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Biomedical subjects

J Alroy

Publications and source records attributed to J Alroy.

At least 19 recordsLinked to original sources

Storage of glycoprotein in NCTR-Balb/C mouse. Lectin histochemistry, and biochemical studies.

A strain of Balb/C mice carrying a lysosomal storage disorder exhibits metabolic and phenotypic abnormalities similar to patients with sphingomyelin-cholesterol lipidoses type II (i.e., Niemann-Pick C and D). Their foamy cells, which belong to the reticuloendothelial system, stained intensely by periodate-Schiff (PAS) reagent and were resistant to predigestion with diastase. To identify the chemical nature of the PAS-positive storage material, we applied lectin histochemistry and biochemical methods. Paraffin embedded sections, and delipidated frozen tissue sections, were treated with biotinylated lectins and localized with avidin-biotin-peroxidase complex. Araldite-embedded semithin sections were incubated with biotinylated lectins followed by avidin-gold and were enhanced with silver. By both histochemical methods the affected foamy cells stained positively as follows: Concanavalia ensiformis agglutinin, Datura stramonium agglutinin, Griffonia simplicifolia-I, Lens culinaris agglutinin, peanut agglutinin, Ricinus communis agglutinin-I, wheat germ agglutinin (WGA), and succinylated-WGA. Biochemical analysis of liver extracts complemented the histochemical data and demonstrated accumulation of glycoproteins containing polylactosaminoglycans in affected mice. Our findings indicate that the storage material in NCTR-Balb/C mice is heterogeneous. The lipids that are extracted by organic solvents during the histologic preparations mask the occurrence of polylactosaminoglycan containing glycoproteins in native frozen sections.

Animals

Adult polyglucosan body myopathy.

This report describes a sporadic late-onset myopathy in two unrelated adults which was marked by polyglucosan inclusions surrounded by abnormally structured mitochondria, the latter finding a localized, possibly reactive phenomenon. The polyglucosan material was characterized by a battery of histochemical and enzyme histochemical techniques; revealed common antigenicity with Lafora bodies, corpora amylacea and muscle fiber inclusions in types IV and VII glycogenoses; and contained ubiquitin. Additional lectin histochemical and associated digestion preparations disclosed the presence of alpha-glycosyl residues as apparently the sole carbohydrate component in polyglucosan bodies while the above mentioned common antigenicity with Lafora bodies and other inclusions suggests an additional, so far unidentified, protein component.

Atrophy

Hepatic morphologic and biochemical changes induced by subacute cocaine administration in mice.

The initial event and site of cocaine-induced hepatic injury have not been elucidated. In an attempt to identify the minimal effective dose and the site of injury, we have examined the livers of mice exposed to small daily doses of cocaine, using morphological and biochemical methods. All doses of cocaine greater than 5 mg/kg were able to cause significant elevation of serum glutamic pyruvic transaminase. Light microscopy revealed a progression of centrilobular necrosis as the dose increased from 10-30 mg/kg. The initial morphologic changes observed prior to necrosis included aggregation of intermediate filaments and dilation of rough endoplasmic reticulum with loss of ribosomes. Immunohistochemistry, using antibodies to cytokeratins, showed staining of individual hepatocytes in livers from cocaine-treated animals but not in controls. In contrast to earlier reports, we found little, if any, disruption of mitochondria. In vitro, the direct application of cocaine, norcocaine, and N-hydroxynorcocaine on isolated mitochondria had no effect on the ADP:O or respiratory control ratios, at concentrations up to 2.0 mM. Our studies demonstrate that any early cellular alterations in cocaine-induced hepatic injury are manifested in intermediate filaments and endoplasmic reticulum with no evidence of mitochondrial involvement.

Alanine Transaminase

Tight junctions adjacent to tumor stromal interface in human invasive transitional cell carcinomas.

Tight junctions adjacent to the tumor stromal interface in invading neoplastic cells of human urinary bladder carcinomas were observed. Basal lamina, collagen and elastic fibers, and cellular debris were found next to the tight junctions. An association between microenvironment (i.e., tumor necrosis) of the invading neoplastic cells and tight junction locations was suggested.

Carcinoma, Transitional Cell

Blood group isoantigen deletion in carcinoma in situ of the urinary bladder.

Blood group isoantigens A and H (O) were measured by the Secific Red Cell Adherence (SRCA) Test in nine radical cystectomy specimens removed from patients with extensive carcinoma in situ of the urinary bladder. All bladders had areas of histologically normal epithelium and areas of epithelial atypia in addition to the carcinoma in situ. In eight cases, tissue-associated blood group isoantigens were deleted in areas showing either atypia or carcinoma in situ. Isoantigens were present in these areas in the ninth case. Blood group isoantigens were absent in approximately half of the sections of histologically normal epithelium. We propose that areas of epithelium which appear benign according to conventional histological criteria but in which the blood group isoantigens are absent may represent areas of low grade carcinoma in situ.

ABO Blood-Group System

Intracytoplasmic lumina in bladder carcinomas.

Intracytoplasmic lumina were identified in neoplastic cells from four human and three canine "spontaneous" bladder carcinomas. They were also found in N-[4-(5-nitro-2-furyl)-2-thiazoly] formamide induced bladder carcinomas in rats as well as in cultured tumor cell lines derived from these experimental tumors. Intracytoplasmic lumina were readily recognized in 5 micrometer. paraffin embedded and 1 micrometer. epoxy embedded sections. Histochemically, intracytoplasmic lumina were strongly positive with PAS and alcian blue-PAS; mucicarmine stain was positive as unevenly distributed droplets. Ultrastructurally lumina were defined by a symmetric unit membrane; they displayed abundant pleomorphic microvilli, which contained prominent cytoskeletal elements. Step section electron microscopic study revealed continuity between intracytoplasmic lumina and the extracellular space in only one case of experimental bladder carcinoma; otherwise they appeared to be entirely encompassed within the cytoplasm. No instance of exocytosis in relation to intracytoplasmic lumina was found. Our observations suggest that intracytoplasmic lumina may be rather frequent in several forms of urothelial carcinoma. They appear to be predominantly but not invariably intracytoplasmic. The mechanism that may determine the development of continuity between intracytoplasmic lumina and the extracellular space and the adduced relationship between intracytoplasmic lumina and the process of secretion remain undetermined.

Animals

Acinar cell carcinoma of the pancreas in a cat.

A feline pancreatic acinar cell carcinoma studied by light and electron microscopy was characterized by three growth patterns: acinar formation, colloid production and sheets of neoplastic cells. Ultrastructurally, the acinar origin of the tumor was determined by the presence of zymogen granules, some of which contained and released microfibrillar material.

Animals

Ultrastructure of canine urinary bladder carcinoma.

Luminal and intraepithelial asymmetric unit membrane plaques were found in the urinary bladder urothelium of normal dogs. Tight junctions were found only at the apical poles of the luminal cells. In four dogs with spontaneous urinary bladder carcinomas the asymmetric unit membrane plaques were replaced by symmetric unit membrane. In the neoplastic luminal cells the tight junctions were partially attenuated. Invasive and metastatic neoplastic cells had some tight junction at the stromal interface. Some gap junctions were seen in the normal urothelium but not in the neoplastic cells. The amount of desmosomes in the neoplastic cells varied according to their direction of differentiation (transitional, squamous or glandular).

Animals

Alterations of intercellular junctions in acinic cell carcinoma of the canine pancreas.

Intercellular junctions in spontaneous canine pancreatic acinic cell adenocarcinomas were compared to those in control canine pancreas. The neoplastic cells displayed proliferation and fragmentation of tight junctions and reduction in size and number of gap junctions. Marked decrease in desmosomal density was observed only in the poorly differentiated carcinoma. In the well differentiated carcinomas a few of the desmosomes were characteristic of those found in squamous cells. No quantatitive or qualitative differences in cell junctions were noted between primary and metastatic tumor.

Adenocarcinoma

Isoantigens A, B and H in urinary bladder carcinomas following radiotherapy.

ABH tissue isoantigens were measured by the Specific Red Cell Adherence (SRCA) test in 66 surgical specimens of urinary bladder, including 53 transitional cell carcinomas, 2 squamous cell carcinomas and 11 controls. The SRCA test was strongly positive in 10 of 11 controls. ABH isoantigens were absent or equivocally present in 68 percent of noninvasive carcinomas (stage 0) and in 65 percent of invasive carcinomas. Clinical histories revealed that all patients with invasive carcinoma who had strongly positive SRCA test results had received prior radiotherapy to the bladder region. None of the patients with invasive bladder carcinoma with negative or weakly positive SRCA tests had been radiated. Histopathology of tumors in both groups was similar. Results of this retrospective study support the hypothesis that radiation may induce differentiation in tumors, possibly through an enhancement of Golgi apparatus function. The SRCA test should not be used as a predictor of the biological behavior of future recurrences in patients with bladder carcinoma who have received therapeutic radiation since radiation may produce "false positive" SRCA test results.

ABO Blood-Group System

Desmosome ultrastructure and biological behavior of chemical carcinogen-induced urinary bladder carcinomas.

In the quantitative electron microscopic study, we examined the relationship of desmosomes to tumor invasiveness in chemical carcinogen (N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide)-induced urinary bladder transitional cell carcinomas in the Fischer rat. The number of a desmosomes per unit area of plasma membrane was significantly reduced in carcinomas. However, the percentage of cell surface area occupied by desmosomes was greater in carcinomas than in controls. This was accounted for on the basis of increases in desmosomal size, which result from squamous differentiation within the tumors. Areas of transitional cell differentiation and squamous differentiation demonstrated an equal capacity for invasiveness. Desmosomes were abundant in invading nests of tumor cells. These findings cast doubt on the validity of the concept of decreased intercellular adhesion as a prerequisite for tumor invasion, since strong interadhesion is probably a function of the area occupied by the intercellular junctions.

Animals

An ultrastructural study of acinic cell carcinomas of the canine pancreas.

Four cases of spontaneous adenocarcinoma of the canine exocrine pancreas were studied by thin section and freeze-fracture electron microscopy. The neoplastic cells in all 4 cases were of acinar origin and showed many alterations of cytoarchitecture compared with normal acinar cells. In the neoplastic cells, zymogen granules varied in number and appearance and contained an abnormal secretory product characterized by 24-nm-thick microtubules. The nuclear volume and surface area and the nuclear cytoplasmic ratio were increased; although the nuclear pore density per nuclear surface area was significantly decreased, there was no change in the nuclear pore density per nuclear volume. There was a decrease in number and size of gap junctions; focal proliferation, fragmentation, and discontinuation of the tight junctions were also noted. The basal lamina (BL) of the neoplastic cells was discontinuous. The tumor microvasculature often appeared as sinusoids and had sparse discontinuous BL. Finally, the endothelium in both tumor and normal tissue contained "tubulo-reticular inclusions" (TRI) which simulated distemper virus and were located in the rough endoplasmic reticulum (RER) and the perinuclear cisternae.

Animals

Freeze-fracture of monolayer cultures.

This paper describes a simple method for the freeze-fracturing of cells in monolayers or multi-layer tissue cultures. The method produces high quality replicas and is applicable to the study of virtually any tissue culture or organ culture system. It uses standard materials and equipment for both tissue culture and freeze-fracturing.

Cell Line

Metal carcinogenesis: a study of the carcinogenic activity of solid metal alloys in rats.

The carcinogenic activity of seven metallic alloys was studied by implanting solid rods of each alloy in the gluteal muscles of Sprague-Dawley rats which were killed after twenty-four months. When the number of tumors in these rats was compared with the numbers in rats not operated on, in rats which had a sham operation, and in rats implanted with Silastic rods, no statistically significant differences in the incidences of the tumors in the several groups were found.

Alloys