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Biomedical subjects

S Hashiguchi

Publications and source records attributed to S Hashiguchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Photodynamic inactivation with acridine orange on a multidrug-resistant mouse osteosarcoma cell line.

Overcoming multidrug resistance (MDR) is an urgent issue to improve the prognosis of osteosarcoma patients. In this study, we undertook to clarify the effect of photodynamic therapy (PDT) with acridine orange (AO) on the MDR mouse osteosarcoma (MOS / ADR1) cell line, by comparing the outcome with the effect on a chemosensitive osteosarcoma (MOS) cell line. Cultured cells of MOS and MOS / ADR1 cell lines were exposed to AO at various concentrations for various times, followed by long- or short-term (10 or 1 min) illumination with blue light (466.5 nm) for excitation. Living cells were counted by means of the trypan blue exclusion test. The results showed that AO rapidly bound to DNA, RNA and lysosomes of living MOS and MOS / ADR1 cells and also that most tumor cells in both cell lines died rapidly (viability ratio to untreated cells: 1/1000) within 48 h under conditions of continuous or 15-min flash exposure to AO at concentrations above 1.0 microg/ml plus 10-min illumination with blue light. Even after flash exposure to AO at concentrations above 1.0 microg/ml plus 1-min illumination, the viability of MOS/ADR1 cells decreased to a viability ratio of less than 1/ 1000 within 72 h. Based on these results, we concluded that AO with photo-excitation has a strong cytocidal effect, not only on chemosensitive mouse osteosarcoma cells, but also on MDR mouse osteosarcoma cells. These results suggested that photodynamic therapy with AO may be a new approach to treating MDR human osteosarcomas.

Acridine Orange↗
PubMed2000

Total tumor cell elimination with minimum damage to normal tissues in musculoskeletal sarcomas following photodynamic therapy with acridine orange.

Acridine orange (AO) has unique biological actions enabling tumor visualization (fluorovisualization) and a strong cytocidal effect (photodynamic therapy: AO-PDT) under illumination with blue light. Accordingly, in this study, we attempted to develop a new surgical technique for total tumor cell elimination using these photodynamic reactions with AO in a mouse osteosarcoma model. The results showed that local tumor recurrence was significantly inhibited (23%) in the group treated with curettage under fluorovisualization and AO-PDT, compared to that (80%) in the control group treated with curettage alone under ordinary light. Therefore, we concluded that the combination of curettage under fluorovisualization and AO-PDT may be useful for total tumor cell elimination with minimum damage to normal tissue in musculoskeletal sarcomas.

Acridine Orange↗
PubMed2000

[A family with DRPLA and chronic renal failure].

We reported a family with dentato-rubro-pallido-luysian atrophy (DRPLA) and chronic renal failure. The proband was a 66-year-old woman who developed gait disturbance, limb ataxia, pyramidal tract signs, and dementia since age 54. T2-weighted brain MR images revealed symmetric high-signal lesions in the cerebral white matter, in addition to cerebellar, brainstem, and cerebral cortical atrophy. She suffered from renal failure and became dialysis-dependent at the age of 59, four years after the onset of chronic nephritic syndrome. At the age of 66, she was admitted to our hospital because of hyperthermia and disturbance of consciousness, and died of DIC. Her CAG repeats in the DRPLA gene were 58 and 12. An autopsy was performed. The brain weighed 910 g. Histological findings confirmed the diagnosis of DRPLA. Her mother died of chronic renal failure. All three siblings had cerebellar ataxia, and two siblings had chronic nephritic syndrome. Among them, only her younger brother was diagnosed as non-IgA glomerulonephritis based on kidney biopsy findings at the age of 48. Though the nature of the association between DRPLA and renal dysfunction remains obscure, the DRPLA gene abnormality may be correlated with chronic renal failure in this family.

Aged↗
PubMed1999

Primary progressive aphasia presenting as conduction aphasia.

We report a case of a woman with primary progressive aphasia (PPA) who presented with conduction aphasia. A 60-year-old, right-handed, Japanese female suffering from progressive aphasia had difficulty in repeating words and phrases. She displayed phonemic paraphasias but had preserved comprehension and had no cognitive or behavior disorder for more than 6 years after the onset of the condition. She was able to continue to work successfully and to perform all her normal daily activities. T1-weighted magnetic resonance imaging revealed minute dilatation of the left inferior horn and sulci in the left hemisphere, and positron emission tomography revealed mild hypometabolism in the left supramarginal gyrus and its surrounding areas. Therefore, she was diagnosed as suffering from PPA presenting as conduction aphasia. We believe that the progressive conduction aphasia of the patient belongs to one of the fluent forms of PPA, and the ability to continue normal work along with the clinical portrayal of preserved memory and cognition skills may be features of a form of PPA presenting as conduction aphasia.

Aphasia, Conduction↗
PubMed1999

Prognostic value of DNA ploidy response to chemotherapy in human osteosarcomas.

We analyzed the DNA ploidy alterations after preoperative chemotherapy in 30 patients with non-metastatic osteosarcomas of the extremities. All of the patients received intensive chemotherapy with doxorubicin, cisplatin and methotrexate as well as wide tumor resection. DNA ploidy was determined by DNA cytofluorometry using isolated and smeared cells from biopsied and resected tumors after preoperative chemotherapy. The results showed that 12 diploid and nine non-diploid osteosarcomas did not change their ploidy pattern, but nine non-diploid tumors changed to a diploid pattern with the disappearance of the aneuploid cells. The nine patients with altered ploidy tumors had a better histologic response to chemotherapy and a better prognosis than the patients with non-altered tumors especially diploid tumors (P = 0.0138). Therefore, we conclude that a decrease in aneuploid cells after chemotherapy is closely correlated with a good prognosis in half of the cases of aneuploid osteosarcoma. These results also suggest that aneuploid cells are more chemosensitive than diploid cells in human osteosarcomas.

Adolescent↗
PubMed1999

Response of DNA ploidy to chemotherapy in primary and metastatic lesions in human osteosarcomas.

Primary and pulmonary metastatic and pulmonary metastatic tumors (two synchronous and seven metachronous metastases) in nine patients with osteosarcomas were studied by DNA cytofluorometry. All patients were treated with both pre and postoperative chemotherapy. The results showed that all five diploid osteosarcomas and three of the four aneuploid tumors did not markedly change their ploidy pattern after preoperative chemotherapy, and had almost the same ploidy patterns as the pulmonary metastatic lesions. Those eight tumors showed poor histologic response and chemoresistance by the doxorubicin binding assay. Only one aneuploid osteosarcoma showing good histologic response and chemosensitivity changed its ploidy pattern to diploid, with the disappearance of aneuploid tumor cells and its synchronous pulmonary metastatic tumor also showed conversion to a diploid pattern with massive tumor necrosis. It is evident that those tumors showing no change in their ploidy pattern after chemotherapy were resistant to the chemotherapy. Therefore, we conclude that regardless of whether the pulmonary metastatic tumors were synchronous or metachronous, they showed the same change in their ploidy pattern as well as their chemosensitivity as the primary human osteosarcoma from which they were derived.

Adolescent↗
PubMed1999

Relationship between P-glycoprotein positivity, doxorubicin binding ability and histologic response to chemotherapy in osteosarcomas.

We previously reported that the doxorubicin binding ability detected by the doxorubicin (adriamycin) binding assay was closely correlated with the chemosensitivity of human osteosarcomas. In this study, we undertook to clarify the relationship between P-glycoprotein positivity (%PPG) and doxorubicin binding ability (%DB) in human osteosarcomas in order to determine which is a more sensitive index of histologic response to chemotherapy. Ten primary osteosarcomas were analyzed by the doxorubicin binding assay and by immunofluorescence to detect cellular P-glycoprotein positivity. Three good responders to chemotherapy containing doxorubicin showed a %DB greater than 90% (average: 96.43%), whereas the seven poor responders had values less than 80% (average: 35.31%). The difference between the two groups was statistically significant (P = 0.0167). However, the average %PPG of the three good responders was 6.73%, whereas the %PPG of the seven poor responders was 14.27%. There was no significant difference in %PPG between the two groups (P = 0.3051). No negative correlation between the %DB and the %PPG of all osteosarcomas (r = 0.536, P = 0.1104) was found, although there was a trend that those tumors with a high %PPG showed a low %DB. These results suggest that osteosarcomas showing a low %DB and %PPG with poor response to chemotherapy, may have multidrug resistance mechanisms other than P-glycoprotein. Therefore, we conclude that doxorubicin binding ability, which reflects all of the doxorubicin-resistant mechanisms, was more sensitive than P-glycoprotein positivity in predicting the chemosensitivity of human osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Prognostic significance of DNA ploidy pattern in osteosarcomas in association with chemotherapy.

In this study, we analysed the DNA ploidy of osteosarcomas at biopsy and attempted to clarify the relationship between DNA ploidy pattern and prognosis. Thirty patients with non-metastatic osteosarcoma of an extremity were studied. All underwent intensive chemotherapy with doxorubicin, cisplatin and methotrexate, in addition to wide tumor resection. DNA ploidy was detected by DNA cytofluorometry, using isolated and smeared cells of biopsied tumor tissue. Twelve tumors showed a diploid ploidy pattern and 18 showed a non-diploid pattern such as aneuploidy (15 tumors) and euploid-polyploidy (3 tumors). The event-free survival rate at 9 years was 63.5% in non-diploid osteosarcoma patients and 13.3% in diploid osteosarcoma patients. There was a statistically significant difference between the two groups (P = 0.0278). These results lead us to conclude that a non-diploid osteosarcoma may be more sensitive to chemotherapy than a diploid tumor.

Adolescent↗
PubMed1999

Cytofluorometric DNA ploidy analysis in giant cell tumor of bone: histologic and prognostic value.

DNA ploidy analysis by DNA cytofluorometry was performed on 41 tumors obtained from 37 patients with primary giant cell tumor of bone (GCT). Histologically, 26 of the tumors from primary or recurrent lesions were evaluated as grade I, and 13 tumors as grade II. Among the 33 primary GCT patients, 4 patients had local recurrence or pulmonary metastasis. The DNA ploidy pattern and the percentage of hyperdiploid cells showing a greater DNA content than diploid cells, were obtained from DNA cytofluorometry. All of the 33 primary tumors were diploid. Of 6 recurrent tumors, 4 were diploid and 2 were euploid-polyploid. One of the two pulmonary metastatic tumors was diploid, but another that demonstrated a malignant transformation to malignant fibrous histiocytoma was aneuploid. The percentage of hyperdiploid cells was significantly different between primary and recurrent tumors (P = 0.0188) and between grade I and grade II tumors (P = 0.0052), while there was no difference between primary tumors in the cases that recurred or metastasized and those that did not. Thus, these data indicate that cell proliferative activity is closely correlated with biological aggressiveness and histological grading, although DNA ploidy is not useful for predicting prognosis.

Adolescent↗
PubMed1999

Clinical outcome of total scapulectomy in 10 patients with primary malignant bone and soft-tissue tumors.

BACKGROUND AND OBJECTIVES: Limb reconstruction after total scapulectomy for malignant bone and soft-tissue tumors around the scapula is difficult. This study was undertaken to clarify the clinical results of total scapulectomy in patients with malignant bone and soft-tissue tumors around the shoulder girdle in our institute between 1984 and 1998. METHODS: Ten patients undergoing total scapulectomy had an age range of 12-82 years (average = 56 years). There were 5 cases of bone tumor and 5 cases of soft-tissue tumor. The follow-up period ranged from 8 months to 13 years 5 months. RESULTS: Seven patients are currently alive; the remaining 3 patients died of other diseases. One case of local recurrence was detected. The 2-year survival rate of all cases was 78.8%, and the 5-year survival rate was 52.5%. The average function evaluated by Enneking's criteria was 64.6%. Although the range of motion in the shoulder joint was seriously limited in all patients, the elbow and hand functions were almost normal. Recently, we have used a bone-anchoring system to suture between the clavicle and muscles, including the biceps, triceps, and deltoid muscles. CONCLUSIONS: Patients who undergo total scapulectomy may achieve much better upper limb function than those who undergo forequarter amputation (interscapulothoracic amputation).

Adolescent↗
PubMed1999

Vascular smooth muscle cell outgrowth, proliferation, and apoptosis in young and old rats.

We attempted to identify the effects of aging on the response of vascular smooth muscle cells (VSMCs) to injury. Rat aortas were injured by ballooning, and cell outgrowth of the aortic explants, as well as cell proliferation and apoptosis induced by 7-ketocholesterol in the culture system were compared in young (6-7 weeks) and old (40-50 weeks) rats. Explant outgrowth in uninjured rats did not differ between young and old rats. However, 14 days after balloon injury, the number of explants with outgrowth increased by a factor of four (P<0.01) in young rats, while that of the old rats did not change. Cell proliferation in cultured VSMCs also did not differ between young and old uninjured rats, but, in the injured group, proliferation doubled in young rats (P<0.01), but did not change in the older group. The rate of unadhered cells in the presence of 7-ketocholesterol (30 microM) did not differ between young and old uninjured rats. In the injured rats, however, that of young rats was lower (P<0.01) while that of older rats was higher (P<0.01). The extent of DNA fragmentation (%) after the addition of 7-ketocholesterol (30 microM) did not differ between young and old uninjured rats. In the injured groups, DNA fragmentation was lower in the young rats (P<0.01), and higher in the old ones (P<0.01), when compared to their respective controls. These results indicate that the VSMC injury responses of cell outgrowth and proliferation were more pronounced in the young, and that 7-ketocholesterol-induced apoptosis was more extensive in old rats.

Aging↗
PubMed1999

Effect of positive end-expiratory pressure on left and right ventricular diastolic filling assessed by transoesophageal Doppler echocardiography.

The effect of positive end-expiratory pressure (PEEP) on left and right ventricular diastolic filling dynamics was assessed by transmitral and transtricuspid flow patterns. Using transoesophageal Doppler echocardiography in fourteen ASA physical status 1 female patients, the following measurements were performed at baseline (0 cm H2O PEEP) and at 5, 10, 15, and 20 cm H2O PEEP: 1. peak velocity of early filling (peak E velocity), 2. peak velocity of atrial contraction (peak A velocity), 3. the ratio of the peak E to A velocity (peak E/A velocity ratio), 4. isovolumic relaxation time (IRT), 5. acceleration half-time (AHT), 6. deceleration half-time (DHT) of early filling, and 7. end-diastolic and end-systolic areas of both ventricles. Increasing PEEP progressively deceased peak E velocity of both ventricles. In contrast, peak A velocity did not change and the peak E/A velocity ratio decreased significantly with PEEP. IRT and AHTs remained unchanged, but DHTs of both ventricles increased following PEEP. End-diastolic and end-systolic areas of both ventricles decreased gradually and significantly with PEEP. It is concluded that PEEP was associated with decreased preload as well as reduced compliance of both ventricles, which was considered to contribute to the changes in diastolic ventricular filling.

Adult↗
PubMed1999

Usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas.

In this study, we undertook to prove the usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas. We analyzed the DNA ploidy of 47 cartilaginous tumors using DNA cytofluorometry, which is more sensitive than flow cytometry. All of these tumors were classified into six groups on the basis of clinical, radiologic, and histologic criteria. The 25 tumors in the No. 1 group showed no histologic signs of malignancy regardless of their clinical signs. The four tumors in the No. 2 group showed histologic signs of malignancy, but had benign clinical signs like small bone origin or Ollier's disease. The No. 3 group (13 tumors), No. 4 group (four tumors), and No. 5 group (three tumors) were conventional grade I, II, and III chondrosarcomas, respectively, and the No. 6 group included three dedifferentiated chondrosarcomas. Tumor cells isolated from fresh tumor materials treated with papain and collagenase were smeared on a glass slide and their nuclear DNA was stained with propidium iodide. The DNA content of each cell was measured by a cytofluorometer as fluorescence intensity. The results of this study showed that all of the tumors in the No. 1 group had a diploid pattern with a significantly lower (P<.001) cell proliferative activity than the grade I chondrosarcomas in the No. 3 group, all of which had a diploid pattern. Cytofluorometric analysis also indicated that grade II and III chondrosarcomas in the No. 4 and 5 groups had a higher frequency of hyperdiploid cells (%HDC), including aneuploid and polyploid cells than grade I chondrosarcomas. Importantly, all of the grade I chondrosarcomas showed a %HDC >8%, whereas all of the tumors in the No. 1 and 2 groups showed a %HDC <8%. Therefore, we believe that a %HDC value of 8% is borderline between biologically benign and malignant states in cartilaginous tumors. Four of five patients with aneuploid chondrosarcoma had tumor recurrence and two of these patients died of metastatic disease, although all of the patients except for one with diploid chondrosarcoma were continuously disease free after surgery. Based on these results, we concluded that the data of DNA ploidy analysis, especially cell proliferative activity expressed as %HDC, is more reliable and clinically more useful than the histologic and clinical signs of malignancy in distinguishing benign cartilaginous tumors from chondrosarcomas and even from low grade chondrosarcomas.

Adult↗
PubMed1998

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma.

BACKGROUND: Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma. METHODS: Doxorubicin (adriamycin [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was assessed by ABA in 14 patients with primary osteosarcoma who were treated with preoperative chemotherapy containing ADM and 6 patients with relapsed osteosarcoma after intensive chemotherapy. Histologic responses to preoperative chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS: Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and demonstrated good histologic responses (>90% of %necrosis) to preoperative chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and demonstrated poor responses. Patients with recurrent osteosarcoma that was clinically evaluated to be resistant to previous chemotherapy also had low %AB (34.2+/-28.3%). CONCLUSIONS: Because the results of the current study revealed that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as well as chemotherapy without ADM for patients with osteosarcoma, and because ABA technically is simple and results can be assessed rapidly, the authors conclude that ABA is a clinically useful chemosensitivity test for patients with osteosarcoma.

Adolescent↗
PubMed1998

Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.

In order to examine the effect of HTLV-I proviral load on the pathogenesis of HAM/TSP, we measured the HTLV-I proviral load in peripheral blood mononuclear cells (PBMC) from a large number of HAM/TSP patients and asymptomatic HTLV-I carriers. To measure the proviral load, we used an accurate and reproducible quantitative PCR method using a dual-labeled fluorogenic probe (ABI PRISM 7700 Sequence Detection System). The mean +/- standard error of mean (s.e.m.) HTLV-I proviral copy number per 1 x 10(4) PBMC was 798 +/- 51 (median 544) in 202 HAM/TSP patients; 120 +/- 17 (median 34) in 200 non HAM-related (general) asymptomatic HTLV-I carriers (RC); and 496 +/- 82 (median 321) in 43 asymptomatic HTLV-I carriers genetically related to HAM/TSP patients (FA). The prevalence of HAM/TSP rises exponentially with log (proviral load) once the proviral load exceeds 1% PBMC. The HTLV-I proviral load of female patients with HAM/TSP was significantly higher than that of male patients, however there was no significant difference in proviral load between sexes in RC. There was a significant correlation between the proviral load and the concentration of neopterin in CSF of HAM/TSP patients. These results indicate that the HTLV-I proviral load in PBMC may be related to the inflammatory process in the spinal cord lesion. The increased proviral load in FA suggests the existence of genetic factors contributing to the replication of HTLV-I in vivo.

Adult↗
PubMed1997

Cervical spondylotic amyotrophy associated with Hirayama's disease.

A 47-year-old man with Hirayama's disease who developed cervical spondylotic amyotrophy (CSA) is presented. The patient had noted weakness and atrophy of hand and forearm muscles bilaterally at the age of 16. At the age of 40, he developed proximal muscle atrophy and weakness bilaterally after 20 years of a non-progressive state. Myelography and computed tomography (CT)-myelography revealed that ventral cord compression at multiple levels of C4-7 vertebral bodies was increased when the neck was extended. The clinical diagnosis was CSA associated with Hirayama's disease. To our knowledge, this is the first such case to be reported.

Cervical Vertebrae↗
PubMed1997

[Axonal motor neuropathy associated with anti-SGPG antibody].

We report a case of axonal motor neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) antibody which has not been reported yet. A 49-year-old man was admitted with asymmetrical patchy weakness which started in his upper extremities. The deep tendon reflexes were absent in the upper extremities, but normal in the lower extremities. There was a slight decrease in the vibratory sensation in the distal portions of the lower extremities. The general laboratory tests including the protein level of the cerebrospinal fluid revealed no abnormalities. Motor conduction studies showed the low amplitudes of CMAP and no demonstrable conduction block in the limbs. Sensory conduction studies showed no abnormalities except for slightly decreased amplitude of SNAP in the limbs. Electromyography showed active denervation in the upper extremities. Serial electrophysiological studies suggested that the predominant process was axonal degeneration of the motor nerves. Thin-layer chromatography with immunostaining showed that his serum IgM reacted with SGPG. Treatment with cyclophosphamide and corticosteroids was unsuccessful. In this case, this anti-SGPG antibody may be involved in the pathogenesis of chronic axonal degeneration of the motor nerves.

Autoantibodies↗