation of bacteremia for the past ten years at the Second Department of Internal Medicine, Jikei University Hospital].

We clinically investigated a total of 288 cases of bacteremia for the past ten years, from January 1986 to December 1995, at the Second Department of Internal Medicine in the jikei University Hospital. All of the subjects who had a positive reaction to blood culture or catheter tip culture were investigated for their basic disease, complications, and detected bacteria. Malignant tumors, chronic renal failure, diabetes mellitus, and hematologic disease were frequent by noted. The cases due to primary infection were mainly respiratory organ infection or urinary tract infection, which were 47.8% of the total. In 31.3% of the total, catheter tip cultures were positive. Except for catheter related infection, Gram-positive coccus were detected in 40.3%, which was most frequent. Methicillin resistant Staphylococcus aureus (MRSA) were 8.1% and Staphylococcus epidermidis were 11.2%. In catheter related infection, Gram-positive coccus were detected in 59.9%, which was most frequent amongst them, MRSA was 17.2%, S. epidermidis was 16.2%. The mortality of bacteremia was 12.5%, mainly from hematologic diseases, immunodeficiency due to long term steroid administration etc. Accordingly, the more the advance of chemotherapy, the better the prognosis of septicemia is. Appearance of catheter related infection was unexpected frequent. Increase of immunocompromised host is thought to be one of the main factors in the outbreak of bacteremia.

Adolescent↗

In vitro and in vivo antidermatophyte activities of NND-502, a novel optically active imidazole antimycotic agent.

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.

Animals↗

Cloning of novel isoforms of the human Gli2 oncogene and their activities to enhance tax-dependent transcription of the human T-cell leukemia virus type 1 genome.

The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by interaction of a viral transactivator protein, Tax, and cellular transcription factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was previously determined to enhance the transactivation by Tax protein. Here we report novel forms of the human homolog of a member of the Gli oncogene family, Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP, which was described previously. Four possible isoforms (hGli2 alpha, beta, gamma, and delta) are formed by combinations of two independent alternative splicings, and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer isoforms, alpha and beta, were abundantly expressed in various cell lines including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms with the DNA-binding domain of Gal4 activated transcription when the reporter contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB binds. This activation was observed only in the presence of Tax. The 21-bp sequence in the reporter was also essential for the activation. These results suggest that simultaneous binding of hGli2 and CREB to the respective sites in the reporter seems to be critical for Tax protein to activate transcription. Consequently, it is probable that the LTR can be regulated by two independent signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S sequences in the vicinity.

Amino Acid Sequence↗

Opioid peptides mediate heat stress-induced immunosuppression during pregnancy.

To clarify the involvement of the opioid system in enhanced immunosuppression induced by heat stress during pregnancy, we examined the effects of heat exposure and intraperitoneal administration of opioid receptor antagonist naloxone on beta-endorphin (beta-EP) in blood, pituitary lobes, and placenta as well as splenic natural killer cell activity (NKCA) and placental steroids in pregnant rats at 15-16 days gestation. Two-way analysis of variance revealed significant increases in blood beta-EP induced by heat and naloxone and a significant interaction between heat and naloxone on blood beta-EP and progesterone (P). Whereas heat reduced NKCA, intraperitoneal administration of naloxone reversed it. Significant increases in blood and placental beta-EP induced by both heat and naloxone administration and a significant interaction on blood and placental beta-EP was observed. These results suggest that immunosuppression produced by heat stress during pregnancy is mediated by the opioid system. A positive correlation between beta-EP in blood and placenta during heat and naloxone administration suggests that increased placental beta-EP during heat results in hypersecretion of beta-EP into blood. P increased by heat during pregnancy may be involved in the immunosuppression.

Animals↗

Role of K+ channels in adrenal catecholamine secretion in anesthetized dogs.

We examined the role of K+ channels in the secretion of adrenal catecholamine (CA) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. K+ channel blockers and the cholinergic agonists were infused and injected, respectively, into the adrenal gland. The voltage-dependent K+ channel (KA type) blocker mast cell degranulating (MCD) peptide infusion (10-100 ng/min) enhanced increases in CA output induced by SNS (1-3 Hz), but it did not affect increases in CA output induced by ACh (0.75-3 micrograms), DMPP (0.1-0.4 microgram), or muscarine (0.5-2 micrograms). The small-conductance Ca(2+)-activated K+ (SKCa) channel blocker scyllatoxin infusion (10-100 ng/min) enhanced the ACh-, DMPP-, and muscarine-induced increases in CA output, but it did not affect the SNS-induced increases in CA output. These results suggest that KA channels may play an inhibitory role in the regulation of adrenal CA secretion in response to SNS and that SKCa channels may play the same role in the secretion in response to exogenously applied cholinergic agonists.

Acetylcholine↗

Role of nitric oxide in adrenal catecholamine secretion in anesthetized dogs.

We examined the role of nitric oxide (NO) in adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS) and exogenous acetylcholine (ACh) in anesthetized dogs. The NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e (NOC 7), and ACh were administered intra-arterially into the adrenal gland. The increases in catecholamine output induced by ACh (0.75-3 microgram) were enhanced by L-NAME (0.1-1 mg/min) and inhibited by NOC 7 (0.2-2 microgram/min). Inhibition by NOC 7 (2 microgram/min) was observed during treatment with L-NAME (1 mg/min). The increases in catecholamine output induced by SNS (1-2 Hz) were inhibited by L-NAME and by NOC 7. No inhibitory effect of NOC 7 was observed during treatment with L-NAME. These results suggest that NO may play an inhibitory role in the regulation of adrenal catecholamine secretion in response to exogenous ACh.

Acetylcholine↗

Management of malignant ovarian tumors in young women. 21 nulliparous cases.

To evaluate the management of malignant ovarian tumors in young women who wish to maintain fertility, we retrospectively reviewed ovarian malignancies in 21 young women who were both nulliparous and under 40 years of age. With stage 1a disease, all 9 patients were treated with conservative surgical therapies, and all of them are still alive, irrespective of histological type. With stage 1c disease, 5 (83%) of 6 patients were treated with conservative surgical therapies. Among them, 2 patients with epithelial tumors, who were treated with conservative surgical therapies and potent cis-diamminedichloroplatinum (CDDP)-based combined chemotherapies, are still alive. Furthermore, one of them had a successful pregnancy. On the other hand, 3 out of 4 patients with nonepithelial tumors were treated with conservative surgical therapies. However, 2 (67%) out of 3 died; both of them were treated with non-CDDP-based chemotherapy. In 6 patients with disease beyond stage 2, 4 (67%) were treated with radical surgical therapies, but 2 (33%) were treated with conservative surgery and CDDP-based combined chemotherapy, one of which was followed by a successful pregnancy in spite of nonepithelial tumor. As above, we could obtain some successful pregnancies in cases beyond stage 1c after conservative surgery by adding definite CDDP-based combined chemotherapy. However, we must carefully select the patients with nonepithelial tumors for conservative therapy by adding definite CDDP-based combined chemotherapy and inform them of the risks of therapy.

Adolescent↗

Prejunctional muscarinic receptors modulating acetylcholine release in rabbit detrusor smooth muscles.

We investigated the presence and subtypes of functionally prejunctional receptors in cholinergic nerve endings of rabbit detrusor smooth muscle strips using high-performance liquid chromatography coupled with a microdialysis procedure. The effects of pretreatment with various drugs on acetylcholine (ACh) release and contractile responses induced by electrical field stimulation were evaluated. Although atropine (a muscarinic nonselective antagonist) and 4-DAMP (a muscarinic M3 antagonist) did not influence the ACh release, they markedly reduced the contractile responses. Pirenzepine (M1 antagonist) decreased ACh release and contractile responses. Methoctramine (M2 antagonist) increased the ACh release, but did not influence to the contractile responses. These results suggest that the muscarinic receptors in the rabbit detrusor smooth muscle are heterogeneous, prejunctional facilitatory (M1 receptors), and inhibitory (M2 receptors) for ACh release and postjunctional M3 receptors mediating contractile responses.

Acetylcholine↗

A novel variant of B-lymphoid leukemia expressing kappa/lambda light chains.

We studied a patient with an indolent leukemia which behaved similarly to chronic lymphocytic leukemia (CLL). Leukemic cells, however, showed larger cell diameters and lower nuclear/cytoplasmic ratios than typical CLL cells, and contained numerous cytoplasmic vacuoles. The cells also demonstrated some morphologic characteristics of hairy cell leukemia. Furthermore, flow-cytometric analysis demonstrated a distinct population of kappa/lambda double-positive tumor cells, as well as kappa single and lambda single populations. Southern blot analysis confirmed rearranged bands for both light chains with a monoclonal heavy chain rearrangement. Despite a decision not to treat this asymptomatic patient, disease progression was not observed. This case may represent a unique variant of B lymphoid leukemia. Possible mechanisms of abnormal light chain expression are discussed.

Aged↗

Electron microscopic observations on sperm penetration in cytochalasin-treated eggs of the rose bitterling.

The effects of cytochalasin B (CB), which acts on microfilaments, on sperm penetration into eggs of a teleost fish were investigated ultrastructurally. Eggs from the rose bitterling, Rhodeus ocellatus ocellatus, were pre-treated in physiological saline containing CB and inseminated in water also containing CB. Microvilli at the sperm entry site (SES) under the micropyle disappeared or shortened in length following CB treatment. However, a spermatozoon attached to and fused with the SES of CB-treated eggs. The spermatozoon present in a swollen mass (SM) remained at the egg surface even after membrane fusion and did not enter the cortex. It was unclear whether or not sperm movement from the cortex to the inner cytoplasm is CB-sensitive. The SM formed and plugged the micropyle. CB did not inhibit cortical alveolus breakdown. Based on the present experiments with fish eggs, it is concluded that CB inhibits sperm movement from the egg surface to the cortex, but not sperm attachment (binding), membrane fusion and SM formation during the process of sperm penetration.

Animals↗

Evaluation of poly(vinyl alcohol)-gel spheres containing chitosan as dosage form to control gastrointestinal transit time of drugs.

Two types of poly(vinyl alcohol)-gel spheres were prepared with chitosan (CS/PVA-GS) and without chitosan (PVA-GS), and comparative studies were performed using these gel spheres (GSs). No change in particle size was observed by the addition of chitosan: nearly 45% of both particles were in the 5-10 microm range. In an in vivo gastrointestinal transit test, CS/PVA-GS prolonged the small-intestinal transit time more than PVA-GS. In an in vitro intestinal perfusion study, the mean transit time of these GSs was markedly reduced by pretreatment of the intestinal surface with a mucolytic agent, N-acetyl-L-cysteine, suggesting that the mucous layer on the intestinal surface plays an important role in controlling the transit rate of these GSs. The oral administration of aminophylline (theophylline) and ampicillin as model drugs incorporated in PVA-GS and CS/PVA-GS was examined in rats. While theophylline absorption from PVA-GS was not affected by the addition of chitosan, the improvement of ampicillin absorption by PVA-GS was enhanced by the chitosan combination.

Administration, Oral↗

Hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) in the perfused rat liver.

The hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) were investigated in perfused rat liver to clarify the mechanism of hepatic clearance which is a major contributor to the rapid clearance of rhIL-11 in vivo. We analyzed the disposition characteristics of [(111)In]-labeled rhIL-11 using a single-pass constant infusion mode at different concentrations of rhIL-11. The venous outflow rapidly reached a steady-state condition at every concentration. Liver extraction ratio at steady-state (Ess) was decreased with increase in the concentration, suggesting that there is a saturable interaction between the liver cells and rhIL-11 molecule. Cellular localization experiments demonstrated that rhIL-11 was taken up by both liver parenchymal and nonparenchymal cells depending on their surface area, suggesting that this uptake was mediated by electrostatic interaction due to cationic charges in the cytokine.

Animals↗

Genetic variation of mitochondrial cytochrome b genes among the subspecies of koala, Phascolarctos cinereus.

A conserved DNA region among the subspecies of koala, of mitochondrial cytochrome b gene, was employed to analyze the genetic variation among 3 available subspecies of koala. This conserved sequence, 307 bp DNA, was sequenced using polymerase chain reaction and direct DNA sequencing technique. Substitutions in the nucleotide sequences were observed, with which koalas can be divided into 3 DNA haplotypes subspecies, but the molecular data provided inconsistency with current classification of the 3 subspecies of koala.

Amino Acid Sequence↗

Expression of growth factor ligand and their receptor mRNAs in bovine ova during in vitro maturation and after fertilization in vitro.

We analyzed the expression of mRNAs for growth factor [epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF) and platelet-derived growth factor A chain (PDGF-A)] and their receptor (R) by reverse transcription-polymerase chain reaction in bovine ova during oocyte maturation in vitro (0-21 hr) and after fertilization in vitro (6-144 hr: zygotes to blastocysts). Transcripts for EGF were not found before fertilization. Transcripts for IGF-I were present in immature oocytes immediately after collection and in embryos from the 2-cell stage onward. Transcripts for bFGF were present in all stages of oocyte maturation and after fertilization up to the 16-cell stage. Transcripts for PDGF-A were present in all stages of oocyte maturation and after fertilization up to the 2-cell stage. Transcripts for ErbB3 (a member of the EGF-R subfamily), and bFGF-R were present in all stages of oocyte maturation, after fertilization up to the 2-cell stage, and the blastocyst stage. Transcripts for IGF-I-R and PDGF-Ralpha were present in all stages of oocyte maturation and embryo development. The results of this study showed that eight different messages for growth factor and their receptor were detectable in bovine ova during oocyte maturation and/or after fertilization in vitro and their expression patterns were the gene-specific rather than the developmental stage of bovine ova.

Animals↗

Factors related to the relapse of bronchiolitis obliterans organizing pneumonia.

STUDY OBJECTIVE: The purpose of this study is to determine factors, including laboratory data, related to the relapse of bronchiolitis obliterans organizing pneumonia (BOOP). DESIGN: Retrospective study. SETTING AND PATIENTS: The medical files of Fukuoka University Hospital and Nishi Fukuoka Hospital patients from 1984 to 1996 were reviewed, and 18 cases of BOOP that had been diagnosed using transbronchial or open lung biopsy were selected for evaluation. MEASUREMENTS: The 18 cases were put into two groups composed of 7 patients who relapsed and 11 who did not relapse. Their clinical symptoms and laboratory data at first admission, including hemograms, blood chemistry tests, and pulmonary function tests were compared. Patients with or without associated diseases, such as collagen vascular diseases, were compared using the same parameters in order to examine the relationship between the associated diseases and BOOP relapse. RESULTS: The serum levels of total protein and albumin in patients who relapsed were significantly lower than in patients who did not relapse, respectively: 5.8 (range, 4.4 to 6.2) vs 6.3 (range, 4.5 to 6.8) g/dL, p < 0.05; and 2.9 (range, 2.5 to 3.4) vs 3.7 (range, 2.8 to 4.3) g/dL, p < 0.01. Levels of serum albumin in BOOP patients with associated diseases, however, were significantly lower than in those without associated diseases, respectively: 2.95 (range, 2.5 to 3.9) vs 3.65 (range, 2.8 to 4.3) mg/dL, p < 0.05. The fall in serum albumin levels in patients who relapsed, therefore, was probably due to associated diseases. The fact that 5 of 8 patients with associated diseases relapsed but only 2 of 10 without associated diseases relapsed suggests that a relationship exists between associated diseases and the prognosis of BOOP, although this finding was not statistically significant because of the small number of cases and the heterogeneity of the associated diseases. The most striking observation was that PaO2 levels in patients who relapsed were significantly lower than in those who did not, respectively: 55.4 (range, 39.9 to 73.2) vs 78.0 (range, 48.4 to 89.4) mm Hg, p < 0.05. However, PaO2 levels were not statistically different between patients with and without associated diseases, respectively: 66.0 (range, 45.4 to 78.8) vs 71.4 (range, 39.9 to 89.4) mm Hg. CONCLUSIONS: The severity of hypoxemia at first medical examination may be an important determinant for the subsequent BOOP relapse.

Aged↗

Distribution and expression of mRNAs for the proto-oncogenes c-fos and c-jun in bone cells in vivo.

In this study we assessed the expression and localization of the proto-oncogenes c-fos and c-jun in normal bone so as to gain more insight into the role of these proto-oncogenes in bone tissue. Femurs of 4-week-old rats were examined by non-radioactive in situ hybridization. cDNA probes for c-fos- and c-jun-labeled digoxygenin were produced by Polymerase Chain Reaction (PCR). C-fos and c-jun exhibited similar distribution in growth plate and bone tissue. Expression of c-fos and c-jun mRNAs in growth plate was observed in the proliferative zone and partly in the upper layer of the hypertrophic zone. In spongy bone, high expression of c-fos and c-jun mRNAs was observed in the osteoblast cytoplasm. However, there was little expression in bone lining cells. In the bony trabeculae, slight expression of c-fos and c-jun was observed in the premature osteocytes situated close to the bone surface, but no expression was detected in osteocytes that possessed relatively large lacunae in the center of the trabeculae. C-fos and c-jun were also slightly expressed in osteoclasts. These data strongly suggest that c-fos and c-jun are involved in regulating chondrocyte proliferation as immediate early genes, and may also be involved in the gene expression of bone matrix proteins as transcription factor (AP-1) in vivo. In addition, the fact that strong expression was observed in osteoblasts but hardly any expression at all in bone lining cells seems to suggest that these genes are also involved in osteoblast activation.

Animals↗

Sequential alterations in clinical biochemical indicators of renal function in 5/6 nephrectomized rats--basic study for renal toxicity using 5/6 nephrectomized rats.

It has been established that progression of renal lesions in 5/6 nephrectomized rats, in which the total right kidney was removed and two poles of the left kidney were excised surgically, and are used as an animal model of renal failure in man, can be morphologically divided into three stages. In the present study, for establishing a renal toxicity study using this animal model on the physiological side, changes of biochemical parameters were sequentially investigated in 20 male 5/6 nephrectomized Wistar rats until 26 weeks after nephrectomy. Creatinine clearance (CLcre) and water as well as electrolyte reabsorption (FRwater and FR Na, K, Cl) were reduced at weeks 2-4, then increased slightly from weeks 6 to 10, and reduced again thereafter. On the contrary, urinary protein was elevated throughout the experimental period, while albumin fraction was increased after week 2 and low-molecular tubular protein increased after week 6 by electrophoresis. Urinary LDH also demonstrated high levels throughout the observation period, but ALP only increased after week 18. The present study thus confirmed that renal function after 5/6 nephrectomy is indeed changed in three stages with clinical biochemical parameters, especially CLcre and FR Na, K, Cl being good indicators to distinguish the three stages of glomerular and tubular dysfunction, respectively. In addition, urinary protein-fractions by electrophoresis in this animal model were examined for the first time, proving useful approach to glomerular and tubular dysfunction.

Albumins↗