Search PubMedSearch

Biomedical subjects

N Baba

Publications and source records attributed to N Baba.

At least 37 records · Page 2Linked to original sources

[A case of polyarteritis nodosa who developed rapidly progressive glomerulonephritis and presented with a tumor-like shadow on head CT in the remission stage].

A 70-year-old woman was admitted to our hospital because of weight loss, fever of unknown origin and rapid deterioration of renal function. Polyarteritis nodosa was diagnosed based on the findings of fever, weight loss, thrombocytosis, arthralgia and crescentic glomerulonephritis with vasculitis in the kidney biopsy specimens. Renal function progressively deteriorated and the patient underwent peritoneal dialysis (PD). Methylprednisolone pulse therapy and subsequent oral prednisolone (PSL) therapy combined with cyclophosphamide (CY) was instituted. Renal function gradually recovered and PD was discontinued 2 weeks later. She was discharged after about 2 months of hospitalization and received a monthly follow-up with daily administration of 10mg of PSL and 25mg of CY. Six months after discharge, PN activity was well controlled by PSL and CY, but mental disturbance gradually developed and head CT disclosed a low-density mass shadow that was enhanced with a ring-like appearance by contrast medium similar to a brain tumor. The follow-up CT did not show any enlargement of the mass shadow. One year later, the patient died of uremia and concomitant dementia. Autopsy disclosed cerebral infarct in the relevant site of the mass on CT and the healed stage of angitis in other tissues.

Acute Disease

Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.

An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which shows almost the same phenotype as CTCL, ie, a helper/inducer T-cell phenotype (CD4-positive, CD8-negative), and usually involves the skin. This article describes differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant physical findings were lymph node, bone marrow and skin involvement, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, in contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was shown. The predominant phenotype of the neoplastic cells in the skin of patients with CTCL was CD3+, CD4+, CD29+, CD45RO+, HLA-DR+, HLA-DQ+, CD7-, L-selectin-, and CD45RA-. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25, and HLA-DR. That is, the predominant neoplastic cell phenotype was helper T-cell, which was CD3+, CD4+, L-selectin+, CD25+, CD45RA+, HLA-DR+, CD29-, and CD45RO- in peripheral blood, and CD3+, CD4+, L-selectin+, CD29+, CD45RO+, HLA-DR+, and CD45RA- in the skin and lymph nodes. Phenotypic heterogeneity of ATL cells and heterogeneity of CD45R isoform expression on ATL cells were evident in different organs. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL. CTCL cells do not share the same phenotype as ATL cells.

Adult

[A case of membranoproliferative glomerulonephritis due to type II cryoglobulinemia probably associated with hepatitis C virus infection].

In recent years, several laboratories have suggested that chronic hepatitis C virus (HCV) infection is strongly associated with type II cryoglobulinemia (CG) and/or membranoproliferative glomerulonephritis (MPGN). We report here a case of MPGN due to type II CG probably associated with chronic HCV infection, and discuss the pathogenesis and treatment of such cases. A 60-year-old-female was referred to us from a local hospital because of progressive peripheral edema, purpura on the lower limbs, pleural effusion, ascites, hypertension, and renal failure. Laboratory findings indicated proteinuria, abnormal urinary sediments, normochromic normocytic anemia and azotemia. Other laboratory findings included positive rheumatoid factor, elevated serum IgM, hypocomplementemia and elevated circulating immune complexes. Cryoglobulin was detected and found to consist of a mixture of a monoclonal IgM kappa with polyclonal IgG. Renal biopsy showed MPGN. These observations suggested a close association between MPGN and type II CG. We did not find any causes of type II CG except for positive HCV antibody and HCV RNA. Therefore, we made the diagnosis of type II CG associated with chronic HCV infection. Symptoms related to CG was responsiveness to steroid, but development of liver dysfunction developed. Treatment with alfa-interferon (alpha IFN) was added and thereafter, the liver dysfunction improved. However, the serum Cryo level was not reproducibly lowered. While in this case it was unclear whether IFN therapy was beneficial, several reports in addition to the findings of this case suggest a close relation between HCV infection and type II CG and MPGN.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryoglobulinemia

Inhibitory effects of a cholecystokinin antagonist, loxiglumide (CR-1505), on the growth of freshly separated and xenografted human pancreatic cancer.

The effects of cholecystokinin (CCK) and a CCK antagonist, loxiglumide (CR-1505), on four freshly separated and six xenografted human pancreatic cancers, were investigated. The level of DNA synthesis in only one of five tested pancreatic cancers was enhanced by CCK at concentrations of 0.01-10 nM, while in the other four cancers DNA synthesis was not affected. The levels of DNA, RNA, and protein synthesis (by 3H-thymidine, 3H-uridine, and 3H-leucine incorporation tests, respectively) in all the tested cancers were dose-dependently inhibited by loxiglumide at concentrations of 20-2000 microM, and the IC50 of loxiglumide for DNA synthesis in pancreatic cancers was 156 +/- 80 microM (means +/- SD). The in vivo effect of loxiglumide was assessed using a xenografted line (PC-HN) transplanted in nude mice. The in vivo 50% lethal dose of loxiglumide for nude mice was about 500 mg/kg. Death was caused by respiratory failure due to severe congestion of the lung after the administration of a large dose of loxiglumide. The growth of a PC-HN transplanted in the nude mice was significantly inhibited by subcutaneous loxiglumide at 250 mg/kg, twice a day for 28 days, which did not cause death. It is suggested that loxiglumide inhibits the in vivo and in vitro growth of human pancreatic cancer, perhaps independently of its action as a CCK antagonist, and this study also suggests that loxiglumide may be a new type of therapeutic agent to be used for the treatment of human pancreatic cancer.

Animals

Effects of hypercholesterolemia on initial and chronic phases of rat nephrotoxic serum nephritis: development of focal segmental glomerulosclerosis, analogous to atherosclerosis.

The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5-6 (3.4 +/- 1.4 in Group 1 against 6.3 +/- 1.0 in Group 2; p < 0.01) as well as at days 21-28 (5.5 +/- 2.6 in Group 1 against 10.9 +/- 2.8 in Group 2; p < 0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14 +/- 10 in Group 1 against 73 +/- 17 in Group 2; p < 0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Evidence for 5-HT2 receptor involvement in the stimulation of preovulatory LH and prolactin release and ovulation in normal cycling rats.

The participation of serotonin (5-HT) in the control of LH secretion and ovulation has been reported in numerous pharmacological experiments, although the results have been contradictory. In this study to determine the physiological involvement of 5-HT2 receptors in the control of preovulatory LH and prolactin (PRL) release and ovulation, ketanserin (KET), a selective 5-HT2 receptor antagonist, was administered to normal cycling rats. Oral administration of KET at 10 mg/kg BW between 0900h and 1300h on the day of proestrus completely blocked ovulation, while the administration after 1500h did not. The ovulation was confirmed 2 days after treatment with KET. There was no consistent effect on the number of ova ovulated. Co-administration of KET with 5-methoxy-N,N-dimethyltryptamine (5-MeDMT), a 5-HT agonist, at a dose of 2 mg/kg BW ip reversed KET-induced inhibition of ovulation. The highest rate (89%) of reversal was obtained by co-administration at 1500h. KET administered at 1100h completely blocked the preovulatory surge of LH and PRL observed in control animals at 1800h. The present study suggests that 5-HT stimulates preovulatory LH and PRL surge and ovulation via 5-HT2 receptor under physiological conditions and that the effect of 5-HT depends on the critical period and the 24-hour periodicity.

Animals

Serotonin stimulates steroidogenesis in rat preovulatory follicles: involvement of 5-HT2 receptor.

The role of serotonin (5-HT) in the regulation of steroidogenesis in the ovary via 5-HT2 receptor was studied in normal cycling rats and their preovulatory follicles. Oral administration of ketanserin (KET), a selective 5-HT2 antagonist, at 10 mg/kg BW at 1100h on the day of proestrus resulted in a marked decrease in serum estradiol levels immediately after the administration. 5-HT stimulated estradiol secretion by preovulatory follicles incubated for 5 hrs in Krebs-Ringer bicarbonate buffer. 5-HT (2.5 microM) -enhanced estradiol secretion was inhibited by KET (1-100 microM) in a dose-dependent manner. Secretion of progesterone and testosterone was also inhibited by about the same order of magnitude as estradiol. Addition of pregnenolone (1 microgram/ml) prevented the KET-inhibited progesterone production. Both testosterone and estradiol increased at the same ratio by the addition of progesterone (1 microgram/ml). The inhibition of secretion of these hormones was overcome by dbcAMP (0.1 mM). The present study suggests that 5-HT stimulates steroidogenesis in the metabolic pathway prior to pregnenolone in rat preovulatory follicles and the action of 5-HT could possibly be mediated by a 5-HT2 receptor.

Animals

Successful treatment of adult T-cell leukemia/lymphoma with MACOP-B, M-FEPA and VEPP-B combination chemotherapy.

A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 x 10(4) cells/mm3. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.

Antineoplastic Combined Chemotherapy Protocols

A case of cutaneous B-cell lymphoma with a storiform stromal reaction.

A case of cutaneous B-cell lymphoma is described. The patient was treated only by surgical excision of the skin tumors five times during a period of about two years from February of 1984 to October of 1986. After the last surgical excision, a continuous disease-free period was achieved. Biopsy samples showed dense lymphocytic infiltrations with discrete masses in the dermis and subcutis; one of them showed a storiform pattern. At the time, the infiltrating cells were composed of medium and large lymphoid cells and spindle-shaped cells. The medium and large lymphoid cells were positive for CD20, CD22 and HLA-DR and negative for CD3, CD4, CD5, CD8, CD43, and kappa and lambda light chain. The spindle-shaped cells were negative for CD20, CD43, kappa and lambda light chain, lysozyme, and S-100 protein.

Adult

A case of cutaneous B-cell lymphoma treated successfully with MACOP-B.

A case of cutaneous B-cell lymphoma successfully treated by MACOP-B therapy is described. The patient was a 43-year-old man with reddish tumors measuring 3 to 7 cm in diameter on the right cheek and the post-auricles. Histopathologically, massive infiltrations of medium-sized atypical lymphoid cells were found in the reticular dermis and subcutis. A clear zone beneath the epidermis was also detected. The atypical lymphoid cells were positive for CD19, CD20, CD22 and HLA-DR but negative for CD3, CD4, CD5, CD10, CD43, CD45RO and CDw75. The patient was treated successfully with the MACOP-B protocol from March of 1990 to May of 1990. Since April of 1990, he has been free of disease.

Adult

Cutaneous B-cell lymphoma--a clinical, pathological and immunohistochemical study.

Eleven cases of cutaneous B-cell lymphoma (CBCL) were studied. The ages at presentation ranged from 34 to 79 years (mean = 59.9 years). Six patients were female and five male. Five of the 11 patients had a solitary tumour and the other six had multiple tumours at initial presentation. According to Burg's classification, six cases were at stage I, two stage II, two stage III and one was at stage IV at initial presentation. Abnormalities in laboratory data were rare, except for serum lactic dehydrogenase values. Epidermotropism was not detected, and the area mainly affected by neoplastic cells was the reticular dermis (seven cases) and subcutis (four cases). Biopsy specimens from the patients analysed by immunohistochemical techniques on paraffin or cryostat sections showed CD20 and/or CD22 positivity. Biopsy specimens from two patients which showed CD10 positivity were diffuse large cell types by the working formulation and presented as pre-B-cell lymphoma. At least two groups of CBCL were demonstrable on the basis of prognosis. One was a benign low-grade lymphoma presenting with solitary tumours, mature B-cell markers and intermediate-grade pathology, and the other was a high-grade lymphoma with multiple tumours, pre-B-cell or mature B-cell markers and a poor prognosis.

Adult

Effects of antihypertensive drugs on the progress of renal failure in hyperlipidemic Imai rats.

Hyperlipidemic Imai rats spontaneously develop hypercholesterolemia, proteinuria and glomerulosclerosis. The aim of the present study was to clarify whether two different antihypertensive regimens (enalapril and a combination of reserpine, hydralazine and hydrochlorothiazide) would offer similar degrees of protection against glomerular injury in male hyperlipidemic Imai rats. Group 1 (n = 4) received no specific therapy. Group 2 (n = 4) was treated with enalapril at a dose of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) was treated with the triple drug regimen (reserpine 5 mg/l, hydralazine 80 mg/l and hydrochlorothiazide 25 mg/l in drinking water). Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were checked and compared among groups. Although enalapril and triple drug therapy were almost equally effective in controlling systemic hypertension, there were striking differences between the two treated groups in proteinuria, hypercholesterolemia and glomerular injury. Enalapril treatment significantly reduced proteinuria (731 +/- 23 vs. 256 +/- 144 mg/kg/day at 36 week; p < 0.005) and hypercholesterolemia (264 +/- 17 vs. 104 +/- 17 mg/dl at 38 weeks; p < 0.001). Triple drug therapy failed to prevent the development of proteinuria (909 +/- 75 mg/kg/day at 38 weeks) and hypercholesterolemia (330 +/- 61 mg/dl at 38 weeks). The glomerulosclerosis index was significantly higher in untreated control rats (229 +/- 65) and in triple drug-treated rats (218 +/- 59) than in the enalapril-treated group (24 +/- 12; p < 0.05, and p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Castration attenuates proteinuria and glomerular injury in hyperlipidemic male Imai rats.

Hyperlipidemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. We investigated the effect of castration on spontaneous proteinuria and progressive renal injury in male Imai ats. Male Imai rats (n = 16) were castrated at 5 weeks of age. Body weight, blood pressure, urinary protein excretion and serum constituents were checked and compared with sham-operated control rats (n = 16) up to 24 weeks. Sham-operated group 1 (n = 5) and castrated group 2 (n = 6) underwent morphological study after 16 weeks of observation and sham-operated group 3 (n = 11) and castrated group 4 (n = 10) were followed for an additional 8 weeks and used for morphological study. Growth rate was significantly stunted in castrated rats as compared with the controls. Castration significantly reduced proteinuria almost throughout the experiment (167 +/- 84 vs. 46 +/- 24 mg/kg/day, p < 0.001, at 8 weeks and 688 +/- 211 vs. 458 +/- 97, p < 0.01, at 20 weeks). The glomerulosclerosis index was significantly higher in sham-operated control rats than in castrated rats (28.8 +/- 18.0 vs. 7.3 +/- 3.1, p < 0.01, at 16 weeks, and 92.1 +/- 35.5 vs. 39.5 +/- 8.9, p < 0.001, at 24 weeks). There were no significant differences in blood pressure, serum cholesterol, plasma renin activity, plasma somatomedin C levels between the two groups. These results raise the possibility that sex hormones may partly contribute to spontaneous proteinuria and progressive renal injury in male Imai rats.

Animals

Effects of an angiotensin II receptor antagonist on the progression of renal failure in hyperlipidemic Imai rats.

This study was undertaken to determine the role of angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in drinking water. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were measured and compared among the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost equally effective in controlling systemic hypertension. Each treatment significantly reduced proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and p < 0.01, respectively). Hypercholesterolemia also decreased (82 +/- 4 and 89 +/- 6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 +/- 26) than in the enalapril-treated rats (2 +/- 3; p < 0.005) and the high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists

[Lymphomas of the skin].

Malignant lymphoma of the skin is a type of extranodal lymphoma, in which the main organ involved is the skin, and 80-90% of cases in Japan show a T-cell phenotype. Mycosis fungoides (MF) and Sézary syndrome (SS) are common T-cell lymphomas of the skin with a benign prognosis. Therefore, various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA) and interferons, have been indicated for the low-risk group (stages I A, I B and II A), whereas electron-beam irradiation, retinoid plus interferon (IFN), photopheresis and deoxycoformycin (DCF) plus IFN have been indicated for intermediate-risk group (stages II B and III). The cutaneous involvement of B-cell lymphoma has been considered an unmistakable sign of progression and dissemination of lymphoid disease, and is thus associated with a poor prognosis. However, some primary cutaneous B-cell lymphomas (CBCLs) show a benign prognosis, and electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). However, the prognosis of high-risk group CTCL (stage IV) and cutaneous B-cell lymphoma (CBCL) (stages III and IV) is poor. Therefore, an effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-Cyta BOM is required for patients with advanced-stage CTCL and CBCL. With regard to age at the time of the first medical examination, patients with CTCL or CBCL at an advanced stage have a tendency to be older. Therefore, a mild but effective therapy, such as DCF plus IFN is recommendable.

Antineoplastic Combined Chemotherapy Protocols

Castration attenuates proteinuria and glomerular injury in unilaterally nephrectomized male Sprague-Dawley rats.

BACKGROUND: To clarify the pathogenesis of focal and segmental glomerulosclerosis, we investigated the effect of castration on the development of proteinuria and glomerulosclerosis in unilaterally nephrectomized male Sprague-Dawley (SD) rats. EXPERIMENTAL DESIGN: At 5 weeks of age, group 3 was castrated, whereas groups 1 and 2 were sham-operated. At 6 weeks of age, groups 2 and 3 received unilateral right nephrectomy and group 1 received sham-operation. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, blood urea nitrogen and serum creatinine were checked every 2 months from 2 through 12 months after right nephrectomy. Control group 1, Nx (nephrectomized) group 2 and castrated (nephrectomized + castrated) group 3 underwent morphologic study 6 months after nephrectomy. In an additional experiment, control group 4, Nx group 5, and castrated group 6 were followed for an additional 6 months and used for morphologic study. RESULTS: Growth was significantly stunted in the castrated rats as compared with control and Nx rats. Nx rats became proteinuric with age. Castration significantly reduced the proteinuria after 2 months of nephrectomy throughout the experiment. The proteinuria in castrated rats tended to decrease as compared with the controls. The glomerulosclerosis index was significantly higher in Nx rats than in either the controls or the castrated rats. The three groups showed no significant differences in blood pressure, plasma renin, activity and plasma aldosterone concentration. CONCLUSIONS: These observations suggest that sex hormones may contribute to the development of proteinuria and glomerulosclerosis in unilaterally nephrectomized male SD rats.

Animals