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Biomedical subjects

R Baumal

Publications and source records attributed to R Baumal.

At least 91 records · Page 5Linked to original sources

Salivary gland components involved in the formation of squamous metaplasia.

Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma.

Animals↗

Histochemical and immunohistochemical characterization of surgically resected and heterotransplanted Wilms' tumor.

Nine surgically resected Wilms' tumors (WIT) and nude mouse heterotransplants from one WIT were studied by histochemistry and immunohistochemistry. Histochemistry showed acid phosphatase in all cells, while alkaline phosphatase and gamma-glutamyl transpeptidase were present in only some tubules. Using immunohistochemistry, antibodies to the intermediate filaments cytokeratin and vimentin distinguished tubular epithelium and mesenchyme, respectively. WIT tubules were also identified using antibody against a structural component (epithelial membrane antigen) and a secretory product (uromucoid) associated with distal convoluted tubules of normal kidney. Basement membrane surrounding the tubules of WIT was demonstrated using antibody to type IV collagen plus laminin. Different blastema subpopulations were negative or stained positively with antibodies to cytokeratin and vimentin. Production of basement membrane by blastema was also shown. Fetal antigen expression in WIT was examined using the monoclonal PI 153/3 and J5 antibodies. The blastema and tubules of WIT were strongly stained by PI 153/3, which did not label normal adult kidney, and weakly stained by J5, which strongly labeled glomeruli and proximal convoluted tubules of normal kidney. These studies show that WIT blastema is heterogeneous in intermediate filament subtypes, while WIT tubules more closely resemble distal than proximal convoluted tubules of adult kidneys but also retain expression of fetal antigens.

Acid Phosphatase↗

Relationship of histology of Wilms' tumor to growth characteristics of nude mouse heterotransplants.

Eighteen Wilms' tumors (WIT), including classical triphasic WIT (blastema, tubules, and mesenchyme) and WIT variants (blastema and tubules, monomorphous tubules, multiloculated cysts, rhabdomyomatous WIT, and clear cell sarcoma), were heterotransplanted in nude mice. Ten (56%) tumors grew and were serially passaged. With two exceptions, the histology of the surgically resected tumors and heterotransplants was found to be similar. Tumors showing a prominent blastema component grew rapidly, whereas those with tubular epithelial or mesenchymal differentiation grew more slowly. Tumors injected s.c. consisted almost entirely of blastema, while tumors injected i.p. consisted of blastema with large areas of tubular epithelium. These results demonstrate that nude mouse heterotransplants of WIT closely resemble the surgically resected tumors from which they derive, that growth rates of WIT heterotransplants depend on the identity of the tumor cells, and that differentiation of WIT heterotransplants can be modulated, depending on the route of administration of tumor cells.

Anaplasia↗

Minimal lesion disease followed by membranous glomerulonephropathy in two children with nephrotic syndrome.

Two children with nephrotic syndrome are described whose clinical course, initial response to steroids, and renal biopsies were consistent with a diagnosis of minimal lesion disease (MLD). Both children subsequently became resistant to steroids and repeat renal biopsies 7 and 8 years after initial biopsies showed membranous glomerulonephropathy (MGN). Explanations are suggested which may account for the occurrence of MLD followed by MGN in a single patient. These cases illustrate the necessity of performing repeat renal biopsies in patients with nephrotic syndrome if the clinical behavior and response to steroids are not typical for MLD.

Basement Membrane↗

Differences in lectin binding in tissue sections of human and murine malignant tumors and their metastases.

Lectin binding to tumor cells in tissue sections of 16 nonmetastatic and 24 metastatic human adenocarcinomas and 5 nonmetastatic and 5 metastatic murine Lewis lung carcinomas (LLCs) was assessed with an avidin-biotin peroxidase technique. In human tumors, Ulex europaeus agglutinin I (UEA I) showed no binding; whereas concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), wheat germ agglutinin (WGA), soybean agglutinin (SBA), and Dolichos biflorus agglutinin (DBA) bound equally to primaries and metastases. However, peanut agglutinin (PNA) bound to less than 5% of cells in 37 of 40 primaries but to greater than 50% of cells in 18 of 24 metastases. In LLC tumors, UEA I and DBA showed no binding; whereas Con A, RCA I, and WGA bound equally to primaries and metastases. SBA bound to greater than 50% of cells in 5 metastases but not to the 5 primaries. There was less than 5% binding of PNA to 10 primary murine tumors after neuraminidase pretreatment of tissue sections but greater than 50% binding in 3 of 5 metastases. These studies indicate, in both human adenocarcinomas and an experimental tumor system, that most tumor cells which metastasize show preferential binding of PNA and SBA.

Adenocarcinoma↗

Interspecies Lewis lung carcinoma x Chinese hamster ovary hybrids as protective agents against Lewis lung carcinoma tumor growth.

Interspecies somatic cell hybrids formed between a clone of Lewis lung carcinoma (LLC/9) and Chinese hamster ovary cells were assessed for tumorigenicity in C57BL/6 mice and capacity to protect mice against a challenge with LLC/9 cells. LLC/9 cells were fused with ouabain-resistant-Chinese hamster ovary cells deficient in hypoxanthine guanine phosphoribosyl transferase. Hybrids were selected in medium supplemented with hypoxanthine: aminopterin: thymidine and 5 mM ouabain. Hybrids were shown to contain chromosomes and surface antigens of both parents. At doses up to 10(7) cells, uncloned hybrids and hybrid clones obtained by limiting dilution were nontumorigenic in C57BL/6 mice, while 10(4) LLC/9 cells were tumorigenic in 80% of mice. In protection experiments, hybrid cells were injected i.p., followed by foot pad challenge with 10(6) LLC/9 cells. Three injections of live uncloned hybrids produced complete protection, while one or two injections gave partial protection. Individual live hybrid clones conferred no or partial but never complete protection. Administration of hybrids or LLC cells killed by freezing and thawing or arrested in division by treatment with mitomycin C failed to confer protection against subsequent challenge with LLC/9 cells. These LLC/9 X CHO hybrid cells will be useful for studying therapy of primary LLC tumors and their pulmonary metastases.

Animals↗

Sex differences in childhood lupus nephritis.

The renal status of 60 children (15 male and 45 female) with systemic lupus erythematosus seen over a 21-year period was evaluated clinically and by renal biopsy. The occurrence of serious clinical renal disease at initial observation, more severe renal impairment at outcome, and diffuse proliferative lupus nephritis were more common in male than in female patients. Although lupus is relatively uncommon in male subjects, our epidemiologic study shows that there is a sex difference in the severity of lupus nephritis, with male subjects being more severely affected than female subjects.

Adolescent↗

Blood supply and drainage of the outer medulla of the rat kidney: scanning electron microscopy of microvascular casts.

Blood supply and drainage of the outer medulla of the rat kidney were studied by scanning electron microscopy of vascular casts, using both arterial (n = 10) and venous (n = 10) injections of resin. Both outer and inner stripes of the outer medulla were supplied through different arterial capillary networks arising from efferent arterioles and arterial (descending) vasa recta. In contrast to previous studies using silicone rubber and light microscopy, a rich arterial capillary network supplying the outer stripe was demonstrated. Capillaries in the outer stripe and outer part of the inner stripe drained into venous vasa recta between vascular bundles, while capillaries in the inner part of the inner stripe drained into venous vasa recta within the bundles. The results indicate that each zone in the outer medulla is supplied through separate capillary networks. The demonstration of a rich capillary network in the outer stripe of the outer medulla suggests that the predilection of this zone for tubular necrosis with ischemic or toxic injury is not related to a sparse capillary blood supply.

Animals↗

The value of immunohistochemistry in increasing diagnostic precision of undifferentiated tumours by the surgical pathologist.

The availability of polyclonal and monoclonal antibodies allows immunohistochemical staining (immunofluorescence and immunoperoxidase) procedures to be used by the surgical pathologist, so as to obtain a definite diagnosis in cases where light microscopic examination of tissue sections from biopsy and surgical specimens in inconclusive. Four cases of undifferentiated tumours are described in which only a differential diagnosis could be obtained using light microscopy but a definite diagnosis was achieved when additional information was provided by immunohistochemistry. A scheme is presented for the use of immunohistochemistry to increase diagnostic precision in assessing tumours.

Adolescent↗

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes.

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.

Adolescent↗

Immunohistochemical localization of epidermal and Mallory body cytokeratin in undifferentiated epithelial tumors. Comparison with ultrastructural features.

Twenty-one anaplastic tumors were studied by light microscopy (LM), immunoperoxidase staining using anti-epidermal cytokeratin (ECK) and anti-Mallory body cytokeratin (MBCK) antibodies, and electron microscopy (EM), to determine whether an epithelial origin could be confirmed. The tumors were derived from lung, stomach, colon, breast, uterus, kidney, bladder, and mesothelium. By LM, the tumors consisted of either large and polygonal, spindle or small, round cells. With immunoperoxidase staining, 11 (52%) of the anaplastic tumors were positive for ECK, positivity being either absent or only weak in the main tumor mass, but marked in areas of infiltration and metastases. In contrast, all of the anaplastic tumors were positive for MBCK in the main tumor mass, infiltrating areas, and metastases. In the case of adenocarcinomas, staining was either web-like or diffuse throughout the cytoplasm with concentration occurring at the cell surface, whereas in mesotheliomas, the staining was either diffuse or showed focal perinuclear accentuation. Twelve of 13 anaplastic tumors examined by EM showed epithelial features (desmosomes, tonofilaments, lumina, and/or microvilli). As controls, 21 non-epithelial tumors (five melanomas, eight sarcomas, and eight lymphomas) showed no reactivity with either cytokeratin antibody. These studies show that the epithelial nature of undifferentiated and poorly differentiated tumors can be confirmed by immunohistochemistry using anti-cytokeratin antibodies.

Epithelium↗

Incidence and prognostic importance of glomerular crescents in renal diseases of childhood.

The renal biopsies of 372 children with various glomerular disorders were reviewed and crescent formation was seen in 56 cases (15%). Four disorders, i.e. systemic lupus erythematosus, membranoproliferative glomerulonephritis (MPGN) types I and II and Henoch-Schönlein disease accounted for 74% of 10 diagnostic categories. Idiopathic rapidly progressive glomerulonephritis (RPGN) was seen in only 2 cases. Crescents associated with MPGN types I or II or idiopathic RPGN had a bad renal prognosis, whereas the presence of crescents in other disorders did not necessarily affect the renal outcome. Immunofluorescent and electron microscopic findings are essential to distinguish many conditions which may be associated with crescent formation in childhood renal disease.

Adolescent↗

Wilms' tumor and glomerular disease. Occurrence with features of membranoproliferative glomerulonephritis and secondary focal, segmental glomerulosclerosis.

A case of bilateral Wilms' tumor occurred in which a renal biopsy performed for proteinuria showed features of membranoproliferative glomerulonephritis (MPGN) type 1 and focal segmental glomerulosclerosis (FSGS). A review of the literature for similar cases revealed 24 patients with Wilms' tumor associated with glomerular disease; MPGN was present in one of these cases and FSGS in six. In our patient, circulating immune complexes were detected in the serum and likely played a role in the pathogenesis of the MPGN; the FSGS may have resulted from hyperperfusion of the remaining glomeruli in a kidney that was largely replaced by Wilms' tumor.

Antigen-Antibody Complex↗

Determination of circulating immune complexes, C3 and C4 complement components and anti-DNA antibody in different classes of lupus nephritis.

Circulating immune complexes (CIC) were measured in 237 sera from children who underwent a renal biopsy during the course of systemic lupus erythematosus. CIC-positive sera contained a lower mean level of C3 but not C4. Anti-DNA antibody was similar in CIC-positive and negative sera. The World Health Organization classification of lupus nephritis was used to categorize the biopsies. CIC, C3, C4 and anti-DNA antibody were determined to assess whether they correlated with the severity of renal lesions. Of 25 sera obtained at renal biopsy from patients with classes 2, 3 and 4, 16 were positive for CIC. C3 was significantly lower in classes 3 and 4 than in class 2. C4 was reduced and anti-DNA antibody was present in classes 2, 3 and 4. Determination of the level of C3 but not C4, CIC or anti-DNA antibody correlates with the severity of lupus nephritis seen on renal biopsies. Nevertheless, performance of a renal biopsy is preferred.

Antibodies, Anti-Idiotypic↗

Changes in Ia expression in mouse kidney during acute graft-vs-host disease.

We induced graft-vs-host disease (GVHD) in mice to determine whether immunologic stimuli could alter renal Ia expression. Two strain combinations were used: B6.C-H-2bm12 into C57BL/6, an I-A mutation difference, and A.SW into A.TL, differing in the I and D regions of H-2. By day 10 after allogeneic reconstitution of lethally irradiated recipients with bone marrow and spleen cells, the recipients had developed acute GVHD, as measured by their spleen to body weight ratio. Histologic examination revealed focal interstitial infiltrates of mononuclear cells in the kidneys. The expression of host Ia in these kidneys was increased up to 10-fold, as measured by absorption, and indirect immunofluorescence indicated that certain renal tubule cells had become strongly positive, suggesting that these were the principal sites of the increase in Ia expression. Similar increases were not observed in donor Ia. Tubule cells may have become Ia positive by passive uptake, or more probably, by the increase of Ia biosynthesis in cells that usually synthesize little or no Ia. Lethal irradiation without reconstitution tended to decrease renal Ia expression, as assessed by absorption and immunofluorescence. The results indicate that renal Ia expression, particularly in renal tubules, can be altered by changes in the immune system, raising the possibility of a role for such altered Ia expression in autoimmune or alloimmune responses involving the kidney.

Absorption↗

Clinical features and glomerular immunofluorescence of renal biopsies from children with nephrotic syndrome due to minimal change disease and two variants of mesangial proliferative glomerulonephritis.

Response to initial course of prednisone and clinical outcome were reviewed in 82 children with nephrotic syndrome (NS) due to minimal change disease (MCD) and 2 variants of mesangial proliferative glomerulonephritis (MesPGN). Renal biopsies in Type I MesPGN showed only increased mesangial cells and matrix, whereas those in Type II MesPGN also showed interstitial fibrosis, tubular atrophy, global glomerulosclerosis and hyalinosis. Response to prednisone was complete in most cases (95% in MCD, 82% in Type I and 72% in Type II MesPGN). Remission of NS for more than 1 year while off prednisone occurred in 91% of patients with Type I MesPGN and 49% with MCD, but in only 14% with Type II MesPGN. The influence of immunoglobulins +/- complement in mesangial regions of glomeruli on initial response and outcome was assessed. Response to prednisone and outcome did not differ in IMF-positive and -negative MCD or in Type I and Type II MesPGN.

Adolescent↗