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R Agarwal

Publications and source records attributed to R Agarwal.

At least 271 records · Page 15Linked to original sources
PubMed1993

Protection against malignant conversion of chemically induced benign skin papillomas to squamous cell carcinomas in SENCAR mice by a polyphenolic fraction isolated from green tea.

Progression of benign tumors to malignant cancer is critical since cancerous lesions are capable of metastatic spread and eventually causing death. Inhibitors of the conversion process, therefore, would likely be useful as cancer chemopreventive agents. In this study, we assessed the protective effect of topical application of a polyphenolic fraction isolated from green tea (GTP) against spontaneous as well as benzoyl peroxide (BPO)- and 4-nitroquinoline-N-oxide (4-NQO)-enhanced malignant conversion of chemically induced skin papillomas in SENCAR mice. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz(a)anthracene as a tumor-initiating agent followed by twice a week application of 12-O-tetradecanoylphorbol-13-acetate as a tumor-promoting agent. Beginning at the 20th week, when papilloma yield was stabilized, enhanced malignant conversion was achieved by twice weekly topical application of either BPO or 4-NQO, whereas spontaneous malignant conversion was associated with topical application of acetone. In these protocols, preapplication of GTP (6 mg/animal) 30 min prior to skin application of acetone, BPO, or 4-NQO resulted in 14, 31, and 29% protection, respectively, in terms of percentage of mice with carcinomas, and 20, 35, and 43% protection in terms of number of carcinomas/mouse. In these experiments, a BPO- and 4-NQO-enhanced rate of malignant conversion was also found to be decreased significantly by the skin application of GTP; however, such effects of GTP were less profound in the cases of spontaneous malignant conversion. The results of this study suggest that, in addition to its chemopreventive effects against tumor initiation and promotion stages of multistage carcinogenesis, green tea also possesses significant protective effects against tumor progression, specifically tumor progression induced by BPO and 4-NQO.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Protective effects of green tea polyphenols administered by oral intubation against chemical carcinogen-induced forestomach and pulmonary neoplasia in A/J mice.

Our studies and others have shown the cancer chemopreventive effects of chronic administration of green tea in several animal tumor models. In this study, the administration of a polyphenolic fraction isolated from green tea (GTP) by oral intubation at a dose of 5 mg in 0.2 ml water 30 min prior to challenge with carcinogen, afforded significant protection against both diethylnitrosamine (DEN)- and benzo(a)pyrene (BP)-induced forestomach and lung tumorigenesis in A/J mice. The protective effects were evident by a decrease in numbers of tumors/mouse in GTP-fed groups compared to non GTP-fed controls. In the forestomach tumorigenesis protocol, GTP afforded 71 and 66% protection against, respectively DEN- and BP-induced tumor multiplicity. In the case of lung tumorigenesis protocol, however, the protective effects of GTP were 41 and 39%, respectively. Histological examination of forestomach tumors showed significantly lesser number of squamous cell carcinoma formation in GTP-fed groups of mice compared to carcinogen alone-treated controls. When pulmonary tumors were examined histologically, no adenocarcinomas were observed in GTP-fed groups compared to 15% mice with adenocarcinomas in DEN and BP alone-treated controls. The results of this study suggest that limited doses of GTP administration by gavage 30 min prior to carcinogen challenge may afford protection against carcinogen-induced tumorigenesis in internal body organs.

Administration, Oral↗
PubMed1993

Clinically guided closure of femoral arterial pseudoaneurysms complicating cardiac catheterization and coronary angioplasty.

Femoral artery pseudoaneurysm formation is a significant problem in patients undergoing cardiac catheterization and interventional cardiac procedures. It is especially more common with the use of anticoagulant and antiplatelet therapy and the use of intracoronary stents. We describe our initial experience with clinically guided bedside compression of femoral pseudoaneurysms in such patients. Eleven patients, 10 undergoing coronary angioplasty (including 3 with intracoronary stents) and 1 undergoing diagnostic cardiac catheterization, developed a femoral pseudoaneurysm. All patients had a femoral bruit and 9 had an expansile groin hematoma. The diagnosis was confirmed in each case by Doppler ultrasound. Seven patients were receiving heparin while 4 were on oral anticoagulants at the time of detection of the pseudoaneurysm. These patients underwent clinically guided graded external compression to close the pseudoaneurysm neck while maintaining femoral arterial flow. External compression for 104.1 +/- 63 min resulted in successful clinical resolution of pseudoaneurysm in all patients without complications. The results were confirmed by Doppler ultrasound at least 12 hr later. Bedside compression of femoral pseudoaneurysms guided by clinical clues is simple and appears to be an effective and safe technique to manage this iatrogenic problem.

Aged↗
PubMed1993

ras gene activation and aberrant expression of keratin K13 in ultraviolet B radiation-induced epidermal neoplasias of mouse skin.

Both papillomas and squamous cell carcinomas (SCC) induced in mouse epidermis by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibit aberrant expression of a type I keratin, K13, that is normally characteristic of terminal differentiation of internal stratified epithelia. There is evidence that the aberrant expression of K13 depends on the presence of an activated ras gene in mouse epidermal keratinocytes (Sutter et al., Mol Carcinog 4:467-476, 1991). To assess the general validity of this hypothesis, we investigated both aberrant K13 expression and activation of each of the three members of the ras gene family in epidermal tumors induced in four different mouse strains (SKH-1 hr, SENCAR, BALB/c, and C3H/He) by chronic irradiation with ultraviolet (UV) B. The tumor collection comprised nine papillomas and 30 well or poorly differentiated SCC. Aberrant K13 expression occurred in only five of 39 tumors and was restricted to SCC of both types. This indicates that aberrant K13 expression in UV-induced epidermal tumors was intrinsically different from that in chemically induced tumors. Polymerase chain reaction analysis of the tumors for different point mutations in codons 12, 13, and 61 of the Ha-ras and Ki-ras genes and in codon 61 of the N-ras gene revealed that only one of the well differentiated tumors from a SKH-1 hr mouse exhibited a GGA-->GAA mutation in codon 12 of the Ha-ras gene. Although this tumor was also positive for aberrant K13 expression, such a correlation could not be made for the remaining K13-expressing tumors. This indicates that the activation of one of the members of the ras gene family is not a general prerequisite for the aberrant expression of K13 in mouse epidermal keratinocytes.

Animals↗
PubMed1993

ras protein p21 processing enzyme farnesyltransferase in chemical carcinogen-induced murine skin tumors.

Farnesylation of ras protein p21 is crucial for the protein's membrane localization, which is essential for its cell-transforming activity, which in turn is thought to be critical for the ultimate induction of cancer. The cytosolic enzyme farnesyltransferase plays a major role in posttranslational modification of p21, but the level of farnesyltransferase activity in mammalian tumors and its relationship to the processing of cytosolic p21 that leads to tumorigenesis are unknown. We report here that farnesyltransferase activity was significantly higher in chemical carcinogen-induced benign skin papillomas in SENCAR mice than in the epidermises of control animals. The enzyme is primarily epidermal in origin, and kinetic studies with cytosol from epidermis and papillomas showed that the reaction was linear with respect to time, substrate concentration, and protein content. Skin papillomas showed significantly elevated levels of both cytosolic and membrane-bound Ha-ras p21, whereas far lesser cytosolic and almost negligible amounts of membrane-bound p21 were present in the epidermis of control mice. There was a positive correlation between increased enzyme activity in papilloma cytosol and the processing of overexpressed cytosolic Ha-ras p21 for its localization to membrane.

Alkyl and Aryl Transferases↗
PubMed1993

Flow cytometric quantitation of sequence-specific mRNA in hemopoietic cell suspensions by primer-induced in situ (PRINS) fluorescent nucleotide labeling.

We modified a technique of RNA detection based upon primed in situ labeling of RNA (PRINS) to quantitate poly(A) and histone mRNA in HL60 cell suspensions by flow cytometry. The direct PRINS technique was used to label poly(A) mRNA, based upon the incorporation of fluoresceinated nucleotides into cDNA chains generated by reverse transcription from the site of oligo(dT) primer-specific annealing on the poly(A) template. By this method, poly(A) fluorescent signals of up to 20-fold above background were obtained when primer concentrations were saturating. Nonspecific binding of the fluorochrome-conjugated nucleotide proved to be the greatest source of background fluorescence in cell suspensions. This was considerably reduced by preincubation of the cells in lysine and an excess of cold nucleotides prior to the PRINS reaction. The application of indirectly fluoresceinated antibodies to the FITC moiety of the conjugated nucleotide (indirect PRINS) enhanced detection of a fluorescent signal generated from cells by the direct PRINS technique after stringent histone priming. Cell cycle analysis, based upon DNA histograms obtained after PRINS labeling, showed the histone fluorescence to be primarily in S-phase cells of an exponentially growing population. Confocal laser scanning microscopy revealed good retention of cellular architecture, with cytoplasmic localization of poly(A) and histone mRNA fluorescence and heterogeneous mRNA expression among cells. Our modified PRINS labeling of RNA represents a useful advance in the precise quantitation of RNA species in cell suspension by flow cytometry.

Flow Cytometry↗
PubMed1993

Gentamicin clearance during hemodialysis: a comparison of high-efficiency cuprammonium rayon and conventional cellulose ester hemodialyzers.

The advent of high-efficiency hemodialyzers has afforded improved efficiency of urea clearance; however, increased clearance of other substances, particularly antibiotics, also may occur, necessitating changes in clinical practice. Accordingly, we compared the efficiency of gentamicin removal using two different hemodialyzers, a conventional saponified cellulose ester (CD 135) and a high-efficiency cuprammonium rayon dialyzer (TAF 175L), in eight hospitalized patients undergoing antibiotic therapy for suspected or proven gram-negative infection. The rate of dialysis, estimated as the ratio of dialyzer urea clearance (K) to urea distribution volume (V) (K/V urea), and the total elimination rate constant (k) of gentamicin were measured during 17 hemodialysis treatments. The K/V urea for the two dialyzers, TAF 175L and CD 135, was 0.390 +/- 0.024 hr-1 and 0.413 +/- 0.129 hr-1 (P = NS), respectively. The TAF 175L hemodialyzer was almost twice as efficient in removing gentamicin as the CD 135: TAF 175, k = 0.263 +/- 0.024 hr-1; CD 135, k = 0.132 +/- 0.027 hr-1 (P < 0.001). Moreover, the rate of dialysis (K/V urea) was correlated with k of gentamicin for the TAF 175L dialyzer (r2 = 0.50, P < 0.02) but not for the CD 135 dialyzer. We conclude that dialyzer characteristics and the rate of dialysis (K/V urea) should be taken into consideration when determining the dosage of gentamicin in patients on hemodialysis.

Adult↗
PubMed1993

Paraparesis due to massive ectopic paravertebral calcification in a patient on maintenance hemodialysis.

Secondary hyperparathyroidism is ubiquitous in patients with end-stage renal disease who are on dialysis. We report a dialysis patient with an unusual manifestation of hyperparathyroidism. Initially, the patient was misdiagnosed to have clavicular osteomyelitis. The underlying hyperparathyroidism was not recognized, only to be discovered later, when the patient presented with spastic paraplegia and massive ectopic calcification in the cervical spine. The patient made a complete recovery following surgical resection and parathyroidectomy.

Calcinosis↗
PubMed1993

Effects of cooler temperature dialysate on hemodynamic stability in "problem" dialysis patients.

Symptomatic hypotension is a common and disabling complication of hemodialysis treatments. The incidence of symptomatic hypotensive episodes is particularly high in patients who have normal or low blood pressure at the initiation of dialysis and in patients who have large interdialytic weight gains. The aim of this study was to determine whether cooling the dialysate temperature from 37 degrees C to 35 degrees C improved tolerance to dialysis in a group of 12 of these "problem" patients. A double-blinded protocol was performed in six hypotension-prone and six large weight gainers who were subjected to two identical hemodialyses except for the dialysate temperature of 37 degrees C or 35 degrees C. Changes in biochemical parameters and weight were comparable during the two maneuvers. Recumbent blood pressure declined significantly (P < 0.01) during 37 degrees C dialysis but not 35 degrees C dialysis; blood pressure was significantly lower at 1, 2, and 3 hours of 37 degrees C dialysis compared to 35 degrees C dialysis (P < 0.05). Further, both supine and upright blood pressure was significantly lower following 37 degrees C dialysis (P < 0.02). This lower blood pressure was present in both subgroups of patients. All 18 episodes of symptomatic hypotension noted during the study occurred during 37 degrees C dialysis. A significantly greater increase in peripheral vascular resistance (calf blood flow was measured directly by venous occlusion plethysmography) occurred upon exposure to the 35 degrees C dialysate in both subgroups of patients (P < 0.01); supine and upright post-dialysis plasma norepinephrine values were also significantly greater (P < 0.001) after 35 degrees dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Inhibition of both stage I and stage II skin tumor promotion in SENCAR mice by a polyphenolic fraction isolated from green tea: inhibition depends on the duration of polyphenol treatment.

The polyphenolic fraction isolated from green tea (GTP) is a potent inhibitor of phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In this study, we assessed the effect of GTP on both stage I and stage II skin tumor promotion, and also analyzed the effect of duration of GTP treatment on skin tumor promotion in SENCAR mice. Topical application of GTP (6 mg/animal) concurrently with each application of either TPA (3.2 nmol) or mezerein (3.2 nmol) in stage I or stage II of the murine skin tumor promotion protocol, respectively, resulted in significant protection against skin papilloma formation in terms of both tumor multiplicity (42-50%) and tumor growth (43-54%). More profound and sustained protective effects of GTP were evident when it was applied continuously during both stage I and stage II of the skin tumor promotion protocol concurrently with TPA or mezerein treatments, respectively. Under this treatment regimen, compared to non-GTP-treated positive controls, GTP application showed 71%, 37% and 74% protection in terms of tumor multiplicity, tumor incidence and tumor growth, respectively. These data indicate that GTP inhibits both stage I and stage II of skin tumor promotion and that the inhibition of tumor promotion depends on the duration of GTP treatment.

Animals↗