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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 37 records · Page 2Linked to original sources
PubMed1992

Clostridium botulinum type C in healthy swine in Japan.

Healthy cattle and swine bred in a district of Japan were examined for the presence of Clostridium botulinum in their liver. Liver specimens were cultivated in chopped meat-glucose medium and the cultures were examined for botulinum toxin. In cattle, none of the cultures of 100 liver specimens yielded the toxin. In swine, however, C1 or C2 toxin was demonstrated in 8 of 100 liver specimens from 36 farms. One of the five farms where the carrier-state swine were present was surveyed for about 2 years to determine whether the carrier-state was transient or resident. C. botulinum type C was found in swine livers and feces, and environmental specimens at extremely high rates during the surveillances, with 76% of specimens yielding botulinum toxin following the culture. These data suggest that it is not uncommon for healthy swine to carry C. botulinum type C in the liver and that there is a close relationship between C. botulinum carrier-state in swine and the presence of this organism in their raising environments. In 20 cattle and 20 swine suffering from parturient paresis of unknown etiology no evidence for involvement of C. botulinum type C was obtained.

Animals↗
PubMed1992

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.

Adult↗
PubMed1992

Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis.

Two kinds of IgG1 monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16.1 kD component of YA-whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA-whole worm extract for guinea-pig-eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56-61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20-34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71-81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA-whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF-YA as well as for elucidating the possible in vivo role of ECF-YA.

Angiostrongylus cantonensis↗
PubMed1992

Down-regulation of cystic fibrosis transmembrane conductance regulator gene expression by agents that modulate intracellular divalent cations.

In cystic fibrosis (CF), epithelial cells are unable to normally up-regulate apical membrane Cl- secretion in response to agents which increase cyclic AMP, but they do increase Cl- secretion in response to increases in intracellular Ca2+. Since intracellular divalent cations regulate the expression of many genes, we hypothesized that mobilization of intracellular Ca2+ and/or other divalent cations might modulate not only Ca(2+)-dependent Cl- channels but also cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. To evaluate this concept, HT-29 human colon carcinoma cells were cultured under various conditions designed to manipulate intracellular divalent cation concentrations and CFTR gene expression was quantified at the levels of transcription, mRNA accumulation, mRNA half-life, and protein. Exposure to the divalent cation ionophores A23187 and ionomycin (agents which increase intracellular divalent cation concentrations) caused dose- and time-dependent reductions of CFTR mRNA levels, which could be blocked by the use of Ca(2+)- and Mg(2+)-free media. Ionophore-induced CFTR gene modulation was also observed with T84 human colon carcinoma cells and freshly isolated normal human bronchial epithelial cells. Incubation of HT-29 cells with thapsigargin, an agent that releases Ca2+ from intracellular stores, or in medium containing increased extracellular concentrations of Ca2+ or Mg2+ also caused down-regulation of CFTR mRNA levels. Transcription run-on analysis showed that, parallel with the decrease in CFTR mRNA levels, A23187 reduced the rate of transcription of the CFTR gene, while CFTR mRNA transcript half-life was unaffected. Consistent with the down-regulation of CFTR gene expression, CFTR protein levels also decreased after exposure to A23187. Thus, despite the independence of Ca(2+)-dependent Cl- channels and cyclic AMP-dependent CFTR-related Cl- channels in epithelial cells, increases in intracellular divalent cation concentrations down-regulate the expression of the CFTR gene at the transcriptional level, with consequent decreases in CFTR mRNA and protein.

Calcimycin↗
PubMed1992

Ontogeny of neonatal pulmonary vascular pressure-flow relationships.

Previously we reported that pulmonary vascular pressure gradients determined by vascular occlusion varied as a function of neonatal age. The purpose of this study was to evaluate the effect of blood flow on pressure gradients during normoxia (inspired O2 28%) and hypoxia (inspired O2 4.2%) in isolated, indomethacin-treated lungs obtained from lambs at less than 1, 2-4, 12-14, and 30-32 days of age (n = 6 at each age). The total pulmonary pressure gradient was partitioned into pressure gradients across relatively indistensible arteries and veins and relatively compliant vessels in the middle region (delta Pm) by inflow and outflow occlusions at flows of 25, 50, 75, and 100 ml.kg-1.min-1. During normoxia, lungs from lambs less than 1 day of age had significantly greater pressures at each flow than lungs from older lambs, due primarily to a significantly greater delta Pm in this age group. During hypoxia, the greatest vasoconstriction occurred in the youngest group, also due mostly to an increased delta Pm. This enhanced response to hypoxia in the younger age groups was due to inhibition of prostaglandin synthesis; without indomethacin treatment, the older age groups had a greater hypoxic pressor response than the younger groups. The arterial vascular resistance at all ages was relatively constant as a function of blood flow during both normoxia and hypoxia, whereas the total and middle vascular resistances generally decreased as a function of flow. The venous resistance initially decreased and then was constant. These results suggest that the neonatal pulmonary circulation h as a fixed arterial resistance, a slightly distensible venous region at low flows, and a more distensible middle region.

Aging↗
PubMed1992

Dibutyryl cyclic AMP attenuates lung responses induced by endotoxin in conscious sheep.

Dibutyryl cyclic AMP (DBcAMP) could inhibit the production of prostanoids and modulate the pulmonary vascular responses induced by endotoxin. Diffuse lung injury after endotoxemia in sheep is accompanied by the production of prostanoids and an increase in endothelial permeability. To determine whether exogenous DBcAMP could prevent the endotoxin responses, we measured pulmonary hemodynamics, gas exchange, and lung lymph responses to an intravenous infusion of Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) in unanesthetized sheep in the presence and absence of DBcAMP (30 micrograms/kg/min) infused intravenously for 6 h beginning 1 h before endotoxin infusion or for 4.5 h after 30 min of treatment with endotoxin infusion. We also measured circulating leukocytes and lung lymph and plasma concentrations of thromboxane B2 (TXB2) and prostacyclin (6-keto-PGF1 alpha) metabolites by radioimmunoassay. DBcAMP infusion before endotoxin infusion decreased endotoxin-induced pulmonary hypertension and hypoxemia and markedly attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP after endotoxin only attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP treatment both before and after endotoxin infusion blocked endotoxin-induced increases in lung lymph and plasma TXB2 and 6-keto-PGF1 alpha. DBcAMP did not affect the number of circulating leukocytes. Although DBcAMP alone did not affect the pulmonary and systemic hemodynamics and lung lymph balance, the potential that DBcAMP directly modulates the pulmonary vascular responses to endotoxin as a vasodilator could be expected. We conclude that DBcAMP infusion attenuates lung dysfunction caused by endotoxemia, possibly by preventing prostanoid release and modulating the pulmonary vascular responses.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.

The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.

Base Sequence↗
PubMed1992

Preclinical and clinical study of FK506 in uveitis.

Efficacy of a new immunosuppressive agent, FK506, in refractory uveitis was studied in 8 patients: 5 with Behcet's disease and 3 with idiopathic retinal vasculitis. The agent was given by oral administration every 12 hours. The previous therapy with systemic corticosteroids or immunosuppressive agents including cyclosporine failed to subside uveitis in these cases. During the observation period of 21.6 +/- 7.8 weeks (mean +/- SD) under FK506 at doses with 0.05, 0.1, 0.15 or 0.2 mg/kg/day, the visual acuity was increased in 44% of treated eyes, unchanged in 44% and decreased in 12%. The inflammatory activity in the ocular fundus was improved in 69% and unchanged in 6% of treated eyes. The effects of FK506 on uveitis by the criteria of improvement of visual acuity and uveitis activity was dose-dependent: 0.05 and 0.1 mg/kg/day were ineffective but 0.15 and 0.2 mg/kg/day were effective in most cases. One patient with Behcet's disease converted from cyclosporine developed moderate renal impairment in 4 weeks under FK506 and the therapy was discontinued in 8 weeks, though the uveitis activity as well as visual acuity was markedly improved. Other 7 cases had no side effect of FK506. Although the number of cases was small and observation period was short, the present clinical data indicate that FK506 is effective to treat refractory uveitis.

Administration, Oral↗
PubMed1992

[Therapeutic effects of cefprozil in the treatment of various infectious diseases in children].

Therapeutic effects of cefprozil (CFPZ, BMY-28100), a new cephalosporin, were examined in various infectious diseases in children. Clinical efficacy rates were 50% (2/4) in acute bronchitis, 80% (4/5) in pharyngitis, 0% in laryngitis, 100% (7/7) in tonsillitis, 100% (8/8) in impetigo contagiosa, furuncle and posthitis. Hence, the overall efficacy rate was 84% (21/25). Adverse effects were observed in 1 case with slightly elevated serum GOT and GPT. Changes in serum concentrations and urinary excretion of CFPZ were examined in 4 and 2 children without infection, respectively. T 1/2 values obtained were between 1 hour to 2 hours (bioassay). Six hour recovery rates in urine were 51.8% and 77.8% (bioassay). CFPZ was considered to be a safe and useful drug in treating various infectious diseases in children.

Administration, Oral↗
PubMed1992

The promoter of the human cystic fibrosis transmembrane conductance regulator gene directing SV40 T antigen expression induces malignant proliferation of ependymal cells in transgenic mice.

Transgenic mice bearing a human cystic fibrosis transmembrane conductance regulator (CFTR) promoter-SV40 T antigen fusion transgene were generated in order to localize in vivo the potential oncogenesis linked to the tissue-specific activity of the promoter for the CFTR gene. Surprisingly, the only site of tumors resulting from expression of the reporter onc gene was ependymal cells lining the brain ventricles. SV40 T antigen expression in these cells led to a consistent pathology in the first weeks of age: ependymoma and consequent hydrocephaly. Tumor-derived cell lines were established, characterized and shown to originate from SV40 T antigen-induced ependymoma. No pathological alterations were found in other organs, such as lungs and pancreas, in which cystic fibrosis is pathologically manifest in humans. Such transgenic mice and derived cell lines may represent valid models for analysing (1) the role of SV40 T antigen in ependymoma formation and (2) CFTR function in ependymal cells.

Animals↗
PubMed1992

[Clinical significance of scintigraphy in pulmonary aspergilloma].

In order to study the scintigraphic findings related to the pathophysiology of pulmonary aspergilloma, chest scintigraphy with T1-201 chloride and perfusion lung scintigraphy were performed in 18 and 19 patients with pulmonary aspergilloma, respectively. In T1-201 scintigraphy, accumulation of T1-201 in the diseased areas related to Aspergillus infection was observed in 18 of 19 foci. Roentgenographic findings related to the accumulation of T1-201 in the lesion were thickness of the cavity wall and pleural thickening adjacent to the cavity, but they showed no relation to the size of the fungus ball, and 2 cases without fungus ball showed positive results. Moreover, in T1-201 single photon emission computed tomography, accumulation of T1-201 was demonstrated in the area surrounding fungus ball. In addition, findings of inflammation such as leukocytosis, elevated erythrocyte sedimentation rate, positive CRP and fever were observed in more than 50% of all cases. These results suggest that tissues surrounding the fungus ball, including the cavity wall and thickened pleura undergo inflammatory process secondary to infection by Aspergillus. Perfusion lung scintigrams showed decreased perfusion in all of 19 cases, which was more marked than that expected from the chest radiograph in many cases. In T1-201 myocardial scintigraphy, visualization of the right ventricle was observed in 15 of 18 cases. T1-201 chest scintigraphy and perfusion lung scintigraphy are useful for evaluation of the activity of the disease process, right ventricular overloading, and regional perfusion in pulmonary aspergilloma.

Adult↗
PubMed1992

[A clinical investigation on renal pelvic and ureteral tumors].

Sixty-six patients with renal pelvic and ureteral tumors were treated in our hospital between June 1974 and June 1991. These cases consisted of 27 renal pelvic tumors, 31 ureteral tumors and 8 renal pelvic and ureteral tumors. Their ages ranged from 43 to 86 years old (average: 65). There were 46 males and 20 females. The surgical method involved total nephroureterectomy with a cuff for 44 patients, nephroureterectomy for 3, nephrectomy for 9, total nephroureterectomy with total cystectomy for 5 and partial ureterectomy for 2. Histologically, there were 60 transitional cell carcinomas (TCC), 2 squamous cell carcinomas (SCC) and 4 TCC with SCC. As for the pathological stage, 13 were pTa, 16 pT1, 12 pT2, 11 pT3, 13 pT4 and 1 pTX. Subsequent bladder tumors were found in 13 patients (19.7%). The overall survival rate at 1, 3 and 5 years were 80%, 68% and 52%, respectively according to the Kaplan-Meier's method. In this series, the pathological staging was the most important prognostic factor.

Adult↗
PubMed1992

[The fate of patients with intermittent claudication-comparison of surgical and non-surgical treatment].

The purpose of this study was to determine the operative indication for patients with intermittent claudication because of arteriosclerosis obliterans, and to compare the late result of the surgical treatment group (182 cases, 250 limbs) with that of the non-surgical treatment group (35 cases, 43 limbs). There were 3 operative deaths and 34 late deaths in the surgical group, and 14 late deaths in the non-surgical group. The number one cause of death was heart failure, including ischemic heart disease, in both groups. The 4-year cumulative patency rates were 91% in the aorto-iliac, 71% in the femoro-distal and 79% in the aorto-femoro-distal arterial reconstructions. Long term symptom free rates of the surgical group and the non-surgical group, except fatal case, were 83% and 44% in the aorto-iliac, 79% and 27% in the femoro-distal, 87% and 33% in the aorto-femoro-distal arterial regions, respectively. Late result of intermittent claudication in the surgical group was better than that in the non-surgical group. We concluded that intermittent claudication should be considered to be the indication for surgery, except for the cases with high risk diseases or malignant diseases.

Aged↗
PubMed1992

[Clinical study on incidental renal cell carcinoma].

Of 93 patients with renal cell carcinoma treated at our hospital between January 1974 and December 1990, thirty-two cases with incidentally detected cancer were evaluated clinically and pathologically. The average age of the patients was 61 years old ranging from 39 to 84 years. There were 25 men and 7 women with a sex ratio of 3.6:1. Fourteen tumors had developed in the right kidney and 17 in the left kidney. One patient had bilateral tumors synchronously and was treated by radical nephrectomy with contralateral enucleation of the tumor. The proportion of incidental renal carcinoma has been increasing steadily; 87.5% of the cases was found by either abdominal ultrasonography or CT scan. Nineteen patients (59.4%) had a tumor smaller than 5 cm in diameter. There were 29 cases with G1 or G2 renal cancer and twenty with pT2. The five-year survival rate in the incidental cases was 52.2% with significantly better survival than in cases when metastasis was initially suspected, but there was no significant difference in survival between the incidentally found cases and the cases of symptomatic renal cancer.

Adult↗
PubMed1992

Infantile multilocular renal cyst.

A case of a Japanese 14-month-old male infant with multilocular renal cyst is presented. He was admitted with a chief complaint of an abdominal mass. Although clinically and radiographically multilocular renal cyst in the right kidney was suspected, total nephrectomy was performed because of extreme difficulty of partial nephrectomy and impossibility of complete neglect of malignant cystic tumor. Microscopically, immature glomeruloid tissue, primitive tubules, rhabdomyocytes and nerve fibers were noted. The histological diagnosis of multilocular renal cyst with partially differentiated dysplasia was made. Since the first report by Edmunds in 1892, the etiology of multilocular renal cyst has been discussed for years. In our present case, the pathologic findings suggest that multilocular cystic formation in the right kidney might be the result of developmental disturbances.

Humans↗
PubMed1992

Induction of the expulsion of Strongyloides ratti and retention of Nippostrongylus brasiliensis in athymic nude mice by repetitive administration of recombinant interleukin-3.

A repetitive administration of recombinant interleukin-3 (rIL-3), which can induce the expulsion of Strongyloides ratti in athymic nude mice, did not affect the expulsion of Nippostrongylus brasiliensis. Nude mice infected with N. brasiliensis were injected i.p. with a total of 6.8 x 10(5) U rIL-3 or medium twice a day from Day 5 to Day 11 post-infection. The kinetics of expulsion estimated by egg excretion in faeces up to Day 20 post-infection and adult worm burden on Day 21 was not affected by the IL-3 administration. A similar administration with a higher dose (total 10.6 x 10(5) U) of rIL-3 did not alter the adult worm burden on Day 13. The number of intestinal mucosal mast cells on Day 13 was markedly increased by the treatment, although the number of intestinal goblet cells was comparable between the treated and control mice. When nude mice were infected concurrently with N. brasiliensis and S. ratti and then injected repeatedly with rIL-3 (total 2.2 x 10(5) U) from Day 5 to Day 11, adult worms of S. ratti were expelled from the small intestine by Day 13; however adult worms of N. brasiliensis were retained. Again in the concurrent infection, the number of intestinal mucosal mast cells was significantly increased but that of intestinal goblet cells was not altered by the rIL-3 administration. These results indicate that the expulsion of S. ratti is dependent on IL-3 whereas that of N. brasiliensis is less dependent on IL-3.

Animals↗
PubMed1991

Interleukin-8 gene expression in human bronchial epithelial cells.

The capacity of cells of the human bronchial epithelium to express the gene for interleukin-8 (IL-8) was evaluated in bronchial epithelium derived cell lines, HS-24 and BET-1A, using tumor necrosis factor-alpha (TNF) as a model inflammatory stimulus. As in other epithelium, TNF markedly increased the level of the 1.8-kilobase IL-8 mRNA transcripts in both bronchial epithelial cell lines. In HS-24 cells, nuclear run-on analyses showed the IL-8 gene transcription rate was dramatically increased, more than 30-fold, after TNF stimulation. The half-life of IL-8 mRNA transcripts in these cells was approximately 40 min and did not change after TNF stimulation, suggesting that TNF up-regulated IL-8 gene expression mainly at the transcriptional level. DNase I hypersensitivity site mapping of chromatin DNA in resting HS-24 cells demonstrated two hypersensitivity sites within 400 base pairs (bp) 5' to exon I and one site within exon I. However, after TNF stimulation, the exon I hypersensitivity site disappeared and a new site approximately 120 bp 5' to exon I emerged. Consistent with these observations, transfection studies with HS-24 cells using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene demonstrated potent promoter activity in a 174-bp segment (-130 to +44 relative to the transcription start site), which also exhibited a response to TNF, while a segment from -112 to +44 showed very low promoter activity and no response to TNF. Thus, human bronchial epithelial cells can express the IL-8 gene, with expression in response to the inflammatory mediator TNF regulated mainly at the transcriptional level, and with elements within the 5'-flanking region of the gene that are directly or indirectly modulated by the TNF signal.

Bronchi↗