Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 73 records · Page 4Linked to original sources

PubMed1999

UFT in bladder cancer.

UFT, a compound containing uracil and tegafur (a prodrug of 5-fluorouracil) in a 4:1 molar ratio, has been used in Japan for the treatment of and as adjuvant chemotherapy for bladder cancer. In phase II studies, 300 to 600 mg/day of UFT given orally for more than 4 weeks produced a 32% overall response rate, including a complete response rate of 19.0%. Toxicity was in general mild and reversible. Gastrointestinal toxicity affected 56% of patients receiving 600 mg/day and 24% of patients receiving 300 mg/day of UFT. A randomized, prospective trial was performed to determine whether long-term treatment with oral UFT (300 to 400 mg/day for 2 years) as adjuvant chemotherapy could prevent intravesical recurrence of superficial bladder cancer. Long-term UFT administration after transurethral resection, in fact, effectively prevented the recurrence of superficial bladder cancer, with acceptably low toxicity. These data suggest that UFT as a single agent is effective against bladder cancer, with mild toxicity when used properly.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Construction of a specific and sensitive sandwich enzyme immunoassay for 20 kDa human growth hormone.

Twenty kilodalton human growth hormone (20K-hGH) is a naturally occurring isoform lacking amino acid residues 32-46 of 22K-hGH. Due to this structural similarity to 22K-hGH, no one has constructed a specific and sensitive assay system for 20K-hGH, which can be used for measuring physiological concentration of this isoform in the circulation. To construct such a specific assay system, we have generated polyclonal antibodies (pAb) and monoclonal antibodies (mAbs) against recombinant 20K-hGH. Binding characteristics to 20K-, 22K-hGH and monkey GH (mGH) of these five mAbs, designated A23, B13, C02, D05, and D14, were analyzed by enzyme immunoassays (EIAs) and surface plasmon resonance analysis. Only one of them, the mAb D05, does not crossreact with 22K-hGH. It was also observed that mAb B13 does not crossreact with mGH, although the later is 96% homologous to hGH. Using these antibodies we have established several sandwich EIA systems for circulating 20K-hGH. The combination of A23 as a solid-phase antibody and B13 as a labeled antibody permitted both high sensitivity to 20K-hGH (< 0.1 ng/ml) and low cross-reactivities with 22K-hGH (< 2%), mGH (< 0.3%) and rat GH (< 0.1%). The clearances of administered 20K-hGH were determined by this combination in both rats and monkeys. In the assay of physiologically circulating 20K-hGH in humans, the combination of D05 and affinity-purified anti-20K-hGH pAb showed the highest sensitivity to 20K-hGH (< 10 pg/ml) and substantially no cross-reactivity with 22K-hGH (< 0.1%). The plasma 20K-hGH concentration in healthy female subjects was determined by this combination. The assay systems constructed here enables us to directly measure circulating 20K-hGH in physiological condition with no interference of 22K-hGH for the first time.

Adult↗

PubMed1998

High alkaline phosphatase activity in 3p-induced human renal cancer cells.

Recent studies have suggested that a tumor suppressor gene is located on the short arm of chromosome 3 (3p) for tumorigenesis of sporadic renal cell carcinoma. In this study, we introduced 3p from normal human fibroblasts into the renal cancer cell line YCR and this introduction clearly resulted in inhibited growth in vitro and in vivo. Furthermore, we investigated several enzyme activities of original YCR cells and 3p-induced clones (YCR-151 and YCR-152) and found that only alkaline phosphatase activity in 3p-induced clones was significantly increased compared to that of the original YCR cells.

Alkaline Phosphatase↗

PubMed1998

Detection of telomerase activity in prostate needle-biopsy samples.

BACKGROUND: Telomerase in an enzyme ribonucleoprotein responsible for cell immortality and oncogenesis. Telomerase activity has been detected in most cancers, including prostate cancer. To verify whether the detection of telomerase in prostate needle biopsy samples could have diagnostic value, we blindly assayed telomerase activity in samples from patients who were clinically suspected of having prostate cancer. METHODS: A total of 183 prostate biopsy samples was obtained from 63 patients who were suspected of having prostate cancer. Telomerase activity was determined by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. An internal telomerase assay standard (ITAS) was used in this study to distinguish false negatives. RESULTS: Telomerase activity was detected in 17 of 19 (89.5%) patients with prostate cancer (chi(2) test, P < 0.005). In 39 of 42 (92.9%) biopsy samples from these 19 prostate cancer patients, confirmed histologically as prostate cancer, telomerase activity (chi(2) test, P < 0.005) was detected. Meanwhile, we also found one false-positive sample. In contrast, all of 44 normal or benign prostate disease patients (124 biopsy specimens) were telomerase-negative. We also revealed that poorly differentiated prostate cancer often expresses a high level of telomerase activity. The area of cancer tissue in biopsy specimens was not associated with relative telomerase activity. CONCLUSIONS: This study suggests that determination of telomerase activity in prostate needle-biopsy samples might be a useful tool for detecting prostate cancer.

Adenocarcinoma↗

PubMed1998

Synapsin III, a novel synapsin with an unusual regulation by Ca2+.

Synapsins I and II are synaptic vesicle proteins essential for normal Ca2+ regulation of neurotransmitter release. Synapsins are composed of combinations of common and variable sequences, with the central C-domain as the largest conserved domain. The C-domain is structurally homologous to ATPases, suggesting that synapsins function as ATP-dependent phosphotransfer enzymes. We have now identified an unanticipated third synapsin gene that is also expressed in brain. The product of this gene, synapsin IIIa, shares with synapsins Ia and IIa three conserved domains that are connected by variable sequences: the phosphorylated A-domain at the amino terminus, the large ATP-binding C-domain in the center, and the E-domain at the carboxyl terminus. Like other synapsins, synapsin IIIa binds ATP with high affinity and ADP with a lower affinity, consistent with a cycle of ATP binding and hydrolysis. ATP binding to the different synapsins is directly regulated by Ca2+ in a dramatically different fashion: Ca2+ activates ATP binding to synapsin I, has no effect on synapsin II, and inhibits synapsin III. Thus vertebrates express three distinct synapsins that utilize ATP but are specialized for different modes of direct Ca2+ regulation in synaptic function.

Adenosine Triphosphate↗

PubMed1998

Performance of a helical undulator of the UVSOR.

A helical undulator was installed in the 0.75 GeV storage ring of the UVSOR facility of the Institute for Molecular Science. The undulator was designed to produce the fundamental of the circularly polarized undulator radiation in the energy range 2-43 eV, and the higher harmonics with elliptical polarization in the energy range up to 300 eV. Recently, the first spectrum from the undulator was observed. The performance of the undulator and the obtained spectrum are reported.

Journal Article↗

PubMed1998

Synapsin I is structurally similar to ATP-utilizing enzymes.

Synapsins are abundant synaptic vesicle proteins with an essential regulatory function in the nerve terminal. We determined the crystal structure of a fragment (synC) consisting of residues 110-420 of bovine synapsin I; synC coincides with the large middle domain (C-domain), the most conserved domain of synapsins. SynC molecules are folded into compact domains and form closely associated dimers. SynC monomers are strikingly similar in structure to a family of ATP-utilizing enzymes, which includes glutathione synthetase and D-alanine:D-alanine ligase. SynC binds ATP in a Ca2+-dependent manner. The crystal structure of synC in complex with ATPgammaS and Ca2+ explains the preference of synC for Ca2+ over Mg2+. Our results suggest that synapsins may also be ATP-utilizing enzymes.

Adenosine Triphosphate↗

PubMed1998

Synapsins I and II are ATP-binding proteins with differential Ca2+ regulation.

Synapsins I and II are abundant phosphoproteins that are localized to synaptic vesicles and have essential functions in regulating synaptic vesicle exocytosis. Synapsins contain a single evolutionarily conserved, large central domain, the C-domain, that accounts for the majority of their sequences. Unexpectedly, the crystal structure of the C-domain from synapsin I revealed that it is structurally closely related to several ATPases despite the absence of sequence similarities (Esser, L., Wang, C.-R., Hosaka, M., Smagula, C. S., Südhof, T. C., and Deisenhofer, J. (1998) EMBO J., in press). We now show that the C-domains of both synapsin I and synapsin II constitute high affinity ATP-binding modules. The two C-domains exhibit similar ATP affinities but are differentially regulated; ATP binding to synapsin I is Ca(2+)-dependent whereas ATP binding to synapsin II is Ca(2+)-independent. In synapsin I, the Ca2+ requirement for ATP binding is mediated by a single, evolutionarily conserved glutamate residue (Glu373) at a position where synapsin II contains a lysine residue. Exchange of Glu373 for lysine converts synapsin I from a Ca(2+)-dependent protein into a Ca(2+)-independent ATP-binding protein. Our studies suggest that synapsins I and II function on synaptic vesicles as ATP-binding proteins that are differentially regulated by Ca2+.

Adenosine Triphosphate↗

PubMed1998

Enhanced expression in seminoma of human zinc finger genes located on chromosome 19.

Six Krüppel-type zinc finger (ZF) genes were cloned from a seminoma cDNA library. One, ZFS-1, showed high sequence homology to the ZNF91 KRAB (Krüppel-associated box) ZF gene family and also the same chromosomal assignment. Interestingly, Northern blot analyses using ZFS-1 and ZNF91 revealed that multiple ZF genes on chromosome 19 were predominantly expressed in seminomas. In addition, the testis and the seminoma showed specific expression of 2.3 kb transcript. Our results suggest that ZF genes on chromosome 19 may be implicated in the development and/or growth of seminomas.

Amino Acid Sequence↗

PubMed1998

Limb salvage and survival rates among elderly patients with advanced limb ischemia.

The purpose of this study was to clarify the incidence of limb salvage and patient survival rates among elderly patients with advanced leg ischemia. We reviewed the records of 159 patients treated for advanced ischemia over a 15-year period at Aichi Medical University, 74 of whom were aged over 75 years and 85, between 65 and 74 years. There was a collective total of 186 limbs; 82 in the older group and 104 in the younger group. The older group had a greater proportion of women, and a higher incidence of coronary heart disease, pulmonary dysfunction, and acute onset of advanced ischemia than the younger group. Limb salvage was achieved in 73% of the affected limbs in the older group and in 92% of the limbs in the younger group. The poor limb salvage rate in the older group was mainly related to the high initial amputation rate. Early recognition of the sentinel ischemic signs before the ischemia is essential, especially in the elderly. Timely revascularization should be attempted whenever possible, and it should not be abandoned simply because the patient is deemed too old. The 1-, 3-, and 5-year survival rates in the older group were 59%, 28%, and 23%, respectively, which were markedly poorer than the expected survival rates of the age- and sex-matched Japanese population at 1, 3, and 5 years, which were 93%, 79%, and 65%, respectively. Thus, advanced limb ischemia carries a poor prognosis to the point of being life-threatening, and further continuous systemic management with the collaboration of physicians and surgeons must be provided even after the patient has left the hospital.

Aged↗

PubMed1998

Successful pregnancy with sperm retrieved from the bladder after the introduction of a low-electrolyte solution for retrograde ejaculation.

OBJECTIVE: To determine the safety and efficacy of the introduction of a low-electrolyte solution into the bladder before masturbation for sperm recovery in patients with retrograde ejaculation. DESIGN: Two case reports. SETTING: Assisted reproduction practice at a university hospital. PATIENT(S): Two men with retrograde ejaculation. INTERVENTION(S): A 0.32-mol/L glucose solution or Ham's modified F-10 medium (GIBCO, Grand Island, NY) with 10% serum was introduced into the urinary bladder before masturbation. The retrieved sperm were used for IUI. MAIN OUTCOME MEASURE(S): The motility of retrieved sperm, achievement of pregnancy, and outcome of pregnancy. RESULT(S): In patient 1, the motility rate of sperm retrieved from the bladder after the introduction of Ham's modified F-10 medium was higher than that after the introduction of a glucose solution. The patient's wife did not become pregnant during 10 IUI cycles after treatment with Ham's modified F-10 medium. However, she became pregnant during the first IUI cycle after treatment with a glucose solution and was delivered of healthy twin infants. The wife of patient 2 also became pregnant during the first IUI cycle after treatment with a glucose solution and was delivered of a healthy female infant. CONCLUSION(S): The introduction of a glucose solution appears to be a safe and simple method for sperm recovery in patients with retrograde ejaculation.

Adult↗

PubMed1998

Transarterial embolization and ablation of renal arteriovenous malformations: efficacy and damages in 30 patients with long-term followup.

PURPOSE: We evaluate the long-term efficacy and side effects of transarterial embolization and ablation for renal arteriovenous malformations. MATERIALS AND METHODS: A total of 30 patients with cirsoid arteriovenous malformations causing massive hematuria underwent 34 procedures of embolization or ablation. We confirmed the ratios of occluded arteriovenous malformation areas on angiograms and those of infarcted areas on computerized tomography. All patients were followed for 4.1 to 15.0 years (mean 8.0 +/- 2.8) after the initial procedures. RESULTS: Hematuria ceased in all patients after the initial procedures, including partial embolization or ablation of the arteriovenous malformations in 8. Massive hematuria recurred in 4 patients, who had undergone absorbable gelatin sponge (2), embolization, combined alcohol and subselective absorbable gelatin sponge embolization (1) and polyvinyl alcohol particles embolization (1). In these 4 cases total ablation of the arteriovenous malformations with alcohol was successful. In 29 patients, including aforementioned 4, no hematuria recurred after 5 years following total or partial ablation with alcohol. Large nontarget embolization with reflux of subselectively infused absorbable gelatin sponge caused a nonfunctioning kidney in 1 patient. The remaining 33 procedures caused 6.3 to 48.0% (mean 15.7 +/- 6.9%) areas of renal infarction. Polyvinyl alcohol embolization caused pulmonary embolism and renin dependent hypertension. CONCLUSIONS: Partial or total transarterial ablation of arteriovenous malformations with alcohol proved effective for long-term cessation of hematuria. However, this procedure as well as transarterial embolization has the potential risk of nontarget infarction.

Adult↗

PubMed1998

Interaction between sodium ascorbate and dopamine.

The interaction between sodium ascorbate and dopamine was investigated by three different parameters: radical intensity, prooxidant action, and cytotoxicity induction. Sodium ascorbate and dopamine produced the doublet and quartet ESR signals under alkaline conditions (pH 8.0-9.5), respectively. Addition of increasing concentrations of sodium ascorbate completely scavenged the dopamine radical and replaced the latter with its own radical. Similarly, dopamine slightly, but significantly reduced the radical intensity of sodium ascorbate. These two compounds stimulated the methionine oxidation and hydrogen peroxide generation in culture medium, but in combination, their stimulation activities were weakened. Both of these two compounds dose-dependently reduced the viable cell number of human oral squamous carcinoma HSC-4 cells, and their cytotoxic activity was significantly reduced by catalase. When these two compounds were mixed together before adding to HSC-4 cells, both of their cytotoxic activities were diminished. The present study demonstrates the interaction between sodium ascorbate and dopamine, which might modify their biological activities and generation of nerve disorders such as Parkinson's disease.

Amino Acids↗

PubMed1998

Inhibitory effects by a submandibular gland extract on luteinizing hormone-stimulated testosterone production by testicular cells.

In order to evaluate the role of the submandibular gland (SMG) on testosterone (T) production by the testis, primary cultured testicular cells were prepared from rats that had the submandibular gland surgically ablated (G-) and control (sham operated) rats (S.O.) respectively. The cells were incubated with or without 100 ng/ml luteinizing hormone (LH) and/or SMG extract. The same linear increase in T secretion was shown by both S.O. and G- cells on multi-stimulation with LH for up to 96 hrs. However, while an equivalent response was shown for S.O. cells after a single LH stimulation at 96 hrs, T secretion by the G- cells reached a plateau after 24 hrs. The level at 96 hrs was thus approximate 30% and 33% of those of S.O. cells with and without multi-stimulus by LH for 96 hrs, respectively. When S.O. cells were cultured with SMG extract, LH-stimulated T secretion was dose-dependently inhibited and there was no effect on basal T secretion. The inhibitory effect was abolished by treatment at 95 degrees C for 5 min. Ultra-filtration indicated that the molecular size of the inhibitory agent was greater than 30,000. It is proposed that SMG may contain a high molecular weight, heat labile soluble factor(s) which affects T secretion by inhibiting LH action in testicular cells.

Animals↗

PubMed1998

Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis.

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavidin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or = 8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P < 0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.

Aged↗

PubMed1998

Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy.

BACKGROUND: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The medication was then withheld and the patients were carefully monitored for an additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82 years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of BPH, and was still effective 16 weeks after the cessation of medication. The prostate volume did not change after treatment cessation nor did the total symptom score, but the MFR reversed to the pretreatment level. Serum testosterone (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy, but were completely reversed by the end of this study. A prostate needle biopsy revealed that after 16 weeks without therapy, some glands showed regressive glandular changes, while some glands showed slight hyperplastic changes of the secretory epithelium. Eight per cent of patients complained of loss of libido during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical treatment for patients with symptomatic BPH. Hormonal and histopathologic findings suggest that the prostate gland may regrow after discontinuation of medication.

Aged↗

PubMed1998

Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases.

We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones. The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient [r] = 0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells). Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration [IC50] = 13.8 microg/ml for S. aureus topoisomerase IV; IC50 = 0.109 microg/ml for E. coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among the quinolones tested. There was also a significant correlation between the inhibitory activities of quinolones against S. aureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme. The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase. These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.

Anti-Infective Agents↗

PubMed1998

[Prognosis in the cases with renal cell carcinoma according to clinical parameters].

BACKGROUND: The objects of this study is to evaluate the clinical prognostic factors in renal cell carcinoma. MATERIALS AND METHODS: During a 30-year period from January 1965 to December 1994, 1301 cases with renal cell carcinoma were treated at the Yokohama City University Hospital and its affiliated hospitals. In these cases, cause specific 679 cases from January 1965 to December 1990 were analyzed in a study undertaken to investigate long-term treatment results and clinical prognostic factors. RESULTS: 1. The cause specific 5-, 10-, 15-, and 20-year survival rates were 48.7%, 41.1%, 32.3%, and 26.5% respectively, indicating thus that a great number of cases had an ominous prognosis even 5 years or moreafter surgical treatment. 2. Among patients under 40 years of age (n = 29) none died more than 2 years after receiving operation, the prognosis for this particular group of cases being relatively good. 3. Female, incidentally detected cancer, small tumor size (< or = 4.0 cm), slow growing type and low stage were proven to be favourable prognostic factors in renal cell carcinoma. 4. The cause specific 5-year survival rate for the patients (n = 239) from 1965 to 1981 was 33.8%, while the rate for the patients (n = 440) from 1982 to 1990 was 56.5%. This improvement of survival rate was brought by the increase of the incidentally detected renal cell carcinoma. 5. In the incidentally detected renal cell carcinoma, the incidence of slow growing cases and the cases of less than 4.0 cm tumor size were higher than in the symptomatic renal cell carcinoma. 6. Multivariate analysis using Cox's proportional hazard model showed that stage was the most important prognostic factor. CONCLUSIONS: These results suggested that sex, age, symptom, tumor size, growing type, and stage were important prognostic factors in renal cell carcinoma.

Adolescent↗