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Biomedical subjects

R S Weinstein

Publications and source records attributed to R S Weinstein.

At least 163 records · Page 9Linked to original sources
PubMed1984

Malignant cell detection and cervical cancer screening.

A study was conducted to determine the isolated, single-cell detection characteristics of human observers as this information relates to cervical cancer screening. Two interrelated experiments were performed. First, the receiver operating characteristic (ROC) was obtained for slide screening. In this experiment, approximately 1,200 slides were examined. Second, ROCs were obtained for human observer cell discrimination, using a rating method. An individual's curves were computed, assuming a multiple decision criterion. In this experiment, 6,375 cells from the same specimens used in the slide screening experiment were studied. In both experiments, results were analyzed using a Gaussian signal-detection model. This approach provided analytical detection criteria and rigorous definition of ROCs. These experiments addressed the problem of where the screening information lies: (1) in individual cells alone or (2) with additional components in global or other a priori information. We quantified the detection requirements of (1) the Papanicolaou smear screening process, Az = 0.99, and (2) the capabilities of trained cytotechnologists on isolated single cells, Az = 0.87. System modeling using intermediate cell detection instead of "rare event" detection resulted in a reduction of the predicted number of cells required for analysis from approximately 60,000 to 750.

Female↗
PubMed1984

Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms.

Histochemical and direct enzyme analysis of osseous tissue from 23 patients with hypophosphatasia revealed that all clinical forms of this inherited metabolic bone disease are characterized by deficiency of alkaline phosphatase (ALP) activity in bone. The severe infantile form has the most profound deficiency, infantile form has the most profound deficiency, yet the cellular source of this enzyme--osteoblasts and their matrix vesicles--are normal by routine light and electron microscopy. Despite radiographic changes in bone metaphyses consistent with rickets, iliac crest biopsy of one affected child revealed no abnormalities; the other had evidence of a mineralization defect, but not as severe as that in affected infants. In this child and several affected adults with osteomalacia, osteoblasts appeared flat and metabolically inactive. Although these histological changes suggested a different pathogenetic mechanism for adult and childhood hypophosphatasia, these changes are most likely secondary to the underlying osteomalacia. Our findings are most consistent with evidence that childhood and adult hypophosphatasia often represent clinical expression of the heterozygous state for ALP deficiency which, when homozygous, results in the clinically severe, recessive, infantile form. Histochemical and direct analysis of bone tissue from controls and patients with hypophosphatasia demonstrated that the severe infantile form is associated with the most severe ALP deficiency. In the milder clinical forms, ALP deficiency in bone is not as profound. In general, the severity of the clinical expression of hypophosphatasia reflects the magnitude of the deficiency of ALP in bone. This is the expected finding for this inborn error of metabolism, which illustrates the major role bone ALP activity has in the process of normal skeletal mineralization.

Adolescent↗
PubMed1983

The band 3-rich membrane of llama erythrocytes: studies on cell shape and the organization of membrane proteins.

The erythrocyte membrane of the llama was characterized in comparison to that of the human. The llama erythrocyte was an elliptical disk that resisted shape alterations in hyperosmotic buffers and following metabolic depletion, both of which induce speculation of the human red cell. Lysophosphatidylcholine incorporation produced minor serrations of the edge of the llama disk but no spicules, whereas human red cells became sphero-echinocytes. The polypeptide profiles in the membranes of the two species were similar, except for several noteworthy differences: a marked elevation in the relative content of band 3; the absence of membrane-bound band 6; and simpler glycoprotein pattern in the llama. The concentration of band 3 in llama was about two and a half to three times that in the human and intramembrane particles in the protoplasmic leaflet of freeze-fractured llama membrane were correspondingly increased. The selective solubilization of bands 1, 2 and 5 in low ionic strength buffer, and all of the peripheral proteins in high alkaline buffer were similar except for increased retention of ankyrin by the llama membrane. These data suggest a similar disposition of membrane proteins. The llama membrane was markedly resistant to the solubilization of integral proteins by the nonionic detergent, Triton X-100. This property and the general resistance to shape changes may be related to the high concentration of band 3.

Animals↗
PubMed1983

Cellular changes in rat urinary bladder carcinomas induced by FANFT: a quantitative electron microscopic analysis.

Morphometric data of normal and neoplastic urinary bladder epithelia have been collected from the Fischer rat FANFT model. Sequential measurements of volumes, surface areas, and numerical densities of organelles, and where pertinent, cellular compartments have been made during FANFT carcinogenesis, utilizing standard point and intersection counting methods. The data show that neoplastic transformation of rat bladder epithelium, and progression of FANFT tumors are associated with increasing volume densities of cells, nuclei, microvilli, rough endoplasmic reticulum, and mitochondria, as well as with decreasing volume densities of the cytoplasmic matrix, fusiform vesicles, Golgi complex, and lysosomes. Surface densities of the plasma membrane (microvillar), nuclei, rough endoplasmic reticulum, as well as mitochondrial outer and inner membranes progressively increase while surface densities of non-microvillar plasma membrane, fusiform vesicles, and Golgi complex decrease with time. Smooth endoplasmic reticulum reaches its maximum volume and surface densities in tumors present 26 weeks after the initiation of FANFT feedings (26-F tumors). This may reflect the function of smooth endoplasmic reticulum as the site of detoxification of the carcinogen, noting that FANFT is metabolized by microsomal enzymes, and in this experiment is fed only for 26 weeks. The nuclear/cytoplasmic ratio is 1:4 in normal Fischer rat urothelium, 1:3 in 26-F and 43-F tumors, which are noninvasive, and 1:2 in 61-F, which are invasive tumors. The quantitative data correlate well with the changes in degree of differentiation of the tumors and with their biological behavior.

Animals↗
PubMed1983

Hypercalcemia and nephrolithiasis provoked by serum phosphorus reduction in a patient with chronic renal failure and sarcoidosis.

A patient with sarcoidosis and chronic renal failure was treated for hyperphosphatemia with aluminum hydroxide. The subsequent fall in serum phosphorus was followed by the development of hypercalcemia and nephrolithiasis. Corticosteroid therapy normalized the serum calcium and halted the progression of the nephrolithiasis, but did not improve renal function. Hyperphosphatemia may have blocked the expression of sarcoid hypercalcemia in the patient. The mechanism is unclear but inhibition of the synthesis or action of 1,25-dihydroxyvitamin D may have been involved. Reduction of serum phosphorus may lead to severe hypercalcemia in some patients with sarcoidosis.

Adult↗
PubMed1983

Prognosis in carcinoma of the urinary bladder based upon tissue blood group abh and Thomsen-Friedenreich antigen status and karyotype of the initial tumor.

Several markers of initial bladder carcinomas described recently may be clinically significant predictors of biological behavior of future recurrences. Comparison of the marker systems and assessment of the value of using multiple markers have been difficult, because the various markers have been studied in different patients. In this study, we compared four markers [chromosome mode, marker chromosomes, and expression of the ABH "blood group" antigens and the Thomsen-Friedenreich antigen (using immunoperoxidase or lectin immunoperoxidase methods)] in 39 patients presenting initially with low-stage bladder carcinoma and followed 3 to 11 years or until deep muscle invasion occurred. Each of the markers was significantly related to subsequent recurrences with deep muscle invasion, and each marker system was able to identify those patients with a very low risk of subsequent invasion. For detection of a subpopulation of patients with Grade II carcinomas who were at high risk for development of subsequent invasion, combinations of markers, especially hyperdiploidy and abnormal expression of the Thomsen-Friedenreich antigen, were significantly more effective than any single marker system.

ABO Blood-Group System↗
PubMed1982

Membrane differentiation in the Golgi apparatus of mammalian urinary bladder epithelium.

The endomembrane system in superficial and intermediate epithelial cells of mammalian urinary bladder was studied by cytochemistry, thin-section and freeze-fracture electron microscopy to determine the sites where special forms of membrane differentiation first appear. Glutaraldehyde-resistant NADH-ferricyanide reductase, distinctive 11-12 nm intramembrane particles (IMP), and asymmetry of membrane leaflets served as markers of membrane maturation. The three markers were specifically associated with the maturing face of Golgi apparatus and were absent from the remainder of the endomembrane system. Activity of this enzyme was associated with the lateral regions of the maturing face, fusiform vesicles, and the plasmalemma. Asymmetric unit membrane (AUM) plaques were not observed in the Golgi apparatus per se but were present in immature fusiform vesicles that had not detached from the maturing face. When freeze-fracture replicas and thin sections were compared, randomly arranged 11-12 nm IMP first appeared in maturing face membranes that were adjacent to clusters of "free" polyribosomes in the Golgi apparatus region. The proximity of these polyribosomes suggests that they may be related to the coincident appearance of the 11-12 nm IMP in the maturing face membrane. Our observations support the hypothesis that membranes undergo differentiation during "flow" through compartments of the endomembrane system. The lateral regions of the maturing face of the Golgi apparatus appear to be a critical location for the morphogenesis of plasma membranes in urinary bladder.

Animals↗
PubMed1982

Decreased mineralization in hemodialysis patients after subtotal parathyroidectomy.

Many hemodialysis patients undergo subtotal parathyroidectomy (sPTx) because of the complications of severe secondary hyperparathyroidism. In some patients, however, renal osteodystrophy fails to regress. In uremia, the high levels of circulating immunoreactive parathyroid hormone (iPTH) which accompany osteitis fibrosa are associated with accelerated bone formation. After sPTx, the fall in iPTH may decrease mineralization and increase osteoid formation. Bone histomorphometry, densitometry, and serum biochemical determinations were done in 20 patients on regular maintenance hemodialysis and after sPTx in 3 additional patients. Densitometry at the radial diaphysis was inversely related to osteoid volume so that low bone mineral content indicated excess osteoid. Elevated serum alkaline phosphatase activity was associated with osteitis fibrosa. Tetracycline double labels identified 5 patients with an increased rate of mineralization. Levels of iPTH and serum phosphorus were positively correlated to the mineralization rate. The fall in iPTH after sPTx was accompanied by a reduction in osteitis fibrosa and decreased mineralization. The nonosteoblastic osteoid became more abundant. After sPTx some hemodialysis patients may convert the osteitis fibrosa to a poorly treatable low turnover osteomalacia.

Adult↗
PubMed1982

Focal mineralization defect during disodium etidronate treatment of calcinosis.

The use of disodium etidronate (EHDP) for the treatment of calcinosis is complicated by the threat of drug-induced inhibition of skeletal mineralization. Adults with Paget's disease of bone treated for 6 months with 10-20 mg/kg/day of EHDP have been reported to show both a marked delay in mineralization and a diffuse excess of unmineralized bone matrix. Drug-induced bone disease is, however, a function of growth as well as of the dose and duration of therapy. Therefore, children treated with EHDP may respond differently to the drug-induced mineralization defect. A 10-year-old girl with dermatomyositis developed incapacitating ectopic calcification. After 9 months of therapy with 12 mg/kg/Day of EHDP, a small decrease in the calcinosis was accompanied by a dramatic increase in joint mobility. Bone mineral content of the radial diaphysis showed a failure to gain mineral density as expected with prepubertal growth (8 cm/year). Bone biopsy revealed a patchy excess of osteoid. Although the percentage of osteoid surface labeled by tetracycline was reduced, normal mineralization was evident in the double-labeled areas. In children, the mineralization defect occurring with EHDP treatment may be focal.

Bone Diseases↗
PubMed1982

Qualitative bone defect in uremic osteosclerosis.

Osteosclerosis, an increased volume of trabecular bone, is a common but often misinterpreted feature of uremic osteodystrophy. Despite the apparent radiographic density of osteosclerotic bone, pain and fracture may be associated. If accumulated osteoid and woven bone exceed the volume of lamellar bone removed in chronic renal insufficiency, bone density may be reduced despite increased trabecular volume. Concomitant histomorphometric and photon absorption determinations of transileal bone biopsies were done to investigate the relationship between quantity and quality of bone in uremic and non-uremic osteopenic patients. In osteopenic patients with uremia, bone core density had no significant relationship to trabecular bone volume or mineralized bone volume whereas in non-uremic osteopenic patients, these parameters were directly related (r = 0.867 and r = 0.921, respectively, p less than 0.001). The bone core density in the uremic patients was negatively correlated with the total osteoid volume (r = -0.764, p less than 0.05) and positively related to the serum phosphorus concentration (r = 0.739, p less than 0.05). Serum levels of immunoreactive parathyroid hormone (iPTH) and alkaline phosphatase activity were higher in the patients with radiographic osteosclerosis than in the other uremic patients. The lack of correlation between bone volume and density indicates a qualitative defect in uremic bone. It appears that in uremia, elevated iPTH and serum phosphorus levels may augment bone formation, albeit poorly mineralized with woven architecture. While radiographic density paradoxically increases, the amount of normally mineralized bone may be reduced.

Adolescent↗