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Biomedical subjects

N Baba

Publications and source records attributed to N Baba.

At least 73 records · Page 4Linked to original sources

[Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis].

Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.

Adult

The augmentative effect of a protein-bound polysaccharide (PSK) on tumoricidal activity of the soluble factor produced by a streptococcal preparation (OK-432)-activated macrophages.

The enhancement of antitumor activities of the tumoricidal soluble factor (SF) from a streptococcal preparation (OK-432)-activated macrophages by the pretreatment with a protein-bound polysaccharide (PSK) was investigated in tumor-bearing mice. Two-step stimulations with OK-432 at in vivo priming and in vitro eliciting were required for the production of the tumoricidal SF by macrophages, and the tumoricidal activity of the SF apparently correlated with the uptake of OK-432 by macrophages at priming phase. Tumoricidal activity of the SF from OK-432-activated macrophages in proteose-peptone (P-P)-pretreated mice significantly decreased with the development of the tumor, whereas in PSK-pretreated mice did not. Pretreatment of tumor-bearing mice with PSK saved a decrease in the macrophages carrying Iak or asialo GM1 antigens and an increase in wheat germ agglutinin (WGA) receptors. Furthermore, the uptake of OK-432 by macrophages at priming phase was enhanced. The tumoricidal activity of the SF from OK-432-activated macrophages was augmented. Thus, PSK may restore the depressed functions of macrophages, and the combination therapy with PSK and OK-432 may be effective to enhance the production of tumoricidal SF in tumor-bearing mice.

Adjuvants, Immunologic

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients.

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.

Administration, Oral

Venous bypass grafting for celiac occlusion in radical pancreaticoduodenectomy.

Radical pancreaticoduodenectomy was performed for cancer of the head of the pancreas in a 65-year-old male patient with congenital celiac occlusion. Preoperative angiography revealed that the arterial flow to the liver, spleen, and stomach was supplied via the pancreaticoduodenal arcade and that the dorsal pancreatic artery arose from the superior mesenteric artery. In order to perform radical pancreatectomy with sufficient clearance of lymph nodes and soft tissues around the pancreas, the celiac arterial circulation was reconstructed. The restoration of flow was effected via a saphenous vein graft between the common hepatic artery and the aorta. Postoperative angiography demonstrated patency of the graft. The patient's postoperative course was uneventful.

Adult

A tail length modifier gene discovered in the Japanese wild mice (Mus musculus molossinus).

The presence of the t haplotypes in strains derived from the Japanese wild mice (Mus musculus molossinus) was investigated. Crosses between the T/+ heterozygous short tailed mice and five normal tailed molossinus strains (MOL-ANJ, MOA, MOL-NEM, MOM and Mns) produced no tailless mice, indicating that these strains possess no t haplotype. In contrast, tailless mice were produced by a cross between the T/+ heterozygotes and a MOL-NIS strain. Mating experiments showed that the tailless character was due to an interaction between the T gene and an autosomal recessive gene carried by the MOL-NIS strain that expresses the short tail character under the homozygous condition. We have tentatively named this gene brachyury-interacting tail length modifier (btm). It remains to be investigated whether the btm gene is located in the t complex region or in the other locus.

Animals

Expression of three cell proliferation-associated antigens, DNA polymerase alpha, Ki-67 antigen and transferrin receptor in nodal and cutaneous T-cell lymphomas.

We studied the expression of three cell proliferation-associated antigens: DNA polymerase alpha, Ki-67 antigen, and transferrin receptor, in 35 T-cell lymphomas of nodal origin (T-NL) and 40 cutaneous T-cell lymphomas (CTCL). Immunohistochemical staining was carried out on frozen tissue sections of these specimens using three monoclonal antibodies, DAKO-PC, CL22-2-42B (DNA polymerase alpha), and OKT9. The proportion of cells positive for CL22-2-42B, DAKO-PC, or OKT9 among all tumor cells was correlated with four histologic subtypes: malignant lymphoma (ML), diffuse, small; mixed; large; and large cell immunoblastic in both T-NL and CTCL. A strong correlation was noted between positivity for CL22-2-42B and that for DAKO-PC or OKT9. On the other hand, no difference in the expression of these three antigens was noted between T-NL and CTCL in the high, intermediate or low grade-malignancy group. In CTCL as well as in T-NL, cells positive for CL22-2-42B, DAKO-PC or OKT9 were significantly more numerous in the high-grade group than the intermediate-grade group, and in the intermediate-grade group than the low-grade group. Furthermore, a significant correlation between survival period and the number of CL22-2-42B-positive cells was noted when the T cell malignancies, CTCL and T-NL were considered (t value = 2.015, p less than 0.05). Thus, the expression of DNA-polymerase alpha, Ki-67 antigen or OKT9 seems to well reflect the biological behavior and/or clinical prognosis of T-cell lymphoma.

Antibodies, Monoclonal

[Effects of CR1505, a CCK antagonist, on pancreatic growth in hamsters].

The effects of CR1505, a CCK antagonist, on CCK-stimulated and normal pancreas were studied in Syrian golden hamsters. The CCK-stimulated trophic effect was inhibited by CR1505 in a dose-dependent manner, in which CR1505 100 mg/kg bw resulted in a complete inhibition of the weight of pancreas, the total pancreatic protein and DNA contents, compared to the control. Otherwise, CR1505 administration in doses of 25, 50, 100 mg/kg bw alone, didn't induce any significant changes among CR1505-treated groups and the control one. However, in the dose of 200 mg/kg bw, the weight of pancreas, the total pancreatic protein and DNA contents were significantly lower than control levels, suggesting pancreatic atrophy in the hamster. It's concluded that CR1505 is an effective CCK receptor antagonist that could inhibit the CCK-induced pancreatic trophic effect. Furthermore, CR1505 administration to normal pancreas brought out pancreatic atrophy, indicating that CCK seems to play an important role in the maintenance of normal pancreatic growth in hamsters.

Animals

[Membranous glomerulonephritis probably related to bucillamine therapy in two patients with rheumatoid arthritis].

We describe here two patients with rheumatoid arthritis who developed nephrotic syndrome after administration of bucillamine, a novel antirheumatic drug developed in Japan. The nephrotic syndrome occurred after six months' and five months' treatment of bucillamine, respectively. The renal biopsy showed early phase of membranous glomerulonephritis (stage 1) in both patients. The first patient was a 64-year-old man who had received gold therapy for two years, and penicillamine therapy for eight months before bucillamine therapy. The nephrotic syndrome occurred after one year's cessation of the gold therapy and six months' cessation of the penicillamine therapy. The other patient, 57-year-old woman, had no history of gold or penicillamine therapy. Our experience suggests that membranous glomerulonephritis might occur in relation to bucillamine therapy.

Anti-Inflammatory Agents

[LAK cell adoptive immunotherapy and its problems].

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.

Aged

Renal failure with nephrotic syndrome: reversal with large doses of furosemide.

The present study documents the occurrence of renal failure in 4 nephrotic patients including 3 with minor glomerular lesions and one with membranoproliferative glomerulonephritis. One patient died of sepsis at 3 months after onset of the acute renal failure. In the remaining 3, forced diuresis employing albumin plus furosemide in increasing doses to 600 mg/day reversed the renal failure independent of corticosteroid therapy. All of the 4 patients showed characteristic findings consisting of a remarkably low fractional excretion of sodium and an unexpectedly low urine osmolality at the onset of acute renal failure, although they were rather hypervolemic. Our findings suggest that the occurrence of a low fractional excretion of sodium and low osmolality may provide a good index of an absolute indication for intensive weight reduction therapy such as high-dose furosemide in nephrotic patients with acute renal failure in order to reverse the acute renal failure.

Acute Kidney Injury

A comparative study of IgA nephropathy between two institutions in Japan and Korea.

As an approach to the geopathological evaluation of kidney disease, we conducted a comparative study on IgA nephropathy (IgANP) between Saga Medical School (SMS) in Japan and Kosin Medical College (KMC) in Korea for the period 1983-1987. The relative incidence of IgANP among primary glomerular diseases was significantly higher (P less than 0.05) at SMS (103 cases of IgANP among 250 cases of primary glomerular diseases, 41.2%) than at KMC (63 cases among 201 cases, 31.3%). Clinical and histological comparisons of the IgANP between the institutions revealed that the SMS series was generally milder than the KMC series. When the renal manifestations at the time of biopsy for all cases with primary glomerular diseases were compared, asymptomatic urinary abnormalities were more commonly found at SMS than at KMC. This suggests that certain differences in medical practice may exist between the two institutions, as follows: 1) the medical checkup system may be more efficient, 2) the accessibility to medical service may be easier, and 3) the biopsy criteria may be more liberal in Japan/SMS than in Korea/KMC. Thus, the real differences in incidence and severity of IgANP between the two institutions could be smaller than those reported here.

Adult

Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. Clinical, histopathologic, and immunohistochemical analyses.

An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which usually shows the same phenotype as CTCL, i.e., a helper/inducer T-cell phenotype (CD4+CD8-), and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. In this study, we demonstrated differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i.e., CD4-CD8-, CD4+CD8-, and CD4-CD8+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL-2R), CD71 (OKT9), HLA-DR, and HLA-DQ was higher in the skin-infiltrating ATL cells than in CTCL cells. Expression of CD29 (4B4) was high, and that of CD45RA (2H4) was low in both the skin-infiltrating ATL and CTCL cells compared with the peripheral blood and lymph node ATL cells. Expression of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotypic difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin-infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL is a disease distinct from CTCL.

Adolescent

The analysis of lymphocyte surface receptors recognized by wheat germ agglutinin for negative regulation of immune responses in cancer patients.

The population of peripheral blood lymphocytes expressing surface receptors for a lectin, wheat germ agglutinin (WGA), which has been shown to recognize the same receptors as the soluble immune suppressor factor (SISF) elaborated from suppressor cells on the lymphocyte surface, was analyzed by using fluorescein isothiocyanate-conjugated WGA on flow cytometry in cancer patients. It was found that the populations of WGA+ lymphocytes in cancer patients were significantly higher than those in either normal volunteers or patients with benign disease and increased with progress of the tumor. The populations decreased after treatment in patients who underwent curative resection of the tumor and in responders of immunochemotherapy but not in those who received non-curative surgery or in non-responders. It was suggested that the increase of receptors for SISF on the lymphocyte surface might play an important role in the negative regulation of immune responses in cancer patients and that WGA might be a useful parameter for immunosuppression.

Antigens, Surface

Interference of the induction of suppressor cells by a streptococcal preparation, OK-432 through the blocking of suppressor inducer T-cells.

The effect of OK-432 on suppressor inducer T cells in the generation of suppressor cells was investigated to determine its mechanism of action as an immunopotentiating agent. Suppressor cell activities induced by sera from patients with advanced cancer (stage III, IV or recurrence) were found to be as high as those induced by Con-A. Suppressor activity induced by Con-A or serum from cancer patients resided in CD8+ T cells, although CD4+ T-cells were required for the induction of suppressor cells. Significant increases in the CD4+2H4+ T cell population after stimulation with either Con-A or sera from the advanced cancer patients were observed when compared with stimulation by normal serum. Stimulation with Con-A induced suppressor cells as well as a significant increase of CD4+2H4+ T-cells. The presence of OK-432 during the generation of suppressor cells, however, significantly reduced the suppressor activity and apparently blocked the increase of CD4+2H4+ T-cells. Thus, it is suggested that OK-432 may interfere with the induction of suppressor cells through the blocking of CD4+2H4+ suppressor inducer T-cells.

Antibodies, Monoclonal

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer.

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.

Adult

Unresponsiveness of insulinoma cells to secretin: significance of the secretin test in patients with insulinoma.

It is well known that B cells in the pancreas release insulin when stimulated by secretin, but there have been few reports on the response of insulinoma cells to secretin. In five patients with insulinoma, changes in serum immunoreactive insulin (IRI) concentration were measured after the intravenous injection of secretin into the peripheral vein before and after extirpation of the insulinoma. The extirpated insulinomas were cultured and tested for their response to secretin. The rise in serum IRI in response to secretin in patients with insulinoma was significantly slower and smaller than in normal volunteers. After removal of the insulinoma, the response to secretin became prompt and increased with time. Cultured insulinoma cells did not release insulin when stimulated by secretin. Therefore, it is concluded that the response of insulinoma cells to secretin is quite different from that of normal beta cells, and that the function of beta cells in the insulinoma-bearing pancreas is suppressed by the autonomous hypersecretion of insulin by the insulinoma. The extent of the decrease in function of the beta cells in patients with insulinoma can be estimated by the intravenous secretin test. Thus, the secretin test is sometimes useful in the differentiation of hypoglycemia due to insulinoma from that due to beta cell hyperplasia or alimentary hyperinsulinemia.

Adenoma, Islet Cell

Treatment of cutaneous T-cell lymphomas (CTCL) with extracorporeal photochemotherapy--preliminary report.

Since August of 1988, we have treated seven CTCL patients with extracorporeal photochemotherapy, including two with tumor-stage mycosis fungoides (MF) showing mucinous degeneration, two with plaque-stage MF, and two with erythrodermatous MF. One was withdrawn just after the first trial. For each patient, the phenotypes of peripheral blood lymphocytes were analyzed by flow cytometry in terms of the percentages of OKT11, OKT3, OKT4, Leu9, OKT8, B1, Tac, OKT9, OKIa1, Leu7, Leu3a/4B4, and Leu3a/2H4 cells. These parameters were compared with the clinical responses according to skin score. The two patients with tumors died, but the five patients without tumors did not. Three of the 6 patients responded to the treatment. Side effects that are often associated with standard chemotherapy, such as bone marrow suppression, gastrointestinal symptoms and hair loss, were not observed. One cardiovascular event (1 patient) occurred. No significant changes in T-cell subsets were seen during the course of therapy. These preliminary data suggest that extracorporeal photochemotherapy may be effective for CTCL other than tumor-stage MF.

Adult

Expression of T-cell receptor (TCR)alpha chain on normal human tonsils and T-cell lymphomas.

We analyzed immunohistologically the expression of T-cell receptor (TCR)alpha chain on human tonsils and on T-cell lymphoma (T-ML) tissues using the avidin-biotin-peroxidase method. A murine monoclonal antibody alpha F1, specific for the constant region of the TCR alpha chain, was employed. On normal tonsil, alpha F1-positive cells were observed mainly in T-zones and germinal centers. In T-zones, the staining intensities varied markedly, with heavy staining evident in less than one fourth. In germinal centers, a proportion of stained cells showed a histiocytic pattern with small cytoplasmic projections. All the T-ML tissues expressed TCR alpha, whereas the staining intensities varied among cases and among lymphoma cells. No correlations were observed in the expressions of TCR alpha chain and other T-cell markers including CD3, CD4 and CD8.

Antigens, Differentiation, T-Lymphocyte