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Biomedical subjects

Y Hosaka

Publications and source records attributed to Y Hosaka.

At least 37 records · Page 2Linked to original sources

Prolonged recovery of cardiac output after maximal exercise in patients with chronic heart failure.

OBJECTIVES: The aim of this study was to characterize the kinetics of cardiac output during recovery from maximal exercise in patients with chronic heart failure (CHF). BACKGROUND: Recent studies have shown that oxygen uptake kinetics during recovery from exercise are delayed in patients with CHF. However, the kinetics of cardiac output during recovery from maximal exercise in CHF has not been examined. METHODS: Thirty patients with CHF performed maximal upright ergometer exercise with respiratory gas analysis. Kinetics of oxygen uptake (VO2) and carbon dioxide output (VCO2) during recovery were characterized by T1/2, the time to reach 50% of the peak values. Cardiac output was measured at 1-min intervals during exercise and recovery. Kinetics of cardiac output during recovery were characterized by the ratios of cardiac output during the first 4 min of recovery to cardiac output at peak exercise. Overshoot of cardiac output was defined as a further increase in cardiac output at 1 min of recovery above the cardiac output at peak exercise. RESULTS: Both T1/2 VO2 and T1/2 VCO2 increased as CHF worsened. The ratios of cardiac output during recovery to cardiac output at peak exercise were significantly correlated with T1/2 VO2 (r = 0.47 to 0.62, p < 0.05) and T1/2 VCO2 (r = 0.40 to 0.70, p < 0.05). There was a negative correlation between cardiac index at peak exercise and both T1/2 VO2 (r = -0.65, p < 0.001) and T1/2 VCO2 (r = -0.60, p < 0.001). Overshoot of cardiac output was recognized in 11 of 30 patients. Cardiac index at peak exercise was significantly lower in patients with overshoot (4.5 +/- 0.9 L/min/m2) than in those without overshoot (6.1 +/- 2.1 L/min/m2, p < 0.05). However, because of a continued increase in cardiac output at 1 min of recovery in patients with overshoot, there were no differences in cardiac index after the first minute of recovery. Heart rate at peak exercise and recovery of heart rate did not differ between these groups. Overshoot of cardiac output was caused by a rebound increase in stroke volume which was due to a reduction in systemic vascular resistance. CONCLUSIONS: Prolonged kinetics of VO2 or VCO2 during recovery from maximal exercise represent impairment of circulatory response to exercise and delayed recovery of cardiac output after exercise. Overshoot of cardiac output at 1 min of recovery was characteristic of severe CHF with poor cardiac output response to exercise.

Analysis of Variance↗

Cystic renal cell carcinoma diagnosed by cystofiberscopy.

A 64-year-old man suffered from hypertensive syncope and was admitted to Branch Hospital, Faculty of Medicine, The University of Tokyo. On admission he had no symptoms; however, two renal cysts of about 5 cm in diameter were found in his left kidney. Cystofiberscopy with a thin optical fiberscope was performed in addition to puncture and cystography. Cytology revealed class I, but the wall surface of the lower cyst was uneven, fluid-filled, colloid-like and white-gray compared with that seen in the upper cyst. It was diagnosed as renal cell carcinoma (RCC) and left nephrectomy was performed (5 cm in diameter, RCC, papillary tubular, common, clear cell subtype, G2>G1, INF beta, pT2, pMx, pV0, ew(-)).

Carcinoma, Renal Cell↗

Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.

Patients with xeroderma pigmentosum variant show clinical photosensitivity, skin neoplasias induced by ultraviolet light, and defective postreplication repair, but normal nucleotide excision repair. We recently reported an alternative, simple method for the diagnosis of xeroderma pigmentosum variant that measures by autoradiography three cellular markers for DNA repair after ultraviolet irradiation: unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis. Among hereditary photosensitive disorders, including other xeroderma pigmentosum groups, Cockayne syndrome, and a newly established ultraviolet-sensitive syndrome, only xeroderma pigmentosum variant cells exhibited normal unscheduled DNA synthesis, normal recovery of RNA synthesis, but reduced recovery of replicative DNA synthesis (51 +/- 6% the rate relative to normal controls). This reduction of recovery of replicative DNA synthesis was enhanced in the presence of a nontoxic level of caffeine to 36 +/- 5%. In this study we assess the cellular markers in two independent families that included two photosensitive patients that were identified as xeroderma pigmentosum variant. Cells from heterozygotic parents showed normal levels of unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis, but reduced rates of recovery of replicative DNA synthesis in the presence of 1 mM caffeine (53 +/- 8% relative to the normal control). Furthermore, with a colony-forming assay, the cells showed normal survival by ultraviolet without caffeine, but slightly reduced survival by ultraviolet with 1 mM caffeine present. In one family, we confirmed inheritance of two heterozygous mis-sense mutations. One mutation is an A-->G transition at nucleotide 1840 that generates a K535E mis-sense mutation. Another mutation is an A-->C transversion at nucleotide 2003 that generates a K589 mis-sense mutation. Each of these mutations were absent in 52 unrelated Japanese individuals. These results suggest that xeroderma pigmentosum variant heterozygotes can be identified by their sensitivity to ultraviolet irradiation in the presence of nontoxic levels of caffeine.

Adult↗

Binding of influenza type A viruses to group B Streptococcus and haemagglutination by virus-bound bacteria.

We studied the bindings of human influenza A type viruses to group B Streptococcus (GBS), types Ia, II, III and IV, of sialic acid (SA)alpha2-3 linkage, using A/PR/8/34(H1N1) and A/Memphis/1/71(H3N2). The viruses were found to bind to all types of GBS, with the exception of PR/8/34 for GBSII, and to elute from GBSIa, III and IV at 37 degrees C, except GBSII. Electron microscopy confirmed these behaviours of the influenza viruses. The virus-binding capability of GBS types seemed to depend on the side chain length of the terminal SA. Treatment of GBSIa, III and IV, except enzyme-resistant type II, with bacterial neuraminidase resulted in the loss of virus-binding capability of GBS. These findings confirmed that SAalpha2-3 linkage of GBS capsules functions as receptor for human influenza viruses. When singular bacteria were prepared from mainly chain-like GBS with sonication, viruses were found to bind to them more efficiently. Untreated and sonicated GBS were both aggregated with high doses of virus. Furthermore, using A/Memphis/1/71(H3N2) and GBSII, we found that virus-bound GBS, untreated or sonicated, caused haemagglutination (HA). The morphological evidence that chicken erythrocytes were bridged with virus-bound native GBSII, supporting occurrences of HA, was obtained. Statistical analysis suggested that HA by virus-bound sonicated (singular) GBS was mediated by bacteria bound by at least two or three virus particles.

Animals↗

[Extratesticular germ cell tumor focusing on treatment and prognosis].

About 3% to 5% of all germ cell tumors are thought to be primary extratesticular tumors, including a small group of benign tumors. Though the testes are clinically normal, diagnosing whether the tumor is primary or metastatic is problematic. Developments in ultrasonography have enabled the detection of tiny testicular lesions, and ultrasonography is applied to determine the biopsy sites. Nevertheless, burned-out tumor and carcinoma in situ are not always easy to find. Extratesticular germ cell tumors are usually treated using methods similar to those for advanced testicular tumors; however, the results are discouraging. Only limited cases are suitable for a monotherapy of surgery, so a combined treatment of cisplatin based chemotherapy and surgery is prevalent. Against seminomas, radiotherapy is effective. In addition to the advent of such pharmaceuticals as G-CSF and serotonin receptor antagonists, recent development of peripheral blood stem cell transplantation is expected to produce improved prognoses among patients burdened with this refractory disease. A prognostic factor-based staging system developed by the International Germ Cell Cancer Collaborative Group is reasonable and useful. Non-seminomas are classified as having good or intermediate prognoses if retroperitoneal tumors having no non-pulmonary visceral metastases show good or intermediate markers. A poor prognosis is associated with extratesticular tumors with mediastinal primary or non-pulmonary visceral metastases or poor markers. Seminomas with normal AFP are classified as having good or intermediate prognoses if no non-pulmonary visceral metastases are seen or discarded. No seminomas are classified in the poor prognosis group.

Adult↗

[Antibacterial activity of 16 antibiotics against Helicobacter pylori].

The susceptibilities of 24 Helicobacter pylori isolates, which were originated from clinical materials, to 5 beta-lactam antibiotics [benzylpenicillin (PCG), ampicillin (ABPC), cephalothin (CET), ceftazidime (CAZ), cefotiam (CTM) and imipenem (IPM)], two macrolides [clarithromycin (CAM) and rokitamycin (RKM)], two aminoglycosides [amikacin (AMK) and gentamicin (GM)], two new quinolones [ciprofloxacin (CPFX) and levofloxacin (LVFX)], two tetracycline [tetracycline (TC) and minocycline (MINO)], rifampicin (RIF) and chloramphenicol (CP) were tested. All of the isolates showed similar susceptibilities against beta-lactam antibiotics. However, MICs of CTM and CAZ were two- to four-fold higher than those of PCG, ABPC, CET and IPM, MICs of rokitamycin for the tested strains were higher than those of clarithromycin. MICs of CPFX and LVFX showed two-modal distributions. The first peak of distributions was observed between 0.06 to 0.5 microgram/ml and second one was between 4 to 16 micrograms/ml. These distributions suggested that MIC values of 4 to 16 micrograms/ml could result from the expression of a resistance mechanism. In addition, some of H. pylori strains were observed drug resistances between CP and AMK, new quinolones and AMK respectively. From the molecular epidemiological study, cryptic plasmids were detected from the 3 isolates among 24 strains tested.

Aminoglycosides↗

Butyrolactone I induces cyclin B1 and causes G2/M arrest and skipping of mitosis in human prostate cell lines.

Several naturally occurring cyclin-dependent kinase (CDK) inhibitors have been isolated from different lower organisms. In this report, we examined the effect of one of the CDK inhibitors, butyrolactone I (BL), on the expression of cyclins D2, A and B1 in three human prostatic cancer cell lines (DU145, PC-3, LNCaP) using two colored flow cytometric analysis. The percentage of DU145 cells in the 4C phase of the cell cycle were increased significantly at both 70 microM and 100 microM BL. Furthermore, an additional 8C peak was observed which had double the DNA content of the 4C phase at these concentrations of BL. The appearance of the 8C peak increased gradually and was more evident in DU145 and PC-3 than LNCaP. Cells in the 8C peak had either two nuclei or abnormal nuclei as observed by Papanicolaou stain. BL also increased the amount of cyclin B1 positive cells in the 4C phase. This increase was apparent on day 1 and returned to normal by day 3. Since BL selectively inhibits cyclin-dependent kinase, cyclin B1 might accumulate without being degraded. Other cyclins were not significantly changed by BL. The data demonstrate that BL inhibited Cdc2 of unsynchronized cultured prostate cancer cells, and interrupted the cell cycle progression toward cell division. The BL inhibition of Cdc2 led to the accumulation of cells in the 4C phase without mitosis resulting in an accumulation of cyclin B1. The appearance of cells in the 8C phase may be due to the progression of cells in the 4C phase through the cell cycle skipping mitosis. Cyclin B1 decreased in correlation with the progression through a new cell cycle. These results suggest that BL does not cause a complete arrest of the cell cycle in G2/M but that BL occasionally allows for the skipping of mitosis and subsequent progression through the cell cycle to occur.

4-Butyrolactone↗

Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation.

BACKGROUND: Proliferation, apoptosis, and angiogenesis are essential for carcinogenesis. Little is known regarding the relation between proliferation, apoptosis, and angiogenesis in untreated prostate carcinoma as well as alterations associated with androgen ablation. METHODS: Eighty patients who underwent radical prostatectomy for clinically localized prostate carcinoma were recruited for the study. The study population included 2 groups: 35 patients receiving 3-month neoadjuvant hormonal treatment using a combination of luteinizing hormone-releasing hormone analogue and the antiandrogen flutamide (NHT group) and 45 patients without prior treatment (non-NHT group). The authors measured the Ki-67 labeling index (Ki-67 LI) by MIB-1 immunohistochemistry, the apoptotic index (AI) by the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling technique, and intratumoral microvessel density (IMVD) by CD31 immunohistochemistry on serial sections of formalin fixed, paraffin embedded tissues. Correlations among these parameters were examined in both groups. RESULTS: A significant decrease in the Ki-67 LI coupled with a significant increase in AI was found in the NHT group compared with the non-NHT group, whereas IMVDs in both groups were not significantly different. AI was related to IMVD inversely in the non-NHT group (correlation coefficient [r] = -0.327; P = 0.03); in contrast, AI was related to IMVD positively in the non-NHT group (r = 0.579; P < 0.001). The Ki-67 LI was related to AI significantly in the non-NHT group but not in the NHT group. There was no correlation between Ki-67 LI and IMVD in either group. CONCLUSIONS: Correlations between proliferation, apoptosis, and angiogenesis in prostate carcinoma are altered significantly in association with androgen ablation. The results indicate that spontaneous apoptosis is suppressed by neovascularization, whereas hormone-induced apoptosis is enhanced in hypervascular tumors.

Adenocarcinoma↗

The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells.

BACKGROUND: Intracellular cyclic adenosine monophosphate (AMP) level changes are thought to play an important role in inhibiting cell proliferation and inducing differentiation in several types of cells. It has been reported that cyclic AMP analogs induce terminal differentiation in human prostate cancer cells. Consequently, phosphodiesterase inhibitors may be useful in delineating the role of cyclic AMP in the differentiation of these cells. Therefore, the effect of phosphodiesterase inhibitors on morphologic differentiation, proliferation and invasive potential of human prostate cancer cells was investigated. METHODS: Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors, papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline, for 6 days. Morphologic changes of these cells induced by phosphodiesterase inhibitors were observed by microscopy. Intracellular cyclic AMP levels in LNCaP cells were measured by radioimmunoassay using a cyclic AMP assay kit. The effect of papaverine on the proliferation and invasive potential of LNCaP cells were measured by cell counting and the Matrigel invasion chamber assay. RESULTS: Of the three agents, examined papaverine (10(-5) mol/L) is the most effective inducer of morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells. However, unlike LNCaP cells, PC-3 and DU145 cells treated with phosphodiesterase inhibitors, including papaverine, showed little change in morphology. Additionally, proliferation and invasive potential of LNCaP cells were significantly inhibited by papaverine. CONCLUSION: The results suggest that papaverine induces terminal differentiation in LNCaP cells, which is correlated with an intracellular cyclic AMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗

The use of otherwise redundant skin to provide nasal lining in the reconstruction of full-thickness alar defects by nasolabial flap repair.

The use of otherwise redundant nasolabial flap skin is described for lining in reconstruction of full-thickness alar defects. The techniques have been successfully used to reconstruct full-thickness alar defects in four patients. The overall procedure has the advantage of providing well-vascularised tissue of appropriate colour, texture and thickness for external skin and nasal lining in one-stage reconstruction.

Aged↗

Experimental vascular graft using small-caliber fascia-wrapped fibrocollagenous tube: short-term evaluation.

This study was undertaken to evaluate the application of autogenous fascia as a framework for a fibrocollagen tube for small-caliber vascular prostheses in Japanese white rabbits (n = 15). The fascia, measuring 10 x 40 mm, was harvested from the dorsal fascia and was carefully wrapped around a silicone rod of 1.5 mm in diameter. Then, the fascia-wrapped silicone rod was implanted into a subcutaneous pocket on the medial thigh. Four weeks later, the fascia-wrapped silicone rod was removed from the subcutaneous pocket. The rod was removed from the material, and the fascia-wrapped fibrocollagen tube was treated to make it antithrombogenic. Subsequently, the 1.5 x 10-mm fascia-wrapped tube was prepared as an arterial conduit. Using microvascular techniques, the tube was interposed into the divided femoral artery. Eleven of 15 grafts maintained patency over the follow-up period and no aneurysmal formation was found at any graft site. Microscopically, there was an ingrowth of endothelium with fibroblast proliferation from each end of the recipient vessel at 2 weeks after interposition; however, no neointima was found to line the center of the conduit. At 5 weeks after interposition, the neointimal growth rate was 70 percent. There was an ingrowth of endothelium with fibroblast proliferation from each end onto the entire internal surface of the conduit at 8 weeks after interposition. Further study is required before any long-term conclusions can be drawn.

Animals↗

ATIII-independence of anticoagulant effect of human urinary soluble thrombomodulin.

We investigated antithrombin III (ATIII)-dependency of the anticoagulant effects of human urinary soluble thrombomodulin (UTM) both in vivo and in vitro, in comparison with those of heparins. For neutralization of rat plasma ATIII activity, we used F(ab')2 fragment of anti-rat ATIII antibody and could establish an appropriate in vivo model to evaluate the ATIII-dependency of antithrombotic agents. The efficacy of UTM on thromboplastin-induced disseminated intravascular coagulation produced in ATIII-decreased rats was almost the same as that in normal rats, whereas unfractionated (UF)-heparin remarkably diminished its effect in ATIII-decreased rats. The prolongation effect of UTM on activated partial thromboplastin time or prothrombin time in plasma in vitro was unchanged in both normal and ATIII-decreased rats, but the effect of UF-heparin remarkably diminished in ATIII-decreased rat plasma. Such ATIII-independence in the anticoagulant effect of UTM was also observed in human plasma. Thus, differing from heparins, since the anticoagulant effect of UTM does not depend on plasma ATIII activity, UTM is expected to be a useful antithrombotic agent for the treatment of thromboembolic diseases, even in the case with low plasma ATIII activity.

Animals↗

Langer-Giedion syndrome associated with submucous cleft palate.

We report a 4-year-old girl with characteristic features of the Langer-Giedion syndrome (trichorhinophalangeal syndrome type II) who also had submucous cleft palate. When she underwent a palatoplasty, a diagnosis of Langer-Giedion syndrome was made because of the characteristic facial features, multiple exostoses, and partial deletion of the long arm of chromosome 8. This is the first case of trichorhinophalangeal syndrome associated with cleft palate. We review the clinical alterations of trichorhinophalangeal syndromes and differential diagnosis of Langer-Giedion syndrome from trichorhinophalangeal syndrome type I and hereditary multiple exostoses. We also describe the importance of trichorhinophalangeal syndrome in plastic surgery.

Cephalometry↗

Alternate splicing in human Na+-MI cotransporter gene yields differentially regulated transport isoforms.

myo-Inositol is a ubiquitous intracellular organic osmolyte and phosphoinositide precursor maintained at millimolar intracellular concentrations through the action of membrane-associated Na+-myo-inositol cotransporters (SMIT). Functional cloning and expression of a canine SMIT cDNA, which conferred SMIT activity in Xenopus oocytes, predicted a 718-amino acid peptide homologous to the Na+-glucose cotransporter with a potential protein kinase A phosphorylation site and multiple protein kinase C phosphorylation sites. A consistent approximately 1.0- to 13.5-kb array of transcripts hybridizing with this cDNA are osmotically induced in a variety of mammalian cells and species, yet SMIT activity appears to vary among different tissues and species. An open reading frame on human chromosome 21 (SLC5A3) homologous to that of the canine cDNA (96.5%) is thought to comprise an intronless human SMIT gene. Recently, this laboratory ascribed multiply sized, osmotically induced SMIT transcripts in human retinal pigment epithelial cells to the alternate utilization of several 3'-untranslated SMIT exons. This article describes an alternate splice donor site within the coding region that extends the open reading frame into the otherwise untranslated 3' exons, potentially generating novel SMIT isoforms. In these isoforms, the last putative transmembrane domain is replaced with intracellular carboxy termini containing a novel potential protein kinase A phosphorylation site and multiple protein kinase C phosphorylation sites, and this could explain the heterogeneity in the regulation and structure of the SMIT.

Alternative Splicing↗

Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells.

In diabetes, activation of the aldose reductase (AR) pathway and alterations of glucose-sensitive signal transduction pathways have been implicated in depletion of intracellular taurine, an endogenous antioxidant and compatible osmolyte. Cellular taurine accumulation occurs by an osmotically induced, protein kinase C (PKC)-regulated Na(+)-taurine cotransporter (hTT). The effects of ambient glucose on taurine content, hTT activity, and hTT gene expression were therefore evaluated in low and high AR-expressing human retinal pigment epithelial cell lines. In low AR-expressing cells, 20 mM glucose decreased taurine content, hTT transporter activity, and mRNA levels, and these effects were unaffected by AR inhibition (ARI). In these cells, the inhibitory effects of high glucose on hTT appeared to be posttranscriptionally mediated, because 20 mM glucose decreased hTT mRNA stability without affecting hTT transcriptional rate. Inhibition of PKC overcame the decrease in hTT activity in high glucose-exposed cells. In high AR-expressing cells, prolonged exposure to 20 mM glucose resulted in intracellular taurine depletion, which paralleled sorbitol accumulation and was prevented by ARI. In these cells exposed to 5 mM glucose, hTT mRNA abundance was decreased and declined further in 20 mM glucose but was corrected by ARI. In 5 mM glucose, hTT transcriptional rate was markedly decreased in high AR-expressing cells, did not decline further in 20 mM glucose, but was increased by ARI to levels above those observed in low AR-expressing cells. Therefore, glucose rapidly and specifically decreases taurine content, hTT activity, and mRNA abundance by AR-unrelated and AR-related posttranscriptional and transcriptional mechanisms.

Aldehyde Reductase↗

Exercise-induced rise in arterial potassium in patients with chronic heart failure.

OBJECTIVES: In patients with chronic heart failure (CHF), exercise is frequently associated with skeletal muscle fatigue and breathlessness due to heightened ventilatory response. The exercise-induced rise in potassium, which is released from the exercising skeletal muscle, has been implicated in ventilatory control during exercise. The aim of the present study was to determine whether the exercise-induced rise in arterial potassium is altered in patients with CHF and to examine the relationship between increased exercise ventilation and exercise-induced hyperkalemia in patients with CHF. METHODS AND RESULTS: We evaluated 88 patients with CHF (25 patients were in class I, 35 in class II, and 28 in class III according to the New York Heart Association functional classification) and 14 normal subjects. Subjects performed symptom-limited ergometer exercise while expired gas, arterial blood gas, and arterial potassium were analyzed. The increases in ventilation (deltaV(E)), effective alveolar ventilation (deltaVA), and carbon dioxide output (deltaV(CO2)) from rest to peak exercise decreased as the severity of CHF advanced. The ratio of deltaV(E) to deltaV(CO2) was significantly elevated in class III patients, although there was no difference in the ratio of deltaVA to deltaV(CO2) among the four groups. Rest and exercise arterial P(CO2) did not differ among the four groups and was controlled within the normal range. The increase in arterial potassium (deltaK+) from rest to peak exercise was markedly reduced as the severity of CHF advanced: (mean +/- SD) 1.70+/-0.32 mmol/L in normal subjects; 1.46+/-0.27 mmol/L in class I patients; 1.15+/-0.24 mmol/L in class II patients; and 0.78+/-0.24 mmol/L in class III patients. The ratios of deltaVA or deltaV(CO2) to deltaK+ were not different among the four groups. The ratio of deltaV(E) to deltaK+, however, was significantly greater in patients in class III than in normal subjects or patients in class I or II. CONCLUSIONS: The deltaK+ from rest to peak exercise was markedly reduced as the severity of CHF advanced. The increased exercise ventilation due to increased physiologic dead space in severe CHF was not accompanied by the corresponding augmentation of exercise-induced hyperkalemia. Exercise-induced hyperkalemia does not contribute to the increased ventilatory drive to keep normal arterial P(CO2) during exercise in the presence of increased physiologic dead space in severe CHF.

Exercise↗