Systemic lupus erythematosus with hereditary deficiency of the fourth component of complement.
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Biomedical subjects
Publications and source records attributed to T Tsuchida.
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An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested.
Among a total of 114 cases of resected lung adenocarcinoma that were examined by sputum cytologic study before bronchoscopy, 17 were sputum cytology-positive, but had no abnormal bronchoscopic findings. In most of these cases, the reason for detection was sputum and bloody sputum (58.8 percent). Pathologically, many cases were classified as stage III A or more (82.4 percent) due to mediastinal lymph node metastases. More than 70 percent of the cases showed vascular invasion. The proportion of well-differentiated cases was also high (52.9 percent). The prognosis of these cases was worse than sputum cytology-negative adenocarcinoma without abnormal bronchoscopic findings and better than sputum cytology-positive adenocarcinoma with abnormal bronchoscopic findings. There was no significant difference between these cases and sputum cytology-negative adenocarcinoma with abnormal bronchoscopic findings. Combined with the bronchoscopic findings, sputum cytologic study is useful for preoperative evaluation of lymph node metastasis and prognosis. This combined approach can provide information necessary to perform sufficient dissection of mediastinal lymph nodes and proper adjuvant therapy in sputum cytology-positive adenocarcinoma cases, even though there are no abnormal bronchoscopic findings.
We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis.
A rare case of retroperitoneal ganglioneuroma incidentally found during an annual health examination is presented. The patient was an asymptomatic female, age 26. Physical examination and routine laboratory studies gave normal results. The plasma concentrations and 24-h urinary excretion of catecholamine and its metabolites were within the normal range. The patient was diagnosed as having a left supra-renal mass (6.3 x 3.6 cm) by abdominal ultrasonography, although by image diagnosis the paraadrenal mass could not be discriminated from an adrenal tumor. Operation was performed under the suspicion of a nonfunctioning adrenal tumor. The tumor removed was 8 x 6 x 4 cm, 98 g and was encapsulated. Histopathological diagnosis of retroperitoneal ganglioneuroma was confirmed. Forty-one cases of retroperitoneal ganglioneuroma in the Japanese literature including the present case are reviewed.
Twelve patients with supratentorial gliomas were treated with intra-arterial ACNU followed by intravenous maintenance chemotherapy. Six of the patients, treated from February 1987 through May 1989, received doses of 120-200 mg/m2 (high dose treatment group); six patients, treated from June 1989 through October 1990, received doses of 80-100 mg/m2 (low dose treatment group). The drug was given via the supraophthalmic portion of the internal carotid artery or vertebral artery at a rate of 10 mg/min. The response rate (CR + PR) on CT scan was 50% (3/6) in the high dose treatment group and 17% (1/6) in the low dose treatment group. Survival periods from first operation, however, did not differ between the high and low dose treatment groups. Bone marrow suppression was dose-related and reversible at these doses. Severe neurotoxicities (hemiparesis and aphasia) developed in the patients who received 200 mg/m2 of ACNU; in one case, this was irreversible. High dose intra-arterial ACNU chemotherapy is effective in reducing tumor size on CT scan but the prognosis is not improved. The dose limiting factor of intra-arterial nitrosourea is neurotoxicity, and doses of more than 200 mg/m2 are considered to be dangerous.
GM2 is usually significantly elevated in human melanoma cells. The lysosomal hydrolase beta-hexosaminidase A (Hex A), is an isoenzyme required for terminal GalNAc hydrolysis from intact GM2 to GM3. The objective of the present studies is to determine if the elevated levels of gangliosides, particularly GM2, correlate with the activity of Hex A in cultured melanoma cells. The Hex A activity in 13 melanoma cell lines ranged from 26%-88.3% There was a inverse correlation between GM2 nmole/g and Hex A activity (r = -0.48; p less than 0.003). An inverse correlation (p less than 0.03) occurred between GD2 nmole/g and Hex A activity. There was an inverse correlation (r = -0.53; p less than 0.05 and r = -0.51; p less than 0.05, respectively) between the ratio of substrate/product (GM2/GM3) and (GD2/GD3) and Hex A activity. These results indicate that the level of GM2 in melanoma is inversely correlated with the level of activity of Hex A.
Glutathione (GSH) and Glutathione S-transferase (GST) plays an important role in the protection of cells against damage from free radicals and also influences cytotoxicity to some kinds of chemotherapeutic agents. GST comprises a group of abundant and widely distributed catalytic and binding proteins that facilitate the conjugation of GSH with the electrophilic center of a large spectrum of hydrophilic molecules. Multiple GST isozymes in mammalian tissues arise from dimeric combination of a number of distinct subunits grouped into three major classes: alpha (alpha), mu (mu), and pi (p). We report the total GST, GST-p activity and GSH content of human brain tumors, C6 rat glioma cells and drug resistant C6 cells. The values of total GST activity in 42 normal brain and brain tumors were quantitatively analyzed. Total GST activity was 92.6 +/- 25.1 units (mean +/- standard deviation) in 8 samples of normal brain tissues, 126 +/- 58.8 units in five grade II or III astrocytomas (154 +/- 63.3 units in grade II astrocytomas, 84.4 +/- 2.7 units in 2 grade III astrocytoma), 66.2 +/- 29.3 in 5 glioblastoma cases, 94.7 +/- 47.7 units in 3 metastatic tumors, 302 +/- 114 unit in 8 meningiomas and 213 +/- 90.4 units in 3 neurinomas. Differences of GST activity between glioblastomas and meningiomas, grade II or III astrocytomas and meningioma, in normal brain tissues and meningioma were statistically significant (p < 0.01). The difference between normal brain tissues and benign tumors (meningiomas and neurinomas), gliomas and benign tumors were also statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
High tibial osteotomy (HTO) was performed on 86 medially osteoarthritic knees in 78 patients. Twelve patients died during the follow-up period. Fifty-six knees of 51 patients were evaluated twice postoperatively: once at six years after surgery and again after ten to 15 years. Results were satisfactory in 88% of the knees at the six-year follow-up evaluation and in 63% at the post-ten-year follow-up evaluation. Ten-year follow-up results significantly deteriorated. The femorotibial angle (FTA) at the time of bone union after HTO was a significant factor that contributed to the ten-year results. In patients maintaining excellent improvement of knee function at the post-ten-year follow-up evaluation, the mean FTA at one year after surgery was 165 degrees; this value was constant through ten years after HTO. An FTA of 164 degrees-168 degrees should be attained to ensure favorable long-term results in HTO.
The protein kinase C (PKC) family of serine-threonine kinases has been implicated in the regulation of a variety of signaling cascades. One member of this family, eye-PKC, is expressed exclusively in the Drosophila visual system. The inaC (inactivation-no-afterpotential C) locus was shown to be the structural gene for eye-PKC. Analysis of the light response from inaC mutants showed that this kinase is required for the deactivation and rapid desensitization of the visual cascade. Light adaptation was also defective in inaC mutant flies. In flies carrying the retinal degeneration mutation rdgB, absence of eye-PKC suppressed photoreceptor cell degeneration. These results indicate that eye-PKC functions in the light-dependent regulation of the phototransduction cascade in Drosophila.
We examined the fine structure of rat folliculo-stellate (FS) cells of the anterior pituitary and pituicytes of the neural lobe using immunoelectron microscopy for S-100 protein. The study proves that S-100 protein is solely expressed in the FS cells and pituicytes. However, the ultrastructural differences between these two cell types demonstrated in this study may argue against the hypothesis that the FS cells and the pituicytes have a common origin.
This report evaluates the relevance of the ratio of the melanoma-associated ganglioside, GD3, and its precursor, GM3, to prognosis and management of Stage II disease. Tumor biopsy specimens from 42 melanoma patients were examined for the ratio and found that GD3 and GM3 constitute 80% of the total lipid bound sialic acids (LBSA) of melanoma. Although the ratio of GM3:GD3 in melanocytes, the progenitors of melanoma, is 19:1 (based on %LBSA), it ranged from 15:1 to 1:5 in tumor biopsy specimens. Patients are categorized into three groups based on their GM3:GD3 ratio (%LBSA) of tumor tissues as Group I (ratio ranged from 15:1 to 1.5:1) (10 of 42), Group II (1.4:1 to 1:1.4) (13 of 42), and Group III (1:1.5 to 1:5) (19 of 42). When the overall survival of patients from the onset of Stage II disease was evaluated among different groups, patients belonging to Group I survived significantly longer than patients of Group II (P = 0.02) and Group III (P = 0.01). Interestingly, Group III expressed immunogenic gangliosides (GD2, GM2, and O-AcGD3) better than the other groups and may benefit more from therapies targeted against these gangliosides antigens. The results of this study indicate that GM3:GD3 ratio is an unusual but well-defined biochemical criteria that may be useful for prognosis and therapeutic management of the disease. Therefore, we propose a routine analysis of the GM3:GD3 ratio of tumors excised after surgery. Screening the ratio is feasible since melanoma expresses a simple profile of gangliosides unlike other forms of cancer.
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T cell growth factors such as interleukin-2 (IL-2) and interleukin-4 (IL-4) act as potent comitogenic factors for purified human T cells in the presence of phorbol myristate acetate (PMA). We investigated the effects of gangliosides on the IL-4-driven or IL-2-driven proliferation of human T cells, using these comitogenic assays. Bovine brain gangliosides inhibited the proliferation of human T cells activated by PMA + IL-4 or PMA + IL-2. These inhibitory effects were dose and time-dependent and were significant at concentrations higher than 50 microM. PMA + IL-2 stimulation was more sensitive to the inhibitory effects of gangliosides (I50 = 77.2 microM) than PMA + IL-4 stimulation (I50 = 105.9 microM). Differential inhibitory effects were also examined among the panel of various gangliosides. GD1b and GT1b showed the most potent inhibitory actions in each assay; the inhibitory effect of GD1a was somewhat less potent than GD1b or GT1b. GM2 and GD3 were only weakly inhibitory, and the inhibitory effect of GM3 was almost negligible. These findings suggest that gangliosides may play an immunomodulatory role by interfering with IL-4 or IL-2-driven proliferation of human T cells.
A patient with neurofibromatosis developed neurofibrosarcoma (NFS). The tumour was composed of spindle-shaped cells with atypical nuclei arranged in a fascicular or sheet-like fashion. The tumour cells had discontinuous basement membrane-like structures and were positively stained with the monoclonal antibody against S100 protein alpha chain. Both the primary tumour and its cultured cells contained GM3 and GD3 as major gangliosides. The ganglioside pattern of the primary tumour corresponds to that of NFS in our previous study. In the cultured NFS cells, the relative amount ratio of GM3 to GD3 is almost reversed compared to that of the primary tumour. This reversion may reflect some environmental influence on the ganglioside metabolism of NFS.
Immune responses to hepatitis B virus (HBV) vaccine in six low- or non-responded health-care workers were tested with an intradermal low dose (5 micrograms) of the recombinant vaccine. The injection was repeated three or four times at fortnightly intervals. These successive doses of the vaccine induced a high concentration of antibodies with delayed-type hypersensitivity (DTH) skin reactions in all six subjects. A few minor temporary side effects, such as irritation and itching at the injection site, were reported by some of the vaccinees. The results suggest low-dose of intradermal HBV vaccinations for low- or non-responders are safe and readily effective.
T and B cell functions were evaluated in eight patients with myelodysplastic syndrome (MDS). We studied the response to stimulation with phytohemagglutinin, concanavalin A, and anti-CD3 monoclonal antibody (OKT3 mAb), and found impairment of response in T cells from MDS patients in comparison with age-matched controls. The decreased proliferative response was not restored by combining normal T cells with monocytes from MDS patients, or by using T cells from MDS patients together with normal monocytes. Furthermore, proliferative responses in the autologous and allogenic mixed lymphocyte reactions were significantly decreased in MDS patients. B cells from MDS patients incorporated significantly less tritiated thymidine than B cells from controls when stimulated with Staphylococcus aureus Cowan I (SAC), and SAC stimulation failed to cause efficient immunoglobulin production by MDS B cells. However, T cells from MDS patients reacted normally when stimulated by phorbol myristate acetate plus a Ca2+ ionophore (ionomycin). Abnormal lymphocyte function may contribute to the failure of hematopoietic regulation and may thus play an important role in the pathogenesis of MDS. The finding that the addition of specific signals allowed the stimulation pathway to function may have important therapeutic implications.