Depersonalization following nitrazepam withdrawal.
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Biomedical subjects
Publications and source records attributed to R Yoshimura.
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We examined the ontogenesis of a subtype of metabotropic glutamate receptors, termed mGluR1, which is linked to phosphoinositide metabolism, in various regions of rat brain during neonatal development. Northern blot analyses of mGluR1 mRNA indicated that mRNA increased monotonously or remained at plateau levels during the first 5 weeks after birth. In situ hybridization analyses supported this conclusion. The result is in contrast with the reported development of the activity in excitatory amino acid-stimulated phosphoinositide turnover during the same period. The latter increases during the first few weeks and then decreases sharply.
The effect of ciclosporin (CS) on cardiac output (CO) and regional blood flow was studied using the microsphere method in heminephrectomized rats with and without renal arterial clamping prior to the administration of CS. The effect of a calcium (Ca) channel blocker, verapamil, was also examined on CS-induced nephropathy. CS at a dose of 40 mg/kg per day was given orally using a gastric tube for 7 days. Verapamil was given in the drinking water for 7 days. Significant increases in blood urea nitrogen (BUN) and serum creatinine (sCr) with a significant decrease in renal inulin clearance (CIn) were noted after 7 days of CS administration in both intact and ischemic-kidney groups, indicating the development of CS-induced nephropathy. The ischemic-kidney group showed a significantly severe nephropathy as compared with the intact-kidney group. As for change in CO and regional blood flow, CS caused a significant decrease in CO, renal blood flow (RBF) and brain blood flow, while hepatic arterial blood flow and muscular blood flow significantly increased. The renal outer cortical blood flow decreased markedly while the inner cortical blood flow remained unchanged. Although verapamil slightly but significantly decreased mean arterial blood pressure in CS-treated rats, CO and its distribution did not change. BUN and sCr were not significantly ameliorated in the intact-kidney group. However, in the ischemic-kidney group, verapamil caused a significant improvement in RBF, ameliorating CS-induced elevation of BUN and sCr, and a decrease in CIn.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have examined the effect of verapamil on CsA-induced nephropathy by measurement of systemic hemodynamics including each organ blood flow using the microsphere method in ischemic kidney model of hemi-nephrectomized Wistar rats. Hepatic and renal microsomal cytochrome P-450 contents and their enzyme activities were measured to study the correlation between CsA-induced nephropathy and induction of hepatic and renal microsomal cytochrome P-450. All rats were hemi-nephrectomized (l-nephrectomy) and were classified into the following 6 groups: 1) control groups, 2) CsA at a dose of 40 mg/kg per day orally for 7 days (CsA group), 3) Oral administration of verapamil for 7 days in the CsA group (CsA + V group), 4) 20 min clamping of the remaining right kidney pedicle (Ischemic, Is group), 5) CsA was administered in the Is group (Is + CsA group), 6) Addition of verapamil to CsA in the Is + CsA group (Is + CsA + V group). Verapamil was given in the drinking water and the average dose calculated from the amount of drinking was 4.7 +/- 1.0 mg/kg per day and 5.2 +/- 0.7 mg/kg per day for the CsA + V group and the Is + CsA + V group, respectively. CsA caused significant increases in BUN and serum creatinine (sCr) with a significant decreases in renal inulin clearance (CIn) in all groups. When compared with the Is group, CsA caused significant decreases in cardiac output and all organ blood flow especially in renal blood flow with significant increases in BUN and sCr in the Is + CsA group.2+ degree of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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The expression of PA8-15 antigen and the blood-group-related antigens A, B, O, Le(a), Le(b), Le(x), and Le(y), as well as CA19-9, were examined in the normal pancreas and in specimens from benign and malignant pancreatic tissue by the avidin-biotin-immunoperoxidase technique. A correlation was found between the expression of PA8-15, Le(a), and CA19-9 in some cases. However, in the cancer tissues in which neither Le(a) nor CA19-9 could be demonstrated, strong expression of PA8-15 was observed. The reactivity of monoclonal antibody (mAb) PA8-15 with pancreatic cancer tissue was not inhibited by the preincubation of the sections with the mAb anti-Le(a) (CO514) and mAb CA19-9 (CO19-9) indicating that the epitope recognized by PA8-15 is different from that detected by the other two antibodies. Moreover, unlike Le(a) and CA19-9, PA8-15 was also expressed in cancer cells of patients of the Le(a-b-) type. The results suggest that mAb PA8-15 recognizes a sialylated molecule related to Le(a) but different from CA19-9, and seems to be an additional useful marker for pancreatic cancer.
We have previously reported the isolation of two forms of cytochrome P-450 (P-450) with omega-hydroxylase activities toward prostaglandin A (PGA) and fatty acids, designated as P-450ka-1 and P-450ka-2, from kidney cortex microsomes of rabbits treated with di(2-ethylhexyl)phthalate [Kusunose, E. et al. (1989) J. Biochem. 106, 194-196]. In the present work, we have purified and characterized two additional forms of rabbit kidney fatty acid omega-hydroxylase, designated as P-450kc and P-450kd. The purified P-450kc and P-450kd had specific contents of 13 and 16 nmol of P-450/mg of protein, with apparent molecular weights of 52,000 and 55,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Both the forms showed absorption maxima at 450 nm in the carbon monoxide-difference spectra for their reduced forms. These P-450s efficiently catalyzed the omega- and (omega-1)-hydroxylation of fatty acids such as caprate, laurate, myristate, and palmitate, in a reconstituted system containing P-450, NADPH-P-450 reductase, and phosphatidylcholine. Cytochrome b5 stimulated the reactions to only a slight extent. They had no detectable activity toward PGA and several xenobiotics tested. The two P-450s showed different peptide map patterns after limited proteolysis with papain or Staphylococcus aureus V8 protease.(ABSTRACT TRUNCATED AT 250 WORDS)
A very rare developmental anomaly showing bilaterally persistent sciatic arteries was found in a cadaver of 89 year old female. Both right and left sciatic arteries arose from the internal iliac arteries and appeared between the piriformis and superior gemellus muscles at the buttock, being about 10 mm in diameter. Each artery, which accompanied by the companion vein, i.e. sciatic vein, sent the branches to the gluteus maximus and the flexor muscles of thigh. On the other hand, the femoral arteries of both lower limbs were smaller than usual, measuring 4.7 mm in left and 5.2 mm in right. The terminal vessels of those were joined to the sciatic arteries at the popliteal fossa. In addition, the present case also had another developmental anomaly, i.e. superficial brachial artery in the right upper limb.
Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 10(8). These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophan and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers.
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A murine monoclonal antibody (MAb), PA 8-15, was produced against a newly established human pancreatic adenocarcinoma cell line, SUIT-2. With the avidin-biotin immunoperoxidase technique, PA 8-15 MAb reacted strongly with 27 of 28 formalin-fixed paraffin-embedded pancreatic adenocarcinoma tissues. All six gall bladder carcinomas and all nine biliary tract carcinomas also showed positive reactions. In addition, PA 8-15 MAb reacted with gastric carcinomas (6/10), colorectal carcinomas (7/11), and some other primary adenocarcinomas. The distribution of PA 8-15 antigen on the same tissues of pancreatic cancer was different from those of CA 19-9 and DU-PAN-2 antigens and CEA. PA 8-15 MAb stained only the epithelium of the pancreatic duct, gall bladder and bile duct in normal adult tissues, and some normal fetal glandular epithelial cells. However, PA 8-15 MAb was not reactive with inflammatory or benign tumors of the digestive system except for the epithelium, as was seen in normal adults. Reactivity of PA 8-15 MAb with tissue specimens largely disappeared after treatment with neuraminidase, while oxidation with periodate or trypsin digestion did not alter the staining intensity, indicating that antigenic determinants may be at least partly of sialylated carbohydrate nature. These results suggest that PA 8-15 MAb detects a new oncofetal antigen in gastrointestinal cancers, especially of the pancreatico-biliary tract.
Intracavernous injection of various vasoactive drugs was performed in six erectile failure patients. The effects of each drug were evaluated in four grades: complete functional erection, incomplete functional erection, nonfunctional expansion and no effect. When papaverine hydrochloride (40 mg/ml) was administered, 4 of the 6 patients had nonfunctional expansion. By administering a mixture of 80 mg/ml papaverine hydrochloride with 1.0 mg/ml phentolamine mesylate, nonfunctional expansion was seen in four patients and incomplete functional erection in two patients. As for the effects of prostaglandin E1, incomplete functional erections were seen in all patients, while complete functional erection was seen in two patients. These findings indicated that the patients reacted differently to the same vasoactive drug, and that the papaverine and phentolamine mixture had a stronger effect than papaverine alone, while prostaglandin E1 had the strongest effect on erection. Intracavernous injection of the these drugs is useful for the treatment and differential diagnosis of impotence.