PubMed Health⌕ Search

Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 19 recordsLinked to original sources
PubMed1992

Consensus sequence for precursor processing at mono-arginyl sites. Evidence for the involvement of a Kex2-like endoprotease in precursor cleavages at both dibasic and mono-arginyl sites.

Many peptide hormones and neuropeptides are produced from larger, inactive precursors through endoproteolysis at sites usually marked by paired basic residues (primarily Lys-Arg and Arg-Arg), or occasionally by a monobasic residue (primarily Arg). Based upon data concerning processing of prorenin and its mutants around the native Lys-Arg cleavage site expressed in mouse pituitary AtT-20 cells, we present the following sequence rules that govern mono-arginyl cleavages: (a) a basic residue at the fourth (position -4) or the sixth (position -6) residue upstream of the cleavage site is required, (b) at position -4, Arg is more favorable than Lys, and (c) at position 1, a hydrophobic aliphatic residue is not suitable. These rules are compatible with those proposed by comparison of precursor sequences around mono-arginyl cleavage sites. We also provide evidence that precursor cleavages at mono-arginyl and dibasic sites can be catalyzed by the same Kex2-like processing endoprotease, PC1/PC3.

Amino Acid Sequence↗
PubMed1992

Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expression.

We used the polymerase chain reaction to identify a mouse testis cDNA that represented another member of a growing class of mammalian endoproteases involved in the processing of precursor proteins. This cDNA encoded a 655-residue protein, designated PC4, containing a bacterial subtilisin-like catalytic domain closely related to those of the recently characterized precursor-processing endoproteases, furin, PC1/PC3, PC2, and Kex2. Within this domain, the amino acid sequence of PC4 was 70, 58, 55, and 45% identical with those of mouse furin, mouse PC1/PC3, mouse PC2, and yeast Kex2, respectively. Northern blot analysis indicated that the PC4 mRNA was detectable only in the testes after the 20th day of postnatal development. Moreover, this message was mainly expressed in the round spermatids. These data suggest that PC4 represents a prime candidate for a precursor-processing endoprotease in the testicular germ cells and that its gene expression is regulated during spermatogenesis.

Amino Acid Sequence↗
PubMed1992

Use of methotrexate, vinblastine, adriamycin, and cisplatin in combination with radiation and hyperthermia as neo-adjuvant therapy for bladder cancer.

In an attempt to improve the poor prognosis of invasive and/or high-grade bladder cancer after total cystectomy, we tried a combination of regional irradiation with hyperthermia (RH) therapy and systemic M-VAC (methotrexate, vinblastine, Adriamycin, and cisplatin) chemotherapy followed by surgery. The short-term results of these treatments were evaluated. A total of 17 patients received the combination of RH and M-VAC therapy between January 1989 and July 1990, and 12 then underwent total cystectomy. Of the 17 patients, 14 were evaluable for tumor response. The objective response rate was 64% (9/14), with 4 patients achieving a complete remission that was confirmed by histological examination. Nausea and vomiting were inevitable, and 71% (12/17) of the patients developed leukopenia. However, these side effects were not serious. Considering the previous results obtained using RH therapy in the absence of chemotherapy for this disease, no significant difference in the tumor response was detected between the RH only group and the RH plus M-VAC group. The long-term results cannot yet be evaluated, but we will continue to follow these patients in the future so as to clarify the usefulness of M-VAC therapy as preoperative therapy.

Adult↗
PubMed1992

In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy quinolone.

AM-1155 is a new quinolone with a wide spectrum of antibacterial activity against various bacteria including anaerobes and Mycoplasma pneumoniae. AM-1155 was 2- to 16-fold more active than ciprofloxacin and ofloxacin against Staphylococcus aureus including methicillin-resistant strains, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis; its MICs for 90% of strains tested were 0.10 to 0.78 micrograms/ml. The activity of AM-1155 was comparable to that of ciprofloxacin against members of the family Enterobacteriaceae, Branhamella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae, but was fourfold less than that of ciprofloxacin against Pseudomonas aeruginosa. Against Xanthomonas maltophilia, Acinetobacter calcoaceticus, and Campylobacter jejuni, AM-1155 was two- to fourfold more active than ciprofloxacin. At a concentration of 1.56 micrograms/ml, AM-1155 inhibited 90% of Bacteroides fragilis strains tested; its activity was 8- to 10-fold higher than those of ofloxacin and ciprofloxacin. Development of resistance to AM-1155 in S. aureus and S. epidermidis occurred at a lower frequency than did that to ciprofloxacin after eight transfers in the presence of drug. In the oral treatment of mouse systemic infections, AM-1155 was four- to eightfold more effective than ciprofloxacin against gram-positive cocci and was as active as ciprofloxacin against gram-negative rods. The efficacy of an oral or a subcutaneous dose of AM-1155 was two- to fivefold greater than that of ofloxacin. Against experimental pneumonia with Klebsiella pneumoniae and P. aeruginosa, AM-1155 was two- to fourfold more active than ciprofloxacin and ofloxacin. AM-1155 also had good efficacy against mouse ascending urinary tract infections with Escherichia coli and P. aeruginosa. These results suggest that AM-1155 may be a potent antibacterial agent applicable to various infections.

Animals↗
PubMed1992

A partial characterization of a Sertoli cell-secreted protein stimulating Leydig cell testosterone production.

To examine whether immature rat Sertoli cells in culture secrete a factor(s) which stimulates testosterone production by mature mouse Leydig cells, Sertoli cell-enriched cultures were prepared from 3-week-old male rats with trypsin and collagenase. Sertoli cells were plated at an initial density of 3-5 x 10(6) cells/35 mm well and cultured in 3 ml serum free media supplemented with insulin (10 micrograms/ml). Sertoli cell culture medium (SCCM) collected every 3rd day was added to Leydig cells (10(6) cells in 1 ml of MEM with 2% steroid-free FCS) prepared from 10-week-old mice by mechanical separation and incubated for 3 h at 34 degrees C. Secreted testosterone was determined by RIA. SCCM 15 times concentrated by Amicon YM10 membrane demonstrated a dose-dependent stimulation of testosterone production, whereas there was no effect on testosterone secretion when Leydig cells were maximally stimulated by LH. Leydig cell stimulating activity was retained by both a dialysis membrane with a pore size of 24 A and an ultrafiltration membrane with a molecular weight cut-off of 10 kDa. However, activity was reduced by heating at 60 degrees C for 30 min and almost lost after incubation with 0.1% trypsin for 1 h at 37 degrees C. This activity was not retained by means of a Con A-Agarose column and was demonstrated only in break-through fractions. HPLC gel filtration of a 15 times concentrated SCCM preparation on a TSK gel G3000SW revealed Leydig cell-stimulating activity at approximately 13 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[A preliminary study to determine the activity of topoisomerase II in human kidney cancer cells with DNA unknotting method].

For the purpose of examining the Topoisomerase II (Topo II) activity in human kidney cancer cells, we performed experiments with using DNA unknotting method. This method check relative Topo II activity with its conversion of knotted form P4 phage DNA to unknotted form. Our preliminary results demonstrate remarkable activity of Topo II with specific conversion of knotted form P4 DNA to unknotted form in human kidney cancer cells, YCR and ACHN. Moreover, addition of etoposide to the same experiment suppressed Topo II activity in a dose dependent manner. Our results suggest that kidney cancer has a certain amount of Topo II, a target for etoposide. We believe this method is useful to measure Topo II activity in cancer cells and to estimate chemotherapeutic potential of Topo II inhibitors including etoposide in human kidney cancers.

DNA Topoisomerases, Type II↗
PubMed1992

[A pathological study of incidental carcinoma of the prostate. Pathological study of age-groups].

We reviewed 66 patients with stage A adenocarcinoma of the prostate who were treated at our 7 affiliated hospitals in Yokohama between 1984 and 1988. Of 1377 patients who underwent subcapsular prostatectomy (SCP) or transurethral resection of the prostate (TUR-P) for benign prostatic hyperplasia, 66 patients (4.8%) were diagnosed as an incidental carcinoma of the prostate. Of these patients, 36 and 30 were in stage A1 and A2, respectively. In the 66 patients, 59 (4.5%) were detected in 1315 TUR-P and 7 (11.3%) in 62 SCP. Elderly patients over 80 years of age had a higher risk of stage A2 disease. In histological grade, well, moderately and poorly differentiated adenocarcinoma were found in 48 patients (72.7%), 13 (19.7%) and 5 (7.6%), respectively. Among the patients with stage A prostate carcinoma the majority of the age-group less than 79 years old had well differentiated adenocarcinoma. In the age-group more than 80 years old, there were 6 (37.5%) moderately and 2 (12.5%) poorly differentiated tumors. In other words, the age-group more than 80 years old tended to have the moderately or poorly differentiated adenocarcinoma more frequently than those other decades. We expect an increase in the number of patients with stage A2 disease in the future with the expansion of the operative indication, especially in elderly patients.

Adenocarcinoma↗
PubMed1992

Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats.

OBJECTIVE: Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN: The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the contribution of endothelin to the in vivo control of blood pressure and renal hemodynamics. METHODS: Endothelin-specific antibodies were administered intravenously into anesthetized SHR and Wistar-Kyoto (WKY) rats, and the effects upon blood pressure and renal function (renal plasma flow and glomerular filtration rate) assessed. Using the same antibodies, baseline plasma levels of endothelin in both strains of rats were determined by radioimmunoassay. RESULTS: Infusion of endothelin-specific antibodies into SHR decreased mean arterial pressure by approximately 10% and renal vascular resistance and renal vascular resistance by approximately 35%. Glomerular filtration rate and renal plasma flow both increased by approximately 50% over control. In contrast, infusion of normal rabbit serum into SHR or of endothelin-specific antibodies into WKY rats did not result in any significant change in renal hemodynamics or arterial blood pressure. Baseline plasma levels of immunoreactive endothelin in SHR were significantly lower than those in WKY rats. CONCLUSION: These results suggest that endothelin plays an important role in the modulation of systemic blood pressure and renal function in SHR.

Animals↗
PubMed1992

[Pedunculated hepatocellular carcinoma suspected of right adrenal tumor: a case report].

We report a rare case of extrahepatic growing hepatocellular carcinoma which was clinically diagnosed as right adrenal tumor. A 61-year-old woman was admitted for further examination of right flank pain and hypertension. Abdominal computed tomographic scan and echogram revealed a suprarenal mass. Hypercatecholaminemia was suspected from urinary analysis. Preoperative diagnosis was right adrenal tumor; suspected pheochromocytoma. On operation, we found the tumor was pedunculated from right lobe of liver and compressing normal right adrenal gland. Its clinical diagnosis was hepatocellular carcinoma. Ten months after operation she is still alive. We discuss the difficulty of differential diagnosis between extrahepatic growing hepatocellular carcinoma and adrenal tumor.

Adrenal Gland Neoplasms↗
PubMed1992

[A clinical study of 115 patients with testicular tumor].

One hundred and fifteen cases of testicular tumors treated at our Hospital between 1970 and 1989 were analyzed. The incidence of testicular tumors was 0.44% in the male outpatient department of our urological clinic. The age of these patients ranged from 6 months to 86 years (average: 31.7 years old) with two peaks in distribution; 0 to 5 and 21 to 45 years. Most of their chief complaints (77%) were painless swelling of scrotal contents. Location of the tumors included 56 in the right, 57 in the left and 2 on both sides. Histologically, there were 68 cases of seminoma, 10 cases each of embryonal carcinoma and teratoma, 22 cases of mixed type, 3 cases of malignant lymphoma and 2 cases of others. Stage of tumor was stage I in 69 cases, IIA in 25 cases, IIB in 8 cases and III in 13 cases. High orchiectomy was performed on all the patients. Radiotherapy, chemotherapy and retroperitoneal lymph node dissection were respectively done in 77, 42 and 16 cases. Seventeen patients died, and the 5-year survival rate calculated by the Kaplan-Meier method was 87.9% in seminoma and 68.9% in non-seminoma. The survival rate for the patients treated by chemotherapy including CDDP after 1983 was compared to those treated by other therapy before 1982. Between the two groups there was no significant difference.

Adolescent↗
PubMed1992

[Clinical analysis of 46 cases of radiation cystitis].

We experienced 46 cases of radiation cystitis between 1973 and 1990, 10 of which showed intractable bleeding and 17 recurrent bleeding. We clinically analyzed these cases to determine the factors responsible for intractable and recurrent bleeding. Intractable bleeding was suggested to related to the aggravation of the local condition of the urinary tract and recurrent bleeding with an increase of complications, especially diabetes mellitus and hypertension. In conclusion, long-term follow up of local conditions and complications is important in the prevention of intractable and recurrent bleeding of radiation cystitis.

Adult↗
PubMed1992

[Clinical studies on tosufloxacin (TFLX) in urology].

We clinically evaluated the usefulness of a new oral antimicrobial agent, TFLX, in the field of urology. The dose administered was 150 mg t.i.d and the duration of administration was 3 days. The clinical effect was evaluated according to the criteria of the Japanese UTI committee. The clinical response obtained on 164 female patients with acute simple cystitis was excellent in 118, moderate in 44 and poor in 2 patients. The efficacy rate was 98.78%. The clinical response obtained on 4 male patients with acute simple cystitis was excellent in 2 and moderate in 2 patients. The efficacy rate was 100%. The clinical response obtained on 3 female patients with simple pyelonephritis was excellent in 2 and moderate in 1 patient. The efficacy rate was 100%. The clinical response obtained on one patient with non-gonococcal urethritis was excellent by doctor's evaluation. The clinical response obtained on 7 patients with complicated UTI was excellent in 3 and moderate in 4 patients. The efficacy rate was 100%. Three patients complained of stomach distress or malaise and 2 patients developed rash. No abnormal laboratory data were observed. Thus, TFLX appears to be safe and suitable for use in the field of urology.

4-Quinolones↗
PubMed1991

Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway.

Many peptide hormones are produced from larger precursors by endoproteolysis at pairs of basic amino acids (e.g. Lys-Arg and Arg-Arg) within the regulated secretory pathway in endocrine cells. However, many other secretory and membrane proteins appear to be produced from precursors through cleavage at multiple, rather than paired, basic residues within the constitutive secretory pathway in non-endocrine cells. By surveying various precursors processed constitutively, we noticed that most of them have the consensus sequence, Arg-X-Lys/Arg-Arg (RXK/RR), at the cleavage site. When expressed in endocrine and non-endocrine cells, a precursor with the RXKR sequence was cleaved in both types of cells, whereas that with the Lys-Arg pair was cleaved only in the endocrine cells. When the RXKR precursor was coexpressed with furin and PC3, both of which are mammalian homologues of the yeast precursor-processing endoprotease Kex2, in non-endocrine cells, enhancement of the precursor cleavage by furin but not by PC3 was observed. By contrast, when the Lys-Arg precursor was coexpressed with the two mammalian proteases in endocrine cells with no endogenous processing activity at dibasic sites, it was cleaved only by PC3. These results indicate that the basic pair and the RXK/RR sequence are the signals for precursor cleavages catalyzed by PC3 within the regulated secretory pathway and by furin within the constitutive pathway, respectively.

Amino Acid Sequence↗
PubMed1991

Cloning and functional expression of a novel endoprotease involved in prohormone processing at dibasic sites.

We cloned and sequenced a cDNA from a library of mouse pituitary AtT-20 cells which are known to cleave an endogenous and various foreign prohormones at dibasic sites. This cDNA encodes a novel 753-residue protein, named PC3, which is structurally related to the yeast Kex2 protease involved in precursor cleavage at dibasic sites and to recently identified mammalian Kex2-like proteins, furin and PC2. Among examined cell lines and tissues, PC3 mRNA was only detected in AtT-20 cells. The substrate specificity of PC3 expressed in mammalian cells was similar to that observed in AtT-20 cells. We conclude that PC3 is a resident prohormone processing endoprotease in AtT-20 cells.

Amino Acid Sequence↗
PubMed1991

[Study of satellite tumor nodules in renal cell carcinoma].

Topography and histological types of main tumor and satellite tumor nodules (STN) were investigated on 60 cases of renal cell carcinoma by gross and microscopic study by making whole area histological sections. 30-100 histological slides were made from the median sagittal section and multiple horizontal sections of renal cell carcinoma. STN were observed in 28 cases of the 60 cases (46.7%) and could be classified into 3 types according to their location relative to the main tumor. STN could not be observed in some cases despite the large main tumor of 10 cm or more, while STN were observed in some cases with the main tumor of only 2.5 cm or less. High grade and high stage cases showed a high incidence of STN. It is considered that, only in cases, with the tumors of low grade, low stage and has only 1 STN or less, conservative surgery on renal parenchyma is possible. When the case is of low grade and low stage and has a possibility of preserving normal renal parenchyma, conservative surgery on renal parenchyma may be justified even if the tumor is large.

Carcinoma, Renal Cell↗
PubMed1991

[Phase II study of 5'-DFUR (Furtulon) capsule for bladder cancer].

A cooperative phase II study of 5'-DFUR at a daily dose of 800 to 1,200 mg was performed on 18 patients with bladder cancer. The therapeutic responses were evaluated by Koyama-Saito's criteria in 13 out of 18 patients, and 3 PR, 1 MR, 6 NC and 3 PD were obtained. Adverse reactions were observed in three out of 15 cases (20.0%). These side effects were reversible gastrointestinal symptoms such as nausea-vomiting, anorexia and diarrhea. The results suggest that 5'-DFUR is a useful drug for bladder cancer treatment.

Adenocarcinoma↗