Genetic variation at the lipoprotein lipase gene associates with coronary arteriosclerosis.
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Biomedical subjects
Publications and source records attributed to K Oka.
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The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients. Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P less than 0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects. Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance.
We report the management of a patient with chronic idiopathic thrombocytopenic purpura and severe aortic valvular disease. Preoperative intravenous high-dose gamma-globulin administration was employed, and aortic valve replacement combined with splenectomy were performed during the same operation. The platelet count at admission was 34,000/mm3 and increased to 146,000/mm3 after the gamma-globulin therapy. Platelet transfusion at the end of the cardiopulmonary bypass was considered no longer necessary in the postoperative period, because the platelet count increased quickly after the procedure. The postoperative course was uneventful. We believe that open heart surgery and splenectomy can successfully be performed simultaneously in a patient with chronic idiopathic thrombocytopenic purpura treated with high-dose gamma-globulin therapy.
Diuretic properties of a synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and a naturally occurring arctigenin were examined in BALB/c male mice and Wistar male rats. Intra peritoneal administration of hattalin (50 mg/kg) in mice increased urine volume by 1.7-3.1 fold that of placebo-treated animals 40-260 min after administration (p less than 0.05 vs control). In contrast, 100 mg/kg of arctigenin had no effect on urine volume in mice. Hattalin (100 mg/kg), arctigenin (100 mg/kg), or furosemide (50 mg/kg) as a positive control was administered orally to rats, and accumulated urine volume was measured for up to 6-12 h. The urine volume of animals administered with hattalin showed 1.4-1.5 fold that of placebo-treated animals after 2-6 h of administration (P less than 0.05, n = 10). On the other hand, arctigenin showed no significant effect on urine volume for up to 12 h after administration (n = 8). The urine volume in animals administered with furosemide (n = 10) was 2.0-3.0 fold that of placebo-treated animals (P less than 0.01). Furosemide increased total Na+, K+, or Cl- excretion by 1.9, 1.8 or 2.2 fold, respectively, when compared with placebo-treated controls (P less than 0.01), whereas hattalin decreased Na+ excretion by 3.6 times (P less than 0.01), K+ excretion by 1.4 times (not significant), and Cl- excretion by 3.1 times (P less than 0.01). Serum Na+ and K+ levels did not change in both furosemide- and hattalin-administered rats, however, serum Cl- levels in these animals significantly decreased (P less than 0.01) when compared with controls. The results suggest that the diuretic property of hattalin is due to a novel mechanism which is different from that of furosemide or other diuretics modifying the ion-exchange at the uriniferous tubules.
A case of xanthoma located within Meckel's cave and the semilunar ganglion is described in a patient with a trigeminal nerve deficit. This is the first case of xanthoma in such a location. The distinctive morphological appearance is illustrated and the possible histogenesis is discussed.
The effects of seven lignans and two neolignans derived from plants and herbs on the concanavalin A-induced proliferation of human peripheral blood lymphocytes in vitro were studied. All compounds showed inhibitory activity with an IC50, ranging from 0.02 to 4.30 micrograms/ml (1.6 x 10(-8) to 1.6 x 10(-5) M). Machilin A (2,3-dimethyl-1,4-dipiperonylbutane), a Lauraceae lignan, was the strongest inhibitor and was quite effective as the synthetic immunosuppressive glucocorticoid prednisolone. The viability of lymphocytes before and after treatment, as assessed by a dye exclusion test, indicated no change, and thus the lignans are not lymphocytotoxic but may inhibit DNA synthesis. The results suggest the value of further assessment of plant lignans as immunosuppressive agents.
Focal segmental glomerular hyalinosis and/or sclerosis (FSHS) was observed in five Wistar-Imamichi rats with congenital unilateral hydronephrosis (CUH rats). Marked proteinuria (164.9 +/- 138.4 mg/day) was observed in the CUH rats. Immunoperoxidase staining for IgM, C3 and IgG was positive in the glomeruli, showing in a focal, segmental pattern that corresponded to the areas of FSHS seen by light microscopy. These glomerular findings were extremely similar to those of human focal glomerular sclerosis (FGS). FSHS was found to be common to both the hydronephrotic kidney and the contralateral kidney without hydronephrosis. Morphometry revealed that the glomerular area of the juxtamedullary glomeruli was greater than that of superficial glomeruli in control rats (11,037 micron2 vs. 6,847 microns2). On the other hand, glomerular hypertrophy was observed in non-sclerotic glomeruli of CUH rats (superficial glomeruli; 12,477-16,123 microns2, juxtamedullary glomeruli; 14,635-18,418 microns2). Also, a decreased in the number of glomeruli within the range 1.8-4.1 per unit area (1 mm2) was seen in CUH rats compared with control rats (mean 4.4). These results suggest that the increased rate of development of FSHS is based on hyperfiltration in the remaining functional nephrons.
Endocrine- and immune-responses to prednisolone and their relation to clinical incidence were assessed in 19 renal transplant recipients. All of the patients were treated with prednisolone and cyclosporin. Response of the hypothalamic-pituitary-adrenal (HPA) system to prednisolone was evaluated by measuring serum cortisol concentration. Cortisol concentration before transplantation was 126.7 +/- 38.6 ng mL-1, while it decreased to 4.1 +/- 2.5 ng mL-1 within the period characterized by a cumulative dose of prednisolone from 300 to 700 mg. A statistically significant high incidence (P less than 0.01) of acute rejections was observed in low HPA responders; (mean cortisol concentration during prednisolone treatment exceeded 3.0 ng mL-1), 6 of 12 with a low HPA response to prednisolone showed signs of rejection, while none of the 7 with a high HPA response showed signs of rejection. The concentrations of prednisolone suppressing the in-vitro response of pretransplant lymphocytes to concanavalin A by 50% (ID50) were determined. Lymphocytes from 8 patients were extremely insensitive (ID50 greater than 500 ng mL-1), and 5 of the 8 showed signs of rejection. Lymphocytes from the other 11 patients showed high sensitivity (ID50 less than 500 ng mL-1), and only one of those showed signs of rejection. Thus, a significantly high incidence of rejection was observed in low lymphocyte-responders to prednisolone (P less than 0.05). The results suggest that an insensitive endocrine response to prednisolone correlates with an impaired lymphocyte response to the steroid, and that both of the indices are related to occurrence of rejection. Evaluation of these pharmacodynamic parameters in combination may serve as a guideline for successful immunosuppressive therapy in renal transplantation.
The ability of cultured peripheral-blood mononuclear cells (PBMC) to release interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta) in response to concanavalin A (con A) was investigated in patients with chronic renal failure (CRF) and in renal transplant recipients. Mean IL-1 alpha level released by PBMC of healthy subjects (n = 42), CRF patients (n = 42), or transplants 2 months after operation (n = 69) was 152 +/- 103, 110 +/- 80, or 154 +/- 87 pg/5 x 10(5) cells/ml culture, respectively. IL-1 alpha release from PBMC of recipients 2 months after renal transplantation was significantly higher than that of CRF patients (p less than 0.05). Mean IL-1 beta level released by PBMC of healthy subjects (n = 34), CRF (n = 30), or transplants (n = 55) was 223 +/- 159, 135 +/- 129, or 276 +/- 155 pg/5 x 10(5) cells, respectively. Similar to IL-1 alpha, the level in CRF was significantly lower than that in healthy subjects (p less than 0.05). A time course study indicated that the ability of PBMC from transplants to release IL-1 alpha and beta promptly decreased following the operation, possibly owing to prednisolone and ciclosporin immunosuppressive therapy. However, after maintaining a low level for 2-3 weeks, IL-1 release from PBMC gradually increased thereafter. The results were consistent with known characteristics of decreased immunity in CRF states, and further suggested that the decreased ability of PBMC to release IL-1 alpha and beta in response to con A in CRF patients is recovered 2 months after renal transplantation.
An increase in cortisol production by the fetal adrenal cortex is an important prepartum event. The increase in ovine fetal adrenal synthesis of cortisol appears to rely in part on the ACTH induction of 17 alpha-hydroxylase cytochrome P-450 (P-45017 alpha) which occurs before parturition. In the present study we examined the effect of ACTH treatment on cortisol production and P-450(17) alpha expression using primary cultures of ovine fetal adrenal cells. In addition, we examined the effects of angiotensin II (A-II) and transforming growth factor-beta (TGF beta) on ACTH-treated cells. We have demonstrated previously that these factors modulate P-450(17 alpha) levels in adult ovine and bovine adrenal cells. Fetal ovine adrenal cells were isolated from 126- to 130-day fetuses (term = 144 +/- 3 days) and placed in monolayer cell culture. After 1 day in culture the cells were treated with ACTH (10 nM) with or without A-II (0.1-100 nM) or TGF beta (1-100 pM). Medium content of cortisol was low under basal conditions, whereas ACTH-stimulated cortisol production by 10- to 100-fold. A-II and TGF beta inhibited ACTH-induced cortisol production by 70-90%. In addition, 3 days of treatment with ACTH caused a greater than 10-fold induction of P-45017 alpha enzyme activity in fetal adrenal cells. A-II and TGF beta inhibited the ability of ACTH to induce P-45017 alpha activity by at least 75%. Using an antibody to P-45017 and immunoblotting techniques the effects of ACTH, A-II, and TGF beta on enzyme activity were observed to correspond to cellular levels of P-45017 alpha protein. The inhibitory effects of TGF beta and A-II could not be overcome by the cAMP analog (Bu)2cAMP. Interestingly, the expression of the enzyme 3 beta-hydroxysteroid dehydrogenase was much less sensitive to inhibition by A-II or TGF beta. The ability of A-II and TGF beta to suppress P-45017 alpha expression could play a role in determining the pathway of steroidogenesis and specifically the amount of cortisol produced by fetal adrenocortical cells in vivo.
Twenty-five patients receiving surgical treatment for brain metastasis from lung cancer were retrospectively studied to evaluate the prognostic factors for survival time. Twenty-two patients had died of respiratory distress by April, 1989. Favorable prognostic factors derived from the median survival time (MST) in these patients included; 1) resection of primary tumor (MST 10 months); 2) total or subtotal removal of metastatic tumor (MST 6.5 months); 3) adenocarcinoma (MST 13 months); 4) metachronous onset of brain metastasis (MST 12 months); 5) single metastasis (MST 8 months). These results suggest that therapy for the primary lung cancer is important before surgery for metastatic brain tumor.
Four rare cases of aneurysm of the lenticulostriate artery (LSA) are presented. LSA aneurysms were located at the origin in three patients and distally in one. Two cases were of multiple aneurysms, one was associated with hypertensive intracerebral hematoma (putaminal hemorrhage), and the other with moyamoya disease. Two patients were successfully treated by microsurgical procedures. The occurrence of LSA aneurysm suggests that aneurysm formation and growth are accentuated by hemodynamic alteration and stress.
Plasma membrane-associated adenosine triphosphatase (ATPase) samples partially purified from the tumor dissections of 15 gastric cancer patients were examined for sensitivity to the synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and ouabain in the presence of Mg2+, Na+, and K+. Hattalin was the strongest Na+, K(+)-ATPase inhibitor among the lignans previously examined. The enzyme from normal gastric tissue of the same patient was used as control. The specific activity of ATPase from cancer tissue (C-ATPase) was inhibited by more than 50% by 2.0 mM hattalin, whereas only 33.1% of the specific activity of ATPase from normal gastric mucosa (N-ATPase) was inhibited by 2.0 mM hattalin. There was statistical significance of lignan sensitivity between C- and N-ATPase (p less than 0.02). Ouabain also inhibited C-ATPase in preference to N-ATPase, though not significantly. Hattalin inhibited both C- and N-ATPase more strongly than did ouabain (p less than 0.05). Moreover, the lignan inhibited both C- and N-ATPase in the absence of Na+ and K+. From these data, it is evident that the sensitivity of plasma membrane-associated to lignan increased by gastric canceration. The target ATPase of hattalin is likely to be one other than sodium- and potassium-dependent, ouabain-sensitive ATPase.
We report two cases of primary gastric mantle zone lymphoma. Histologic examination revealed numerous lymphoid vague nodules in the mucosa and submucosa of the resected stomach. The neoplastic cells in these nodules were slightly larger than small lymphocytes and had more or less cleaved nuclei. Immunostaining on paraffin-embedded sections showed that the neoplastic cells in the nodules of these cases were LN-1- and LN-2+ and had monotypic immunoglobulin (IgM-lambda and IgM-kappa, respectively). Immunostaining on frozen tissue specimens showed that the neoplastic cells or nodules were positive for surface IgM, surface IgD, alkaline phosphatase, and DRC-1. One third to two thirds of the cells were Leu-1+ (CD5+). These results indicated that these cases were primary gastric mantle zone lymphoma. More attention should be paid to primary gastric mantle zone lymphoma because this disease might be erroneously diagnosed as either pseudolymphoma or reactive lymphoid hyperplasia of the stomach.
We investigated the changes in anionic sites of the mesangial matrix related to aging in rats, employing polyethyleneimine (PEI) as a cationic probe. We compared the numbers of anionic sites detected by the immersion method and by the intravenous administration of PEI. Analysis of the mean numbers of PEI particles per 0.1 micron2 in the mesangial matrix revealed a significant decrease related to aging. Our results suggested that there was no significant difference in efficacy between the immersion and intravenous methods. Loss of negative charge of the mesangial matrix is believed to promote mesangial dysfunction and the entrapment of macromolecular substances, and so to play an important role in the onset of glomerular sclerosis.
A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRD molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH-SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation.
A 65-year-old man who had a left atrial ball thrombus without mitral disease is reported. Ultrasonic cardiogram gave this diagnosis. His ECG showed atrial fibrillation and severe bradycardia. Thrombus attached to the left appendage with short stalk was removed under extracorporeal circulation and a pacemaker (VVI mode) was implanted. Postoperative course was not eventful.
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