Effect of ureteral obstruction on proximal tubular functions of rat kidney

The effect of complete unilateral ureteral obstruction (CUUO) on proximal tubular functions was studied in rats, using the K+-sensitive microelectrode technique and split oil drop method. In the control kidneys peritubular membrane potential (EMperi) and intracellular potassium activity (aKi) were -70.8 +/- 7.0 mV and 81.2 +/- 22.0 mEq/liter (mean +/- SD), respectively. In the CUUO kidneys both EMperi and aKi were progressively reduced with the duration of obstruction. However, in all tubules aKi values were still above the electrochemical equilibrium. In the three days' CUUO kidneys EMperi and aKi were -51.5 +/- 11.7 mV and 53.8 +/- 22.8 mEq/liter, respectively. Rate of fluid absorption (JVL;nl./sec. mm.) across the proximal tubular epithelium from Ringer solution in the control and three days' CUUO kidneys was 0.029 and 0.0065 respectively. In the CUUO kidneys there were wide variations in JVL and EMperi, but there was a clear correlation between these two variables. JVL from choline chloride solution was negligible in both control and CUUO kidneys. From above results, it was suggested that the proximal tubular reabsorption primarily depending on the Na+-K+ pump might be reduced but still working in the CUUO kidney, and thus the proximal tubular reabsorption might take part in preservation of glomerular filtration during the obstruction.     

A case of congenital antithrombin II deficiency with pulmonary infarction

A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 year old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years. Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5,000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8 mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.     

Effects of testosterone, and testosterone plus estrogen, in the castrated rat ventral prostate--histopathological and immunocytochemical studies.

The effects of testosterone (T) and 17 beta-estradiol (E2) on the prostate of castrated rats were investigated by histopathological and immunocytochemical procedures. A significant increase in prostatic weight occurred after 6 weeks treatment with T alone and in combination with E2. The greatest increase in prostatic weight occurred after the administration of T plus E2. Histopathologically, glandular hyperplasia of the prostate was noted, and the number of bromodeoxyuridine (BrdU)-positive cells showed a significant increase over that induced by testosterone alone.     

Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin.

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.     

Surgical management of endocrine tumor of the pancreas in Japan

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor. This study was carried out as a group project. The authors' institutions are as follows     

Vasodilator effects of C-type natriuretic peptide on cerebral arterioles in rats

The vasodilator effects of C-type natriuretic peptide (CNP) were investigated in isolated rat cerebral arterioles. CNP caused dose-dependent vasodilation, maximally by 10.0±2.2% at 10⁻⁶ M. The median effective concentration (EC₅₀) was 5.2×10⁻¹⁰ M. In contrast, atrial natriuretic peptide and B-type natriuretic peptide, other members of the natriuretic peptide family, produced little or no vasodilation. Pretreatment with methylene blue (10⁻⁴ M) abolished CNP-induced vasodilation, whereas pretreatment with N^G-monomethyl-

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-arginine or indomethacin did not inhibit vasodilation. Thus, CNP is suggested to cause significant vasodilation in cerebral arterioles via a cyclic guanosine monophosphate-dependent mechanism. © 1997 Elsevier Science B.V. All rights reserved.     

Polyglucosan bodies in the central nervous system of a fox.

Polyglucosan bodies (PGB) in the central nervous system of an old male fox, Vulpes vulpes japonica, without neurological signs were examined by light and electron microscopy, lectin histochemistry and immunohistochemistry. Fox PGB were round, slightly-basophilic and PAS-positive structures. Most of the bodies were situated free in the neuropil. Electron microscopically, fox PGB were composed mainly of branching filaments and electron-dense material. Lectin histochemistry revealed that fox PGB contained mannose and galactose in addition to glucose. Fox PGB were immunoreactive for monoclonal antibodies raised against human polyglucosan. These findings indicate that fox PGB are similar to feline ones.     

The anterior choroidal artery syndrome

We reviewed 12 cases of infarcts in the territory of the anterior choroidal artery (AChA) on CT and/or MRI. In each case vascular occlusion in the region was verified angiographically. Although the extent of the lesion on CT/MR images was variable, all were located on the axial images within an arcuate zone between the striatium anterolaterally and the thalamus posteromedially. The distribution of the lesions on mutiplanar MRI conformed well to the territory of the AChA demonstrated microangiographically. The variability of the extent of the infarcts may be explained by variations in the degree of occlusive changes in the AChA or the development of collateral circulation through anastomoses between the AChA and the posterior communicating and posterior cerebral arteries. The extent of the lesion appeared to be closely related to the degree of neurological deficit.     

C3 Deposition in IgA Nephropathy in Children and Adolescents

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5–21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1 + (N = 4): mesangiocapillary and 1 +; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1 + (N=18): mesangial 1 +; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.     

An experimental study on development of gallstone disease after curative gastrectomy for cancer--postoperative alteration of the composition of canine gallbladder bile after subtotal gastrectomy with truncal vagotomy]

In connection with gallstone (GS) formation after gastrectomy for cancer, we examined alteration of the composition of gallbladder bile after subtotal gastrectomy with truncal vagotomy. Of 11 mongrel dogs with cholecystostomy, 3 underwent B-I and 4 B-II gastrectomy. Four dogs without gastrectomy were served as controls. Bile was collected for 12 months. Bile acids were quantified by GLC. The bile was cultured for bacteriology. TBA did not significantly differ among the three groups of the dogs. In the two gastrectomized groups, CDA (a secondary bile acid) kept a higher level and CA (a primary bile acid) maintained a lower concentration compared with those in the controls. A remarkable increase of non-conjugated bile acids was recognized in both gastrectomized groups. Lithogenicity was low for all of the 3 groups. All but 1 control dog incurred bile infection that persisted long. Black pigment stones containing calcium bilirubinate developed in 1 of the 3 B-I and 2 of the 4 B-II dogs but none in the controls. The bile infection seemed to be involved in the development of GS. As the alteration of bile composition and GS occurred solely in the gastrectomized dogs, subtotal gastrectomy with truncal vagotomy might precipitate the GS formation.