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Biomedical subjects

J D Elema

Publications and source records attributed to J D Elema.

At least 37 records · Page 2Linked to original sources

Histopathologic classification of small cell lung cancer. Changing concepts and terminology.

Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

Carcinoma, Small Cell↗

AA amyloidosis associated with systemic lupus erythematosus.

A 54-year-old female with a 23-year history of systemic lupus erythematosus was admitted because of loss of renal function and nephrotic syndrome. Renal biopsy showed deposition of AA amyloid as demonstrated by Congo red staining and reactivity with protein AA-specific antibodies. Immune deposits were present in the mesangium and the glomerular basement membrane, but histopathological changes consistent with lupus nephritis were not detected. The rare association of systemic lupus erythematosus and amyloidosis is discussed in view of the characteristics of the acute phase reaction in systemic lupus erythematosus.

Amyloidosis↗

Graft versus host disease after transfusions of non-irradiated blood cells in patients having received autologous bone marrow. A report of 4 cases following ablative chemotherapy for solid tumors.

In four patients with solid tumors (three small cell lung cancers, one germ cell cancer) high dose chemotherapy with autologous bone marrow infusion was given. Graft versus host disease (GVHD) was the cause of death in one patient and at autopsy signs of GVHD were found in the other three patients. In these four patients GVHD was caused by blood cell transfusion. Patients treated with aggressive chemotherapy for solid tumors are at risk for the development of GVHD after allogeneic blood cell transfusions and preventive measures are definitely needed.

Adult↗

Two small cell lung cancer cell lines established from rigid bronchoscope biopsies.

Two new, good growing cell lines (GLC-8, GLC-11) have been established from biopsies of small cell lung cancer (SCLC). Tumor biopsies were procured by rigid bronchoscopy from tumor recurrences at the site of the primary lesions. Both tumors were clinically resistant to chemotherapy. Cytogenetic analysis revealed deletions in the short arm of chromosome 3. GLC-8 shows amplification of N-myc. Both cell lines show SCLC differentiations; neurosecretory granules were present and the SCLC related hormones dopa-decarboxylase and creatine kinase were elevated. Both cell lines behave as so-called 'classic' SCLC cell lines.

Antigens, Neoplasm↗

The use of electron microscopy for the diagnosis of cancer in bronchial biopsies.

To investigate whether electron microscopic examination of bronchial biopsy specimens was of any additional value in the diagnosis of lung cancer, we examined 235 consecutive biopsy specimens embedded in Epon. Semithin sections were used to establish a light microscopic diagnosis, and the results were compared with those of electron microscopy. Ninety-six biopsies contained tumor. In 13 instances, the light microscopic diagnosis had to be revised after electron microscopic examination. Another 5 biopsies contained tissue suspected to be tumor; in 1 biopsy this possibility could be ruled out. Three biopsies contained tumor suspected of being small cell cancer, and this diagnosis was confirmed by electron microscopy. Electron microscopy was helpful in 17 of 106 biopsies. Histopathologic examination of surgically resected material from 18 patients confirmed the electron microscopic results of biopsies. We conclude that electron microscopy of bronchial biopsy specimens gives important additional information for accurate diagnosis. For practical purposes, however, specimens should be embedded in Epon or glycol-methacrylate for light microscopy. Developments in immunohistologic techniques will change choices of histologic techniques.

Adenocarcinoma↗

Differences in puromycin aminonucleoside nephrosis in two rat strains.

Administration of puromycin aminonucleoside (PAN) to Wistar rats induces proteinuria and enhanced mesangial deposition of circulating macromolecules. After proteinuria of longer duration focal and segmental glomerular hyalinosis and sclerosis (FSGHS) develops. The present report analyzes these aspects of PAN nephrosis in PVG/c rats, a strain previously shown to be remarkably resistant to proteinuria and FSGHS with aging or after uninephrectomy. In Wistar rats multiple injections of PAN during five months resulted in sustained severe proteinuria and FSGHS lesions in 8.1 +/- 1.0% (mean +/- 1 SEM) of their glomeruli (N = 6). In PVG/c rats a 1.3-fold higher dose of PAN was needed to induce chronic proteinuria similar to the Wistar rats. After five months 3.3 +/- 0.9% of their glomeruli showed FSGHS (N = 6, P less than 0.01) and the glomerular lesions were considerably less advanced. In acute PAN nephrosis induced by a single intravenous injection of PAN the mesangium of Wistar rats contained large amounts of lipid in contrast to a few small mesangial lipid droplets in nephrotic PVG/c rats. After injection of colloidal carbon in nephrotic PVG/c rats no enhanced carbon accumulation was found in the mesangium when compared to nonproteinuric controls. This result clearly differs from the increased mesangial sequestration of circulating material in nephrotic Wistar, and most other rat strains. The unchanged mesangial traficking of macromolecules in nephrotic PVG/c rats and the low incidence of FSGHS lesions in the presence of sustained glomerular proteinuria may reflect a relative resistance to PAN-induced glomerular damage in this particular rat strain.

Acute Disease↗

Gastrointestinal toxicity of chemotherapy and the influence of hyperalimentation.

The effect of combination chemotherapy on human small intestinal morphology and disaccharidase activities and their relation with clinical and chemical (fecal wet weight and K-excretion) parameters for gastrointestinal toxicity were evaluated in patients with disseminated malignant melanoma receiving enteral normoalimentation (NA). Also evaluated were the supposed protective effects on gastrointestinal toxicity of enteral hyperalimentation (HA) with an elemental diet. After chemotherapy, a comparable decrease in villus height, total mucosal height, and mitotic index was found in jejunal biopsy specimens of both groups. However, in the NA group, the crypt depth decreased (in contrast to the HA group), whereas the disaccharidase activities in the HA group deteriorated to lower values than in the NA group. The authors found no correlation between disaccharidase levels and mucosal morphology, nor was there a correlation between these variables, fecal parameters and clinical diarrhea, suggesting that diarrhea occurring after chemotherapy was not due to loss of mucosal tissue or decrease in enzyme activities. A protective effect of HA with an elemental diet on gastrointestinal toxicity could not be established.

Adult↗

Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition.

The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes.

Animals↗

Glomerular sclerosis in Wistar rats: analysis of its variable occurrence after unilateral nephrectomy.

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) were studied in rats after unilateral nephrectomy. A total of 20 male Wistar rats underwent unilateral nephrectomy at 3 months of age. Glomerular number in the removed kidney ranged from 17,000 to 32,700 with a mean value of 25,997 (n = 19). At death 30 weeks later, the incidence of glomeruli with FSGHS in the remaining kidney varied from 0 to 20% with a mean of 4.4%. However, the percentage of glomeruli with FSGHS and the degree of proteinuria did not correlate either with glomerular number per kidney (left and right kidneys were shown to be equivalent for glomerular number) or with glomerular volume on killing. The occurrence of FSGHS correlated significantly with mean protein excretion (P less than 0.01) and serum cholesterol levels (P less than 0.01). In conclusion, in the rat a relatively low number of nephrons in the kidneys does not increase susceptibility to the development of FSGHS.

Animals↗

Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis.

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) after loss of renal mass were studied in two rat strains. Male Wistar rats, and most other rat strains, were found to develop FSGHS associated with proteinuria with ageing, a process which could be accelerated by unilateral nephrectomy (UN). In male PVG/c rats, however, a complete resistance to the development of FSGHS was found even at 1 year after UN. The Wistar rat was found to have a lower number of nephrons per kidney and to differ from the PVG/c rat in its response to UN: Wistar rats showed an increase of whole kidney glomerular filtration rate and renal plasma flow in the remaining kidney with expansion of glomerular volume and with increased mesangial deposition of circulating macromolecules. In the PVG/c rat, UN led to a comparable proportional increase in glomerular filtration rate and renal plasma flow in the remaining kidney. However, in contrast to the Wistar rat neither glomerular hypertrophy nor enhanced mesangial macromolecular accumulation were observed after UN. Although the precise mechanisms underlying these effects are not identified, the current data support the "mesangial overloading" concept of FSGHS in which a local enhanced mesangial accumulation of circulating macromolecular material is thought to initiate the development of the sclerotic glomerular lesions. Moreover, to our knowledge this is the first description of a rat strain showing complete resistance to the development of FSGHS after UN. This PVG/c strain therefore seems to be a useful laboratory animal in comparison to other rat strains to further study the renal adaptation process after kidney ablation.

Animals↗

TNO-6-induced acute renal failure. A case report.

A case of fatal acute renal failure during treatment with 1,1-diaminomethyl cyclohexane sulphato platinum II (TNO-6) is reported. Pathologic investigation showed focal tubular necrosis with interstitial infiltration and edema. Despite the development of proteinuria no changes of the glomeruli were found, either by light or electron microscopic investigation. The pathologic changes caused by TNO-6 are similar to those found in renal failure caused by cisplatin (CDDP).

Acute Kidney Injury↗

The spectrum of splenogonadal fusion. Case report and review of 84 reported cases.

Splenogonadal fusion is a rare congenital malformation in which there is an abnormal fusion between the spleen and the gonad or derivatives of the mesonephros. It can occur in both sexes but has been reported far more frequently in males. There are two types of this malformation: the continuous and the discontinuous type, depending on the presence or absence of a structural connection between the regular spleen and the ectopic splenic tissue that is fused to the gonad. In one-third of all reported cases splenogonadal fusion is associated with other congenital defects. This association is predominantly found within the continuous type. Peromelia is present in a high percentage of cases, varying from total absence of all limbs to absence of parts of the lower limbs. On the basis of a case report and a review of 84 published cases, the causal, pathogenetic and nosologic aspects of this malformation are discussed. We hypothesise that splenogonadal fusion with peromelia and splenogonadal fusion without peromelia represent two ends of one spectrum determined by the developmental stage during which the causal factor acts.

Abnormalities, Multiple↗

Localization and distribution of anionic charges in the glomerular mesangium of normal and nephrotic rats.

Sulfated glycosaminoglycans and sialoglycoproteins are thought to play a pivotal role in the glomerular capillary wall barrier to filtration since these anionic charged elements are important in the maintenance of capillary wall integrity and constitute a charge-selective filter. The development of proteinuria in puromycin aminonucleoside (PAN) nephrosis is associated with polyanion loss from the glomerular capillary wall structures. Since in PAN nephrosis the permeability of the mesangial area to plasma proteins and tracer substances has also been shown to be increased, the purpose of this study was to analyse the localization and distribution of anionic charges in the glomerular mesangium in this experimental model. Glycosaminoglycans were labeled by perfusion of the kidneys with ruthenium red solution (RR). Electron microscopic examination revealed the presence of distinct small RR granules ("anionic sites") in the mesangial intercellular matrix substance and in the laminae rarae of the glomerular basement membrane (GBM). The center-to-center spacing of the granules was measured and a frequency distribution of intervals in different interval classes was constructed. In normal glomeruli the anionic sites in the mesangial matrix showed a distribution pattern identical to the GBM with a maximal interval incidence at the 31-40 nm class. In nephrotic rats anionic site distributions in matrix and GBM did not change significantly. Sialoglycoproteins were labeled with colloidal iron (CI). In PAN nephrosis a decrease of CI binding was observed at the epithelial-basement membrane junction of the glomerular capillary wall. However, CI labeling of the mesangial matrix and mesangial cell membranes did not differ from that of normal glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The ultrastructure of small cell lung carcinoma in bronchial biopsy specimens.

Forty-three bronchial biopsy specimens from patients with small cell lung cancer (SCLC) were studied by electron microscopy. In 38 specimens the diagnosis was based on the light microscopic examination of Epon-embedded tissue; 36 of these specimens contained dense-core granules on electron microscopic examination. In five cases the light microscopic diagnosis was either different from the electron microscopic diagnosis or in doubt. Electron microscopy revealed dense-core granules as the only sign of differentiation, and the diagnosis was changed to SCLC. The tumor cell populations in the biopsy specimens were quite heterogeneous. Cells of the oat cell type were always present and, on electron microscopic examination, always showed degenerative changes. It was therefore decided that this cell type represents an artifact. The true SCLC tumor cell, which constitutes only a small portion of the tumor in biopsy specimens, is characterized by a regular oval or rounded cell with pale cytoplasm and a ground-glass nucleus with finely dispersed chromatin. Nucleolated cells, similar to those seen in large cell cancer, are often present but are not ultrastructurally different from nonnucleolated tumor cells.

Biopsy↗

Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis.

The possible relationship between mesangial dysfunction and development of glomerular sclerosis was studied in the puromycin aminonucleoside (PAN) model. Five male Wistar rats received repeated subcutaneous PAN injections; five controls received saline only. After 4 weeks the PAN rats were severely proteinuric (190 +/- 80 mg/24 hr), and all rats were given colloidal carbon (CC) intravenously. At 5 months glomerular sclerosis was found in 7.6 +/- 3.4% of the glomeruli of PAN rats; glomeruli of the controls were normal. Glomeruli of PAN rats contained significantly more CC than glomeruli of controls. Glomeruli with sclerosis contained significantly more CC than non-sclerotic glomeruli in the same kidneys. CC was preferentially localized within the sclerotic areas of the affected glomeruli. Since mesangial CC clearance from the mesangium did not change during chronic PAN treatment, we conclude that this preferential CC localization within the lesions is caused by an increased CC uptake shortly after injection in apparent vulnerable areas where sclerosis will develop subsequently. Cluster analysis showed a random distribution of lesions in the PAN glomeruli in concordance with the random localization of mesangial areas with dysfunction in this model. Similar to the remnant kidney model in PAN nephrosis the development of glomerular sclerosis may be related to "mesangial overloading."

Animals↗