[Tumor-specific immunotherapy model utilizing virus-reactive helper T-cell activities].
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Biomedical subjects
Publications and source records attributed to T Hamada.
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Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) and tropical spastic paraparesis belong to a new group of neurological diseases associated with retroviral infection. An HTLV-I-like virus has recently been implicated in multiple sclerosis as well. We studied paired cerebrospinal fluid and serum specimens from HAM and multiple sclerosis patients by isoelectric focusing and an isoelectric focusing HTLV-I p24 overlay technique to clarify the role of HTLV-I in these diseases. We detected oligoclonal bands by isoelectric focusing with silver-staining in cerebrospinal fluid, but not serum, from all 5 HAM and all 9 multiple sclerosis patients. An isoelectric focusing HTLV-I p24 overlay technique demonstrated anti-p24 antibody in HAM cerebrospinal fluid at a different pI distribution than that seen in paired serum, indicating local synthesis of anti-p24 antibody within the central nervous system. Oligoclonal bands in HAM cerebrospinal fluid corresponded in pI distribution to anti-p24 antibody activity, suggesting the presence of an ongoing HTLV-I infection in the central nervous system. Multiple sclerosis patients had no evidence of anti-HTLV-I activity by p24 radioimmunoprecipitation assay, Western immunoblots, or isoelectric focusing HTLV-I p24 overlay analysis. Our data support a role for HTLV-I as an etiological agent in HAM, but not in multiple sclerosis.
Tissue distribution of type V collagen in normal human skin was studied using an indirect immunofluorescent technique to determine whether type V collagen is present in the interstitium or in the basement membrane. Type V collagen was isolated from the human placenta by pepsin digestion and was purified with fractioning salt precipitations. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that type V collagen contained alpha 1(V) and alpha 2(V) chains, but not the alpha 3(V) chain. Specificity of the rabbit antibodies to type V collagen was assessed using enzyme-linked immunosorbent assay (ELISA) and an immunoblotting method. Antibodies showed no cross-reactivity to other collagens, laminin, and fibronectin. With an indirect immunofluorescent technique, type V collagen was found to be widely distributed throughout the dermis. Intense fluorescent staining was noted in the papillary dermis and adnexal dermis surrounding hair follicles and eccrine glands. The basement membrane of the dermoepidermal junction, skin appendages, and capillaries was not stained. By indirect immunoperoxidase double staining, type V collagen was not found to be deposited on type IV collagen present in the basement membrane. Immunoelectron microscopic studies showed that type V collagen was not located in the basal lamina. These results suggest that type V collagen is distributed in the interstitium, but not in the basement membrane of normal human skin.
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Three kittens underwent unilateral removal of the lateral suprasylvian area of cortex at the age of 1 month. After normal rearing for two years, their monocular optokinetic nystagmus was studied. During the experiment one eye was 'seeing' the optokinetic stimulus, but the other eye was 'covered'; by implanting scleral coils on both eyes, we measured movements not only in the 'seeing' eye, but also in the 'covered' eye. The stimulus was moved at a velocity between 1 and 40 degrees/s. Additionally, movements of the both eyes were simultaneously recorded in a normal cat. The previous results on movements of both eyes in normal cats which had been derived from the recordings by one coil (Vision Res., 26: 1311-1314, 1986) were confirmed by this experiment and were compared with the results of the lesioned cats. The gains (slow phase velocity/stimulus velocity) of the 'seeing' eye were not significantly different from the normal values. However, the gains of the 'covered' eye were significantly higher than the normal values when the stimulus was presented in the temporonasal direction, at the velocities between 1 and 40 degrees/s to the eye ipsilateral to the lesion and at the velocity of 40 degrees/s to the eye contralateral to the lesion; in the other conditions of stimulation the gains were not significantly different from the normal values.
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Human, guinea pig and rat sera or plasma protein binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl)benzimidazole difumarate (KG-2413) were investigated by equilibrium dialysis. There were pronounced interspecies differences in binding affinity and binding capacity which were the highest in guinea pig and human species, respectively. In humans, the binding index (n1P1/Kd1) of isolated alpha 1-acid glycoprotein (alpha 1-AG) was seven times higher than that of isolated albumin, and the dissociation constant for human serum at the high affinity binding site was comparable to that for alpha 1-AG. These facts suggested that the free base of KG-2413 was mainly bound to alpha 1-AG in human serum. The contribution of albumin to the binding of KG-2413 in guinea pig and rat plasma may be relatively small. The interspecies differences in KG-2413 binding observed in this study may be due to species differences in the binding affinity and/or capacity of alpha 1-AG.
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99mTc-HSA-D has been developed as a new blood pool scanning agent. Clinical comparison of 99mTc-HSA-D and 99mTc-HSA was made in 16 cases. The activity concentration of 99mTc in blood was measured during 2 hours after the injection in five cases. 99mTc-HSA-D showed higher concentration compared to 99mTc-HSA with the passage of time. Quantitative analysis of contrast between left ventricle and septum was performed on end diastolic frames of gated images 10 minutes after the injection. There was no obvious difference between 99mTc-HSA-D and 99mTc-HSA. The subjective comparison of detectability of lesions between the two agents was performed on three directional gated images. 99mTc-HSA-D was superior to 99mTc-HSA, because the images of the latter deteriorated with the passage of time. On anterior view images 1 hour after the injection, left ventricle/lung and abdominal aorta/background count ratios were greater for 99mTc-HSA-D in many cases. There was no obvious difference in liver/background and kidney/background count ratios between the two agents. Urinary excretion of 99mTc was considerably lesser for 99mTc-HSA-D. The results indicated that 99mTc-HSA-D was superior to 99mTc-HSA for cardiac blood pool imaging.
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Anti-type I and type III collagen polyclonal antibodies and anti-type III collagen monoclonal antibodies were produced using type I and type III collagen extracted from the human placenta. An indirect immunofluorescence technique using these antibodies showed the same distribution of type III as well as type I collagen in the entire dermis of the normal human skin in nearly identical patterns. Previous immunofluorescent study indicated that type III collagen is present predominantly in the papillary dermis. However, our observation that monoclonal antibody recognizing the helical portion of type III collagen reacted with the entire thickness of the dermis which suggested the presence of type I and III collagen in close proximity in the whole thickness of normal human dermis.
Between 1958 and 1985 (28 years), 53 cases of uterine sarcoma were seen at the Cancer Institute Hospital. Their cytological examination produced the following findings: 1) The positive rate in preoperative cytologic diagnostic tests was a low 21.7 percent for pure sarcoma and 70.0 percent for mixed mesodermal tumor. 2) The preoperative cytologic diagnosis and the final histologic diagnosis agreed in only 13.0 percent of pure sarcoma and 16.7 percent of mixed mesodermal tumor cases. 3) About one-half of the cases of mixed mesodermal tumor were diagnosed preoperatively as adenocarcinoma. 4) The positive rate in the cytologic diagnosis and the clinical stage were not correlated. 5) The positive rate in the cytologic diagnosis was high in cases of intracavity growth type sarcoma, but all cases of intramuscular localized type sarcoma were negative.
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