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Biomedical subjects

M Hosaka

Publications and source records attributed to M Hosaka.

At least 19 recordsLinked to original sources
PubMed2005

Heparin-induced thrombocytopenia complicated with massive thrombosis of the inferior vena cava after filter placement.

A 45-year-old man presented with deep vein thrombosis of the right leg and bilateral pulmonary embolism. Heparin was administered on the initial one and a half days. On the 3rd day, an inferior vena cava (IVC) filter was placed with a heparin flush, after which massive IVC thrombosis developed. The platelet count was 221000/mm3, decreased 42% from the initial level, but remained within the normal range. Heparin was replaced by argatroban on the 13th day. The platelet count increased to 355000/mm3 on the 15th day. The patient was positive for antibody against complexes of heparin and platelet factor 4, and was diagnosed as heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). When thrombosis develops during heparin treatment, it is important to suspect HITTs and to assay for the associated antibodies, regardless of the actual platelet count.

Anticoagulants↗
PubMed2004

Gluteal compartment syndrome after abdominal aortic aneurysm repair.

A 66-year-old man underwent emergency surgery for a ruptured abdominal aortic aneurysm associated with right common and internal iliac aneurysms. Postoperatively, his right buttock was distended and tender to compression. A CT scan revealed an extremely swollen right gluteus maximus with decreased density. Macromyoglobinuria was noted, and creatine kinase and myoglobin were elevated: 87,800 IU/l and 144,300 ng/ml, respectively. Renal function had deteriorated and he was treated with hemodialysis until the 15th postoperative day. The patient recovered without any discomfort to the buttock or intermittent claudication. To our knowledge this is the first documented case of gluteal compartment syndrome after the repair of an abdominal aortic aneurysm.

Aged↗
PubMed2002

Indications for and limitations of exercise training in patients with intermittent claudication.

BACKGROUND: The selection of candidates for exercise training among patients with intermittent claudication is still a matter of debate. PATIENTS AND METHODS: Forty-nine patients with intermittent claudication due to arteriosclerosis obliterans were tested. Forty-six patients were men and 3 were women, with an average age of 65 years (range, 46 to 76 years). The patients walked on a treadmill at 2.4 km/h on a 12% upgrade followed by an appropriate period of rest for 30 minutes twice a day during a 3-week hospitalization. Programs were individualized for each patient. Four parameters were assessed after exercise training: (1) Ankle-brachial index (ABI) at rest, (2) Fall in ABI after 40 m of treadmill walking (ABI Fall 40), (3) the recovery time (RT 40) required for the ABI to return to resting levels after 40 m of walking, and (4) the maximal walking distance (MWD) on the treadmill. RESULTS: The average ABI at rest before the 3-week training period was 0.60 +/- 0.02 (mean +/- SE), and after training it was 0.62 +/- 0.02. There was a small although not statistically significant increase in the ABI after training. This increase in the ABI did not exceed 0.21. The average ABI Fall 40 before training was 0.36 +/- 0.01, and after training it was 0.30 +/- 0.02. The average RT 40 before training was 9.9 +/- 0.8 min, and after training it was 6.2 +/- 0.6 min. There were significant decreases in the ABI Fall 40 and RT 40 after training (p < 0.01 and p < 0.001, respectively). The MWD increased after training in 48 of the 49 patients. The average MWD increased from 134 +/- 13 m to 226 +/- 32 m after training (p < 0.001). The occlusion levels did not influence the results as training effects and hemodynamic parameters. Fourteen of 49 patients desired arterial reconstruction after exercise training. CONCLUSIONS: Patients with shorter RT 40's before training achieved greater increases in the MWD after training. In patients with an RT 40 under 12 min, exercise training is indicated. However, there is some discrepancy between the increase in MWD and the degree of satisfaction in individual patients.

Aged↗
PubMed2001

Tumor suppressor protein VHL is induced at high cell density and mediates contact inhibition of cell growth.

In spite of the general recognition of von Hippel-Lindau (VHL) as a tumor suppressor gene, the physiological and pathological importance of VHL protein in cell growth regulation and tumorigenesis remains unclear. Here we show that in normal human renal proximal tubule epithelial cells (RPTEC), the steady-state amount of VHL protein is strictly regulated by cell density. The cellular VHL content is more than 100-fold higher in dense cultures than in sparse cultures. The increase in VHL protein at high cell density was also observed for NIH3T3 fibroblasts, suggesting the generality of the phenomenon. The growth rates of renal cell carcinoma cells lacking an intact VHL gene and their derivatives with wild-type or mutant VHL expression vector do not differ significantly when they are growing in log-phase. Importantly, however, there is a difference when they reach confluency: cells lacking wild-type VHL grew continuously, while cells expressing exogenous VHL protein showed relatively limited cell growth. Using an ecdysone-inducible VHL expressing cell line, we also show that the growth inhibition at high cell density can be released by attenuating the VHL expression. Taken together, we propose that VHL protein functions as a growth suppressor at high cell density, and this might be the basis of the tumor suppressor function of VHL.

3T3 Cells↗
PubMed2001

PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines.

Extensive allelotyping studies have implicated several tumor-suppressor loci on chromosomes 3p, 5q, 6q, 8p, 9pq, 10q, 11q, 14q, 17p, 18q and 19p in human kidney tumorigenesis. The PTEN (also called MMAC1 and TEP1) gene, a candidate tumor suppressor located at chromosome 10q23.3, is mutated in a variety of sporadic malignancies as well as in patients with Cowden disease. To investigate the potential role of the PTEN gene in renal tumorigenesis, we searched for abnormalities of the gene in 68 primary renal-cell carcinomas (RCCs) as well as in 17 renal carcinoma-derived cell lines, using DNA-SSCP, sequencing and microsatellite analysis. Five of 68 (7.5%) primary RCCs exhibited intragenic mutations (3 missense, 1 deletion and 1 splice-site), and 1 of 17 (5.9%) cell lines had an insertion mutation. Loss of heterozygosity of the PTEN gene occurred in 25% of primary RCCs, including the 3 cases with intragenic mutation and the 1 PTEN-mutated cell line. Clinical and histopathological examinations revealed that 4 of the 5 primary tumors with PTEN mutation were high-grade, advanced clear-cell RCCs with distant metastases or renal vein tumor invasions, resulting in poor prognostic courses. The other was a low-stage papillary/chromophilic RCC. Our data suggest that PTEN mutation is observed in a subset of RCCs and that, especially in clear-cell RCCs, it occurs as a late-stage event and may contribute to the invasive and/or metastatic tumor phenotype.

Carcinoma, Renal Cell↗
PubMed2001

Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist.

BACKGROUND: A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients. METHODS: Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa. RESULTS: Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone. CONCLUSION: These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels.

Administration, Oral↗
PubMed2001

Imaging features of intraosseous lipomas of the calcaneus.

We report two cases of intraosseous lipoma arising in the calcaneus of a 36-year-old and a 22-year-old women complaining of heel pain. Plain radiographs and computed tomography scans revealed cystic lesions in the calcaneus triangle. On magnetic resonance images, the lesions had high signal intensities on both T1-weighted and T2-weighted images, corresponding to adipose tissue. Histological examination revealed mature fat cells with small bone fragments. Curettage and bone grafting were performed. There was no recurrence identified on plain radiographs 2 years following the surgery.

Adolescent↗
PubMed2001

Glomus tumors with cystic changes around the ankle.

Sizable glomus tumors with cystic changes in the ankle are extremely uncommon. This paper describes painless glomus tumors with cystic changes arising in the ankle of a 22-year-old woman. At the age of 14, a painless mass was noticed on the lateral side of the left ankle, and at age 21, another mass appeared on the medial side of the same ankle. Magnetic resonance imaging (MRI) and computed tomography (CT) scanning revealed 4.5 x 4.0 cm and 2.0 x 2.0 cm sized masses on the medial side and a 3.0 x 4.0 cm sized cystic mass on the lateral side of the ankle. The tumors were removed en bloc. Microscopically, the tumor consisted of perivascularly arranged cells with punched-out, round, and regular nuclei. Immunohistochemically, the tumor cells expressed SMA and HHF-35, indicating smooth muscle cell characters. The patient had no recurrence at 2 years after surgery.

Adult↗
PubMed2001

Treatment for aortic graft infection.

Nine patients with an aortic graft infection presented after undergoing aortic grafting. Seven of 9 patients underwent an initial aortic reconstruction in our hospital. The incidence of aortic graft infection was 1.5% (7/456). There were 6 cases of paraprosthetic infection and 3 cases of aortointestinal fistulas. The treatments consisted of a complete graft excision and an axillofemoral bypass in 6 patients, a complete graft excision alone, a partial graft excision and a femorofemoral bypass, and the preservation of the graft with omental wrapping and irrigation in 1 each. Broad-spectrum antibiotics were intravenously administered to all patients and were then replaced by selective antibiotics for the responsible organisms. All surviving patients received antibiotics orally for 3-6 months. The early postoperative mortality rate was 11.1%. Aortoduodenal fistula occurred in 1 patient with graft excision alone. Graft thrombosis occurred in 2 patients with an axillofemoral bypass. No late graft infection or stump blowout occurred in any patient. We believe that a complete excision of the infected graft as well as the maintenance of distal tissue perfusion is necessary. However, based on the condition of the patient, the appearance of the operating field, and the difficulty of a repeat operation, we would like to stress the importance of selecting the best and safest treatment plan for each case.

Administration, Oral↗
PubMed2001

A cell line with multinucleated giant cell formation established from a human giant cell tumor of tendon sheath--preliminary report.

We first established a cell line with unique giant cell formation properties from a human giant cell tumor of tendon sheath (GCTTS) arising in the right ankle of a 7-year-old girl. The specimen for cell culture taken from the tumor was heterotransplanted into the back of a BALB/c (nu/nu) nude mouse. An in-vitro cell line was established from a tumor that grew after this heterotransplantation. Only mononuclear cells were observed in the primary culture, and these remained constant in growth. Multinucleated giant cells appeared at passage 3 and were constantly observed thereafter. The fusion of mononuclear cells into giant cells was verified by light and phase-contrast microscopy. This cell line was confirmed to be derived from a human by karyotype analysis and DNA fingerprinting. The cell-doubling time was 150 h. This cell line should be useful for studies of the mechanism of multinucleation in giant cell tumors.

Animals↗
PubMed2001

In vitro method for prediction of the phototoxic potentials of fluoroquinolones.

The phototoxic potential of eight fluoroquinolones (norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin and gatifloxacin) was evaluated by using three in vitro methods of cytotoxicity against mammalian cells, erythrocyte lysis and DNA strand breakage. All fluoroquinolones tested with the exception of gatifloxacin, an 8-methoxy quinolone, showed DNA strand breaking activities under UV-A irradiation. Their cytotoxicity against HeLa cells was also enhanced by UV-A irradiation. In particular, the phototoxic potential of sparfloxacin, enoxacin and lomefloxacin was high in both methods. Ofloxacin is very photocytotoxic against HeLa cells, while it has low potential to cause DNA strand breakage. Norfloxacin, ciprofloxacin and enoxacin were very photohemolytic, but sparfloxacin was not, indicating that the in vivo phototoxic potencies of fluoroquinolones might not be predictable by the photohemolysis study. Gatifloxacin, a non-phototoxic quinolone, showed no phototoxic potential in any of these three in vitro tests. These results suggest that determination of DNA strand breaking activity, combined with cytotoxicity against mammalian cells, is available to predict the phototoxic potential of fluoroquinolones without laboratory animals.

Cell Survival↗
PubMed2001

GnRH analog, leuprorelin acetate, promotes regeneration of rat spermatogenesis after severe chemical damage.

BACKGROUND: Future fertility is a major concern for cancer patients who undergo intensive chemotherapy. There has been controversy about whether hormonal treatments may have protective effects against the severe spermatogenic damage caused by chemotherapy or irradiation. Recently, it has been proposed that gonadotrophin-releasing hormone (GnRH) analogs administered after testicular damage stimulate the recovery of spermatogenesis. In this study, we have investigated the effects of GnRH agonist, leuprorelin, on the damage to spermatogenesis induced by busulfan. METHODS: Fisher rats were treated with busulfan, 25 mg/kg, intraperitoneally. The effects of subcutaneous injections of leuprorelin before or after treatment were evaluated histologically 18 weeks later. RESULTS: The percentage of 'recovered' seminiferous tubules was 27.7 +/- 12.6% in control rats without leuprorelin and 26.9 +/- 10.2% in rats with leuprorelin injected 4 weeks before busulfan. Rats in both groups showed poor recovery of spermatogenesis with an increase of intratesticular fluid. However, rats treated with leuprorelin three times (4 weeks apart) after busulfan showed an improvement of up to 56.5 +/- 12.0% (P < 0.05). A focal but massive necrotic lesion in the testis was observed only in this group of rats. CONCLUSIONS: The results demonstrated that leuprorelin administered after chemical testicular damage enhanced the recovery of spermatogenesis. At the same time, a possible significant side-effect of leuprorelin was noted.

Animals↗
PubMed2001

SPARC expression in primary human renal cell carcinoma: upregulation of SPARC in sarcomatoid renal carcinoma.

SPARC (secreted protein acidic and rich in cysteine, also called osteonectin, BM-40, and 43K protein) is a matricellular protein and is associated with cell-matrix interactions during cell proliferation and extracellular remodeling. It is also implicated in the neovascularization, invasion, and metastasis of human malignancies. To investigate a potential role of the SPARC in renal tumorigenesis, we examined primary renal cell carcinomas (RCCs) for SPARC expression by Northern blot analysis and for protein distribution by immunohistochemistry. We found that 6 (100%) of 6 sarcomatoid and 25 (70%) of 36 clear-cell carcinomas had enhanced SPARC transcription compared with that of the corresponding normal kidney tissue. In contrast, papillary and chromophobe RCCs characterized by a hypovascular or avascular tumor phenotype had undetectable SPARC expression. Immunohistochemical analysis showed that SPARC was strongly stained in the cytoplasm of the sarcomatoid neoplastic cells in sarcomatoid RCCs, whereas it was expressed only in the vascular endothelial cells and fibroblasts in clear-cell RCCs. SPARC staining intensity in the stromal cells was increased in the invading portion in some clear-cell RCCs. These findings suggest that tumor development, including neovascularization and invasion in clear-cell RCCs, might be regulated by SPARC from stromal endothelial cells and fibroblasts and that sarcomatoid transformation from common-type RCCs is associated with upregulation of SPARC expression; SPARC may contribute to its aggressive tumor phenotype.

Blotting, Northern↗
PubMed2001

Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition.

The antibacterial activities and target inhibition of 15 quinolones against grlA and gyrA mutant strains were studied. The strains were obtained from wild-type Staphylococcus aureus MS5935 by selection with norfloxacin and nadifloxacin, respectively. The antibacterial activities of most quinolones against both mutant strains were lower than those against the wild-type strain. The ratios of MICs for the gyrA mutant strain to those for the grlA mutant strain (MIC ratio) varied from 0.125 to 4. The ratios of 50% inhibitory concentrations (IC(50)s) of quinolones against topoisomerase IV to those against DNA gyrase (IC(50) ratios) also varied, from 0.177 to 5.52. A significant correlation between the MIC ratios and the IC(50) ratios was observed (r = 0.919; P < 0.001). These results suggest that the antibacterial activities of quinolones against the wild-type strain are involved not only in topoisomerase IV inhibition but also in DNA gyrase inhibition and that the target preference in the wild-type strain can be anticipated by the MIC ratios. Based on the MIC ratios, the quinolones were classified into three categories. Type I quinolones (norfloxacin, enoxacin, fleroxacin, ciprofloxacin, lomefloxacin, trovafloxacin, grepafloxacin, ofloxacin, and levofloxacin) had MIC ratios of <1, type II quinolones (sparfloxacin and nadifloxacin) had MIC ratios of >1, and type III quinolones (gatifloxacin, pazufloxacin, moxifloxacin, and clinafloxacin) had MIC ratios of 1. Type I and type II quinolones seem to prefer topoisomerase IV and DNA gyrase, respectively. Type III quinolones seem to target both enzymes at nearly the same level in bacterial cells (a phenomenon known as the dual-targeting property), and their IC(50) ratios were approximately 2.

4-Quinolones↗
PubMed2001

Contributions of the 8-methoxy group of gatifloxacin to resistance selectivity, target preference, and antibacterial activity against Streptococcus pneumoniae.

Gatifloxacin (8-methoxy, 7-piperazinyl-3'-methyl) at the MIC selected mutant strains that possessed gyrA mutations at a low frequency (3.7 x 10(-9)) from wild-type strain Streptococcus pneumoniae IID553. AM-1147 (8-methoxy, 7-piperazinyl-3'-H) at the MIC or higher concentrations selected no mutant strains. On the other hand, the respective 8-H counterparts of these two compounds, AM-1121 (8-H, 7-piperazinyl-3'-methyl) and ciprofloxacin (8-H, 7-piperazinyl-3'-H), at one and two times the MIC selected mutant strains that possessed parC mutations at a high frequency (>2.4 x 10(-6)). The MIC of AM-1147 increased for the gyrA mutant strains but not for the parC mutant strains compared with that for the wild-type strain. These results suggest that fluoroquinolones that harbor 8-methoxy groups select mutant strains less frequently and prefer DNA gyrase, as distinct from their 8-H counterparts. The in vitro activities of gatifloxacin and AM-1147 are twofold higher against the wild-type strain, eight- and twofold higher against the first-step parC and gyrA mutant strains, respectively, and two- to eightfold higher against the second-step gyrA and parC double mutant strains than those of their 8-H counterparts. These results indicate that the 8-methoxy group contributes to enhancement of antibacterial activity against target-altered mutant strains as well as the wild-type strain. It is hypothesized that the 8-methoxy group of gatifloxacin increases the level of target inhibition, especially against DNA gyrase, so that it is nearly the same as that for topoisomerase IV inhibition in the bacterial cell, leading to potent antibacterial activity and a low level of resistance selectivity.

Anti-Infective Agents↗
PubMed2001

Extraskeletal osteosarcoma arising in the buttock.

Extraskeletal osteosarcoma is a rare sarcoma that accounts for about 1% of malignant soft tissue tumours. We report an very unusual case of a small-size extraskeletal osteosarcoma arising in the superficial subcutaneous region of the buttock. The patient was a 55 year-old female. She incidentally noticed a small nodule in the right trochanteric region. It was removed under local anesthesia at a private clinic. An additional wide excision was performed at our hospital. There was an 8 mm? 10 mm mass in the subcutaneous tissue. No invasion of the underlying fascia was observed. Microscopic examination of the removed tumour showed bizarre-looking spindle and giant cells with lace-like osteoid. The tumour was diagnosed as extraskeletal osteosarcoma. Chemotherapy with Rosen T-20 was administered to the patient. The patient has survived without recurrence or metastasis for 4 years since the primary surgery. Its superficial location, very small size, wide excision, and chemotherapy were thought to contribute to her long survival.

Buttocks↗