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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 577 records · Page 32Linked to original sources

Image analysis of CNS neurotrophic factor effects on neuronal survival and neurite outgrowth.

We have developed a method for quantifying the effects of neurotrophic factors by using digital image processing techniques to enhance the morphometric analysis of cultured neurons. Dissociated cell cultures from rat embryonic cerebral cortex were selected as a model biological system. Binary images of neuronal neurites were extracted from gray images of cultured neurons stained with Coomassie brilliant blue. Pattern recognition techniques were used to estimate the number of neurons per culture dish and the average length of the neurites on each cell. In 4-day cultures, addition of extracts from 2-week-old rat cortices dose-dependently increased both parameters. The method proved suitable for use in bioassays of factors influencing neuronal survival and neurite promotion.

Animals↗

Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen).

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.

Antibodies, Monoclonal↗

Autologous tumor-specific cytotoxic T-lymphocytes in a child with neuroblastoma.

Activation of peripheral blood lymphocytes from a neuroblastoma patient by co-cultivation with autologous neuroblastoma cells in a mixed lymphocyte-tumor cell culture (A-MLTC) resulted in the generation of cytotoxic activity against the autologous neuroblastoma cell line HNB-MS. A-MLTC was set up in the presence of recombinant human interleukin-2 (IL-2). HNB-MS stimulator was treated with recombinant human interferon-gamma (IFN-gamma) prior to A-MLTC. CTL generated in short-term culture effectively lysed HNB-MS, while they had no effect on an Epstein-Barr virus transformed autologous B-cell line EB-MS. Moreover, CTL lysed 3 different allogeneic neuroblastoma cell lines, but not a rhabdomyosarcoma cell line RBB. Recombinant human tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) enhanced and suppressed CTL generation, respectively, when added to the A-MLTC from the beginning of culture. CD3+ CD4- CD8+ T cells were the major anti-tumor effectors. Furthermore, 111indium-labeled CTL clearly accumulated in metastatic sites. These results indicate that CTL can be used for adoptive immunotherapy in neuroblastoma.

Abdominal Neoplasms↗

Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression.

In cerebellar Purkinje cells, conjunctive stimulation of parallel fibers and the climbing fiber causes long-term depression of parallel fiber-Purkinje cell transmission. It has been postulated that calcium is an intracellular mediator of the climbing fiber to induce this synaptic modification. To directly test the hypothesis, a calcium-chelating agent, EGTA, was intracellularly injected into Purkinje cells. In these injected cells, conjunctive stimulation failed to induce depression. Instead, it caused potentiation similar to that observed after repetitive stimulation of parallel fibers alone.

Animals↗

The role of CD8+ and CD4+ cells in islet allograft rejection.

The requirements of CD8+ and CD4+ cells for islet graft rejection in combinations with different histoincompatibilities were investigated by in vivo administration of anti-Lyt-2.2 (CD8) mAb, anti-L3T4 (CD4) mAb, or both to recipient mice. In B10.AQR----B10.A (H-2K-incompatible) and B10.A(5R)----B10.A (H-2K- and IA-incompatible) combinations, administration of either anti-Lyt-2.2 (CD8) or anti-L3T4 (CD4) mAb completely blocked islet graft rejection, indicating that neither CD8+ cells nor CD4+ cells alone were capable of mediating rejection, and that collaboration of CD8+ cells and CD4+ cells was necessary. On the other hand, in the BALB/c----B6 (H-2- and non-H-2-incompatible) combination, administration of anti-Lyt-2.2 (CD8) or anti-L3T4 (CD4) mAb resulted in rejection of most of the grafts, although survival was prolonged significantly, and administration of both anti-Lyt-2.2 (CD8) and anti-L3T4 (CD4) mAb together completely blocked rejection. These results suggested that either CD8+ or CD4+ cells were capable of mediating rejection, but that rejection was maximal in the presence of both T cell subsets. Immunohistochemical analyses showed marked depletion of CD8+ cells and CD4+ cells in grafted islets as well as spleens when anti-Lyt-2.2 (CD8) and anti-L3T4 (CD4) mAb, respectively, were injected.

Animals↗

Sequential malignant transformation of cardiac myxoma.

We describe a case of cardiac myxoma in a 44-year-old Japanese man, who died after developing metastases in the skin, brain and muscle. A satellite tumor which was attached to the wall of the abdominal aorta induced marked hypertension due to obstruction of the renal arteries. Although the primary heart tumor had typical histological features of benign cardiac myxoma, the recurrent heart tumor, which was partly resected three months before the patient's death, showed apparently malignant characteristics resembling malignant fibrous histiocytoma (MFH). Since the histological features of the initial and recurrent tumors were different, the grade of malignancy was investigated using the cellularity of the tumor as an arbitrary criterion. A gradual but significant increase in the cellularity was observed over the course of five years. Immunohistochemically, tumor cells in the muscle metastasis contained vimentin and factor VIII-related antigen, and multinucleated giant cells in the recurrent heart tumor contained desmin, which is rarely detectable in MFH. Therefore, we considered that the present case represented malignant transformation of benign cardiac myxoma.

Adult↗

Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group.

The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis.

Adolescent↗

Benign lymphoepithelial lesion with large cysts: case report.

A case of benign lymphoepithelial lesion with two large cysts and many foci of duct dilatation is reported. Clinical features, except for absence of dry eyes, indicated the case was Sjögren's syndrome. The cysts were found in the left parotid gland of a 60-yr-old woman and were surgically removed. The size of each cyst was 20 mm in diameter and one of them was located in the lymph node. Because of the HLA-DR expression by the epithelium, the cysts are considered to have formed as a result of duct dilatation due to autoimmune response. As for one cyst, it is also possible that the pre-existing lymphoepithelial cyst might be involved in the autoimmune phenomenon because of its relation to the lymph node.

Cysts↗

Lack of correlation between interferon levels induced by polyribonucleotides and their antimetastatic effect.

The inhibitory effect of poly(A)poly(U) on the pulmonary metastasis of B16-F10 melanoma was examined in comparison with that of poly(I,C)-L,C and poly(I)poly(C). The correlation between interferon (IFN) level and antimetastatic effect was also investigated. Intraperitoneal injection of poly(A)poly(U) (50 mg/kg) into C57BL/6 mice 24 h before intravenous inoculation of B16-F10 melanoma (1 X 10(5] caused a significant decrease (p less than 0.01) in the number of pulmonary nodules 14 days after tumor challenge. But poly(I,C)-L,C (1 or 0.2 mg/kg) and poly(I)poly(C) (5 mg/kg or 1 mg/kg) did not. From the kinetic study of IFN levels induced by polyribonucleotides, poly(I,C)-L,C showed the most potent IFN-inducing activity, followed by poly(I)poly(C) and poly(A)poly(U), in this order. Plasma IFN reached a peak at 6 h and still continued to be detected at 24 h after intraperitoneal injection of the polyribonucleotides. Against B16-F10 melanoma, the cytotoxicity of spleen cells stimulated by poly(A)poly(U) (50 mg/kg) was significantly (p less than 0.05) higher than that of spleen cells stimulated by poly(I)poly(C) (5 mg/kg) both at 12 and 24 h after intraperitoneal injection of those agents. The above results that there is no correlation between the IFN levels induced by polyribonucleotides and their antimetastatic effect. More extensive study of poly(A)poly(U) might give more fruitful results, which will give valuable information for future clinical trials of this lowly toxic promising agent.

Animals↗

Current urinary mass screening for catecholamine metabolites at 6 months of age may be detecting only a small portion of high-risk neuroblastomas: a chromosome and N-myc amplification study.

We studied 96 infants and children with untreated neuroblastomas. Chromosomes of tumor cells were analyzed in 68, and N-myc copy numbers were determined in 67 patients. Patients found by a mass screening program for 6-month-old infants (group A1, 39 patients) or those less than 12 months of age found clinically (group A2, 13 patients) were rarely in the disseminated stage (A1, three of 39; A2 one of 13); their tumors usually had near-triploid (3n) or hypertetraploid (greater than 4n) karyotypes (A1, 28 of 37; A2, nine of 11), and never had N-myc amplification (A1, zero of 34; A2, zero of 11). In contrast, children 12 months or over (group B, 27 patients) were usually in the disseminated stage (19 of 27) (P less than .0001); their tumors usually had near-diploid (2n) or near-tetraploid (4n) karyotypes (16 of 20) (P = .0027), and often had N-myc amplification (nine of 22) (P less than .0001). Of the 40 clinically found patients (A2 and B), six had undergone the screening with a negative result at the age of 6 months. Two of the six patients had N-myc amplification in the tumors. Most tumors found by the screening showed known characteristics predicting a good prognosis, and the majority of tumors showing characteristics predicting a poor prognosis were found in patients aged between 12 and 36 months. Our chromosome and N-myc amplification studies suggest that a low-risk tumor does not usually evolve to a high-risk tumor. Thus, the current mass screening program may be detecting only a small portion of highly malignant neuroblastomas at the earliest stage. Infants should be screened twice, at 6 months as well as at 12 months of age, for the early detection of high-risk neuroblastomas.

Age Factors↗

Syntheses and biological activities of renin inhibitors containing statine analogues.

Syntheses and biological activities of dipeptide renin inhibitors that contain statine analogues are described. The key steps of the synthetic approach to dipeptide renin inhibitors are the asymmetric synthesis of 2(R)-substituted-3-aminocarbonylpropionic acids and the diastereoselective syntheses of (3S,4S)-statine analogues. These inhibitors (2,14-40) inhibited human renin in the 3-140 nM range. Inhibitor ES 6864 (2) was found to be a highly potent inhibitor of human renin (IC50: 4.6 x 10(-9) M) and showed high enzyme specificity. Oral administration of ES 6864 at 3 mg/kg to conscious, sodium-depleted marmosets inhibited plasma renin activity (PRA) more than 80% after 1 h.

Amino Acids↗

[Etoposide-induced deoxyribonucleic acid (DNA) damage and its effects on nucleotide pools in murine leukemia L1210 cells].

The effect of etoposide-induced deoxyribonucleic acid (DNA) damage and its effect on nucleotide pools were examined in murine leukemia L1210 cells. Etoposide (15 mg/kg) was administered intraperitoneally on the third day after peritoneal inoculation of 1 x 10(6) L1210 cells. The dosage of etoposide produced 175% of the increase of lifespan as described previously. Strand breaks in DNA occurred within 10 min after i.p. injection, but as the time interval between injection and removal of the cells from the mice was elongated to 1 and 3 h, the continuous repairing of DNA was observed. At 6 h after the injection, the maximum concentration of DNA was located in the vicinity of that of control. In our previous study, ara-C was most effective when given at 3 to 6 h after the administration of etoposide. The sensitivity to ara-C might increase during the repairing period from the etoposide-induced DNA damage. All four dNTPs increased progressively within 6 h up to 3-fold of control. The changes in rNTPs were similar, but the degree of the changes was smaller than that of dNTPs. These changes in dNTPs and rNTPs would be an important factor for the combination to determine the antitumor effect of etoposide and nucleoside analogues.

Animals↗

Regenerating nodules in hepatic cirrhosis: MR findings with pathologic correlation.

To establish clearly the pathologic basis for small low-intensity nodules seen on MR images of the cirrhotic liver, we obtained MR images in 26 patients with cirrhosis in whom partial hepatectomy for hepatoma (15 patients), laparoscopy for cirrhosis (10 patients), or autopsy (one patient) was subsequently performed. Small low-intensity nodules were seen on gradient-echo images with short TEs (10-13 msec) in 13 of the 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition. We conclude that small low-intensity nodules observed on MR images are caused by iron deposits in regenerating nodules, and that gradient-echo images with short and prolonged TEs are useful to confirm the presence of iron deposits in regenerating nodules.

Adult↗

[Renal function study assessed by 99mTc-DMSA renal scintigraphy before and after PNL].

99mTc-DMSA renal scintigraphy was carried out in 54 patients with unilateral renal stones before and after PNL. Four to 8 weeks after PNL the DMSA renal uptake significantly decreased to 17.2 +/- 6.0% from 18.2 +/- 6.7% before PNL. DMSA renal uptake did not change in the contralateral side. Since in some patients changes in the DMSA renal uptake of 5-7% were observed after PNL not only in the PNL side but also in the contralateral side, the renal function was assessed by the formula: DMSA renal uptake in the PNL side/DMSA renal uptake in the contralateral side, and the change of this ratio was evaluated in 44 patients, in whom the renal DMSA uptake in the PNL side was less than two times that in the contralateral side. The DMSA renal uptake ratio decreased to 95.6 +/- 8.7% from the base line 4-8 weeks after PNL. This change was statistically significant. Some functional risks such as massive bleeding with PNL, the fever after PNL and the number of nephrostomy tract did not affect the decrease in the renal function. In 29 patients in whom renal function was reevaluated one year after PNL, the DMSA renal uptake ratio significantly decreased to 94.2 +/- 9.6% from the base line 4-8 weeks after PNL. But the ratio significantly improved to 99.6 +/- 11.6% about one year after PNL. In two patients with a cold area on the renal image, the renal function of the operated side still remained at about 80% levels from the base line even one year after PNL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tenotomy and postoperative brace treatment for muscular torticollis.

A postoperative corrective brace for congenital muscular torticollis is introduced and the results and indications for its use are presented. Thirty-three of 55 patients who underwent open tenotomy of the sternocleidomastoid muscle with application of the brace following surgery were evaluated in follow-up. Tenotomy was performed at the sternoclavicular origin of the muscle. The mean age at operation was six years; the mean follow-up period was seven years. The results were good in 21 patients (64%), fair in seven (21%), and poor in five (15%). Facial asymmetry remained in all patients over the age of ten who underwent operation. Alopecia, one of the complications of the brace, was found only in patients under age five. This combined treatment with tenotomy and postoperative brace is considered best indicated for patients between six and ten years of age.

Adolescent↗

[Clinical study of intravesical instillation therapy of superficial bladder tumor--combination therapy of mitomycin C, adriamycin, peplomycin and cytosine arabinoside].

The effect of intravesical combination chemotherapy on superficial bladder tumors was analyzed. Seventy-two patients were treated with intravesical instillation of the following anticancer drugs. MMC group: Mitomycin C (MMC) 10 mg and cytosine arabinoside (CA) 300 mg. ADM group: Adriamycin (ADM) 30 mg and CA 300 mg. PEP group: Peplomycin (PEP) 30 mg and CA 300 mg. MAC group: MMC 10 mg, ADM 30 mg and CA 300 mg. Antitumor effects in the MMC, ADM, PEP and MAC groups were evaluated in 16, 18, 17 and 21 patients and objective response (CR + PR) of tumor was observed in 87.5%, 50.0%, 35.3% and 28.6% of these patients. The papillary tumors, small tumors and low grade tumors responded better to these intravesical chemotherapies than the non-papillary tumors, the middle grade tumors and the high grade tumors. The recurrence rate in 72 patients was 6.9, 14.6 and 26.8% within 1, 2 and 3 years. No significant difference in the recurrence rate was observed between the MMC, ADM, PEP and MAC group, but the MMC group tended to have a lower recurrence rate than the other groups. The recurrence rate for the low grade tumors and the middle grade tumors was significantly lower than that for the high grade tumors and the small tumors. The major side effect of instillation therapy with these drugs was bladder irritation which appeared in 16.7% of all the patients (78 cases). In conclusion, intravesical chemotherapy is a useful approach for controlling superficial urinary bladder tumors, especially the combination of MMC and CA.

Administration, Intravesical↗