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Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 163 records · Page 9Linked to original sources
PubMed1994

Photokilling of T-24 human bladder cancer cells with titanium dioxide.

A photoexcited titanium dioxide surface has a strong ability to decompose water into hydrogen and oxygen. We have studied this effect in order to use it to kill cancer cells in vitro and in vivo. A distinct cell killing effect was observed on cultured T-24 human bladder cancer cells treated with titanium dioxide particles and 300-400 nm UV light irradiation. Titanium dioxide plus UV light also dramatically suppressed the tumour growth of T-24 cells that were implanted in nude mice. Cells cultured on the titanium dioxide electrode were also killed under UV irradiation when the electrode was anodically polarised, suggesting that photogenerated holes are involved in the cell killing. The cell killing effect caused by titanium dioxide particles plus UV light irradiation was significantly hampered in the presence of L-cysteine and catalase, scavengers of hydroxyl radicals and hydrogen peroxide respectively. Transmission electron microscopic observations showed the titanium dioxide particles to be distributed on the cell surface and inside the cells. These results suggest that titanium dioxide particles under UV light irradiation produced photogenerated holes on the surface yielding hydroxyl radicals and hydrogen peroxide inside or outside the cells and the cells were then killed by the action of these highly oxidising molecules. The possible application of photoexcited titanium dioxide particles to cancer treatment as a new anti-cancer modality is discussed.

Catalase↗
PubMed1994

Schedule-intensified M-VAC chemotherapy for advanced urothelial cancer with recombinant human granulocyte colony stimulating factor (rhG-CSF).

M-VAC (Methotrexate, vinblastine, adriamycin and cisplatin) combination systemic chemotherapy is useful for treating invasive or metastatic transitional cell carcinoma. Granulocytopenia is the major dose-limiting factor of this chemotherapy and it takes 4 weeks or more to complete a single course of M-VAC. We have tried to shorten the period of M-VAC chemotherapy from 4 to 3 weeks by using rhG-CSF. With this modified M-VAC regimen, the number of days on which the absolute neutrophil count was less than 1000/mm3 was significantly reduced and the period to reach the neutropenia nadir was shortened. No severe side-effects were observed. In all patients treated with 2 courses of this modified M-VAC short regimen, the period of hospitalization could be reduced by 2 weeks. We emphasize the possibility of shortening the M-VAC regimen.

Aged↗
PubMed1994

Reduced uptake and accumulation of norfloxacin in resistant strains of Neisseria gonorrhoeae isolated in Japan.

OBJECTIVE: To investigate the alteration of cell permeability toward fluoroquinolones in Neisseria gonorrhoeae, which is a major quinolone-resistance mechanism along with the alteration of DNA gyrase in gram-negative bacteria. The prevalence of fluoroquinolone-resistant N gonorrhoeae strains is rapidly increasing in Japan. MATERIALS AND METHODS: The uptake and accumulation of norfloxacin by gonococcal cells, including six clinical and five World Health Organization (WHO) reference strains, were measured. Of the six clinical strains, two were highly resistant to norfloxacin (MIC 8.0 and 4.0 micrograms/ml), two were moderately resistant (MIC 1.0 and 0.5 microgram/ml), and two were sensitive (MIC 0.063 and 0.004 microgram/ml). All five WHO reference strains were sensitive to norfloxacin (MIC < or = 0.001 to 0.063 microgram/ml). RESULTS: Mean initial norfloxacin uptake in the four resistant strains (104 ng/mg of dry cells) was significantly lower than that in the seven sensitive strains (158 ng/mg of dry cells) (p < 0.05). The mean uptake after 20 minutes was also significantly lower in the four resistant strains (130 ng/mg of dry cells) than in the seven sensitive strains (194 ng/mg of dry cells) (p < 0.05). However, there was no significant difference in mean norfloxacin accumulation after 20 minutes between the four resistant strains (26 ng/mg of dry cells) and the seven sensitive strains (36 ng/mg of dry cells). The accumulation of norfloxacin after 20 minutes was almost zero in two of the four resistant strains, while the remaining two strains accumulated norfloxacin as well as the sensitive strains. CONCLUSIONS: These findings suggest that alteration of bacterial cell permeability is a quinolone-resistance mechanism in N gonorrhoeae isolated in Japan, and that this bacteria may exhibit other mechanisms such as alteration of DNA gyrase.

Cell Membrane Permeability↗
PubMed1994

[Adrenal cyst with an immunohistochemical evidence of mesothelial origin. Report of a case].

A case of adrenal cyst with an immunohistochemical evidence of mesothelial origin is presented. A 73-year-old Japanese woman was referred to our hospital with a complaint of left flank pain. The diagnosis of left adrenal cyst was made based on the radiographic and hormonal examinations. The adrenal cyst was removed surgically. Histological examination revealed that the cyst was lined with either a single layer of squamous or cuboidal cells. In immunohistochemistry testing, the cells were positive for keratin and carbohydrate antigen 125, while they were negative for epithelial membrane antigen, vimentin, desmin, and factor VIII related antigen. Thus, the present case was classified as epithelial cyst of mesothelial origin.

Adrenal Gland Diseases↗
PubMed1994

[M-VAC chemotherapy for advanced urothelial cancer--side effects and their management].

Since the M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen was reported by Sternberg in 1985, it has been widely accepted for the treatment of metastatic transitional cell carcinoma. This regimen has a significantly high response rate, but bone marrow suppression and gastrointestinal (GI) symptoms are inevitable. To complete this M-VAC regimen, preventive therapy for side effects is necessary. From November 1986 to March 1993, a total of 72 patients were admitted and received M-VAC therapy at our hospital. All of them had metastatic or invasive transitional cell carcinoma and they received a total of 163 complete courses of M-VAC therapy. We examined the side effects of this M-VAC regimen, and evaluated the effectiveness of colony-stimulating factor for prevention of granulocytopenia or granisetron for prevention of GI symptoms. Twenty-three patients (39 courses) were given recombinant colony-stimulating factor. This cytokine prevented the nadir of neutropenia and shortened the period to reach the nadir and period that the neutrophil count was below 1,000/mm3. Twelve patients (26 courses) were given granisetron, with significant reduction of the incidence of GI symptoms. These findings suggest that M-VAC therapy is effective and safe when used in combination with these drugs.

Adult↗
PubMed1994

[A case of rheumatoid arthritis associated with agranulocytosis during bucillamine treatment].

Bucillamine has been reported to have beneficial effects in rheumatoid arthritis. This report concerns a case of RA in which agranulocytosis developed while on a course of bucillamine. A 52-year-old female with RA developed a rapid fall in white blood cell count after 4 weeks of bucillamine treatment at daily dose of 50 mg. Agranulocytosis was diagnosed (WBC 1300/mm3, granulocytes 5%). The administration of bucillamine was halted and she was treated with only prophylactic antibiotic regime. The peripheral granulocyte count result rapidly reversed within 3 days after discontinuation of the bucilamine treatment. Anti-leukocyte antibody was detected by the leukocyte lysis phenomenon method during the period of agranulocytosis. And high intrinsic G-CSF activities were detected in the patient serum before the recovery period of agranulocytosis. Agranulocytosis is a rare side effect of bucillamine but it is potentially more harmful than other side effects. In treatment with bucillamine, therefore, the drug should be carefully administered and regular blood examinations carried out to prevent the occurrence of this side effect.

Agranulocytosis↗
PubMed1994

[A study on reservoir function of Kock pouch during a 3-year postoperative period].

Kock continent ileal reservoir has been one of the major options of urinary diversion for the patients with bladder cancer. We performed Kock pouch operation in 16 patients (male 12, female 4; from 41 to 66 years old, mean age 57 years old). Since the reservoir function of Kock pouch after a long postoperative period is not well known, we examined the volume capacity, the compliance and the length of efferent valve of Kock pouch in 8 patients during a 3-year postoperative period. Although the compliance was stable, the volume capacity and the length of the efferent valve showed a decreasing tendency. The shorter efferent valve was not always associated with the case of urinary incontinence. Most of the complications in 15 patients was trouble of efferent valve (prolapse of efferent valve in 7 cases and eversion or fistula formation that required reconstruction surgery in 3 cases). Although some complications were observed, the reservoir function of the pouch was stable. Therefore this method is reliable for permanent urinary diversion.

Adult↗
PubMed1993

Prophylactic oral UFT therapy for superficial bladder cancer.

BACKGROUND: A randomized prospective trial was performed to determine whether long-term oral UFT (a 1:4 mixture of tegafur and uracil) (Taiho Pharmaceutical Co., Tokyo, Japan) therapy was effective in preventing the intravesical recurrence of superficial bladder cancer. METHODS: A total of 112 patients with newly diagnosed superficial transitional cell carcinoma of bladder (Ta, T1 and G1 or G2) were randomized into a UFT-treated group (300-400 mg/d for 2 years) and a control group. RESULTS: After a median follow-up period of 24.5 months, the recurrence rate was 25.7% for the UFT group and 43.3% for the control group (P = 0.015, log-rank test). Side effects of UFT administration were acceptably low. CONCLUSIONS: These results suggest that long-term UFT administration after transurethral resection is effective in preventing the recurrence of superficial bladder cancer.

Administration, Oral↗
PubMed1993

Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4.

We used the polymerase chain reaction to identify a mouse cDNA which represented a new member of a growing class of mammalian endoproteases homologous to the yeast Kex2 protease involved in the processing of precursor proteins. This cDNA encoded a 915-residue protein, designated as PC6, containing a subtilisin-like catalytic domain closely related to those of other Kex2-like members (furin, PC2, PC1/3, PC4, and PACE4). It exhibited striking sequence similarity to PACE4 and contained similar protein domains, such as the COOH-terminal Cys-rich region. Northern blot analysis revealed that PC6 mRNA, as with furin and PACE4 mRNAs, was expressed in various tissues and cell lines, with the highest level in the intestine. Transfection experiments revealed that PC6 was capable of cleaving precursors at dibasic sites. These observations suggest that PC6 is a candidate for a processing endoprotease responsible for the maturation of gastrointestinal peptides.

Amino Acid Sequence↗
PubMed1993

[New salvage chemotherapy (cisplatin, adriamycin, bleomycin, methotrexate, etoposide) for advanced nonseminomatous testicular cancer: experience in three cases].

Three patients with advanced non-seminomatous testicular tumor were treated with a new salvage chemotherapy. All patients were refractory to prior PVB (cisplatinum, vinblastine, bleomycin) or VAB-6 (cisplatinum, bleomycin, vinblastine, dactinomycin, cyclophosphamide) therapy. They were treated with the following combination chemotherapy: Cisplatin 30 mg/body day 1-5; adriamycin 40 mg/body day 1; bleomycin 30 mg/body/day 1: methotrexate 400 mg/body day 1; etoposide 150 mg/body day 1-5 (CABME therapy). This treatment was repeated monthly and in total four courses were given. One complete response and one partial response were obtained. Especially, we achieved 65% and 63% remission of liver metastases and residual tumors could be resected. Myelosuppression was marked, but other toxicity was tolerable. Therefore, we postulated that CABME therapy played an important role for the refractory testicular tumors.

Adult↗
PubMed1993

Analyses of p53 gene mutations in primary human bladder cancer.

Mutations in the tumor suppressor gene p53 have been detected in many tumors. p53 gene mutations are also known to be involved in the progression of human bladder cancers. We investigated structural alterations in the entire coding region of the p53 gene in primary human bladder cancers, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, 6 (24%) were found to have p53 alterations. DNA sequencing of the PCR products revealed 6 point mutations resulting in single amino-acid substitutions in the regions of exons 5, 6, 7, 8, and 10 of this gene, respectively. Five of 6 cases with p53 mutations were invasive, with metastasis or high-grade tumors. Interestingly, the one remaining case was a recurrent, low-grade, and superficial (pTa) tumor. In this early stage tumor, allelic loss of the p53 gene was also found, using a polymerase chain reaction-based restriction fragment length polymorphism assay. Our findings are in agreement with previous observations that p53 mutations occurred in a high percentage of high grade or invasive bladder cancers. Since mutation and allelic loss of the p53 gene were also detected in a low-grade and low-stage tumor in the present study, it is suggested that the p53 gene is involved in early stages of some bladder cancers as well as in their late stages.

Aged↗
PubMed1993

[Malignant lymphoma of the prostate--a case report].

We report a case of prostatic malignant lymphoma causing bilateral hydronephrosis. A 73-year-old man was referred to our department, suffering from urinary frequency and gross hematuria. The mild elevation of serum prostatic tumor markers made us suspect prostatic carcinoma. He was admitted to our hospital and needle biopsy of the prostate was performed. Unexpectedly histological findings revealed "malignant lymphoma, diffuse large cell type". CT scan showed bilateral hydronephrosis, and renal function was decreased. As the patient suddenly vomited blood, gastric fiberscopy and biopsy was performed. Histological diagnosis of stomach was the same as for the prostate. After systemic chemotherapy of cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) regimen, renal function improved and the tumor of stomach reduced, but his respiratory condition rapidly worsened, and he died about 1 month after chemotherapy. Malignant lymphoma involving the prostate is very rare. Especially in Japan only 19 cases have been reported including our case. Four of the 19 men were in their twenties and so we remind the urologists of the possibility of "malignant lymphoma of the prostate" in young patients with dysuria or frequency.

Aged↗
PubMed1993

[Phase I study of flutamide, a nonsteroidal antiandrogen, in patients with prostatic cancer].

A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1,500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1,500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1,500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1,125 mg/day in the phase II study.

Administration, Oral↗
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↗