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Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 127 records · Page 7Linked to original sources

[Analysis of the mechanism of trophoblast infiltration].

A cytotrophoblast (CT) infiltrates into the stroma, forming an extravillous trophoblast (EVT) in the placenta early in gestation and the phenomenon is strictly controlled, differing from the infiltration of cancer cells. The expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9), which deeply involve infiltrative metastasis of cancer, and the reactivity to transforming growth factor beta 1 (TGF beta 1), which controls the expression of these MMPs and inhibits the growth of epithelial cells, were investigated in CT derived from villi at normal gestational week 6 (early CT) and CT derived from villi at normal gestational week 37 (full-term CT), and also the choriocarcinoma cell line BeWo (BeWo). The ability of normal epithelial cells and BeWo cells to proliferate and infiltrate were evaluated in vitro by northern blotting, gelatin zymography, and invasion assay. It was revealed that early CT had a higher capacity for infiltration than full-term CT as well as BeWo. MMP2 and MMP9 appeared in the early CT, whereas only MMP9 was observed in the full-term CT. MMP2 and MMP9 were more abundantly observed in the early CT and the full-term CT rather than in BeWo. In uterine stroma-derived cells, membrane type matrix metalloproteinase (MT-MMP), which activates MMP2, was observed. These results indicated that the motility of normal villous cells was higher in the early CT than in the full-term CT. The expression of MMP2 in the early CT, which was not observed in the full-term CT, was thought to be related to this difference in motility. As for the responsiveness to TGF beta 1, which is a growth inhibiting factor for epithelial cells, the villous carcinoma cell line was insensitive to the growth inhibiting effect of TGF beta 1, but the early CT was sensitive to this effect. When TGF beta 1 was added, MMP2 and MMP9 increased in the early CT. This response was also seen in BeWo. That is, it was assured that the growth capacity was not inhibited in BeWo, but was certainly inhibited in the early CT. The overall results of these evaluations indicated that the development to EVT by infiltration of the early CT was associated with the increase in the mobility of cells caused by MMP2 and the increase in amounts of MMP2 and MMP9 caused by TGF beta 1, and the predominant inhibitory effect of TGF beta 1 on the growth of normal epithelial cells could explain why normal epithelial cells do not grow as cancer cells do.

Animals↗

[Bilateral renal cell carcinoma with extension into the vena cava associated with von Hippel-Lindau disease: a case report and review of the literature].

We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

Carcinoma, Renal Cell↗

[Extirpation of total urinary tract as a final treatment for asynchronous multicentric urothelial cancer: a case report].

A 48-year-old male patient underwent transurethral resection (TUR) for solitary bladder tumor in January 1985. Pathological finding of the specimen was non-invasive transitional cell carcinoma (TCC) G2 > G1. Following the operation, prophylactic intravesical instillation of antitumor agents, intrapelvic irradiation, and hyperthermia were done for the recurrences. In June 1987, left renal pelvic tumor revealed, and nephroureterectomy was performed. Histological examination of renal pelvic tumor showed TCC G1. Five months later, multiple bladder tumors and right renal pelvic tumor were detected. A total cystectomy, partial nephrectomy and nephrostomy were performed in February and March 1988. Pathology of the bladder and right kidney were TCC G3. One month after these operations, tumors recurred in the rest of the right kidney. Complete remission was achieved after systemic chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). In January 1992, right renal pelvic tumor recurred again. After two cycles of M-VAC therapy, the rest of the right kidney was extirpated. Postoperative hemodialysis has been uneventful. He has lived without tumor recurrence for three years after the introduction of hemodialysis.

Antineoplastic Combined Chemotherapy Protocols↗

[Consideration of therapeutic choice for grade 3 superficial bladder cancer].

Between January, 1977 and December, 1994, 90 patients with grade 3 (G3) superficial bladder cancer were treated at Yokohama City University Hospital, Yokohama Municipal Hospital and Kanagawa Cancer Center. These patients were clinically observed. The prognostic factors of the patients with G3 superficial bladder tumors were age and growth pattern of tumors. Patients older than 67 showed significantly poor survival compared with younger patients (p < 0.01). Patients with non-papillary sessile tumors showed significantly poor survival compared with the other groups (p < 0.05). The five-year survival rate of the patients with G3 superficial tumors who were treated by total cystectomy was 75%, whereas all the patients who were treated by bladder preservation therapy died within 4 years, the difference being significant (p < 0.05). Eleven patients with G3 superficial bladder tumors died of cancer, and most of these patients had multiple and non-papillary sessile tumors. These findings suggest that the patients with G3 superficial tumors, which are non-papillary sessile tumors, should be treated by radical cystectomy.

Adult↗

[Unilateral and synchronous occurrence of renal cell carcinoma and ureteral tumor: a case report].

An 81-year-old woman was admitted to our hospital with left flank pain. Excretory urography revealed left hydronephrosis. Abdominal computed tomography (CT) revealed a large heterogenous tumor in the upper pole and marked hydronephrosis and hydroureter in the lower portion of the left kidney. Left total nephroureterectomy was performed under the diagnosis of renal pelvic and ureter tumor. The pathological diagnosis was of renal cell carcinoma (spindle type, grade 3) in the kidney and transitional cell carcinoma (grade 2) in the ureter. Postoperative chemotherapy was not given. Convalescence was uneventful and fifteen months after the operation she is alive with no recurrence or metastasis.

Aged↗

Telomerase activity in human bladder cancer.

Telomerase can synthesize telomeric DNA repeats onto chromosome ends. Telomere length and telomerase activity have recently been implicated in the control of the proliferative capacity of normal and malignant cells. The expression of telomerase activity is concomitant with the attainment of immortality in tumor tissues and cells. Thus, enzyme activity may indicate a prevalent or even ubiquitous tumor producer. In this report, telomerase activity was analyzed in 40 human bladder cancers, 7 normal tissues, and 2 bladder epithelia with dysplasia using a PCR-based telomeric repeat amplification protocol assay. Telomerase activity was detected in almost all bladder tumors (97.5%); only one sample, which was in an early stage, did not express telomerase activity. None of the normal tissues displayed telomerase activity. One of the two bladder epithelia with dysplasia expressed low telomerase activity. The expression of telomerase activity has a clear association with the pathological grade and clinical stage. Most of the tumors with high telomerase activity were in an advanced grade and had deep invasion. Thus, telomerase activity might be suggested to represent an additional required event in the multigenetic process of tumorigenesis in human bladder cancer.

Humans↗

Expression of transforming growth factor-beta 1 in human bladder cancer.

BACKGROUND: Elevated expression of transforming growth factor-beta 1 (TGF-beta 1) has been reported in several types of human cancer. However, the significance of TGF-beta 1 expression in clinical bladder cancer is not well known. METHODS: The levels of TGF-beta 1 expression were quantitated using a polymerase chain reaction-based method in tissue specimens obtained from 51 patients with bladder cancer. RESULTS: Transforming growth factor-beta 1 expression in bladder cancer was higher than that found in normal bladder epithelium (P < 0.01). Significantly higher levels of TGF-beta 1 transcripts were observed in low and intermediate grade (Grade 1 and 2) tumors than in high grade (Grade 3) tumors (P < 0.02). Superficial (pTa and pT1) tumors had higher levels of TGF-beta 1 than invasive (pT2 or higher) tumors (P < 0.05). CONCLUSIONS: These results suggest that enhanced expression of TGF-beta 1 is specific to low grade and stage bladder cancer. Transforming growth factor-beta 1 may play an important role in the early stages of human bladder cancer development, and TGF-beta 1 expression could provide a new relevant tumor marker for determining tumor progression in patients with bladder cancer.

Actins↗

A protein kinase C isozyme, nPKC epsilon, is involved in the activation of NF-kappa B by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat 3Y1 fibroblasts.

In order to examine whether PKC is involved in the activation of NF-kappa B by TPA, we overexpressed a variety of PKC isozymes in rat 3Y1 fibroblasts and monitored the expression of the co-transfected reporter NF-kappa B gene. In contrast to TPA response element (TRE), where overexpression of a variety of PKC isozymes results in enhanced activation by TPA, activation of NF-kappa B by TPA is not enhanced by overexpression of PKC isozymes such as cPKC alpha, nPKC delta, or nPKC theta. However, the overexpression of nPKC epsilon does result in enhancement. A kinase-negative point mutant of nPKC epsilon, where Lys at the ATP binding site is altered to Arg, does not cause this enhancement of NF-kappa B activation. Further, the kinase-negative nPKC epsilon partially suppresses endogenous NF-kappa B activity. These results suggest that nPKC epsilon is specifically involved in the activation of NF-kappa B when cells are treated with TPA.

Animals↗

Polymorphisms in the human DNA polymerase beta gene.

Recently, evidence has accumulated that mutations in DNA repair genes might be associated with certain steps in carcinogenesis. The DNA polymerase beta gene is one of the DNA repair genes, and mutations in it have been detected in 83% of human colorectal cancers. To assess the involvement of polymerase beta gene mutations in the development of human prostate cancers, we performed sequence analyses of human DNA samples. Unexpectedly, we found six regions that were polymorphic. This information should be taken into consideration at the time of sequence analysis of the DNA polymerase beta gene.

Base Sequence↗

Benefits of arterial reconstruction in claudication.

We conducted a midterm follow-up of 150 claudicants who underwent surgical reconstruction by assessing cumulative patency, survival, and palliation (graft patency in live patients) rates. Eighty-nine claudicants (group I) underwent direct (in situ) proximal revascularization, 33 (group II) had indirect (ex situ) proximal revascularization, while 28 (group III) had distal revascularization. The secondary patency rates at 3 years were 97.5% in group I, 97.0% in group II, and 75.0% in group III, respectively. Only one patient with limb graft thrombosis required below-knee amputation. There were 3 perioperative deaths (2 in group I and 1 in group II). The survival rates at 3 years were 86.0% in group I, 69.5% in group II, and 95.8% in group III, respectively. The palliation rates at 3 years were 84.8% in group I, 70.0% in group II, and 77.9% in group III, respectively. These findings indicate the midterm benefits of supra- and infrainguinal arterial reconstructions, and also suggest that the preoperative assessment of risks in individual patients, the selection of the appropriate operative procedure and graft material, and intensive postoperative follow-up and management of any associated disease are all important aspects in the treatment of claudicants.

Aged↗

Conservative treatment of thoracic outlet syndrome using an orthosis.

We describe a strapping device for elevation of the shoulder in patients with thoracic outlet syndrome (TOS). The device was used by 86 patients with TOS whose symptoms had been alleviated by passively raising the shoulder. Symptoms of TOS were classified as proximal, including pain in the shoulder girdle, and distal, in which there were neurological deficits related to the brachial plexus. The device was more effective in patients with distal symptoms: pain disappeared or improved in 67% of patients; numbness in 85%; sensory disturbance in 84%; and motor disturbance in 80%. However, proximal symptoms were relieved in only 65% of the patients. The ability to perform activities of daily living was rated as excellent in 33% of patients, good in 44%, fair in 12%, and poor in 9%. The shoulder orthosis described in this report can counterbalance downward traction on the brachial plexus and reduce the tension on it, thereby relieving symptoms of TOS.

Activities of Daily Living↗

Antibacterial properties of AM-1155, a new 8-methoxy quinolone.

AM-1155 is a new 8-methoxy quinolonecarboxylic acid with a broad spectrum of antibacterial activity. It inhibited more than 90% of clinical isolates of methicillin-susceptible Staphylococcus aureus, streptococci, Enterococcus faecalis, most of the Enterobacteriaceae, Acinetobacter calcoaceticus and Haemophilus influenzae at the concentration of 0.39 mg/L. AM-1155 was 2- to 16-fold more active than ciprofloxacin against Gram-positive organisms including methicillin-resistant staphylococci. The antibacterial activity of AM-1155 was almost equal to that of sparfloxacin against a wide range of Gram-positive and Gram-negative species. AM-1155 also showed a good activity against anaerobes. The protective efficacy of AM-1155 against experimental systemic infections with Gram-positive and Gram-negative pathogens in mice was almost equal or superior to that of sparfloxacin. AM-1155 was 5- to 28-times more effective than ciprofloxacin, in terms of ED50 at one week, in staphylococcal and streptococcal infections.

Animals↗

Renal oncocytoma containing "chromophobe" cells.

We report a rare case of renal oncocytoma containing occasional "chromophobe" cells. This case suggests an intimate relationship between oncocytoma and "chromophobe" renal cell carcinoma.

Adenoma, Oxyphilic↗

nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa.

Quinolone resistance gene nqr-T91 in a clinical isolate of Pseudomonas aeruginosa P1481 was cotransducible with catA1 in P. aeruginosa PAO. The nqr-T91 transductant, PKH-T91, was resistant to norfloxacin, imipenem, and chloramphenicol and showed less norfloxacin accumulation than the parent strain did. Loss of the 46-kDa outer membrane protein (D2) and an increase in the 50-kDa outer membrane protein in PKH-T91 were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Lipopolysaccharides in the transductant were also changed. These alterations were considered to be related to lower levels of norfloxacin accumulation in PKH-T91. These genetic and biochemical properties suggested that an nfxC type of quinolone-resistant mutation occurred in a clinical isolate of P. aeruginosa P1481.

4-Quinolones↗

Protection of mice from Mycobacterium avium infection by recombinant interleukin-12.

Treatment with interleukin-12 (IL-12) significantly reduced the number of viable bacteria in mice infected with Mycobacterium avium. IL-12 itself, however, could not inhibit directly mycobacterial growth in vitro. IL-12 exerts antimycobacterial activity in vivo with a low level of toxicity, possibly by enhancing the host defense against the infection.

Animals↗

Purification of a 54-kilodalton protein (OprJ) produced in NfxB mutants of Pseudomonas aeruginosa and production of a monoclonal antibody specific to OprJ.

The 54-kDa outer membrane protein (designated OprJ) of a norfloxacin-resistant nfxB mutant of Pseudomonas aeruginosa PAO1 was purified by ion-exchange high-performance liquid chromatography. Mobility of OprJ in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was not affected by reduction and heating. A murine monoclonal antibody (MAb) against OprJ was prepared to investigate existence of this protein in fluoroquinolone-susceptible and -resistant strains of P. aeruginosa. Western blot (immunoblot) analysis with this MAb revealed a single band at the position corresponding to OprJ in outer membrane proteins of NfxB mutants derived from clinical isolates. However, the MAb did not react with any outer membrane proteins of the respective parent strains. Complementation of the NfxB mutation by transformation with plasmid pNF111, which contained the wild-type nfxB gene, led to disappearance of the single band corresponding to OprJ. The existence of OprJ was associated with fluoroquinolone resistance. Furthermore, the MAb did not react with any outer membrane proteins of other fluoroquinolone-resistant nalB and nfxC mutants. These results suggest that OprJ is newly produced in NfxB mutants of P. aeruginosa and is involved in fluoroquinolone resistance specific to NfxB, and it appears that the MAb to OprJ should aid in detection of the NfxB mutation in P. aeruginosa.

Anti-Infective Agents↗