Tumour cell damage and leucocyte infiltration after laser immunotherapy treatment.

Immune response after laser-photosensitiser application could be crucial in treatment of cancers, because without it there could be no systemic, long-term tumour control. Laser immunotherapy, a novel method for treatment of metastatic tumours, uses a near-infrared laser, a laser-absorbing dye indocyanine green, and an immunoadjuvant glycated chitosan. This modality has shown an induced antitumour immune response in treatment of rat mammary metastatic tumours. The influence of this new method on the cellular structure of the tumours and on the infiltrating immune cells was studied using optical and electron microscopes. The tumour samples were examined before and immediately after the treatment for acute effects, which appeared mainly photothermal. Two weeks after treatment, significant infiltrating lymphocytes and plasma cells were found around the surviving tumour cells. These morphological findings suggest that both cell-mediated and humoral immune responses could be responsible for the observed tumour eradication and induced long-term tumour resistance.

Diabetic nephropathy associated with fibrin formation.

This communication describes the electron microscopic study of a renal biopsy specimen from a patients with diabetic nephropathy, the nephrotic syndrome, and renal insufficiency. There were large amounts of electron dense materials within glomerular basement membranes and masses of fibrin within glomerular capillaries and Bowman's spaces. The presence of glomerular fibrin suggests that thrombosis may be pathogenetically related to diabetic nephropathy.

Renal functional and organic changes induced by salt and prostaglandin inhibition in spontaneously hypertensive rats.

The prolonged (3 months) effects of high sodium intake and sodium meclofenamate were studied in two groups of male spontaneously hypertensive rats. Group 1 (8 rats) received 1% NaCl in tap water ad libitum and served as control. Group 2 (8 rats) received, besides 1% NaCl in tap water, 50 micrograms/ml of sodium meclofenamate per rat daily. Renal metabolic, hemodynamic and histologic studies were done at the end of the study. The renal functional studies were performed in the unanesthetized, unrestrained state. Group 2 rats developed significantly higher arterial pressures, renal vascular resistance and histologic changes (p less than 0.005), larger left ventricular weights (p less than 0.05) and significantly lower effective renal plasma flow, renal blood flow (p less than 0.005) and glomerular filtration rate (p less than 0.05) than group 1 rats. There were no differences between the two groups of rats with respect to heart rate, hematocrit, right ventricular weight, body weight, fluid intake, urine output, sodium and potassium excretion and serum electrolytes. The results suggest that the combination of high sodium intake and prostaglandin synthesis inhibition exert a greater damaging effect on the arterial pressure and renal function of spontaneously hypertensive rats than salt alone.

Electron microscopy studies of papillary interstitial granules in normal human kidneys.

The papillae of five kidneys from four heart-beating cadaver donors (one child and three young adults) were studied using electron microscopy (EM) technique. The kidneys were made available for EM study after they were found unsuitable for transplantation owing to low antigen match. All papillae had interstitial cells (IC), stellate processes, and intracellular and free granules. The three types of granules observed were (1) homogeneously dark, (2) gray and (3) layered; the free (outside the IC) granules were identical to the granules within the IC. The child kidney had more IC but fewer granules than the adult kidneys. The granules are ultrastructurally identical to those found in the rat renal papilla. Since rat renal papillary granules have been implicated as the source of renal vasodepressor substance(s), this ultrastructural resemblance suggests that human papillary interstitial granules likewise may be the source renal vasodepressor substance.

Effects of acute and chronic splenectomy on experimental acute renal tubular lesions.

The first half of this study describes the effects of acute splenectomy on epinephrine-induced ATL in the dog. Renal morphology and hematocrit were compared in 12 dogs without splenectomy (group I), six dogs with antecedent splenectomy (group II), and seven dogs with antecedent splenectomy after splenic contraction was induced by topical application of epinephrine (group III). Splenectomy was performed in groups II and III 20 to 30 min prior to epinephrine infusion; all three groups received equal infusions (4 microgram/kg/min) for 6 hr before the kidneys were harvested. ATL and renal congestion were consistently severe in group I but infrequent and less severe in groups II and III. The second half of this study describes the apparent protective effect of chronic (2-week) splenectomy on epinephrine-induced ATL. Renal morphology and hematocrits were compared in 13 intact dogs (group IV) and 10 dogs splenectomized 2 weeks before the epinephrine infusion (group V). The severity of the ATL and the degree of renal congestion were significantly less in the chronically splenectomized dogs. This chronic protection afforded by acute and chronic splenectomy observed after epinephrine infusion remains unclear.

Ultrastructural analysis of renal arteriolopathies in glomerular and tubulointerstitial diseases.

This communication describes the electron microscopy (EM) study of the small arterial vessels in renal biopsies from 32 patients with a variety of glomerular and tubulointerstitial diseases. With the possible exception of lipoid nephrosis, all types of glomerular and tubulointerstitial diseases were associated with abnormal arterial vessels. The vascular abnormalities included variable thickening and irregularity of the basement membranes (sclerosis), excessive elastic tissue and collagen fibers, atrophic or necrotic smooth muscle cells, and electron-dense deposits. The EM of glomeruli and tubules from the same biopsy specimens often revealed similar features, i.e., sclerosis, necrotic changes and electron-dense deposits. The pathogenesis of the arteriolopathies, like that in many glomerular and tubulointerstitial diseases, remains unclear. Hypertension was considered a factor, but only 15 percent of the patients were hypertensive. Furthermore, vascular lesions in patients with hypertension were no worse than those without it. Whatever may be the pathogenesis of these arteriolopathies, the similarities between the renal arteriolar and glomerular abnormalities and between arteriolar and tubular lesions suggest a common mechanism of inducement of the lesions.

An etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis); an electron microscopic study.

Renal tissues were studied using electron microscopy (EM) and immunofluorescence microscopy (IFM) from three patients who were found to have chronic interstitial nephritis (pyelonephritis) by light microscopy (LM). By LM, 90% of the glomeruli in two patients and all glomeruli in one patient were normal. By EM, glomerular capillaries in all patients revealed generalized fusion of epithelial foot processes. In two patients, IFM for immunoglobulins, third component of complement and fibrinogen were negative. These two patients received corticosteroids for 6 to 12 weeks. In one, proteinuria markedly decreased (from 17.9 to 1.1 gm) in four weeks and in the other follow-up studies of renal histology revealed normal glomeruli and partial restoration of foot processes by LM and EM respectively. Thus, this study offers evidence for lipoid nephrosis (or minimal lesion disease) as an etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis). The impaired renal function in these patients is attributed to tubulo-interstitial disease rather than glomerular pathology. It remains to be determined whether the two disparate pathological conditions have coexisted or chronic interstitial nephritis had led to the appearance of lipoid nephrosis through an unidentified mechanism.

Rapid development of glomerular crescents in epinephrine-infused dogs.

A serendipitous finding in the kidneys examined by light, electron, and immunofluorescence microscopy (LM, EM, and IFM, respectively) in mongrel dogs infused intravenously with epinephrine (4 microgram per kg per min) alone or in combination with therapeutic agents over a six hour period was proliferating epithelial cells in Bowman's space and adhesion to the Bowman's membrane (crescent). This lesion was observed in 10 of 17 dogs. In five, over 50 percent of the glomeruli were involved. In seven additional dogs infused with epinephrine, renal biopsy studies (LM) at 0, 3 and 6 hr periods revealed crescents only in the six hr specimens. By EM, the crescents were composed of actively proliferating epithelial cells with many large mitochondria containing conspicuous intramitochondrial particles. Fibrin was found within glomerular and peritubular capillaries, within tubules but rarely in the crescent. IFM revealed granular deposits of IgG only in the glomerular basement membrane and mesangium. Other changes included necrosis of the tubules in all dogs receiving epinephrine alone and necrosis of arterioles in some of the dogs studied. Dogs receiving normal saline infusions (control) did not reveal any abnormalities in the kidney. This model should prove useful in determining the morphogenesis of crescent formation and in evaluating the effect of therapeutic agents in the prevention of this lesion.

Glomerulopathy and arteriolopathy in congenital nephrotic syndrome: light, electron, and fluorescence microscopy studies.

This report describes the light, electron, and fluorescence microscopy studies of the kidney from a one month old, prematurely born infant with the nephrotic syndrome. Light microscopy revealed enlargement of Bowman's space, an excessive number of glomerular epithelial cell nuclei, and cystic dilatation of cortical tubules. By electron microscopy two disparate types of glomerular lesions were found: a thin basement membrane with fusion of foot processes suggestive of lipoid nephrosis and linear electron-density in the basement membrane with excessive mesangial matrix and capillary collapse suggesting an antibasement membrane type of glomerulonephritis or mesangial sclerosis. Conspicuous cystic spaces were found in the proximal tubules only. In the arterioles there were cystic spaces in the endothelial cells and smooth muscle cells, thickening of the basement membranes of endothelial cells and smooth muscle cells, and excessive amounts of nonstriated fibrils in the subendothelial basement membrane. Masses of fibrin were noted in the lumina of veins, peritubular capillaries, and interstitium between veins and peritubular capillaries. Such multiple glomerular and arteriolar lesions have not been reported previously in congenital nephrotic syndrome. These lesions suggest an antigen-antibody reaction in the mother that might have been directed toward the glomerular basement membrane in the fetus, producing these lesions.

An electron microscopic technique for the study of elastic tissue in small arteries and arterioles of the kidney.

Elastic tissue content and distribution were studied by electron microscopy of small arteries and arterioles of kidneys obtained from normotensive Wistar and spontaneously hypertensive rats, normal dogs and patients with hypertension and glomerular diseases. Specificity and sensitivity of silver tetraphenyl porphyrin sulfonate stain are discussed. This specific electron microscopy technique should prove useful in analysis of elastic tissue in pathologic states of other organs, especially where elastic tissue normally appears to be sparse or absent.

Focal glomerular sclerosis.

Focal glomerular sclerosis was diagnosed in nine patients by renal biopsy. Proteinuria, hematuria, hypertension, and slowly progressive renal insufficiency unresponsive to corticosteroid and immunosuppressive therapy were consistent clinical findings. Focal, segmental, and global glomerular sclerosis with intraluminal deposits of hypereosinophilic and strongly PAS-positive material, intracapillary foam cells, and moderate interstitial involvement were consistent morphologic findings. The importance of this clinicopathologic entity in the spectrum of renal diseases has only recently been appreciated.