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Biomedical subjects

S Sugihara

Publications and source records attributed to S Sugihara.

At least 73 records · Page 4Linked to original sources

A clinical analysis of malignant schwannoma.

In this study, we reviewed the clinical features of 11 patients with malignant schwannoma who were treated in our institute. Five patients had coexistent von Recklinghausen's disease and one of them showed multifocal occurrence. Patients with the centrally located tumors had a poorer prognosis than those with the others. The overall 3-year survival rate was 36%; 40% in patients with von Recklinghausen's disease and 33% in the others. At the time of the last follow-up, 9 patients had died of the tumor, one continued to be tumor free, and one was alive with tumor. Postoperative local recurrence developed in 5 patients (45%); 4 out of 6 patients (67%) who underwent a marginal excision and one out of 3 (33%) who underwent primary amputation. There was no local recurrence in patients after a wide excision with at least 3 cm of normal tissue removed surrounding the tumor in all directions. Nine patients (82%) developed pulmonary metastasis. The effect of adjuvant chemotherapy was not clear in this study. The high risk of pulmonary metastasis in this disease indicates the necessity of more effective adjuvant chemotherapy.

Adolescent↗

Association of HLA-DR, DQ genotype with different beta-cell functions at IDDM diagnosis in Japanese children.

Japanese IDDM patients have been demonstrated to have unique and different HLA associations from white patients. To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific primers (SSP). Of the 88 IDDM patients, 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the present study (X does not contain protective alleles). Clinical heterogeneity such as age distribution at onset, prevalence and serum level of anti-GAD antibodies (GADAb), and residual pancreatic beta-cell function after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0-10 years) than in the older (11-16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11-16 years) age-group. Although no association of DR-DQ genotypes with the prevalence and serum level of GADAb was found among newly diagnosed patients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4. While no difference in time course of serum C-peptide (CPR) levels was detected between GADAb+ and GADAb- patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients. The residual pancreatic beta-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12-18 months after diagnosis. These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response (T-helper 1 function) against target beta-cells than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.

Adolescent↗

Telomere elongation observed in immortalized human fibroblasts by treatment with 60Co gamma rays or 4-nitroquinoline 1-oxide.

Telomeres are the tandemly repeated (TTAGGG)n sequences that make up the structural and functional ends of all chromosomes in mammals. Many lines of evidence indicate that telomeres stabilize chromosomes, prevent aberrant recombination, and direct chromosome attachment to the nuclear membrane. Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' DNA synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this end-replication problem. To overcome this problem, most eukaryotic cells use telomerase, an enzyme that elongates telomeres. However, this enzyme has not been detected in normal human cells, and these cells lose telomeres with cell division. Cellular senescence might be the result of this loss. Thus, activation of telomerase seems to be critical for the immortalization of human cell lines. In addition, substantial evidence indicates that immortalization in itself is a rate-limiting step for the malignant transformation of human cells. We have treated normal human fibroblasts (AD387, KMS-6, and OUMS-24 lines) intermittently with either 60Co gamma rays or 4-nitroquinoline 1-oxide (4NQO) during serial subcultivations, and have obtained three immortalized cell lines, SUSM-1, KMST-6, and OUMS-24F. In KMS-6 and OUMS-24, the mean terminal restriction fragment length significantly decreased as the population-doubling level increased. The rate of telomere loss was 40 and 50 bp/population doubling in the KMS-6 and OUMS-24 cell lines, respectively. Once these normal cell lines were immortalized, their telomeres became elongated. Similar data were obtained for AD387 cells and their immortalized SUSM-1 cells. These results suggest that telomeres play a critical role in cellular senescence and in the immortalization processes of human cells.

4-Nitroquinoline-1-oxide↗

Multiple osteocartilaginous exostosis. A follow-up study.

Deformity of the lower extremities in 26 patients with multiple cartilaginous exostosis was examined radiologically. Follow-up periods ranged between 3 and 33 years (mean 10.3 years). Twenty-four patients had deformity of the joints. A femoral neck-shaft angle (FNA) of more than 150 degrees was noted in 14 patients (26 of 51 hip joints) at diagnosis. After approximately 10 years of age, the FNA tended to decrease. Eleven patients (22 of 52 knee joints) had genu valgum (the femorotibial angle < mean -2 SD of normal control) which was caused by valgus deformity of the distal femur in one-third of the patients and that of the proximal tibia in two-thirds. Fifteen of 21 patients (29 of 42 joints) had valgus deformity of the ankle (antero-posterior mortise angle of the ankle > 94 degrees), and in half of them, the valgus deformity progressed with growth. Two patients (aged 10 and 11 years) underwent varus osteotomy of the tibia with partial excision of the fibula. However, their deformity relapsed. Surgical treatment for hip deformity is unnecessary during the growth stage. Progressive deformity of the knee and ankle should be detected in an early stage, and the surgical indication has to be examined.

Adolescent↗

The importance of doxorubicin and methotrexate dose intensity in the chemotherapy of osteosarcoma.

The relationship between dose intensity of cytotoxic agents and therapeutic results was examined in a retrospective analysis of 32 patients with non-metastatic high-grade osteosarcoma of the extremities. The average dose intensities of individual agents were 9.8 mg/m2/week for doxorubicin, 1.2 g/m2/week for methotrexate, and 10.5 mg/m2/week for cisplatinum. The dose intensities of doxorubicin and methotrexate were significantly correlated with the clinical results, while that of cisplatinum was not. These results indicate that maximal dose intensification of doxorubicin and methotrexate is an important determinant of treatment outcome for patients with osteosarcoma.

Adolescent↗

The immunophenotype of perivascular cells in the human brain.

The immunophenotype of perivascular cells (PC) in temporal lobe tissues obtained at autopsy in 48 patients (aged 41-88 years) was characterized using light and electron microscopic immunocytochemistry with a variety of antibodies. In all cases studied, PC bearing CD11c (Ki-M1P) and CD68 (KP1) were distributed throughout the temporal cortex. In addition to Ki-M1P and KP1, the monoclonal antibodies against major histocompatibility complex (MHC) class II antigen (Ag) (LN-3, CR3.43), anti-leucocyte common antigen (LCA), LN-5, Mac 387 were all found in PC with variable immunoreactivity. In contrast, LN-1 and OPD4 were not found in PC, although the former showed nearly constant staining of resting microglia. Semiquantitative analysis disclosed differences in the numbers of cells labeled with the markers in the 21 normal brains (Ki-M1P > KP1 >> LCA, LN-3, LN-5 >> Mac 387). Ultrastructurally, immunoreactivity for Ki-M1P, KP1, and LN-3 was observed in PC with cytoplasm containing dense lysosomal bodies. In brains from patients with Alzheimer's type dementia, PC were seen in the wall of beta-amyloid protein-positive small vessels. However, there was no definite alteration of antigenicity in PC from AD brains compared with those from normal brains. The immunophenotype of PC was similar to that of macrophages, which were observed in the perivascular spaces and the leptomeninges in some normal and diseased brains. In contrast with PC, however, macrophages showed high incidence of labeling for some macrophage markers LN-5 and Mac 387. These findings demonstrate that PC may be a normal constituent of the adult human brain with a variable expression of monocyte/macrophages markers and MHC class II Ag and that PC could be distinguished from resting microglia by their morphology and by their immunophenotype.

Adult↗

Clinical significance and time course of antibodies to glutamic acid decarboxylase in Japanese children with type I (insulin-dependent) diabetes mellitus.

Although anti-glutamic acid decarboxylase antibodies (GADAb) have been reported to be a useful diagnostic and predictive marker of insulin-dependent diabetes mellitus (IDDM, type 1 DM) in Caucasians, a precise analysis of GADAb in Japanese children has not been reported. We examined the clinical significance and time course of GADAb in Japanese IDDM children, who have different genetic backgrounds from Caucasians. Twenty-three of 34 (67.6%) sera from recent-onset (< 6 months) IDDM, and 16 of 49 (32.7%) sera from long-standing (> or = 2 years) IDDM patients were positive for GADAb. This prevalence of GADAb in IDDM patients was significantly higher than in normal controls and the other groups including non-insulin-dependent DM, autoimmune thyroid disease and congenital hypothyroidism, and was also significantly higher in recent-onset than in long-standing IDDM. Time course analysis suggested that autoimmune response against GAD could follow different courses in individual cases after the initiation of insulin therapy. The incidence of GADAb was significantly higher in females than in males in the older age group (11-15 years). Other clinical features including residual pancreatic beta-cell function after diagnosis were demonstrated to be similar between GADAb-positive and -negative patients. In conclusion, this study using the newly established radioimmunoassay (RIA) for GADAb revealed a high prevalence of autoimmune reactivity to GAD in Japanese IDDM children. These results, using this RIA procedure, might assist in laying the groundwork for future trials of immunomodulation therapy for IDDM in Japan.

Adolescent↗

Time-course changes of contrast enhancement in iron colloid enhanced MRI in patients with hepatocellular carcinoma.

Time-course changes in contrast enhancement of chondroitin sulphate iron colloid (CSIC), an MR contrast agent, were determined in 12 patients with 20 lesions of classical hepatocellular carcinoma (HCC). Spin echo T1 weighted (T1WI) and T2 weighted images (T2WI) were obtained before administration of CSIC and 1, 6 and 24 h after injection. The signal-to-noise ratio (SNR) in the tumour region and the liver and the tumour-to-liver contrast-to-noise ratio (CNR) were calculated, and time-course changes of these ratios were determined. SNRs for tumour before the administration of contrast medium did not differ significantly from SNRs after administration on T1WI or T2WI. SNRs for the liver on both T1WI and T2WI were significantly lower at each time point after administration than before administration. The tumour-to-liver CNRs for both T1WI and T2WI were significantly higher after administration than before administration. The maximum CNR was observed 6 h after administration on both T1WI and T2WI. The contrast enhancement was maintained for at least 24 h, with a peak at 6 h after administration. The prolonged enhancement obtained with CSIC has extended the time during which effective contrast is maintained.

Aged↗

Surgical treatment for metastatic tumors of the spine.

We report herein the results of anterior or posterior neural decompression with spinal stabilization in 16 patients with spinal metastases. Intractable back pain was relieved in 14 patients (87.5%) and 4 had complete pain relief. Neurologic recovery was observed in 8 out of 13 patients (61.5%) who had some neurologic deficits before surgery. The activities of daily living improved in 7 of 9 (77.7%), and 5 out of 8 patients (62.5%) who had been unable to walk before surgery became ambulatory after surgery. The average operation time was 3h 15 min with an average blood loss of 2150 ml. No patient died within 1 month after surgery and the median survival was 19.1 months. The results indicated that, if properly indicated, anterior or posterior neural decompression and spinal stabilization is a safe and effective treatment for patients with spinal metastases to improve the quality of life for the patients' remaining years.

Adolescent↗

[Adherent reaction among activated platelets, polymorphonuclear cells and vascular endothelial cells under thrombin stimulation or shear stress].

Platelet activation in addition to blood coagulation abnormality is regarded as a primary factor of thrombosis by atherosclerotic obstruction. Therefore, the platelet activation on atherosclerosis is considered to correlate with shear stress generated between blood cells and endothelial cells in blood flow. P-selectin on the surface of the platelet membrane is measured by flowcytometry as a marker of platelet activation. Herein, we examined the phenomena of platelet activation and adherent platelets with leukocytes (ad-P.L) on stored platelet concentration (PC) and chronic rheumatoid arthritis (RA), moreover, of the adherent platelets or polymorphonuclear cells (PMN) with endothelial cells (EC) in shear stress by using an apparatus we devised. The rate of platelet activation and ad-P.L increased in PC with storage, and the sensitivity of platelets to thrombin decreased. The rate of platelet activation and ad-P.L increased in RA in vivo. Many adherent platelets with EC were found at a low shear rate on normal EC but at a high shear rate on denatured EC without any specific adherent property. Adherent PMN with EC had several hundred times more denatured EC than normal EC and the relationship with shear rate disappeared on denatured EC. The platelet activation and relationship between platelets or leukocytes and EC as to the cause of thrombosis are important subjects for future studies.

Arteriosclerosis↗

Correlation between serum level of, and tissue positivity for, alpha-fetoprotein in hepatocellular carcinoma.

The serum level of alpha-fetoprotein (AFP) is a marker for primary liver tumors. To evaluate the relationship between the serum level of AFP and the positivity of liver tissue for this marker, specimens of liver were obtained at autopsy from patients with hepatocellular carcinoma (HCC). Tissues were fixed with formalin or Kryofix and immunostained for AFP. Serum AFP titer at autopsy was positively correlated with AFP staining in tissue fixed by Kryofix and stained with monoclonal antibody against AFP. The correlation was significant for plasma levels of AFP above 5,000 ng/ml. Results suggest that elevated serum AFP levels are an indicator of the progression of HCC.

Aged↗

Self-thyroid epithelial cell (TEC)-reactive CD8+ T cell lines/clones derived from autoimmune thyroiditis lesions. They recognize self-thyroid antigens directly on TEC to exhibit T helper cell 1-type lymphokine production and cytotoxicity against TEC.

Self-thyroid epithelial cell (TEC)-reactive CD8+ and CD4+ T cell lines were established by culturing T cells that infiltrate in autoimmune thyroiditis lesions. We investigated the properties of CD8+ T cell lines and clones in comparison with previously characterized CD4+ T cell lines/clones. Although the recognition of self-Ag by anti-TEC CD4+ T cell lines/clones required the cooperation of syngeneic spleen cells as APC, a representative CD8+ line (N4C) was stimulated with syngeneic TEC in the absence of APC. Precise analysis of MHC restriction using N4C-derived clones revealed that CD8+ clones recognize self-Ag on TEC in the context of class I MHC molecules. Most CD8+ clones were also found to express TCR with V beta specificities that were different from those observed for anti-TEC CD4+ clones. N4C cells produced IL-2, IFN-gamma, and TNF-alpha beta, but not IL-4 and IL-5 after stimulation with TEC, thus exhibiting the profile of lymphokine production similar to that expressed by CD4+ Th1 on one hand, but on the other, they showed the functional property that has not been observed for anti-TEC CD4+ clones. Namely, they elicited appreciable levels of cytolytic effects on syngeneic TEC in a short-term (4-h) 51Cr release assay. Thus, these results indicate that self-TEC-reactive CD8+ T cell lines/clones recognize Ag directly on TEC in a class I MHC-restricted way so as to exhibit various functions including the Th1-like profile of lymphokine production and anti-TEC cytolysis. The results are also discussed in terms of the nature of self-Ag presented with class I MHC molecules on TEC, as well as the potential roles of anti-TEC CD8+ T cells in the pathogenesis of thyroiditis.

Animals↗

Cerebral beta amyloid deposition in patients with malignant neoplasms: its prevalence with aging and effects of radiation therapy on vascular amyloid.

We examined immunohistochemically 123 autopsy brains from patients aged between 30 to 59, who died as a result of malignant neoplasms. Using antiserum to amyloid beta protein (A beta), we found that cerebral A beta deposits began in the subjects' fifth decade; its prevalence was 0%, 9.8% and 21.5% in the fourth, fifth and sixth decades, respectively. The major form of A beta deposition was diffuse-type plaques, although one third of the brains with A beta deposition showed amyloid angiopathy. Subpial A beta deposition is frequently associated with amyloid angiopathy. The prevalence of cerebral A beta deposits was about two times higher in the patients who had received brain radiation therapy (27.8%) compared to non-radiated patients (14.8%). Amyloid angiopathy was much more prominent (P < 0.05) with radiation therapy (22.2%) than without (8.0%). We found that cerebral A beta-deposition is dependent on aging, even in patients with malignant tumors and at beginning in their forties, and that brain radiation therapy is a possible risk factor of A beta deposition, especially in the form of amyloid angiopathy.

Adult↗

Effect of calcium antagonist, nicardipine, on cerebral blood flow in postasphyxial newborn piglets.

An experiment was carried out in nine piglets within 24 h after birth (control group: four, nicardipine group: five) for the purpose of evaluating the effects of a calcium antagonist, nicardipine, on cerebral blood flow changes induced by asphyxia neonatorum. Under respiratory control with a mechanical ventilator, the animals were exposed to hypoxia. The inspiratory oxygen level was lowered at 15 min intervals from 0.08 to 0.06 and then to 0.05. When bradycardia (heart rate; 60/min or less) was observed, 100% oxygen, adrenaline, and sodium bicarbonate were administered for resuscitation. Nicardipine was administered at a dosage of 10 micrograms/kg via bolus injection 30 min after the resuscitation. It was administered thereafter at a rate of 10 micrograms/kg per h. The cerebral blood flow was measured using a laser Doppler velocimeter. The cerebral blood flow, electroencephalograph (EEG), blood pressure, and heart rate were continuously measured for 120 min after the resuscitation. In the control group, the mean arterial pressure 35 min after the resuscitation was 60 mmHg or more. However, the cerebral blood flow was lower than the prehypoxia value in the animals with a mean arterial pressure of 75 mmHg or less. In the nicardipine group, the mean arterial pressure was lower, but the cerebral blood flow was higher than the prehypoxia value and cerebral ischemia was not induced. The mean arterial pressure 120 min after the resuscitation was 72.0 +/- 8.2 mmHg in the control group, while it was 56.7 +/- 7.5 mmHg in the nicardipine group. It was significantly lower in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rotationplasty for patients with osteosarcoma around the knee joint.

The results of rotationplasty for patients with osteosarcoma around the knee joint are presented. After an average observation period of 13.3 months, there has been no local recurrence or metastasis. The ankle joints (the new knee joints) of the patients were able to support their body weight with an average range of motion of 75 degrees. All patients could walk well without crutches and without risk of the giving way phenomenon. The average rate of the functional evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0-86.7%). No patient had psychological trouble in accepting the shortened and rotated extremity. The results show that rotationplasty is a useful reconstructive method for the treatment of osteosarcoma around the knee joint.

Adolescent↗

Pathomorphologic characteristics of small hepatocellular carcinoma: a special reference to small hepatocellular carcinoma with indistinct margins.

Some surgically resected small hepatocellular carcinoma (HCC) up to 2 cm in diameter have indistinct margins, and it is sometimes difficult to identify the margins of the cancer nodule in the resected specimen. We classified such tumors as small HCC with indistinct margins and carried out a morphological study to define their characteristics in comparison with small HCC with distinct margins as a control group. We have encountered 27 examples among 86 tumors smaller than 2.0 cm in diameter. The tumors of this type indistinctly retained the basic architecture of the background and were vaguely demarcated. Most tumors were uniformly composed of well-differentiated cancer tissue, which is characterized by increased cell density with increased nuclear/cytoplasm ratio, increased cytoplasmic eosinophilia, and irregular thin-trabecular pattern with occasional pseudoglandular pattern. Portal tracts were included within the cancerous tissue. There was a "replacing" growth pattern at the tumor/nontumor boundary. Four of the 27 lesions had a nodule-in-nodule appearance, and the inner nodules consisted of moderately differentiated HCC without portal tracts. In all of the small HCC with indistinct margins, tumor invasion into the portal vein and intrahepatic metastasis were not found. In a control group, the tumors were well-demarcated, and 53% of them were encapsulated. They were well-differentiated in 9, moderately differentiated in 38 and mixed well and moderately in 12. Tumor invasion into the portal vein and intrahepatic metastasis was found in 16 (27.1%) and 6 (10.2%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Salvage chemotherapy for recurrent Ewing's sarcomas.

Metastatic disease tends to recur after remission of Ewing's sarcoma. The effectiveness of ifosfamide in patients with recurrent Ewing's sarcoma was reported in recent years. We administered IFOS combined with etoposide, pirarubicin, and cyclophosphamide to 4 Ewing's sarcoma patients with metastatic disease, and succeeded in inducing second remissions in all cases.

Adolescent↗