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Biomedical subjects

M Pratap

Publications and source records attributed to M Pratap.

11 recordsLinked to original sources

Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression.

BACKGROUND: Reduced dopaminergic transmission has been implicated in the pathophysiology of major depression. The aim of the present study was to measure striatal D(2) receptor availability and amphetamine-induced dopamine release in nonpsychotic, unmedicated, unipolar patients during an episode of major depression. METHODS: The striatal equilibrium specific to nonspecific partition coefficient (V(3)") of the D(2) receptor antagonist [(123)I]IBZM was measured with single photon emission computerized tomography before and after amphetamine administration in 9 depressed subjects and 10 matched healthy control subjects. RESULTS: No significant differences were observed in preamphetamine D(2) receptor availability between depressed patients (0.73 +/- 0.08) and control subjects (0.78 +/- 0.10, p =.23). Amphetamine-induced reduction in [(123)I]IBZM V(3)" (DeltaV(3)") was similar in depressed patients (-9.8 +/- 5.5%) and control subjects (-7.8 +/- 2.5%, p =.32). Amphetamine induced a transient improvement in symptomatology in depressed patients, but this improvement did not correlate with [(123)I]IBZM DeltaV(3)". CONCLUSIONS: This study did not replicate previously reported alterations in striatal D(2) receptor density in depressed patients and suggests that stimulant-induced dopamine release is not altered in major depression.

Adolescent↗

Frequent amplification of C-erbB2 (HER-2/Neu) oncogene in cervical carcinoma as detected by non-fluorescence in situ hybridization technique on paraffin sections.

Sixty primary untreated squamous cell carcinomas were studied for C-erbB2 gene amplification by non-fluorescence in situ hybridization technique. Amplified tumour cells showed intranuclear dark brown, often paired signals under light microscopy. Twenty-two out of 60 tumours (36.6%) showed signs of amplification of different degree (+ to +). Considerable heterogeneity of C-erbB2 amplification per cell was seen within each amplified tumour. The proportion of amplified cells ranged between 10 and 90% in these tumours. The arrangement of C-erbB2 in clusters in most amplified tumours suggests that C-erbB2 amplification occurs intrachromosomally. No significant difference in the frequency of amplification was observed according to clinical stage or the histological patterns of the tumours. The results of the present study showed frequent amplification of C-erbB2 in cervical carcinoma on paraffin sections. This technique was found to be more sensitive than the Southern blot technique which could detect amplification in 14% of the tumours of the same cohort.

Carcinoma, Squamous Cell↗

In vivo biodistribution of a radiotracer for imaging serotonin-1A receptor sites with PET:[11C]LY274601.

LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg/kg, s.c.), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocampus CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2-2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Genetic alterations at 5p15: a potential marker for progression of precancerous lesions of the uterine cervix.

BACKGROUND: Development of uterine cervical cancer is preceded by preneoplastic proliferative changes in the cervical epithelium called "intra-epithelial neoplasia" or "dysplasia." The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. PURPOSE: To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5p14-ter in precancerous and cancerous lesions. METHODS: Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS); the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic microsatellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. RESULTS: LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Among the loci tested, D5S406 (5p15.1-15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5p14-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. CONCLUSION: These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. IMPLICATIONS: The future molecular cloning of the candidate tumor suppressor gene at 5p15.1-15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers.

Biomarkers, Tumor↗

Allelotype analysis of cervical carcinoma.

To identify the genetic events which may play a role in the development of cervical carcinoma, we performed a detailed allelotype analysis utilizing DNA from 53 primary tumors and corresponding normal cells and 57 polymorphic probes mapped to each of the chromosomal arms, excluding the short arms of the acrocentric chromosomes. Loss of heterozygosity (LOH) of > 25% was observed at sites on 11 chromosomal arms, which included 1q (26%), 3p (35%), 3q (31%), 4q (46%), 5p (53%), 5q (38%), 6p (28%), 10q (28%), 11p (42%), 18p (38%), and Xq (26%). The most frequent LOH was noted on 4q (ADH3) and 5p (D5S19), suggesting that loss of candidate tumor suppressor genes on these chromosomal arms may play a role in the development of cervical carcinoma. The two sites of deletions identified on 5p and Xq represent novel candidate tumor suppressor gene sites which have so far not been reported in any other tumor type. Human papilloma virus status did not correlate with any of the sites which showed frequent LOH. TP53 mutation analysis by single-strand conformation polymorphism analysis was performed in 17 tumors that either showed 17p deletions (TP53, D17S5, or D17S28) or were human papilloma virus negative. One of the 7 human papilloma virus-negative tumors, which also showed LOH at the D17S28 locus, had a mutation in exon 5. This study represents the first comprehensive genetic analysis of this cancer and identifies several novel features of significance to genetic etiology of cervical carcinoma.

Adult↗

ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix.

We evaluated a panel of 22 protooncogenes for amplification in 50 primary, untreated squamous cell carcinomas of the uterine cervix. The tumors studied belonged to clinical stages II and III; histologically, the majority of them were moderately to well differentiated. Amplification represented by 5 or more copies was observed for the genes MYCL1, SEA, CCND1, BCL1, and GLI in one case each (2%); HRAS in 2 cases (4%); and ERBB2 in 7 cases (14%). Amplification of ERBB2 ranged from 5 to 68 copies. In addition, 2 tumors with ERBB2 amplification showed additional restriction fragments suggesting possible mutation or rearrangement of the gene. The high incidence of ERBB2 amplification in cervical cancer suggests that this gene may play an important role in tumorigenesis.

Carcinoma, Squamous Cell↗

i(5p) and del(6q) are nonrandom abnormalities in carcinoma cervix uteri. Cytogenetics of two newly developed cell lines.

The karyotypes of two recently developed cell lines derived from squamous cell carcinomas of uterine cervix have been analyzed and are described here. Several clonal rearrangements were identified in both cell lines. Abnormalities common to these two cell lines were i(5)(p10) and del(6)(q15q26). The i(5p) was confirmed by use of whole chromosome 5 painting probe in fluorescence in situ hybridization. Based on these findings and review of published data on the cytogenetics of carcinoma of uterine cervix these two lesions are considered to be nonrandom abnormalities associated with this tumor.

Carcinoma, Squamous Cell↗

Cervix tumour cell line established from tumour after long term passages as heterotransplant in nude mice.

One human cancer of the uterine cervix xenograft was established in tissue culture only after repeated passages in nude mice suggesting that with the repeated passages in nude mice, tumour cells acquire some properties which allow them to grow in vitro. Attempts to establish cell line tumours from earlier passages were not successful. The established cell line is tumourigenic. On inoculation of cultured cells in nude mice tumour take was found to be 100%. Karyotypic analysis revealed human origin.

Animals↗

Percutaneous tracheostomy by guidewire dilating forceps technique: review of 98 patients.

BACKGROUND: Percutaneous tracheostomy to a large extent has replaced conventional surgical tracheostomy by virtue of its low incidence of complications and the rapidity with which the procedure can be performed at the bedside avoiding transport of critically ill patients to the operating rooms. Since it is a blind approach, bronchoscopic guidance has been suggested which might not always be possible due to logistic reasons. METHODS: A retrospective study of 98 patients who had guide wire dilating forceps technique of percutaneous tracheostomy without the aid of a bronchoscope was undertaken. By ensuring the free mobility of the guide wire at each step of the procedure, a safe placement of the tracheostomy tube was achieved. RESULTS: The mean operating time was 3.05 mins [S.D:2.20]. Two patients had peristomal bleeding as an early complication. 34 patients could be decannulated with good primary approximation of the stomal tissues [mean: 3.92days, S.D: 1.46]. There were no deaths or life threatening complications attributable to this technique. CONCLUSIONS: In the absence of bronchoscopic guidance, adopting the simple but effective precaution of free movement of guide wire at each step of the procedure, a safe tracheostomy tube placement is possible.

Adolescent↗