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Biomedical subjects

A R Patel

Publications and source records attributed to A R Patel.

At least 37 records · Page 2Linked to original sources

Polyamines modulate transcription but not posttranscription of c-myc and c-jun in IEC-6 cells.

The goal of the current study was to examine whether polyamines are involved in the regulation of transcription and posttranscription of the protooncogenes c-myc and c-jun in intestinal epithelial cells. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Administration of alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis, for 4 or 6 days not only almost completely depleted total (whole) cellular and nuclear polyamines but also significantly decreased expression of the protooncogenes c-myc and c-jun in IEC-6 cells. Using nuclear run-on transcription assay, we demonstrated that the basal rate of transcription of c-myc was decreased by 55% at 4 days and by 60% at 6 days in the DFMO-treated cells. The c-jun transcription in DFMO-treated cells was decreased by 75% at 4 days and 85% at 6 days. The transcription rates of c-myc and c-jun were dramatically stimulated by 5% dialyzed fetal bovine serum (dFBS) in normal quiescent cells. However, polyamine depletion significantly prevented the increased transcription of these two genes in the DFMO-treated cells exposed to 5% dFBS. Furthermore, direct administration of spermidine to isolated nuclei from polyamine-deficient (caused by DFMO) cells resulted in a 2- to 2.5-fold increase in c-myc and c-jun transcription. There were no significant changes in the half-lives of c-myc and c-jun mRNAs between the controls and the DFMO-treated cells. These results indicate that 1) polyamines are required for the transcription of the protooncogenes c-myc and c-jun in IEC-6 cells and 2) depletion of intracellular polyamines has no effect on posttranscriptional regulation of c-myc and c-jun mRNAs. These findings suggest that polyamines play an important role in the regulation of the transcription of protooncogenes, and this may be one mechanism by which polyamines modulate mucosal cell division.

Animals↗

Pressure natriuresis after adrenomedullin in anesthetized spontaneously hypertensive rats.

Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.

Adrenomedullin↗

Chronic sodium-potassium-ATPase inhibition with ouabain impairs renal haemodynamics and pressure natriuresis in the rat.

1. Chronic Na+, K(+)-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 micrograms day-1 kg-1 body weight) or vehicle for 6 weeks. 2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 +/- 2 mmHg; n = 9) than in control rats (116 +/- 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 +/- 73 microliters/min at 150 mmHg, and fell significantly to 322 +/- 64 microliters/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 +/- 0.2 compared with 0.29 +/- 0.2; P < 0.05). Renal blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 +/- 57.1 compared with 82.1 +/- 14.8 mumol min-1 mmHg-1). 5. Thus, chronic inhibition of Na+,K(+)-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25-30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.

Animals↗

Acute Na+,K+-ATPase inhibition with bufalin impairs pressure natriuresis in the rat.

Although it has been reported that Na+,K+-ATPase inhibition with bufalin induces acute and chronic hypertension in the rat, the mechanisms mediating this response are unclear. To examine the role of the kidney in this process, glomerular filtration rate, renal blood flow, and pressure natriuresis were determined in rats treated with bufalin or vehicle during changes in renal perfusion pressure. Mean arterial pressure increased from 123 +/- 4 to 149 +/- 3 mm Hg (P < .05) after 40 minutes of intravenous bufalin and remained at this level. In control rats, glomerular filtration rate was well autoregulated. In bufalin-treated rats, glomerular filtration rate fell with decreasing renal perfusion pressure. Glomerular filtration rate autoregulatory index was greater in bufalin-treated than control rats (P < .05). Renal blood flow showed a similar pattern. Urine flow and sodium excretion were less in bufalin-treated than control rats at equivalent renal perfusion pressures. The slope of the line describing the relation between urine flow and renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Similarly, the slope of the line relating sodium excretion to renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Thus, acute increases in blood pressure during Na+, K+-ATPase inhibition are associated with impaired renal autoregulation and pressure natriuresis. This effect may be important in chronic hypertension associated with Na+,K+-ATPase inhibition in the rat.

Animals↗

The effect of carbon dioxide laser on acid resistance of human tooth enamel: an evaluation by wet chemical analysis and scanning electron microscopy.

The use of the laser in improving acid resistance of tooth enamel has captured the imagination of most researchers. Man's susceptibility to dental caries presents itself as one of the most complicated problems to solve. The carbon dioxide laser at a wavelength of 10.6 microns is highly efficient for dental purposes as this wavelength is close to optimum absorption of dental enamel. A study was carried out using a pulsed carbon dioxide laser to find the effects of laser beam on human tooth enamel in an energy range of 2-20 J/cm2 at a pulse rate of 5 Hz. The effective resistance to acid was determined by wet chemical analysis whereas superficial changes seen on the surface were determined using the scanning electron microscope.

Acid Etching, Dental↗

Hyperferritinemia in reactive hemophagocytic syndrome report of four adult cases.

Four patients were diagnosed with reactive hemophagocytic syndrome (RHPS) during a 7 month period. Of these, three patients were diagnosed with acquired immunodeficiency syndrome complicated by disseminated Mycobacterium tuberculosis infection, incompletely treated Pneumocystis carinii pneumonia and disseminated histoplasmosis respectively. The fourth patient had non-Hodgkin's lymphoma of the mature T-cell phenotype. Fever, bicytopenia, or pancytopenia, elevated serum lactate dehydrogenase (LDH) level (> 1,000 IU/L), and hemophagocytic histiocytosis in smears of bone marrow aspirate were present in all patients. Hyperferritinemia (> 10,000 ng/ml) was present in all (range 34,976 to 425,984 ng/mL) and showed a decrease in the two patients who responded to therapy. Hyperferritinemia (> 10,000 ng/ml) and elevated serum LDH (> 1,000 IU/L) are important clues to the diagnosis of RHPS in the febrile cytopenic patient with immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Reactive hemophagocytic syndrome: a new presentation of disseminated histoplasmosis in patients with AIDS.

We report the cases of six patients with AIDS in whom reactive hemophagocytic syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was diagnosed by established criteria, including fever (duration of > or = 7 days, with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the basis of the results of cultures of the bone marrow sample. The serum lactate dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984 ng/mL). Five patients had features resembling severe sepsis with multiorgan dysfunction. Three patients recovered, and the findings of RHPS resolved following therapy with amphotericin B. In patients with AIDS, the combination of fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in establishing the diagnosis.

AIDS-Related Opportunistic Infections↗

Denitration of glycerol trinitrate by resting cells and cell extracts of Bacillus thuringiensis/cereus and Enterobacter agglomerans.

A number of microorganisms were selected from soil and sediment samples which were known to have been previously exposed to nitrate ester contaminants. The two most effective bacteria for transforming glycerol trinitrate (GTN) were identified as Bacillus thuringiensis/cereus and Enterobacter agglomerans. For both isolates, denitration activities were expressed constitutively and GTN was not required for induction. Dialysis of cell extracts from both isolates did not affect denitration, which indicates that dissociable and depletable cofactors are not required for denitration. With thin-layer chromatography and high-performance liquid chromatography, the denitration pathway for both isolates was shown to be a sequential denitration of GTN to glycerol dinitrate isomers, glycerol mononitrate isomers, and ultimately to glycerol. GTN was observed to be completely converted to glycerol during a long-term incubation of cell extracts.

Bacillus cereus↗

Segmental chloride transport in the Dahl-S rat kidney during L-arginine administration.

L-Arginine normalizes pressure natriuresis in Dahl salt-sensitive (DS) rats. The nephron segments responsible for improvement in sodium chloride handling during L-arginine administration are unknown. Micropuncture techniques were used to examine fluid and chloride transport along superficial nephron segments in DS rats maintained on an 8% sodium diet and given L-arginine or vehicle ip for 3 wk. Renal perfusion pressure in vehicle-treated DS rats was reduced to that of L-arginine-treated DS rats with an aortic snare. Dahl salt-resistant (DR) rats receiving vehicle were examined for comparison. In agreement with previous studies, urinary sodium chloride excretion was greater (P < 0.05) in L-arginine DS rats than in vehicle DS rats and not different from DR rats at equivalent renal perfusion pressures. Whole-kidney and single-nephron GFR were not different (P = not significant) among groups. Fractional proximal tubule chloride and fluid reabsorption was not different among groups. Fractional loop chloride reabsorption was greater in vehicle-treated DS rats than in DR rats (58.5 +/- 1.5 versus 46.6 +/- 1.7%; P < 0.05), confirming the enhanced chloride reabsorption at this location in DS rats previously reported. Fractional loop chloride reabsorption was identical in vehicle- and L-arginine-treated DS rats (58.4 +/- 1.4 versus 58.9 +/- 3.9%; P = not significant). Fractional loop fluid reabsorption was not different among groups. Fractional distal fluid and chloride reabsorption was not different between DS rat groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

L-arginine improves transmission of perfusion pressure to the renal interstitium in Dahl salt-sensitive rats.

L-Arginine normalizes pressure natriuresis in Dahl salt-sensitive (DS) rats. To determine the role of renal interstitial hydrostatic pressure (RIHP) in this phenomenon, we measured RIHP determined by servo-null during acute changes in renal perfusion pressure in anesthetized DS rats receiving L-arginine (300 mg.kg-1.day-1 ip) or vehicle for 3 wk. Dahl salt-resistant (DR) rats were controls. As observed previously, the slope of the pressure-natriuresis relationship was greater (P < 0.05) in L-arginine-treated DS rats than vehicle DS rats and not different from DR rats. The slope of the relationship between renal perfusion pressure and RIHP was greater (P < 0.05) in DR rats than vehicle DS rats. In L-arginine-treated DS rats the slope of this relationship was greater (P < 0.05) than that in vehicle DS rats and not different from DR rats. Removal of the renal capsule blunted the pressure-natriuresis relationship in L-arginine-treated DS rats but had no effect in vehicle DS rats. Thus L-arginine improves transmission of perfusion pressure into the renal interstitium in DS rats and may contribute to the improved pressure-natriuresis response.

Animals↗

Concurrent sickle cell hemoglobin C disease and diabetes mellitus: no added risk of proliferative retinopathy?

Of 148 adults with sickle cell hemoglobin C (SC) disease seen at Cook County Hospital and Clinics, Chicago, Illinois, eight patients had coexistent noninsulin-dependent diabetes mellitus. The clinical findings were notable for the paucity of retinal vascular changes. No patient showed proliferative diabetic retinopathy; one patient showed background diabetic retinopathy consisting of a few microaneurysms. Six of the eight patients showed no lesions of proliferative sickle retinopathy. Coexistence of noninsulin-dependent diabetes mellitus and SC disease does not appear to have an additive adverse effect on the presence or severity of proliferative retinopathy in the affected patient.

Adult↗

Craniofacial excision for recurrent osteogenic sarcoma of maxilla.

Two cases of recurrent osteogenic sarcoma of the antro-ethmoidal complex treated at our hospital by a craniofacial resection are presented. The imperative need to treat osteogenic sarcomas of the maxilla primarily by a radical approach such as a craniofacial resection is emphasized.

Adolescent↗

The accuracy and precision of the Accutracker ambulatory blood pressure monitor.

Prerequisite to the use of ambulatory blood pressure monitors in epidemiologic research is demonstration of a satisfactory level of accuracy and precision. Previous evaluations of these devices raise a number of methodological concerns which complicate interpretation of their findings. Also, important issues regarding the precision of blood pressure measurements and the identification of factors associated with measurement inaccuracies remain unaddressed. To assess the accuracy and precision of the Accutracker ambulatory blood pressure monitor, we obtained five serial estimates of resting blood pressure on 120 ambulatory subjects in The Johns Hopkins Medical Institutions in 1987. Two Accutrackers and two manual observers independently recorded blood pressure with the order determined at random. The fourth observer in each sequence obtained a replicate measurement. For both systolic and diastolic blood pressures, the mean difference between Accutracker and manual measurements was less than 3 mmHg for each pairwise comparison. Scatter plots and regression analyses demonstrated that both Accutrackers tended to underestimate high systolic and diastolic blood pressures. In bivariate and multivariate analyses, increased age was significantly associated with underestimation of systolic blood pressures by both Accutrackers. With respect to the precision of blood pressure measurement, no significant differences were present among the four observers. In summary, our data suggest that the Accutracker has satisfactory accuracy and precision, but that accuracy is not uniform across patient subgroups.

Adult↗