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Biomedical subjects

P K Gupta

Publications and source records attributed to P K Gupta.

At least 19 recordsLinked to original sources
PubMed1992

Considerations in bringing a cancer biomarker to clinical application.

Specific challenges face our application of emerging biomarkers to early lung cancer detection. These challenges might be considered frontiers to be bridged between established biomedical disciplines, requiring expertise often beyond the range of individual investigators. Cross-disciplinary research already has led to new appreciation of the mechanisms which underlie the phenotypic expression of the transformed cell and places within our grasp the tools which might lead to successful early lung cancer detection. Prior to the successful application of newly described markers, further cross-disciplinary research must (a) refine the selection of biologically appropriate markers, (b) validate such markers against acknowledged disease end points, (c) establish quantitative criteria for marker presence/absence, and (d) confirm marker predictive value in prospective population trials.

Biomarkers, Tumor↗
PubMed1992

Whipple's disease involving the mesenteric lymph nodes diagnosed by fine-needle aspiration.

Although it traditionally presents with signs and symptoms of small intestine involvement, such as diarrhea and malabsorption, Whipple's disease (WD) can involve many other organs. Typically, WD diagnosis is established by biopsy of the small intestine. A case of WD, established by duodenal biopsy, in a 36-yr-old male is presented. This patient developed mesenteric lymphadenopathy, prompting computerized-tomography guided fine-needle aspiration (FNA), which showed typical features of WD. Electron microscopy (EM) studies confirmed the diagnosis. To our knowledge, this is the first reported case of lymph-node involvement in WD diagnosed by FNA biopsy.

Adult↗
PubMed1992

Rounded atelectasis: diagnosis by fine-needle aspiration cytology.

Rounded atelectasis, a rare, benign mass lesion, is most often seen in association with asbestos-related pleural changes. Often a presumptive diagnosis can be made on the basis of characteristic CT and chest radiographic findings. However, not infrequently radiographic imaging fails to differentiate rounded atelectasis from primary bronchogenic carcinoma, a disease which is seen with increased frequency in patients with asbestos exposure. We describe two cases where the diagnosis of rounded atelectasis was made by fine-needle aspiration (FNA) cytology. The cytologic features included abundant pulmonary parenchymal material with thickened alveolar walls containing pulmonary macrophages and connective tissue. It is important to realize that this is a useful positive finding indicating rounded atelectasis, rather than a negative finding suggesting the absence of neoplasm. Needles with a cutting action may be necessary to obtain sufficient material to make the diagnosis of rounded atelectasis.

Aged↗
PubMed1992

Rational targets for the early detection of lung cancer.

The fact that routinely effective treatments for disseminated lung cancer are not available has prompted the search for effective early detection systems. It is important to identify lung cancer while it is still confined to the bronchial epithelium and is potentially curable with local modalities. We have previously reported on an immunologically based assay to identify antigens expressed on shed bronchial epithelial cells. This assay resulted in a statistically significant correlation of immunostaining with the eventual development of lung cancer 2-4 years prior to routine clinical detection. Attempts to further improve this approach require an understanding of the basis for its success. Based on the work of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely marker of carcinogenic transformation of the bronchial epithelium. In fact, an antibody to this structure was useful for sputum immunocytochemistry analysis for early lung cancer detection. Other carbohydrate structures would also be reasonable markers to evaluate for early detection application, based on the known pattern of expression of these structures in fetal, dysplastic, and neoplastic lung tissue. Another antibody used for sputum immunostaining recognizes a 31-kd protein structure; the antibody is not a known member of a likely class of early detection targets. The reported cases of lung cancer missed by the immunostaining approach included principally adenocarcinoma of the lung, suggesting that the addition of a marker(s) of that type of morphologic differentiation should be considered. Markers to dissect the various forms of lung adenocarcinoma are being characterized and are available for evaluation in early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1991

Relative bioavailability of oral sustained-release and regular-release oxprenolol tablets at steady-state.

The relative bioavailability of a test sustained-release (SR) oxprenolol tablet against an approved regular-release (RR) tablet has been investigated at steady-state. In a randomized two-way crossover study, one tablet of 160 mg SR oxprenolol once every 24 h and one tablet of 80 mg RR oxprenolol once every 12 h were given to 12 healthy volunteers for 5 days. Blood samples were collected from each subject just prior to each dose-administration on days 1 through 4, and at scheduled time points on day 5 and analysed for oxprenolol concentration using HPLC. The SR tablet resulted in 42 per cent reduction in mean peak drug levels (p = 0.0341) and a statistically non-significant 14 per cent increase in mean trough levels (p = 0.8357) than the RR tablet. However it required 160 per cent longer time to reach average steady-state concentrations (Css) on day 5 (1.38 h for SR versus 0.53 h for RR; p = 0.0205). The mean area under the plasma drug concentration-time curve at steady state (AUC96-120) with the SR tablet was approximately 18 per cent lower than that observed with the RR tablet, and the degree of fluctuation (DF) was reduced by 30 per cent (2.81 for SR versus 4.11 for RR; p = 0.0069). On average, a single dose of SR tablet and two doses of RR tablets maintained the drug levels above a constant Css of 204.6 ng ml-1 for 7.88 and 7.65 h, respectively (p = 0.3513).

Adult↗
PubMed1991

Induction of mutations by N-acetoxy-N-acetyl-2-aminofluorene modified M13 viral DNA.

The specificity of N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (G-8-AAF) adducts in double-stranded DNAs from M13mp8 and M13mp9 bacteriophage was determined following transfection of modified DNA with multiple adducts into competent JM103 cells. Mutant phages were selected by phenotypic screening for colorless or light blue plaques indicating a defective beta-galactosidase marker enzyme. Mutation frequencies of phage DNA with G-8-AAF adducts were increased up to 8-fold in SOS-induced host cells as compared to the uninduced JM103 host cells. DNA sequencing of mutants from SOS-induced host cells indicated approximately 52% frameshifts and 39% base substitutions in M13mp8 DNA and 65% frameshifts and 25% base substitutions in M13mp9 DNA. Mutation spectra exhibited mutations at many sites within the bp 6200-6400 region; one mutational hotspot at position 6343-6347 (5' GGGGG 3') for frameshifts was also observed. The G-8-AAF adduct induced mostly single base deletions at this site. In contrast, a deacetylated adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (G-8-AF) in our previous experiments induced mostly single base additions at the same position indicating the ability of adduct structure to modulate the specificity of frameshift mutations. A number of other frameshift mutations (11 out of 29) were observed within non-repetitive and non-palindromic sequences. Molecular mechanisms for the induction of these mutations by DNA perturbations produced by the G-8-AAF adducts are discussed.

2-Acetylaminofluorene↗
PubMed1990

Application of regression analysis in the evaluation of tumor response following the administration of adriamycin either as a solution or via albumin microspheres to the rat.

Regression analysis has been applied to compare the tumor response following the administration of free and microsphere-loaded adriamycin to the rats. A nonmetastasizing sarcoma was induced in male A.S. inbred rats. When the sarcoma was in its fourth passage and 12 days old, four groups of animals received intratumoral injections of 2 or 8 mg/kg of adriamycin as a solution or via albumin microspheres. The animals in each group were monitored over a period of three weeks for changes in body weight and tumor size and their survival, and the results were statistically compared with the data obtained from an untreated group of animals (control). The use of regression analysis in conjunction with partial F-test revealed that the microsphere-delivered drug exhibited a meager but significantly greater response than the free drug. The implications of intratumoral administration of microsphere-loaded drug in the treatment of sarcomas is discussed.

Albumins↗
PubMed1990

Drug targeting in cancer chemotherapy: a clinical perspective.

Drug targeting is a phenomenon which maneuvers the distribution of drug in the body in such a manner that the major fraction of the drug interacts exclusively with the target tissue at a cellular or subcellular level. Numerous strategies have been developed to accomplish this goal; some of them have been tried clinically for improving cancer chemotherapy. This review updates the current status of research in the area of targeted drug delivery, with particular emphasis on its application in the clinical management of carcinomas.

Animals↗
PubMed1990

Comparative disposition of adriamycin delivered via magnetic albumin microspheres in presence and absence of magnetic field in rats.

The multiple tissue disposition of adriamycin hydrochloride delivered via magnetic albumin microspheres, in absence (control) and presence of magnetic field (experimental), has been investigated in rats. The animal tail was demarcated into three segments: T1, the dosing-site; T2, the target-site; and T3, the post target-site. Following the arterial cannulation at T1, 0.4 mg/kg of microsphere associated drug was administered to the control as well as the experimental animals. In experimental group, the target-site T2 was exposed to a 8000 G magnetic field for 30 min. In both groups the animals were sacrificed in triplicates over a 48 hr period and their various tissues monitored for drug concentrations using HPLC. In presence of magnetic field, the microspheres demonstrated 16 fold increase in the maximum drug concentration, 6 fold increase in drug exposure and 6 fold increase in the drug targeting efficiency for T2. Drug delivery to most non-target tissues, including heart and liver, was substantially reduced. The results quantitatively suggest that the efficacy of magnetic albumin microspheres in the targeted delivery of incorporated therapeutic agent is predominantly due to the magnetic effects, and not alone due to the characteristics of the micro-carrier system.

Albumins↗
PubMed1990

An approach for immunodiagnosis of clinical cases of filariasis.

In this communication an immunodiagnostic approach has been adopted for detection of antigen and antibody in amicrofilaeamic Mf(-) patients by countercurrent immuno electrophoresis (CCIE) and immunodiffusion (ID). Using Setaria cervi and Immune Complex (IC) antigens, out of fifteen clinical cases the number of positive patients in CCIE were twelve and ten respectively. Sixty percent of the Mf(-) cases were positive in antigen detection against both the homologous and heterologous antibody. In ID nine Mf(-) cases gave precipitin bands against S. cervi antigen while with IC antigens ten patients were positive. In similar experiments, it was found that out of fifteen Mf(-) cases nine and eleven patients were positive in antigen detection against microfilaraemic Mf(+) sera and S. cervi antibody respectively. All the Mf(+) cases were positive in both antibody and antigen detection. From the standpoint of immunodiagnosis the data were analysed by two-way analysis of variance study and a newly developed system using Binomial distribution. The sera from the control group were negative in all the immunodiagnostic tests.

Adolescent↗
PubMed1990

A physiological pharmacokinetic model describing the disposition of lead in the absence and presence of L-ascorbic acid in rats.

The influence of L-ascorbic acid (As-Ac) on the multiple-tissue disposition of lead has been evaluated. Lead concentrations in femur, liver, kidney and plasma of rats were monitored over a 120h period after its intravenous bolus administration (1.0 mg/kg) in the absence and presence of As-Ac at steady state. The observed lead concentration-time data in different tissues of the rats, in the absence and presence of As-Ac, have been simulated using a physiological pharmacokinetic modelling technique. In both cases, the predicted lead concentrations in various tissues were in adequate agreement with the observed data. The model developed in the present investigation supports the previous finding that As-Ac may be useful as a prophylactic agent for lead poisoning.

Animals↗
PubMed1990

Immunohistochemical detection of chlamydial antigens in association with cystitis.

To investigate the etiologic role of Chlamydia trachomatis in cystitis, the authors used the immunoperoxidase technique with a monoclonal antibody against Chlamydia and examined paraffin sections from 36 cases of histologically proven cystitis. The average patients' age was 60 (range, 2-85) years. Biopsies were taken for follow-up of treated bladder carcinoma (19), hematuria (8), and other nonneoplastic conditions (9). Chlamydial antigens were detected by immunohistochemistry in 12 (33%) of these 36 cases. Staining for Chlamydia occurred in the upper layers of the transitional epithelium and involved long stretches of epithelium. Underlying inflammation was usually chronic but did not have specific distinguishing features. Eight of the Chlamydia-positive biopsies were taken for follow-up of treated carcinoma, two were for hematuria, one for neurogenic bladder, and one for evaluation of sterile pyuria. Eleven (92%) of these 12 positive cases had a history of recent urologic instrumentation, in contrast to only 11 (46%) of 24 negative cases (P less than 0.02). There was no significant difference in the age or sex distribution between the two groups. The authors conclude that Chlamydia trachomatis can ascend the urethra and infect the bladder urothelium. Urologic instrumentation enhances the ability of Chlamydia to reach the bladder. Chlamydia trachomatis may play an etiologic role in cystitis.

Adolescent↗
PubMed1989

Mutagenesis by single site-specific arylamine-DNA adducts. Induction of mutations at multiple sites.

Two related carcinogen adducts, N-(deoxyguanosin-8-yl)-2-aminofluorene (AF) or N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (AAF), were introduced into the lacZ' gene at base position 6253 of the minus strand of M13mp9 viral DNA. The construction of this site-specifically modified DNA was accomplished by first preparing a gapped heteroduplex missing 7 nucleotides at position 6251-6257 followed by ligation with an unmodified heptamer or with a heptamer containing either an AF or AAF adduct. These site-specifically modified templates were transfected into competent wild-type Escherichia coli cells (JM103) and a uvrA strain (SMH12). The mutation spectrum was determined by phenotypic selection of colorless plaques indicating a defective beta-galactosidase marker enzyme and by an in situ hybridization procedure to detect single base pair mismatches in the adduct region. DNA sequencing was used to characterize 179 of the mutants obtained. We found that both adducts were capable of inducing base substitution mutations at the adduct site and in the local region of the adduct. A specific frameshift (+1G) was also observed at a displaced site. All of the frameshift mutations occurred at the ligation site of the modified oligonucleotide. Control experiments with an unmodified oligonucleotide did not show an enhancement of mutations at this site, indicating that the adducts may have been responsible for these frameshifts. The mutations spectra induced by these adducts suggest that mutagenesis depends not only on adduct structure but also the sequence in which the adduct is located and the host cell type used for mutation expression.

2-Acetylaminofluorene↗