Search PubMed⌕ Search

Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

792 records · Page 44Linked to original sources

Acquisition of multidrug resistance in osteosarcomas, analyzed by doxorubicin binding assay, and histologic response to chemotherapy.

BACKGROUND: The mechanism by which multidrug resistance is acquired in human osteosarcomas remains unclear. In this study, we analyzed the changes in doxorubicin (DOX) binding ability (%DB), showing chemosensitivity before and after chemotherapy with DOX and cisplatin (CDDP), and evaluated the histologic response of human osteosarcomas to chemotherapy. MATERIALS AND METHODS: Eight osteosarcomas were analyzed. %DB by the DOX binding assay was measured in fresh tumor tissues at biopsy and at resection after preoperative chemotherapy. The histologic response to chemotherapy was also evaluated. RESULTS: Changes in %DB before and after chemotherapy were classified into 4 patterns; A: high (> 80%) to low (< 80%), B: high to high, C: low to low, D: low to high. The two tumors, classified as type A and B were responders (> 90% necrosis), whereas the 6 tumors of type C and D were classified as non-responders (< 90% necrosis). Based on these data, we speculated that the fraction of cell populations with different chemosensitivities to DOX and CDDP varied and found that type B tumors have no population of resistant cells, whereas type C tumors have a large fraction of resistant cells. CONCLUSION: We concluded that osteosarcomas are composed of mixed cell populations with different chemosensitivities to anticancer agents and also that survival of multidrug resistant cell populations may be the most important mechanism in acquisition of multidrug resistance of osteosarcomas after chemotherapy.

Adolescent↗

Geriatric trauma patients at a suburban level-I trauma center in Japan.

BACKGROUND: Despite the increases in the aged population in Japan, there are little data on geriatric patients with traumatic injuries. A prospective clinical study was carried out to evaluate the use of the emergency medical services (EMS) system, mechanisms of injury, and prehospital assessment and triage of elderly victims of trauma. PATIENTS AND METHODS: From July 1996 through June 1997, a group of geriatric trauma (Group G, n = 22) and a control group of younger trauma patients (n = 173) were compared with respect to transfer method to an Emergency Center (direct or indirect), Revised Trauma Scores on the scene of the accident (RTS-1) and on admission to the Emergency Center (RTS-2), and outcome (survival). RESULTS: The mean values for RTS-1 in the Control Group (Group C) were not different from those in Group G, but RTS-2 of the indirect-transfer patients (IP) in Group G were significantly lower than were those for Group C. Group G mortality rates were significantly higher than were the control rates (p = 0.0001). The mortality rate of the IP subgroup was significantly lower than that of the direct transfer subgroup (DP) (30/68 vs. 5/70, p < 0.0001) in the Group C, but mortality rate of the IP subgroup exceeded that of the DP subgroup of Group G (8/14 vs. 5/8). CONCLUSION: The data suggest that in geriatric-age patients, direct transfer patients have a lower mortality rate than do indirect transfer patients when controlled for ISS. Therefore, it seems that a different set of triage criteria should be developed and implemented for geriatric-age victims with trauma-induced injuries and that those who meet these more stringent criteria should be transferred directly to a Trauma Center.

Accidents, Traffic↗

Case report: natural development of osteosarcoma from precancerous lesion.

We encountered a very rare case that suggested the natural development of osteosarcoma from a precancerous lesion. The patient presented with a huge osteosarcoma in the distal femur on the initial consultation to our hospital. He had undergone X-ray examination twice previously, due to a knee injury. The findings of the lesion detected by the first X-ray examination were similar to a fibrous cortical defect (FCD), differing from those of an osteosarcoma lesion detected by second and last X-ray examinations. We retrospectively estimated the growth rate of the FCD-like and osteosarcoma lesions and found that FCD-like lesion was not osteosarcoma, but might have been a precancerous lesion. We also speculated that this osteosarcoma lesion might have appeared 18 months before the patient consulted our hospital.

Accidental Falls↗

Peritoneal seeding of hepatocellular carcinoma after ethanol injection therapy.

The tumor seeding due to percutaneous ethanol injection therapy has been considered to be a very rare complication. Four cases of peritoneal seeding of hepatocellular carcinoma following percutaneous ethanol injection therapy are presented here. All patients had been initially treated for hepatocellular carcinomas with percutaneous ethanol injection therapy. Between 5 and 20 months after the percutaneous ethanol injection therapy, peritoneal seeding tumors were detected and resected surgically. Three patients recurred in the liver and one patient recurred in the abdominal cavity. Two died of cancer and 2 are still alive. The incidence of seeding following percutaneous ethanol injection therapy should not be so rare as considered referring to that due to fine needle biopsy, therefore careful attentions should be paid during the follow-up of those patients after percutaneous ethanol injection therapy.

Adult↗

DNA cytofluorometric analysis of benign and malignant nerve sheath tumors.

The present study was undertaken to examine the ploidy patterns of benign and malignant nerve sheath tumors using PI-DNA cytofluorometry and to clarify the relationship between the ploidy patterns and pathological findings for these lesions. The benign nerve sheath tumors (schwannomas and neurofibromas) were found to be dipolid or to be euploid-polyploidization, with a few DNA synthetic cells. The number of polyploid cells increased with increase in the frequency of cells with large and atypical nuclei in histology, regardless of the natures of cellular arrangements. Malignant schwannomas were composed of many polyploid and aneuploid cells with DNA synthetic cells, indicating their active cell proliferation. Thus, benign nerve sheath tumors exhibited low-proliferative ploidy patterns that were clearly different from those of malignant nerve sheath tumors. As Takeshita has already stated, it is difficult to ascertain why some of the neurogenic tumors show euploid-polyploidization (19). Further investigations will be needed in this direction. Finally, it is clear from the results of this study that the cytofluorometric analysis mentioned above is useful for assessing malignancy and that it may be useful for predicting prognosis of nerve sheath tumors.

Adolescent↗

Case report of secondary chondrosarcoma showing spontaneous regression after frequent recurrences.

We report a case of secondary chondrosarcoma arising in the ilium showing spontaneous regression after frequent local tumor recurrences followed by multiple surgeries of marginal or intralesional excision. The patient was a 16-year-old boy who had been diagnosed as having multiple exostosis from 9 years of age. He experienced an increasing abdominal tumor mass that formed a huge tumor. Although marginal resection of the tumor was attempted, intraperitoneal dissemination was caused by rupture of the tumor capsule and the peritoneum, as a result of severe tumor adhesion to the peritoneum. During the 5 years after the initial operation, local recurrences occurred seven times in various areas of the intra- or retro-peritoneum and marginal or intralesional excision was performed every time for a total of 14 tumors. However, since the seventh operation, the patient has had no evidence of recurrence or metastasis of the disease for more than 10 years. Therefore, we considered that the cancer might have spontaneously regressed.

Adolescent↗

Extraabdominal desmoid tumor with dissemination detected by thallium-201 scintigraphy.

Extraabdominal desmoid tumor is a locally aggressive tumor despite being histologically benign. To avoid local recurrence, it is important to preoperatively detect the exact localization and extension of the infiltrating or disseminating lesion in this tumor. We report a case of recurrent extraabdominal desmoid tumor, which arose in the posterior thigh region, detected with Tl-201 (Tl) scintigraphy. In this case, Tl accumulated in the small disseminating lesion and to the recurrent tumor. This lesion was not identified by palpation because of its small size, deep localization and absence of symptoms, although MR imaging, which was performed after the Tl scintigraphy, clearly showed the lesion. After tumor resection, Tl did not accumulate in any region. These results suggest that Tl scintigraphy may be useful, not only for the diagnosis of extraabdominal desmoid tumor, but also for the detection of the exact localization or extension of small infiltrating or disseminating lesions before treatment.

Female↗

Assessment of chemosensitivity in patients with malignant bone and soft tissue tumors using thallium-201 scintigraphy and doxorubicin binding assay.

This study was performed to compare the accumulation of thallium (Tl)-201 which is correlated with malignancy and the doxorubicin binding ability, which is correlated with chemosensitivity, in nine patients who received preoperative chemotherapy with doxorubicin and cisplatin. Tl-201 scintigraphy was performed at 15 minutes (early image) and 3 hours (delayed image) after injection of 111 MBq of Tl-201. The change of degree of the radionuclide uptake between the early and delayed images was evaluated before and after preoperative chemotherapy. The doxorubicin binding ability (%DB) to nuclear DNA in living tumor cells isolated from biopsy materials was assessed by doxorubicin binding assay. The histologic response to preoperative chemotherapy was evaluated by the percentage of tumor necrosis. Before preoperative chemotherapy no changes of Tl-201 uptake between the early and delayed images was detected in any tumors. Five patients, who had no change of Tl-201 uptake after preoperative chemotherapy, showed a poor histologic response and had a %DB ranging from 10% to 70% (mean: 36.0%). The other four patients, who had a %DB greater than 90%, showed a good histologic response. All of these four patients had decreased Tl-201 uptake after preoperative chemotherapy. This study demonstrated that doxorubicin binding assay and midcourse Tl-201 scintigraphy are useful methods to assess the response to chemotherapy early in malignant bone and soft tissue tumors.

Adolescent↗

Drug resistance modification using pulsing electromagnetic field stimulation for multidrug resistant mouse osteosarcoma cell line.

Multidrug resistance (MDR) is one of the major problems in osteosarcoma chemotherapy. Therefore, methods of overcoming MDR are urgently needed. In this study, we investigated the effects of pulsing electromagnetic field stimulation (PEMFs) on a MDR murine osteosarcoma cell line which strongly expresses P-glycoprotein (P-gp). To assess the reversal effects of PEMFs on doxorubicin (DOX) resistance, MTT assay was applied. Viable cells were assessed by the trypan blue exclusion test. Fluorescence intensity of DOX binding to nuclear DNA of each cell was measured using a cytofluorometer. Changes in P-gp expression in each cell were detected by the indirect immunofluorescence method using an antibody to Pgp. PEMFs increased DOX binding ability to nuclear DNA and inhibited cell growth, although it had no significant effect on P-gp expression. These findings indicated that PEMFs reversed the DOX resistance of the MOS/ADR1 cells by inhibiting P-gp function. The results suggested that PEMFs may be useful as a local treatment for MDR osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Eleven cases of intraosseous lipoma of the calcaneus.

Intraosseous lipomas are rare benign primary bone tumors, with an incidence of one per thousand bone tumors. We studied eleven cases of intraosseous lipoma of the calcaneus. All the patients received radiographic examinations and MRI with T1-and T2-weighted images with Gd-DTPA enhancement. Seven patients received tumor curettage. Plain radiographs demonstrated that all of the lesions showed clear osteolysis surrounded by a sclerotic margin in the central body of the calcaneus. MRI revealed that all the lesions had demarcated homogenous high signal intensity lesions on both T1- and T2-weighted images, which strongly suggested adipose tissue. In 5 cases, the center of the lesion showed low signal intensity lesions on T1-weighted images, suggesting the existence of central necrosis or cyst formation. After excising the tumors of 7 patients, there was no local tumor recurrence. Surgical intervention was considered unnecessary in all cases after the diagnosis of an intraosseous lipoma was determined by MRI.

Adolescent↗

Prognostic and therapeutic values of peritoneal cytology in gastric cancer.

Exfoliative cytology of peritoneal lavage was performed at the time of laparotomy for 458 patients with gastric cancer. Positive cytologic specimens were obtained from 28 per cent of all cases and from 16 per cent of patients with curative surgery. Peritoneal cytology has revealed itself to be a good predictor of prognosis and an indicator for adjuvant therapies. In the group treated with curative surgery, the five year survival rate was 86 per cent for patients with intact serosa and negative cytologic specimens, and 52 per cent for patients with involved serosa and negative cytology. None of the patients who had involved serosa and positive cytologic specimens survived more than five years. A slight benefit of adjuvant chemotherapy was observed in the patients who had curative surgery with negative cytology. Long term immunochemotherapy, including repeated intraperitoneal administration of mitomycin-C, improved the lifespan of patients with non-curative surgery.

Ascitic Fluid↗

[Comparative histological-morphometric study of the marginal zone and the germinal center of the rat spleen after endotoxin injection (author's transl].

Basing on the knowledge of structure and function of the marginal zone of the lymph follicle of the spleen in correlation with migration of lymphocytes to the red pulp and from there back to the lymph follicle (filtration of lymphocytes, so-called marginal zone bridging channel, role of the marginal sinus) a comparative study on the size of the marginal zone and germinal center following endotoxin-injection is presented.

Animals↗

Cytologic studies of malignant melanoma of the vagina.

Four cases of primary malignant melanoma of the vagina are described and discussed with respect to vaginal smears. Two cases treated with radiotherapy began to increase the amount of the melanin pigment during the course of irradiation. Characteristic cytologic features found in the four cases are summarized as follows: a) Distribution of cell 1) Scattering, no tendency of grouping 2) Moderate anisocytosis and anisokaryosis b) Cytoplasm 1) Cyanophilic wispy cytoplasm 2) Indistinct cytoplasmic rim 3) Relatively clear cytoplasm 4) Relatively low N/C ratio c) Melanin pigment 1) In melanoma cells-finely granular and diffusely packed in cytoplasm 2) In histiocytes-coarsely granular and densely packed in cytoplasm d) Nucleus 1) Extremely eccentric nucleus 2) Thin and irregular nuclear membrane 3) Relatively regular chromatin distribution 4) Finely or moderately granular chromatin pattern 5) Prominent nucleolus 6) Giant malignant cells (3-4 nuclei) 7) Intranuclear vacuole (punched out).

Adult↗

A neurophysiological study among Chinese CS2-exposed workers.

A neurophysiological study was carried out to examine peripheral neurotoxicity of extremely low levels of CS2, that is, less than 2 ppm (TWA-8hr) among Chinese viscose rayon workers. From the subjects who participated in a 1981 cross-sectional medical survey, 70 male workers exposed to CS2 and age-matched unexposed workers were randomly selected for the present neurophysiological examination. The conduction velocities of motor, sensory and slower motor fibres of the right ulnar nerve were measured using the same methods as those in the study by Seppäläinen (1974). Skin temperature was measured at the middle of the volar surface of the right forearm with a Thermistor thermometer. According to an earlier occupational hygiene survey in the plant, current personal exposures determined by a passive dosimeter method were very low; the average of daily exposure of 7 jobs studied was 1.45 ppm (range 0.2-5.0). Past and current area sampling data also suggested that occupational hygiene conditions regarding CS2 exposure in the plant had been extremely good for the previous 6 years. The present neurophysiological study clearly showed that significant reduction in the conduction velocities of motor and slower motor fibres of the ulnar nerve was detected as a consequence of chronic exposure to low levels of CS2. In the previous cross-sectional medical survey, no retinopathy was found among Chinese workers exposed to CS2 at this level. These results suggested that an effect of CS2 on the peripheral nerve would appear earlier than that on the retina.

Adult↗

A cross-sectional study on nerve conduction velocities among workers exposed to carbon disulphide.

We examined nerve conduction velocities (NCVs) in the ulnar nerve (motor, slower motor fiber and mixed), the peroneal nerve (motor, MCV) and the sural nerve (sensory, SCV) among 46 Japanese workers exposed to carbon disulphide (CS2, CS2-exposed group) and 28 normal control workers (group C). The subjects had not suffered from diseases or injuries of the peripheral or central nervous system. MCV in the peroneal nerve and SCV in the sural sural nerve in the CS2-exposed group were significantly reduced compared with those of group C (p < 0.05 in both), but no significant difference in NCVs of the ulnar nerve was noted between the two groups. In the two subgroups of the CS2 exposed group (currently exposed: group E n = 24; removed from exposure: group R n = 22), NCVs of group E tended to be lower than those of group R in spite of the younger age of group E. MCV in the peroneal nerve and SCV in the sural nerve in group E were significantly reduced compared with those in group C, but not significantly in group R. These findings indicate the existence of a toxic effect of CS2 exposure on the NCV, predominantly evident in the lower limbs in those workers. On removal from CS2 exposure, NCV recovery seemed to be possible.

Adult↗

Avoidance of doxorubicin resistance in osteosarcoma cells using a new quinoline derivative, MS-209.

P-glycoprotein (Pgp), a membrane drug efflux pump, is thought to be responsible for the observed drug resistance in osteosarcoma. We have recently developed Pgp-positive, multidrug resistant (MDR) murine osteosarcoma cell lines, which may be suitable models for the study of drug resistance in osteosarcoma. In this study, we investigated the effect of a newly synthesized quinoline compound, MS-209, on the reversal of doxorubicin (DOX) resistance in these cell lines. Three different types of resistance modifying agents (RMAs) as well as MS-209 were studied. These included the calcium channel blocker verapamil, and the immunosuppressive agents cyclosporin A and FK506. The reversal effects of the RMAs on DOX resistance were assessed by the MTT assay. In the absence of RMAs, the MDR osteosarcoma cells were 20-fold more resistant to DOX than the parental cells. When MS-209 was added at a final concentration of 0.1 to 3 microM to the MDR cells, 3-to 74-fold sensitization was observed. A complete reversal (37-fold sensitization) of the resistance was obtained at 1 microM MS-209. This concentration of MS-209 was 3-, 8- and 28-fold more effective than the same concentration of FK506, verapamil and cyclosporin A, respectively. These results indicate that MS-209 may be a more effective RMA, and that DOX resistance in osteosarcoma cells could be reversed by comparatively low doses of MS-209.

Antineoplastic Agents↗