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Biomedical subjects

P C Patel

Publications and source records attributed to P C Patel.

At least 19 recordsLinked to original sources
PubMed1999

HIV-1 long terminal repeat modulation by glucocorticoids in monocytic and lymphocytic cell lines.

Glucocorticoid gene regulation can be carried out through direct binding of glucocorticoid receptor to glucocorticoid responsive elements (GRE), regulating directly gene transcription and modulating some signaling pathways. The human immunodeficiency virus type 1 (HIV-1) expression can be activated by different immunomodulators through binding of particular nuclear factors to its long terminal repeat (LTR). In order to investigate the effect of glucocorticoids in pathways that activate HIV-1 expression, we transfected promonocyte (U937) and T lymphocyte (CEM-T4) cell lineages with a plasmid containing the chloramphenicol acetyl transferase (CAT) reporter gene under the control of the HIV-1 LTR. In U937 cells, dexamethasone (DEX) downregulates CAT expression induced by either phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNFalpha) or granulocyte/macrophage-colony stimulating factor (GM-CSF). In CEM-T4 cells the CAT activity was slightly upregulated by DEX following the induction by either PMA or TNFalpha. Interestingly, in both cell lines transactivation of this reporter gene by transactivator protein (TAT) was downregulated by DEX. When the CAT gene was under control of HIV-1 enhancer isolated from its LTR background, the CAT activity induced by PMA was not affected by the presence of glucocorticoids. In all experiments, comparable data were obtained when DEX was replaced by hydrocortisone (HC). Our results show that, depending on the cell line, glucocorticoids can differently affect HIV-1 expression, probably by interfering in cellular pathways involved in virus expression. Moreover, the target of this regulation in LTR is probably not the enhancer region itself.

Cell Line↗
PubMed1998

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease.

OBJECTIVE: To evaluate the utility of a rapid intraoperative parathyroid hormone (PTH) immunoradiometric assay in the surgical management of parathyroid disease, particularly with reference to limiting extent of cervical exploration. DESIGN: Nonrandomized prospective study. SETTING: Academic tertiary care center. PATIENTS: Forty-three consecutive patients undergoing parathyroid exploration for adenoma or hyperplasia had rapid PTH assays performed from blood drawn at induction and 7 minutes after resection of all hyperfunctioning parathyroid tissue. OUTCOME MEASURES: Excision of all hyperfunctioning parathyroid tissue as assessed by bilateral neck exploration, postoperative normalization of serum calcium and PTH levels, and resolution of clinical symptoms. RESULTS: The intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning parathyroid tissue was excised in every patient. In 41 patients, all hyperfunctioning parathyroid tissue was resected at the time of surgery and confirmed by a corresponding decrease in the intraoperative postexcision rapid PTH determination as well as by subsequent normalization of postoperative serum calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the postexcision rapid PTH assay determination was not consistent with removal of all hyperfunctioning parathyroid disease and both patients demonstrated persistent hyperparathyroidism postoperatively. CONCLUSIONS: The intraoperative rapid PTH assay may be of significant benefit in permitting directed unilateral parathyroid explorations for adenoma when combined with preoperative localization with a technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be of benefit in confirming excision of all hyperfunctioning parathyroid tissue in patients with multiple gland hyperplasia, particularly those who may harbor ectopic parathyroid tissue.

Adenoma↗
PubMed1997

Congenital esophageal webs.

Congenital esophageal webs are rare entities. These lesions generally occur in the upper one third of the esophagus and present symptomatically in early childhood. Dysphagia and 'feeding' difficulties are characteristic presenting symptoms. Radiographic studies generally reveal a normal appearing esophageal lumen with the exception of a single thin indentation of the esophageal lumen that is located either anteriorly or circumferential in nature. We describe two children with congenital esophageal webs and review the pathophysiology, diagnosis and management of these unusual lesions.

Adolescent↗
PubMed1997

Isolated congenital internal auditory canal atresia with normal facial nerve function.

The internal auditory canal forms as a result of mesoderm enveloping the eighth cranial nerve in the developing embryo. The mesoderm eventually transforms into cartilage and ultimately ossifies around the nerve, forming the internal auditory canal. It is theorized that atresia or stenosis of the internal auditory canal results from altered cochleovestibular nerve development secondary to faulty chemotactic mechanisms or a lack of end organ targets. Unilateral internal auditory canal anomalies are frequently seen in conjunction with other inner ear anomalies and occasionally with middle or external ear anomalies. Infrequently, it will occur as either an isolated or bilateral finding, but rarely simultaneously. The few citations of isolated, unilateral or bilateral internal auditory canal anomalies that are reported in the literature are usually associated with other systemic developmental anomalies, such as, cardiac septal defects, polycystic kidney disease, skeletal deformities and duodenal atresia. We present a case report of a patient with bilateral, congenital, internal auditory canal atresia and cochleovestibular deficits but, normal facial nerve function. A review of the literature is discussed as well as diagnostic considerations and treatment options including audiologic and communication rehabilitation.

Child, Preschool↗
PubMed1995

Cloning of a thymic stromal cell capable of protecting thymocytes from apoptosis.

A clone of thymic stromal cells, namely 2BH4, was established by primary culture, cellular transfection and limiting dilution. Morphological analysis by transmission electron microscopy revealed that these cells grow as multilayers, producing a well-defined basement membrane to which they attach and frequently form structures similar to hemidesmosomes. The adjoining cells are connected by intercellular junctions, as tight junctions, intermediate junctions, and desmosome-like junctions, as well as interdigitations. Their cytoplasm contains microtubules, strands of actin filaments, and scarce intermediate filaments. Fluorescence microscopy revealed that 2BH4 cells stain with anti-cytokeratin antibodies, the majority of them giving a faint reaction. In addition, they express Thy-1.1, LFA-1, ICAM-1, and the gp23 epithelial antigen, and synthesize laminin. They have a doubling time of 16 hr and are able to bind thymocytes. Thymocytes cultured in the presence of 2BH4 cells are partially protected from both spontaneous and PMA- or dexamethasone-induced apoptosis. This protection is conferred neither by soluble factors normally produced by the 2BH4 cells nor by the sole contact with fixed 2BH4 cells. Rather, thymocytes must interact with metabolically active 2BH4 cells in order to receive the protective signal(s).

Animals↗
PubMed1994

Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis.

BACKGROUND: Somatostatin analogues inhibit peptide release and cell growth through multiple postreceptor signal transduction mechanisms (PRSTM), including G proteins (GP), cyclic adenosine monophosphate (cAMP), calcium, protein kinase C (PKC), and tyrosine phosphatase (TP). Octreotide acetate (OA), a somatostatin analogue, has been shown to inhibit angiogenesis; however, the PRSTM involved are unknown. METHODS: Fertilized chicken eggs were obtained and incubated. On day 3, embryos were removed and placed in plastic wrap hammocks. On day 7, disks containing OA, test substances that interfere with PRSTM, or combinations of OA plus a test substance were placed on the developing chorioallantoic membrane. Blood vessel growth under each disk was assessed at 24 hours. Data were evaluated by chi-squared analysis. RESULTS: OA's ability to inhibit angiogenesis is significantly diminished when combined with calcium, bradykinin (increases calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1-methylxanthine (increases cAMP). In contrast, no significant decrease is noted in OA's ability to inhibit angiogenesis when combined with phorbol ester (activates PKC) or vanadate (inhibits TP). CONCLUSIONS: OA-induced inhibition of angiogenesis is GP, calcium, and cAMP dependent and is PKC and TP independent. Better understanding of the PRSTM involved with OA-induced inhibition of angiogenesis may lead to enhancement of OA's effect on angiogenesis.

Animals↗
PubMed1993

Regulation of prostatic acid phosphatase expression and secretion by androgen in LNCaP human prostate carcinoma cells.

The expression and the secretion of human prostatic acid phosphatase (PAcP), a differentiation antigen which is the major acid phosphatase in prostate epithelial cells, are thought to be regulated by an androgen. We investigated this regulatory mechanism at the post-transcriptional level in LNCaP human prostate carcinoma cells using a cDNA clone for the secretory form of PAcP. 5 alpha-Dihydrotestosterone (DHT, an active form of endogenous androgen) stimulated the secretion of PAcP from cells grown in a steroid-reduced medium and in a defined serum-free medium, respectively. The secreted PAcP activity was increased following a DHT dose in a dose-dependent fashion at concentrations of up to 1 microM. Further, the stimulation of PAcP secretion occurred following the period of exposure to DHT. During a 5-day treatment period, with 10 nM of DHT in the steroid-reduced medium, the secretion of PAcP was stimulated approximately 150% over that from control cells. Nevertheless, PAcP was secreted from cells grown in the absence of added DHT. First, the androgen dependency of PAcP expression was examined. The expression and the secretion of PAcP were observed in cells that were grown in a defined serum-free medium and grown in a steroid-reduced medium, in the absence of DHT. The increased secretion by DHT was further demonstrated to be in part due to an increase in PAcP mRNA level, as evidenced by Northern blot analysis. PAcP mRNA levels were elevated approximately 2-fold and corresponded to an increase of approximately 2.5-fold in the secreted level of newly synthesized 35S-PAcP. Then, the effect of DHT on the secretory process was investigated. Results of pulse-chase labeling experiments indicated that the secretory rate of PAcP was stimulated by about 50% on average by DHT. In conclusion, our data demonstrated that, in LNCaP cells, the expression and the secretion of PAcP regulated by androgen are apparently hormone-responsive processes. Further, DHT stimulation of PAcP secretion operates within at least two levels: increased PAcP mRNA and stimulation of the secretory pathway.

Acid Phosphatase↗
PubMed1993

Inhalant atopic sensitivity to grasshoppers in research laboratories.

BACKGROUND: Atopic sensitivity to insects, in both occupational and nonoccupational settings, is common. METHODS: A 26-year-old man with atopic asthma experienced worsened asthma and urticaria on exposure to grasshoppers in a research laboratory; he along with 16 other persons who work with grasshoppers from two laboratories and 26 control subjects were studied. The patient underwent a controlled allergen inhalation test with aqueous grasshopper dropping antigen. All subjects were assessed by means of a questionnaire. All but one (who refused because of severe skin reactions after contact with grasshoppers) had skin prick tests with three extracts of grasshopper and with grass pollen, cat dander, and Dermatophagoides farinae. RESULTS: The allergen challenge was positive with an isolated early asthmatic response (23% fall forced expiratory volume in 1 second [FEV1]) at 1:4096 (approximately 25 micrograms/ml), and a borderline fall in provocative concentration of methacholine causing a 20% fall in FEV1. Seven of 16 (43.8%) workers had positive grasshopper skin test results compared with one of 26 (3.8%) control subjects (p = 0.0052). Sensitization occurred even in otherwise nonatopic workers (5 of 12). Symptoms of asthma on exposure (n = 4) correlated better with positive skin test results than did cutaneous symptoms (n = 8). CONCLUSION: Atopic sensitization to grasshoppers in research laboratories is a significant occupational health problem.

Adult↗
PubMed1992

The effect of repirinast on airway responsiveness to methacholine and allergen.

Repirinast, a novel ingested antiallergic asthma medication from Japan, was compared versus placebo on airway responsiveness to methacholine and was compared versus placebo and cromolyn on airway responses to allergen. In 14 patients with mild, stable, atopic asthma, we performed a double-blind, double-dummy, random-order trial with ingested repirinast 300 mg twice daily for 7 days, inhaled cromolyn 40 mg spincaps single dose, and double placebo on allergen-induced early (EAR) and late (LAR) asthmatic responses and increased airway responsiveness. In the 14 subjects, no difference occurred in methacholine PC20 after 6 days of repirinast or 6 days of placebo. In the 13 subjects who completed the allergen study, single-dose cromolyn significantly reduced the EAR by 63% and the LAR by 65% versus placebo (p < 0.02); repirinast was not significantly different from placebo, both the EAR and LAR being reduced by less than 10%. Allergen-induced increase in methacholine responsiveness was borderline (p = 0.052), and no significant drug effects occurred. In these models, a 1-week treatment period with repirinast, like other oral antiallergic asthma medications (e.g., ketotifen, fumarate), provides no protection against airway responses to methacholine or allergen.

Adolescent↗
PubMed1992

Occupational asthma caused by exposure to cooking lobster in the work environment: a case report.

A 25-year-old male chef developed symptoms of cough, wheezing, and dyspnea following repeated exposure to cooking lobster in his work environment. Skin prick tests to lobster, mixed shellfish, haddock, cod, oysters, and clams were strongly positive. Skin prick tests to other routine antigens were negative except for Alternaria fungal spores. Bronchial inhalation of aqueous lobster extract resulted in an isolated early asthmatic response.

Administration, Inhalation↗
PubMed1992

Anterior urethroplasty--changing concepts.

The management of complex anterior urethral strictures, not amendable to dilatation or internal urethromotomy, is difficult. Our experience of treating long strictures of anterior urethra with one-stage urethroplasty in 16 cases and two-stage Johanson's in 12 cases are reviewed here. The strictures had varied etiology and many were associated with fistula, diverticulum, etc. Three cases had concomitant posterior urethral strictures and were managed by one-stage anterior and posterior urethroplasty simultaneously. The one-stage repair was done using vascularized flap of longitudinal ventral penile skin in most cases. Transverse scrotal flap and Duckket's transverse preputial flap were utilized in 2 cases each. In one-stage repair success was 100% and in two-stage repair it was 75%. Our preference is now for one-stage repair irrespective of length and number of strictures.

Adult↗
PubMed1991

Establishment and characterization of Epstein-Barr virus gp350-expressing transfected human lymphoid (Raji) cell clones.

Gp350, a late Epstein-Barr-virus (EBV) glycoprotein expressed on both the envelope of viral particles and EBV-producing cells, is also the candidate for the development of an anti-EBV subunit vaccine. This glycoprotein is thought to play an important role in anti-EBV immunity. However, studies on the role of this viral antigen in cellular cytotoxicity and other immune functions have been hampered by the lack of a suitable model expressing gp350. We describe here a study in which we successfully transfected a gp350-negative cell line resistant to natural-killer(NK)-cell activity (i.e., Raji) with a recombinant plasmid (pZIP-MA) containing the EBV-gp350 and the neomycin resistance gene. Three clones with a stable and strong expression of gp350 on their surface membrane, as demonstrated using a gp350-specific (i.e., 2LI0) monoclonal antibody (MAb) were isolated, characterized and used as targets in an antibody-dependent cellular cytotoxicity (ADCC) assay. However, gp350 expression on 2 of the 3 isolated clones was not recognized by an anti-gp350 MAb (72AI) which is specific to a unique gp350 epitope with a dual function (i.e., involved in both EBV binding to its target cell receptors and in inducing virus-neutralizing antibody). We have also found that gp350 expression on our 3 selected clones does not affect EBV-receptor (CR2) density. Our model of gp350-expressing, NK-cell-activity-resistant targets revealed very useful in determining that gp350 serves as a target antigen for EBV-specific ADCC. These gp350-expressing cell clones appear to represent a valuable tool for diagnostic purposes (i.e., for detecting and titrating gp350 antibodies in patients with EBV-associated diseases). Our approach should also prove useful for studying the expression of other cell-surface-associated viral and tumor antigens and their role in specific cellular immunity and immunosurveillance.

Antibodies, Monoclonal↗
PubMed1991

Epstein-Barr virus (EBV) glycoprotein gp350 expressed on transfected cells resistant to natural killer cell activity serves as a target antigen for EBV-specific antibody-dependent cellular cytotoxicity.

Cell surface-associated viral glycoproteins are thought to play a major role as target antigens in cellular cytotoxicity and antiviral immunosurveillance. One such glycoprotein is the Epstein-Barr virus (EBV)-encoded glycoprotein 350 (gp350), which is expressed on both virion envelope and EBV producer cells and carries the virus attachment protein moiety. Although it is known that some antibodies to gp350 can neutralize the virus, the role of this glycoprotein in EBV-specific cellular cytotoxicity is not yet clear. We describe here a study in which we successfully used a new approach to demonstrate that gp350 is a target antigen for EBV-specific antibody-dependent cellular cytotoxicity (ADCC). Transfection of gp350-negative cells resistant to natural killer (NK) cell activity (i.e., Raji) with a recombinant vector (pZIP-MA) containing the gene encoding the EBV-gp350 and the neomycin resistance gene enabled us to isolate cell clones with a stable and strong expression of gp350 on their surface membranes. ADCC determined by using two clones clearly demonstrated that gp350 is the target of the EBV ADCC. Interestingly, this ADCC was comparable to that obtained against the EBV-superinfected (coated) Raji cell expressing the same percentage of gp350 positivity as the two clones. No cytotoxic activity was detected against either nontransfected (gp350-negative) Raji cells or cells transfected with the vector [pZIP-neo-SV(X)1] lacking the gp350 gene. In addition to demonstrating that gp350 is a target molecule for EBV-specific ADCC, our approach in using NK-resistant transfectants provides a lead for probing the role of cell surface-associated viral antigens in specific cellular killing and immunosurveillance.

Antibodies, Monoclonal↗
PubMed1991

Transvesical vesicovaginal fistula repair: a revival.

Vesicovaginal fistulae are usually traumatic in nature, following obstetric or gynecologic trauma. Here, our experience with vesicovaginal fistula repair in 68 cases, performed transvesically (58 cases) or transperitoneally-transvesically, with pedicled omental interposition in 10 cases over the last 8 years is described. The size of fistulae ranged from 1 to 5 cm, and most were situated near or above the trigone. Two cases required ureteric reimplantation. Recurrent fistulae were found in 4 cases. We attribute our success to the simple access, the construction of a vascularized flap, the tension-free grid-iron closure, and the utilization of Vicryl suture.

Cesarean Section↗