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A Agarwal

Publications and source records attributed to A Agarwal.

At least 19 recordsLinked to original sources
PubMed1999

Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism.

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen-activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Breast Neoplasms↗
PubMed1999

The effect of graded steatosis on flow in the hepatic parenchymal microcirculation.

BACKGROUND: Steatosis is a major cause of microcirculatory impairment and graft dysfunction after liver transplantation. The mechanism of this circulatory compromise is unclear. The aim of this study was to evaluate in vivo the effect of steatosis on parenchymal microcirculation and on total hepatic blood flow in an animal model. METHODS: Four groups of New Zealand White rabbits (n=24) were investigated. Group 1 were fed on normal diet (controls). In groups 2, 3, and 4 graded steatosis was induced by feeding on a high cholesterol diet (1.5%) for 4, 8, and 12 weeks, respectively. After laparotomy and exposure of the liver, total hepatic blood flow (THBF) and the hepatic parenchymal microcirculation (HPM) were measured. These parameters were correlated with the degree of histological fat infiltration classified as mild (<30%), moderate (30-60%), or severe (>60%). RESULTS: The 4-, 8-, and 12-week cholesterol diets resulted in mild, moderate, and severe steatosis, respectively. There was an inverse correlation between the degree of fat infiltration and both HPM (Spearman r=-0.967, P<0.0001) and THBF (r=-0.893, P<0.0001). THBF was 137+/-6 ml/min in controls, which reduced to 121+/-3, 99+/-5, and 63+/-5 ml/min in steatotic livers of groups 2, 3, and 4, respectively. HPM was 226+/-5 flux units in the controls and 197+/-7, 119+/-8, and 37+/-9 flux units in steatotic livers of groups 2, 3, and 4 respectively. Comparing with controls using analysis of covariance, the fall in HPM and THBF was found to be significant (P<0.002) in the moderate and severe groups, but not significant (P>0.050) in the mild group. Parenchymal perfusion was reduced to a greater extent than total liver blood flow in moderate and severe grades of steatosis. CONCLUSIONS: Fatty infiltration reduces hepatic blood flow and parenchymal microcirculation. The latter is more markedly reduced with severe steatosis. This may explain the development of microcirculatory impairment and graft failure after transplantation of fatty livers despite adequate liver blood flow.

Animals↗
PubMed1999

B cell responses to a peptide epitope. VIII. Immune complex-mediated regulation of memory B cell generation within germinal centers.

Using an in vivo reconstitution assay, we examine here the role of immune complexes in both formation of germinal centers (GC) and processes that occur subsequently within. The presence of Ag, as immune complexes, was found not to constitute a limiting requirement for the initiation of GC formation. No detrimental effect either on numbers or sizes of the resulting GC was observed when Ag-containing immune complexes were omitted during reconstitution. Thus, both recruitment and proliferation of Ag-activated B cells within GC appear not to be limited by Ag concentrations. In contrast, the presence of immune complexes was observed to be obligatory for the generation of Ag-specific memory B cells. This optimally required immune complexes to be constituted by IgG-class Abs with epitope specificities that were homologous to those of the GC B cells. The GC reaction was also found to be characterized by an enhancement of Ab specificity for the homologous epitope. Although some improvement in specificity was noted in recall responses from immune complex-deficient GC, the presence of appropriate immune complexes served to further optimize the outcome. Here again, isotype and epitope-specificity of the Ab constituent in immune complexes proved to be important.

Amino Acid Sequence↗
PubMed1999

Unusual Contact-Line Dynamics of Thick Films and Drops.

We report several novel phenomena in contact-line and fingering dynamics of macroscopic spinning drops and gravity-driven films with dimensions larger than the capillary length. It is shown through experimental and theoretical analysis that such macroscopic films can exhibit various interfacial shapes, including multi valued ones, near the contact line due to a balance between the external body forces with capillarity. This rich variety of front shapes couples with the usual capillary, viscous, and intermolecular forces at the contact line to produce a rich and unexpected spectrum of contact-line dynamics. A single finger develops when part of the front becomes multivalued on a partially wetting macroscopic spinning drop in contrast to a different mechanism for microscopic drops of completely wetting fluids. Contrary to general expectation, we observe that, at high viscosity and low frequencies of rotation, the speed of a glycerine finger increases with increasing viscosity. Completely wetting Dow Corning 200 Fluid spreads faster over a dry inclined plane than a prewetted one. The presence of a thin prewetted film suppresses fingering both for gravity-driven flow and for spin coating. We analyze some of these unique phenomena in detail and offer qualitative physical explanations for the others. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy.

Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either >90% micro- or macrofilaricidal activity or sterlization of female worms. These compounds have also been screened against Litomosoides carinii, and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure-activity relationship (SAR) associated with position 1 and 3 substituents in beta-carbolines has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3, 4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days (ip) and against B. malayiat 50 mg/kg x 5 days (ip) or at 200 mg/kg x 5 days (po).

Animals↗
PubMed1999

Cryopreservation of sperm from patients with leukemia: is it worth the effort?

BACKGROUND: Intracytoplasmic sperm injection (ICSI) allows pregnancies to be established with a single sperm, improving the chances for men with severely impaired sperm quality to cause a pregnancy. Men with leukemia typically are of reproductive age and their fertility is threatened by initially impaired semen quality and cytotoxic chemotherapy. The authors examined the feasibility of sperm cryopreservation in men with leukemia before treatment and whether the type of leukemia is related to prefreeze or postthaw semen quality. METHODS: Records of 25 patients with acute (n=13) or chronic (n=12) leukemia who banked their sperm were reviewed. Semen characteristics were compared with those of normal donors (n=50) and between the 2 patient groups before and after cryopreservation. Motile sperm count (MSC), motility, curvilinear velocity (VCL), linearity, and amplitude of lateral head movement were compared between patients and healthy donors. No patient had undergone chemotherapy before sperm banking. The nitrogen vapor technique was used for sperm cryopreservation. RESULTS: Patients with leukemia had significantly lower prefreeze and postthaw MSC (P=0.0001), motility (P<0.05), and VCL (P<0.05) compared with healthy donors. The percentage change from prefreeze to postthaw in MSC and motility (P<0.05) was significantly greater in patients than in healthy donors. The effect of cryopreservation on semen quality was similar in patients with both acute and chronic leukemia. CONCLUSIONS: Patients with leukemia have poor prefreeze and postthaw semen quality compared with healthy donors. In this study the type of leukemia did not appear to affect prefreeze or postthaw semen quality and the postthaw MSC was sufficient for use with ICSI. Sperm cryopreservation should be offered to all men of reproductive age before the initiation of therapy for leukemia.

Acute Disease↗
PubMed1999

p53 inhibits entry into mitosis when DNA synthesis is blocked.

Human and mouse fibroblasts with normal p53 fail to enter mitosis when DNA synthesis is blocked by aphidicolin or hydroxyurea. Isogenic p53-null fibroblasts do enter mitosis with incompletely replicated DNA, revealing that p53 contributes to a checkpoint that ensures that mitosis does not occur until DNA synthesis is complete. When treated with N-(phosphonacetyl)-L-aspartate (PALA), which inhibits pyrimidine nucleotide synthesis, leading to synthesis of damaged DNA from highly unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA replication, but cells with wild-type p53 do not, revealing that p53 also mediates a checkpoint that monitors the quality of newly replicated DNA.

Animals↗
PubMed1999

Spinal epidural abscess - a report of six cases.

Six cases of spinal epidural abscess are presented. All patients were young with no predisposing conditions. All were treated with laminectomy and intravenous antibiotics. The patients with no neurological deficit recovered completely, while patients with pre-existing neurological deficit had a poorer outcome. Emphasis is given to early detection and surgical management to prevent irreversible damage to the spinal cord.

Adolescent↗
PubMed1999

Use of the laparoscope to perform intraoperative enteroscopy.

BACKGROUND: In a small number of patients with recurrent gastrointestinal bleeding, standard diagnostic studies fail to identify the source. Intraoperative enteroscopy is useful in these cases. Usually a colonoscope is used to perform peroperative enteroscopy. METHOD: We describe the technique that we use to perform intraoperative enteroscopy via a laparoscope. RESULTS: The bleeding site was identified in two of three cases. In one patient, a vascular malformation in the proximal jejunum was found. In the other, an ulceronodular lesion was seen in the midjejunum. CONCLUSION: The laparoscope can be used successfully to visualize the entire small bowel in the diagnosis of obscure gastrointestinal bleeding.

Biopsy↗
PubMed1999

Effect of seminal oxidative stress on fertility after vasectomy reversal.

OBJECTIVE: To evaluate seminal oxidative stress in men after vasectomy reversal and to determine whether seminal oxidative stress could predict fertility after vasectomy reversal. DESIGN: Measurement of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) in normal donors, men who were fertile after vasectomy reversal, and men who were infertile after vasectomy reversal. SETTING: A male infertility clinic of a tertiary care center. PATIENT(S): Thirty men who underwent vasectomy reversal and 17 normal donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen characteristics, seminal ROS, and TAC were measured with chemiluminescence assays in samples from donors and reversal patients. RESULT(S): Mean adjusted seminal ROS (log [ROS+1]) was higher in infertile reversal patients (2.38+/-0.25) than in normal donors (1.30+/-0.14). Seminal ROS was also higher in all (fertile and infertile reversal combined) reversal patients than in donors. Total antioxidant capacity did not differ between groups. The ROS-TAC score, a composite index of seminal oxidative stress, was a significant predictor of fertility. A ROS-TAC score of 45 or greater had a positive predictive value of 73% in predicting fertility. CONCLUSION(S): Seminal oxidative stress is associated with vasectomy reversal. The ROS-TAC score is a possible predictor of infertility after vasectomy reversal.

Adult↗
PubMed1999

Risk factors for multiple gestation in women undergoing intrauterine insemination with ovarian stimulation.

OBJECTIVE: To identify whether sperm characteristics after washing and/or ovulation induction cycle characteristics can predict the occurrence of multiple conception in patients undergoing ovarian stimulation and IUI. DESIGN: Retrospective study. SETTING: A gynecology clinic and an andrology laboratory at a tertiary care facility. PATIENT(S): One hundred patients with single pregnancies and 22 patients with multiple pregnancies. INTERVENTION(S): Patients underwent ovarian stimulation and IUI with their partner's sperm. MAIN OUTCOME MEASURE(S): Relation of patient characteristics, ovarian stimulation, and sperm characteristics after washing to the occurrence of multiple pregnancy. RESULT(S): The mean serum E2 level on the day of hCG injection was significantly higher in the multiple conception group, but the number of follicles was not. The total sperm count, total motile sperm count, and sperm motility after washing did not differ between the groups. However, couples with multiple pregnancies had sperm with a significantly higher amplitude of lateral head movement than couples with single pregnancies. A peak E2 level of >583 pg/mL on the day of hCG injection and sperm with an ALH of >4 microm after washing predicted the occurrence of multiple pregnancy. CONCLUSION(S): Sperm with an amplitude of lateral head movement of >4 microm and a peak E2 level of >583 pg/mL are significant risk factors for multiple pregnancy in patients undergoing IUI.

Adult↗
PubMed1999

Treatment of erectile dysfunction with sildenafil citrate (Viagra) after radiation therapy for prostate cancer.

OBJECTIVES: To determine the response to sildenafil citrate (Viagra) in patients with erectile dysfunction after radiation therapy for localized prostate cancer. METHODS: Baseline and follow-up data from 21 patients presenting with erectile dysfunction after radiation treatment for clinical T1-2 prostate cancer were obtained. Two patients had undergone iodine-125 seed implantation and the remaining 19 conformal external beam irradiation. All 21 patients were considered to have erectile dysfunction as assessed by the International Index of Erectile Function (IIEF) and were prescribed sildenafil at a dosage of 50 mg, with a titration to 100 mg if needed. The mean time between the completion of radiation therapy and initiation of sildenafil was 24.6 +/- 5.8 months. The quality of the erectile function was assessed after a minimum of four doses by using the Cleveland Clinic Erectile Function (CCEF) questionnaire and the IIEF questionnaire. A positive response to sildenafil on the CCEF questionnaire was defined as an erection sufficient for vaginal penetration. The responses on the IIEF questionnaire were rated on a scale of 1 (almost never) to 5 (almost always), with 0 being no sexual activity. RESULTS: On the CCEF questionnaire, 71% (15 of 21) of patients had a positive response, with a mean duration of 12.7 +/- 2.5 minutes of intercourse, and a corresponding spousal satisfaction rate of 71%. Twelve (80%) of the 15 responders required titration to the 100-mg dosage for maximal effect. The most common side effects seen were transient flushing (19%), abnormal color vision (14%), and headaches (10%). No patient discontinued the drug because of side effects. On the IIEF questionnaire, the responses to questions 3 (frequency of penetration), 4 (maintenance of erection), 7 (satisfactory intercourse), and 15 (erection confidence) increased from mean baseline scores of 1.3, 1.1, 1.2, and 1.8 to final mean scores of 4.0, 3.9, 3.2, and 3.4, respectively (P <0.001). On the global efficacy question (ability to achieve firm erections), 71% of the patients responded positively. CONCLUSIONS: Sildenafil citrate can improve the ability to achieve and maintain an erection in most patients with erectile dysfunction after radiation therapy for prostate cancer.

Aged↗
PubMed1999

Sperm cryopreservation in patients with testicular cancer.

OBJECTIVES: To review a large experience with sperm cryopreservation in patients with testicular cancer and determine the effect of clinical stage and tumor histologic features on semen quality. METHODS: The prefreeze and post-thaw sperm quality of 157 patients with testicular cancer was compared with that of 50 normal donors. The impact of tumor stage and histologic features (pure seminoma, pure embryonal, or mixed germ cell) was also determined. A computer-assisted semen analysis was performed before and after cryopreservation. The motile sperm count (MSC), motility, and motion characteristics were measured before and after cryopreservation and compared between groups. RESULTS: Patients with testicular cancer had lower prefreeze and post-thaw MSC and motility compared with normal donors (P = 0.0001 for both). The curvilinear velocity and linearity were also significantly less in patients with testicular cancer (P <0.05 for both). The percentage of change in the semen characteristics did not differ between patients and donors, indicating that sperm from both patients and donors withstood the cryopreservation process equally well. Tumor stage (n = 143) and histologic features (n = 136) did not significantly influence semen quality. No individual histologic component significantly influenced MSC or motility. CONCLUSIONS: The effect of cryopreservation on sperm was similar in patients with testicular cancer and donors. Patients with poor prefreeze semen quality have poor post-thaw semen quality, and the effects of cryopreservation were not significantly affected by histologic features or stage. Our results indicate that routine sperm banking should be recommended for men with a diagnosis of testicular cancer to preserve future fertility potential.

Adolescent↗
PubMed1999

Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy.

Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines) identified in our laboratory as potential pharmacophore for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilarical activity was initially evaluated in vivo against Acanthoeilonema viteae. Amongst all the synthesized compounds, only twelve compounds namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i and 7h have exhibited either > 90% micro- or macrofilaricidal activity or sterilization of female worms. These compounds have also been screened against Litomosoides carinii and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure activity relationship (SAR) associated with position-1 and 3 substituents in beta-carbolines have been discussed. It has been observed that the presence of carbomethoxy at position-3 and an aryl substituent at position- in beta-carbolines effectively enhance antifilarial activity particularly against A. viteae. Amongst the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxyla te (3a) has shown highest microfilaricidal action against A. viteae at 50 mg/ kg x 5 days (i.p.). Another derivative of this compound namely 1-(4-chlorophenyl)-3-hydroxymethyl-9H-pyrido[3,4-b]indole (5a) exhibited highest activity against L. carinii at 30 mg/kg x 5 days (i.p.) and against B. malayi at 50 mg/kg x 5 days (i.p.) or at 200 mg/kg x 5 days (p.o.).

Animals↗
PubMed1999

Relationship of total motile sperm count and percentage motile sperm to successful pregnancy rates following intrauterine insemination.

PURPOSE: This study sought (i) to investigate the relationship between postwash total motile sperm count and postwash percentage motile sperm in predicting successful intrauterine insemination and (ii) to determine the minimal postwash total motile sperm count required to achieve pregnancy with intrauterine insemination. METHODS: Five hundred four women, who underwent 1636 intrauterine insemination cycles with their partner's sperm for infertility treatment from 1993 through 1995, were included in this retrospective study. All patient charts were reviewed for age, infertility etiology, ovarian stimulation regimens, semen characteristics, and treatment outcome. To determine the relationship between total motile sperm count and intrauterine insemination outcome, patients were grouped as (1) less than 0.5 million, (2) 0.5 to 1 million, (3) 1 to 5 million, (4) greater than 5 million, and (5) greater than 20 million. RESULTS: Similar live birth rates (per cycle) were seen among the postwash total motile sperm count groups: group 1, 3.5%; group 2, 2.4%; group 3, 7.0%; group 4, 6.9%; and group 5, 7.0% (P = 0.37). However, regardless of the postwash total motile sperm count, the postwash motility predicted intrauterine insemination success at a cutoff value of 40%. CONCLUSIONS: The percentage of postwash sperm motility, and not the postwash total motile sperm count, can predict successful intrauterine insemination outcome. Such information can be useful in counseling patients regarding their chance of success with intrauterine insemination and in determining when alternate methods of assisted reproduction may be a better approach.

Female↗
PubMed1999

Mechanisms of G2 arrest in response to overexpression of p53.

Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was suppressed in response to the induction of p53. Suppression requires the regions -287 to -123 of the cyclin B1 promoter and -104 to -74 of the cdc2 promoter. p53 did not affect the inhibitory phosphorylations of CDC2 at threonine 14 or tyrosine 15 or the activity of the cyclin-dependent kinase that activates CDC2 by phosphorylating it at threonine 161. Overexpression of p53 may also interfere with the accumulation of CDC2/cyclin B1 in the nucleus, required for cells to enter mitosis. Constitutive expression of cyclin B1, alone or in combination with the constitutively active CDC2 protein T14A Y15F, did not reverse p53-dependent G2 arrest. However, targeting cyclin B1 to the nucleus in cells also expressing CDC2 T14A Y15F did overcome this arrest. It is likely that several distinct pathways contribute to p53-dependent G2 arrest.

Apoptosis↗