EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N0₂^? and N0₃^? (UNO*V). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and iV^G-nitro-L-arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNO_xV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide-induced renal vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is related to NO production stimulated by this peptide.     

Effects of continuous distraction on cartilage in a moving joint: An investigation on adult rabbits

An animal model, using distraction force on adult rabbits, was developed to study the effects of nonweight-bearing on articular cartilage in a moving joint. Histologic evaluation was used to compare the morphology of chondrocytes, safranin O intensity, cartilage thickness, and structural changes between the test and contralateral joints. At 3 and 6 weeks, the chondrocytes in superficial and intermediate zones were round, with an increase in cellular volume density and mean cell volume and with less metachromasia; the safranin O intensity and cartilage thickness were the same as in the controls. In cartilage of the 9-week group, mean cell volume decreased with cell cloning in the superficial zone, while numerical density increased and mean matrix volume per cell decreased in the superficial and intermediate zones. The cartilage, with a 34% reduction in thickness and a 53–72% decrease in safranin O intensity from the superficial to the deep zone, had superficial fibrotic proliferation, suface erosion or depression, ard tidemark irregularity. Continuous distraction in a moving joint caused morphological changes in chondrocytes prior to degeneration of cartilage. These results support the hypothesis that the forces perceived by cells may dictate their shape and then stimulate alterations in cellular biochemistry and matrix metabolism.     

AUGMENTED ENDOGENOUS NITRIC OXIDE PRODUCTION IN PARTIAL PORTAL VEIN-LIGATED RATS

1. Endothelium-derived nitric oxide (NO) is a potent vasodilator. Because the body oxidizes it to nitrate ions, NO₃-, measurement of the serum concentration and the urinary excretion of NO₃- may be an index for endogenous NO. We investigated the role of NO on hyperdynamic circulation in cirrhotic and partial portal vein-ligated rats by measuring NO₃. 2. Liver cirrhosis was induced by administration of thioacetamide. Systemic and splanchnic haemodynamics and splenic-systemic shunting were determined by tracer microspheres. The concentration of NO₃- was measured by using high-performance liquid chromatography with an anion-column. 3. We found that systemic and splanchnic hyperdynamic circulation existed to almost the same extent in cirrhotic and in portal vein-ligated rats as compared to the controls and sham-operated rats, respectively. Splenic-systemic shunting was markedly greater in portal vein-ligated rats than in cirrhotic rats. 4. Serum NO₃- levels and urinary excretion of NO₃- in cirrhotic rats tended to increase as compared to the controls. On the other hand, the levels in portal vein-ligated rats were significantly increased as compared to those of the sham-operated rats, and were significantly and negatively correlated to the splanchnic arterial resistance and total vascular resistance. The amount of urinary excretion of NO₃- significantly correlated to splenic-systemic shunting (r = 0.61, P<0.05) only in portal vein-ligated rats. 5. We suggest that these high levels of NO₃- in portal vein-ligated rats relate to the extensive formation of porto-collateral vasculature or acute changes in systemic and splanchnic haemodynamics due to portal vein-ligation.     

Synthesis and antiviral activity of sulfonamidobenzophenone oximes and sulfonamidobenzamides

To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction. The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization. The anti isomer had more potent antipoliovirus activity than the syn isomer. Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reactions of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride. Antiviral activity was examined by the plaque-inhibition test. Compounds 5, 36, and 69 exhibited strong antipicornavirus activity. The structure-activity relationships are discussed.     

Differential diagnosis of adrenal masses by chemical shift and dynamic gadolinium enhanced MR imaging

Chemical shift MRI is widely used for identifying adenomas, but it is not a perfect method. We determined whether combined dynamic MRI methods can lead to improved diagnostic accuracy. Fifty-seven adrenal masses were examined by chemical shift and dynamic MR imaging using 2 MR systems. The masses included 38 adenomas and 19 non-adenomas. In chemical shift MRI studies, the signal intensity index (SI) was calculated, and the lesions classified into 5 types in the dynamic MRI studies. Of the 38 adenomas studied, 37 had an SI greater than 0. In the dynamic MRI, 34 of 38 adenomas showed a benign pattern (type 1). If the SI for the adenomas in the chemical shift MRI was considered to be greater than 0, the positive predictive value was 0.9, and the negative predictive value was 0.94 and kappa = 0.79. If type 1 was considered to indicate adenomas in the dynamic MRI, the corresponding values were 0.94, 0.81 and kappa = 0.77 respectively. The results obtained when the 2 methods were combined were 1, 0.95 and kappa = 0.96 respectively. The chemical shift MRI was found to be useful for identifying adenomas in most cases. If the adrenal mass had a low SI (0 < SI < 5), dynamic MRI was also found to be helpful for making a differential diagnosis.     

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sj?gren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.     

EARLY CHANGES IN CEREBRAL ANEURYSMS IN THE INTERNAL CAROTID ARTERY/POSTERIOR COMMUNICATING ARTERY JUNCTION

In order to obtain information about preaneurysmal changes, the junction of the internal carotid artery/posterior communicating artery (ICA/PComA) in the circles of Willis in subjects with aneurysms at sites other than the junction, and in control subjects without aneurysms, were studied by light microscopy.
Small evaginations and thinnings of the media with and without dilatation were observed at the apical areas of the forks with a significantly higher incidence in the aneurysm series than in the control, suggesting some predisposing factor in subjects with aneurysms. As well as funnel-shaped dilatations previously described as the only type of ICA/PComA preaneurysmal change, other more localized types were observed. All the small evaginations and about half of the thinnings and dilatations were observed at the apex in association with a medial gap, but the other half occured at some distance from the apex. The thinned arterial wall showed degenerative changes of the elastic lamina and media. Intimal pads were observed at the apex, the ICA/PComA lateral angle and the ICA stem/branch curve. Their combination with preaneurysmal changes was more frequent in the aneurysm series in comparison with the control.
Degenerative changes of the elastic lamina and media caused by hemodynamic stress due to branching structures including intimal pads are thus presumed to be the initial lesions existing prior to aneurysm formation.     

Imaging of the varicella zoster virion in the viral highways: comparison with herpes simplex viruses 1 and 2, cytomegalovirus,pseudorabies virus,and human herpes viruses 6 and 7

Imaging by scanning electron microscopy (SEM) can provide insight into viral egress. At a low magnification level, varicella zoster virions (VZV) emerge from an infected cell surface in a distinctive pattern previously described as "viral highways." Viral highways consist of thousands of particles arranged in linear pathways across the syncytial surface. This egress pattern has not been described with other herpesviruses, but a systematic analysis has not been performed. Therefore, the characteristic arrangement of VZV egress was compared with that of six other members of the herpes virus family, including herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus (CMV), pseudorabies virus (PRV), and human herpesvirus types 6 and 7 (HHV-6 and HHV-7). Only VZV-infected cells exhibited viral highways. Subsequent SEM examination of VZ virions at an ultra high-resolution revealed that more than 70% were aberrant. Further imaging of the other herpesviruses demonstrated that VZV structure was more closely related to PRV than HSV-1 or HSV-2. Finally, it is noted that the individual members of the herpesvirus family have distinguishable SEM profiles.     

Three Kinds of Foamy Cells in the Spleen: Comparative Histochemical and Ultrastructural Studies

By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)

The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.

In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris.