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Biomedical subjects

A Grover

Publications and source records attributed to A Grover.

At least 91 records · Page 5Linked to original sources

Roles of extracellular matrix components in differentiating teratocarcinoma cells.

F9 embryonal carcinoma cells treated with 5 X 10(-8) M retinoic acid and cultured in suspension for 8 days form aggregates consisting of an outer epithelial layer of alpha-fetoprotein-producing visceral endoderm cells. We have previously shown (Grover, A., Oshima, R. G., and Adamson, E. D. (1983) J. Cell Biol. 96, 1690-1696) that the differentiation of F9 cells to visceral endoderm is accompanied by the activation of several genes, and increased laminin synthesis is one of the earliest events. Here we analyze in detail the syntheses and secretion of fibronectin, type IV collagen, and laminin during the 8-day process. Employing immunoprecipitation and enzyme-linked immunosorbent assay, we show that the levels of all three components change with different patterns. Unstimulated F9 cells synthesize and secrete relatively high levels of fibronectin and low levels of type IV collagen. Fibronectin synthesis and secretion decreases to 10% of its original level whereas type IV collagen synthesis rises approximately 3-fold during the differentiation process. Laminin synthesis also rises at least 2-fold, and the proportions of its subunits change as the syntheses of B1 and A accelerate starting on day 2. However, unlike fibronectin and type IV collagen, laminin is largely accumulated in the aggregates. The data suggest that fibronectin has a role in aggregation whereas laminin is important in the differentiation process.

Animals↗

Morphologic changes in rat urothelial cells during carcinogenesis: II. Image cytometry.

Improved early detection of neoplasia by screening of urothelial cells requires an understanding of the features distinguishing normal and neoplastic cell populations. We have begun a program of study based upon a rat model system for the controlled observation of early-stage lesions produced by the carcinogen N-butyl-N-(4-hydroxybutyl)- nitrosamine. Cells dissociated directly from normal and malignant urothelium were characterized by conventional cytopathology techniques and by quantitative microscopy (for nuclear texture and nuclear and cytoplasmic size, shape, and stain content) to derive a comprehensive picture of bladder tumor development. By following the changes that occur in the dissociated urothelial cells we have found that the nuclear area, total nuclear stain, nuclear shape, and the nuclear chromatin change significantly over a 48-wk interval as the lesions progress toward malignancy.

Animals↗

Sorting out in heterotypic cell aggregates is regulated by differences in the cell surface charge.

Random aggregates of heterotypic cells derived from two different embryonic tissues sort out into homotypic zones, one enclosing the other. The specification of the enclosed or enclosing position is based on a tissue hierarchy. Cells differ in their net negative charge as indicated by their different isoelectric points (pI). The cells of higher pI enclose the cells of lower pI. Cell pI is lowered by treatment with heparin. Cells with experimentally altered pI also sort out, and their position is specified by the differences in their pI. It is suggested that the cell surface ionogenic groups determine the free surface energy which controls the positioning of cells in a mixed aggregate.

Animals↗

Epithelial layer formation in differentiating aggregates of F9 embryonal carcinoma cells.

F9 embryonal carcinoma (EC) cells, cultured in suspension in medium containing 5 X 10(-8) M retinoic acid, aggregate and differentiate into embryoid bodies with an outer layer of visceral endoderm cells that synthesize and secrete alphafetoprotein (AFP) (Hogan, B. L. M., A. Taylor, and E. Adamson, 1981, Nature (Lond.). 291:235-237). Here we analyze the formation of the outer layer of cells as a model for epithelial differentiation. Three morphological phases are described, but analyses of cell numbers and the synthetic rates of some proteins, as well as the appearance of markers of visceral endoderm and basement membrane, show that the formation of the outer layer occurs as an orderly progression of multiple events. The markers used to follow the ontogeny of epithelial layer formation include SSEA-1, l, and i blood group antigens, laminin, fibronectin, type IV collagen, cytoskeletal intermediate filament proteins (vimentin, Endo A, and B), and AFP. The onset of epithelium formation occurs between the third and fourth day of culture, but its function is maximally expressed only when it is well organized. We found the rate of AFP secretion to be a measure of the proper alignment and maturity of the epithelium which occurs at the seventh or eighth day. This model of epithelium formation may help to explain how similar processes occur during embryogenesis.

Animals↗

Role of laminin in epithelium formation by F9 aggregates.

The formation and maturation of the outer epithelial layer is essential for maximal alphafetoprotein (AFP) production during differentiation of F9 embryoid bodies in the presence of 5 X 10(-8) M retinoic acid (Grover et al., 1983. J. Cell Biol. 96:1690-1696). The critical phase is between the third and the fourth day when the components of the extracellular matrix organize into a basement membrane. The role of some of these components in the process of epithelium formation and maturation is analyzed in this paper. The role of laminin was investigated by testing the effect of exogenous laminin and antilaminin in cultures of differentiating F9 aggregates. Tests included growth rates, morphological changes, AFP production, determination of AFP mRNA levels, and fluorescent staining for basement membrane components and for epithelial markers. At concentrations greater than 5 micrograms/ml, exogenous laminin inhibited the production of AFP and prevented AFP gene transcription. On the basis of immunofluorescence tests, exogenous laminin appeared to act by preventing the accumulation of a basement membrane and by disrupting the organization of the outer layer into an epithelium. No such effects were produced by fibronectin or collagens type I or IV. Aggregates cultured in the presence of antilaminin also failed to organize an epithelium and did not produce AFP, whereas those in normal rabbit serum differentiated normally. Therefore, endogenous laminin plays a key role not only as a basement membrane structural component but also in organizing the epithelial layer of endoderm cells and hence (indirectly) in gene expression.

Animals↗

Depression of endostreptosin, streptolysin O and streptozyme antibodies in patients with idiopathic nephrosis with and without a nephrotic syndrome.

We determined antibody titers to Endostreptosin (ESS), a recently described protein antigen in the cytoplasm and the plasma membrane of Group A streptococci in 286 normals of different age groups and in 34 children and 19 adults who had or had had at one time a nephrotic syndrome due to idiopathic nephrosis. Antistreptolysin O titers were also determined in 33 of the idiopathic nephrotics. Similarly, antibody titers to Streptozyme were determined in 21 patients with idiopathic nephrosis and 61 normals with a similar age distribution. Severe depression of these antibody titers was found in almost all patients with this disease not only during the presence of a nephrotic syndrome but for long periods up to 20 years following an episode of a nephrotic syndrome when the patients were in complete remission. Patients with a nephrotic syndrome due to chronic glomerulonephritis (5), S.L.E. (4), membranous nephropathy (5), diabetes mellitus (1) or amyloidosis (1) did not show abnormally low values for antibodies to Endostreptosin, Streptolysin O or Streptozyme. High-dose steroid medication as such for prolonged periods of time does not depress Endostreptosin or Streptolysin O antibody titers below the expected mean, as demonstrated in 15 patients with S.L.E.

Adolescent↗

Estrogen action in rooster liver. Modification of a tRNASer-inactivating activity.

The hepatic synthesis of the yolk protein, phosvitin, can be induced in rooster by the administration of estrogen and this provides a model for studying the regulatory mechanisms involved. Since phosvitin is unusually rich in serine the effect of estrogen on the metabolism of serine transfer RNA (tRNASer) was examined. Rooster liver contains an activity capable of inactivating rooster liver tRNASer. This activity has specificity in that it inactivates only part of the tRNASer in the unaminoacylated form. Upon estrogen administration this activity is modified with a change in specificity and the modified activity is able to inactivate only a significantly smaller amount of tRNASer than the unmodified activity. This novel mechanism may be involved in the regulation of some species of tRNASer and thus may be part of the translational control involved in estrogen-induced phosvitin synthesis.

Animals↗

Body fluid compartments in rabbits on exposure to acute hypobaric hypoxia.

Body fluid compartments were studied in rabbits divided into three groups--control, exposed to acute hypoxia, and exposed to hypoxia after treatment with 2 mg frusemide intramuscularly. Total body water, extracellular body water, and plasma space were determined using the triple radiotracer technique. Total body water decreased insignificantly with no change in extracellular body space on exposure to hypoxia. Plasma volume and blood volume showed a significant decrease with a significant increase in haematocrit. In rabbits pretreated with frusemide, total body water, extracellular body water, plasma volume, blood volume, and interstitial fluid space decreased significantly on hypoxic exposure. This study suggested hypohydration on acute hypoxic exposure with a loss of intracellular water, while pretreatment with frusemide resulted in further hypohydration with a loss from both intracellular and extracellular compartments. The results have been discussed in relation to suggested use of diuretics on induction to high altitude.

Altitude Sickness↗

Haematologic changes in rabbits during acclimatisation, deacclimatisation, and reinduction to hypoxia.

Haematologic changes were studied in 16 albino rabbits during acclimatisation, deacclimatisation, and reinduction to hypobaric hypoxia. Of these, four animals died during reinduction. Haemoglobin, haematocrit, and red blood cell count attained maximum values by the 15th day during acclimatisation and by the 10th day during reinduction. Reticulocyte count reached maximum level by the fifth day, both during acclimatisation and reinduction. All these parameters returned to initial control levels by the 10th day of deacclimatisation. The erythrocytes became macrocytic during acclimatisation and remained so during deacclimatisation and reinduction. Blood volume increased on acclimatisation, returned to control values during deacclimatisation, and remained low at this level on reinduction. Red cell mass increased both during acclimatisation and reinduction and returned to control levels on deacclimatisation. Plasma volume did not change on acclimatisation and deacclimatisation, but was reduced on reinduction. The erythrocyte life span and erythrocyte glutamic oxaloacetic transaminase (EGOT) decreased during acclimatisation and reinduction. There was no change in RBC osmotic fragility, indicating no change in the integrity of the red cell wall. The deaths during reinduction were possibly due to haemoconcentration and increased blood viscosity as a result of reduction in plasma volume. It has been concluded that reinduction to hypoxia after a phase of deacclimatisation imposes a more severe stress than experienced during acclimatisation.

Acclimatization↗

A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina.

BACKGROUND: Unfractionated heparin has been used extensively for the treatment of unstable angina/non-Q wave myocardial infarction but it has several disadvantages. Low-molecular weight heparins are now recommended although they are 3-5 times costlier than unfractionated heparin since they are convinient to administer and do not require activated thromboplastin time monitoring. Whereas enoxaparin, a low-molecular weight heparin, has been demonstrated to be superior to unfractionated heparin, the results of other low-molecular weight heparins have not been so convincing. METHOD AND RESULTS: Through manual, MEDLINE and EMBASE search, we identified five randomized trials (excluding enoxaparin trials) that compared low-molecular weight heparins with unfractionated heparin in unstable angina. The prespecified efficacy end point of interest included a composite of death, myocardial infarction, recurrent angina and urgent revascularization. The safety end point was taken as a composite of major hemorrhage, minor hemorrhage, thrombocytopenia, allergic reaction and any other adverse event. We calculated odds ratio (95% confidence interval) for each trial for the composite end point, and the pooled odds ratio (95%) confidence interval) was calculated using two established methods of meta-analysis, the Mantel-Haenszel-Peto method and the DerSirmonian-Laird method. Both the methods yielded similar odds ratio (95% confidence interval). Separate odds ratio were calculated for efficacy and safety end points. There was a nonsignificant reduction in the incidence of the composite efficacy end point: the odds ratio (95% confidence interval) was 0.83 (0.70-0.99: p=0.08). The odds ratio (95% confidence interval) for the safety data was 0.78 (0.69-1.26: p=0.33). CONCLUSIONS: No statistically significant difference was observed when the efficacy and safety of low-molecular weight heparins were compared with those of unfractionated heparin. A cost-effectiveness analysis of low-molecular weight heparins versus unfractionated heparin must be done urgently to establish more firmly the place of low-molecular weight heparins in the management of unstable angina.

Adult↗

Secondary lymphoma of the heart presenting as recurrent syncope.

A 12-year-old male child presented with recurrent syncope. Ventricular tachycardia was noted on the electrocardiogram. Transthoracic echocardiogram revealed a homogeneous tumor mass in the right ventricular cavity with extension into the outflow region. Left cervical lymph node biopsy confirmed the diagnosis of non-Hodgkin's lymphoma. The tumor resolved completely with chemotherapy without surgical intervention.

Amiodarone↗

A cardiac evoked response algorithm providing automatic threshold tracking for continuous capture verification: a single-center prospective study.

BACKGROUND: The AutoCapture algorithm as implemented in Regency and Microny pacemakers (Pacesetter Inc., Sylmar, CA, USA) provides beat-by-beat monitoring of capture based on proper detection of the evoked response, provides high output back-up pulse when loss of capture occurs, performs periodic threshold evaluations and acquires the capture threshold data in a time-based event counter for later retrieval. The safety and efficacy of this algorithm was prospectively evaluated at a tertiary care hospital of north India. METHODS AND RESULTS: Fifty-four patients (38 males, mean age 66+/-13 years) received a ventricular pacemaker model Regency SC+ with low polarization bipolar lead for high-grade atrioventricular block (n=42) and sick sinus syndrome (n=12). Evoked response and polarization signal were assessed initially at 24 hours postimplant, and follow-up measurements were systematically conducted at week 1 and months 1, 3 and 6. Further evaluation of eligible patients was performed at 6-monthly intervals. Lead implantation parameters were optimum in all patients. At 6 months, the algorithm was functional in 51 patients. The pacing threshold increased to 0.89+/-0.36 V (p<0.001) in the first month and stabilized thereafter. Significant saving of energy was accomplished by a constant output safety margin of 0.3 V instead of the traditional 100%. While the evoked response signal remained stable throughout the study period, the potential signal increased significantly from 0.6+/-0.7 mV to 1.0+/-0.6 mV (p<0.001) in the first month and remained steady subsequently. Back-up pacing in the event of exit block was confirmed in all 25 patients who underwent a 24-hour Holter test. Based on the suggested sense margins, ventricular undersensing was observed in 7 (28%) patients, the majority of whom had competitive cardiac rhythms. An elderly patient with pneumonic illness succumbed to pulmonary embolism at 6 months. CONCLUSIONS: This large single-center experience on AutoCapture demonstrates the success of this algorithm in low-energy ventricular pacing without compromising the patient's safety.

Adolescent↗