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Biomedical subjects

A Sehgal

Publications and source records attributed to A Sehgal.

At least 91 records · Page 5Linked to original sources

Molecular genetic analysis of circadian rhythms in vertebrates and invertebrates.

In recent years, there has been a flurry of activity directed towards identifying the molecular basis of circadian (approximately 24 h) rhythms. The past year has seen the isolation of the first clock mutations in a number of organisms (mice, Arabidopsis, cyanobacteria), the identification of a new circadian rhythm gene in Drosophila that interacts with the well known period gene, and considerable progress in the analysis of the 'clock genes', period and frequency. A combination of genetic, molecular and biochemical approaches is leading to an emerging picture of how molecular events enable organisms to keep time.

Animals↗

Significance of inflammatory cervical smears.

Two hundred and fifty-seven women attending a Maternal and Child Health Centre (MCH) were examined for different colposcopic and histological patterns associated with cervical inflammation as detected by cytology and for their association with different gynaecological infections. The cytodiagnosis revealed inflammation in 207 women (80.5%) and non-inflammation in 49 (19.5%); one smear was inadequate for evaluation. Fifty-six per cent of the women with inflammation and 20% with non-inflammation had an atypical transformation zone (ATZ), the risk of ATZ being 4.9-fold higher in those with inflammation. Biopsies from 128 women with abnormal colposcopy revealed morphological changes suggestive of human papillomavirus (HPV) in 89 (69.5%) and dysplasia of varying grades in 8 (6.3%). Seventy per cent of histologically diagnosed HPV lesions stained immunohistochemically, whereas 84% reacted with a biotinylated Pan-HPV probe by DNA in situ hybridization (DISH). In addition to HPV, chlamydia (OR 15.6, 95% CI 2.2, 311.6), T. vaginalis (OR 18.4), bacterial vaginosis (OR 24.7, 95% CI 3.5, 492) and herpes simplex virus (OR 4.9, 95% CI 1.4, 20.9) were significantly associated with inflammatory smears. Of 11 dysplasias detected by colposcopy and confirmed by biopsy, 8 (72.7%) had inflammatory cytology in the initial Pap smears. Thus a large proportion of women with inflammatory smears had multiple gynaecological infections and may be at increased risk of developing preneoplastic or neoplastic changes. Furthermore, they risk transmitting the infections to their partners.

Adolescent↗

Isolation and characterization of a low-abundance splice variant from the human cytomegalovirus major immediate-early gene region.

The major immediate-early (IE) gene region of human cytomegalovirus (HCMV) encodes several proteins as a result of differential RNA splicing events. By expression vector cloning of HCMV IE mRNA, we isolated and characterized a cDNA for a novel splice variant from the major IE gene region. The RNA product is a derivative of the IE55 mRNA and contains an additional splice from nucleotides 170,635 to 170,307 in the IE2 gene region (UL122), resulting in a 1.4-kb mRNA. The predicted open reading frame codes for a 164-amino-acid protein with a calculated molecular mass of 18 kDa (IE18). Mung bean nuclease analysis and PCR were used to characterize expression of IE18 mRNA in HCMV-infected cells. While the 1.4-kb mRNA was detected in infected human fibroblasts in the presence of a protein synthesis inhibitor, it was not detectable during a normal infection. However, the 1.4-kb mRNA was readily detected in infected human monocyte-derived macrophages at IE times. These results suggest that the novel IE18 mRNA exhibits cell type-specific expression indicating differential regulation of the major IE gene region in different permissive cell types.

Amino Acid Sequence↗

Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless.

Eclosion, or emergence of adult flies from the pupa, and locomotor activity of adults occur rhythmically in Drosophila melanogaster, with a circadian period of about 24 hours. Here, a clock mutation, timeless (tim), is described that produces arrhythmia for both behaviors. The effects of tim on behavioral rhythms are likely to involve products of the X chromosome-linked clock gene period (per), because tim alters circadian oscillations of per RNA. Genetic mapping places tim on the left arm of the second chromosome between dumpy (dp) and decapentaplegic (dpp).

Animals↗

Block in nuclear localization of period protein by a second clock mutation, timeless.

In wild-type Drosophila, the period protein (PER) is found in nuclei of the eyes and brain, and PER immunoreactivity oscillates with a circadian rhythm. The studies described here indicate that the nuclear localization of PER is blocked by timeless (tim), a second chromosome mutation that, like per null mutations, abolishes circadian rhythms. PER fusion proteins without a conserved domain (PAS) and some flanking sequences are nuclear in tim mutants. This suggests that a segment of PER inhibits nuclear localization in tim mutants. The tim gene may have a role in establishing rhythms of PER abundance and nuclear localization in wild-type flies.

Animals↗

Role of male behavior in cervical carcinogenesis among women with one lifetime sexual partner.

BACKGROUND: The role of male behavior in the genesis of cervical cancer was examined. In India, where the incidence of cervical cancer is among the highest in the world, promiscuity among women is virtually unknown. In this study, the authors investigated the role of male behavior in cervical carcinogenesis among Indian women who had one lifetime sexual partner. METHODS: A case-control study was used. RESULTS: Premarital sexual relationships (relative risk [RR], 1.9; confidence interval, 1.2-3.2) and extramarital sexual relationships (RR, 2.7; confidence interval, 1.5-4.9) of husbands were risk factors. When husbands had sexual relationships both before and during the marriage, their wives' risk of getting cervical cancer increased by 6.9 (CI, 2.3-20.7). Risk also increased with husbands having three or more extramarital sexual partners (RR, 3.05; CI, 1.25-12.6). Sexual contact with prostitutes before or after marriage, however, did not increase the risk. History of sexually transmitted disease before marriage (RR, 2.9) or after marriage (RR, 5.9) was an important risk factor, which persisted after controlling for other factors. Sexual abstinence for 40 or more days after a wife's giving birth or having an abortion provided protection. Sex with uncircumcised men or men circumcised after age 1 year increased the risk of cervical cancer (RR, 4.1). Bidi smoking (bidi is a cheap smoking stick of 4-8 cm, consisting of a rolled piece of dried temburni leaf [Diospyres melanoxylon] containing 0.15-0.25 g of coarsely ground tobacco) for more than 20 years was a significant risk factor (RR = 2.4), whereas cigarette smoking was not a risk factor. CONCLUSIONS: Male sexual partners play a role in cervical carcinogenesis.

Adult↗

Factors associated with awareness and knowledge of cervical cancer in a community: implication for health education programmes in developing countries.

An attempt has been made to study the correlates of knowledge of cervical cancer in a community. The survey undertaken is a part of Knowledge, Attitude and Practice (KAP) study prior to initiation of cytological screening. Total women interviewed by KAP survey were 1411 selected through 2 stage stratified random sampling. Subjects for the present analysis consisted of a group of women who had reported previous gynaecological problems related to cervical cancer. The study brought out that younger women had better awareness and knowledge about cervical cancer and related information. Literacy status for education and exposure to family planning was influential in creating awareness about cervical cancer. Lastly, the earlier episodes of gynaecological problems, and treatment seeking behaviour lead to higher awareness (efforts may be made to innovate ways to reach older and illiterate women at risk of cervical cancer for better awareness in the community.

Adult↗

Screening for cervical cancer by direct inspection.

OBJECTIVE: To assess the efficacy of visual screening for cervical cancer in the maternal and child health setting. DESIGN: Clinical and cytological screening. SETTING: Maternal and child health centres, Delhi. SUBJECTS: 44,970 women attending the centres from May 1988 to March 1991. RESULTS: 238 cancers in early stages (0-IIa) were detected cytologically and proved through biopsy. Prevalence of cancer in women defined as high risk through examination by speculum was 29/1000 as compared to 1.53/1000 among women with a normal looking cervix. Though only 11.4% women belonged to the high risk category, 63% had early stage cancer. If all women with bleeding symptoms were included in the high risk category, the yield of cancer would be 71.4% (170/238) by referring only 15.6% of women attending maternal and child health centres for further evaluation through cytology or colposcopy. CONCLUSION: Though visual screening is a suboptimal strategy in comparison to the cytological screening, it may be useful where there is a heavy load of prevalent cancer and where cytological screening may not be available for years to come.

Biopsy↗

Ontogeny of a biological clock in Drosophila melanogaster.

Drosophila melanogaster born and reared in constant darkness exhibit circadian locomotor activity rhythms as adults. However, the rhythms of the individual flies composing these populations are not synchronized with one another. This lack of synchrony is evident in populations of flies commencing development at the same time, indicating that a biological clock controlling circadian rhythmicity in Drosophila begins to function without a requirement for light and without a developmentally imparted phase. It is possible to synchronize the phases of rhythms produced by dark-reared flies with light treatments ending as early as the developmental transition from embryo to first-instar larva: Light treatments occurring at developmental times preceding hatching of the first-instar larva fail to synchronize adult locomotor activity rhythms, while treatments ending at completion of larval hatching entrain these rhythms. The synchronized rhythmic behavior of adult flies receiving such light treatments suggests that a clock controlling circadian rhythms may function continuously from the time of larval hatching to adulthood.

Age Factors↗

How strictly do dialysis patients want their advance directives followed?

OBJECTIVE: The Cruzan case and the Patient Self-Determination Act will encourage patients to specify in advance which life-sustaining treatments they would want if they become mentally incompetent. However, strictly following such advance directives may not always be in a patient's best interests. We sought to determine whether patients differ in how strictly they want advance directives followed. DESIGN: Interview study. SETTING: Seven outpatient chronic dialysis centers. PARTICIPANTS: One hundred fifty mentally competent dialysis patients. INTERVENTION: Using a structured questionnaire, we asked the subjects whether they would want dialysis continued or stopped if they developed advanced Alzheimer's disease. We then asked how much leeway their physician and surrogate should have to override that advance directive if overriding were in their best interests. Subjects granting leeway were also asked what factors should be considered in making decisions for them. RESULTS: Subjects varied greatly in how much leeway they would give surrogates to override their advance directives: "no leeway" (39%), "a little leeway" (19%), "a lot of leeway" (11%), and "complete leeway" (31%). Subjects also varied in how much they wanted various factors considered in making decisions, such as pain or suffering, quality of life, possibility of a new treatment, indignity caused by continued treatment, financial impact of treatment on family members, and religious beliefs. CONCLUSIONS: Strictly following all advance directives may not truly reflect patients' preferences. To improve advance directives, we recommend that physicians explicitly ask patients how strictly they want their advance directives followed and what factors they want considered in making decisions.

Adolescent↗

New short period mutations of the Drosophila clock gene per.

Earlier work has indicated that the period length of Drosophila circadian behavioral rhythms is dependent on the abundance of the period (per) gene product. Increased expression of this gene has been associated with period shortening for both the circadian eclosion (pupal hatching) rhythm and circadian locomotor activity rhythms of adult Drosophila. In this study it is shown that a wide variety of missense mutations, affecting a region of the per protein consisting of approximately 20 aa, predominantly generate short period phenotypes. The prevalence of such mutations suggests that short period phenotypes may result from loss or depression of function in this domain of the per protein. Possibly mutations in the region eliminate a regulatory function provided by this segment, or substantially increase stability of the mutant protein.

Amino Acid Sequence↗

Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection.

The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers.

Carrier State↗

Vertical transmission of hepatitis B in north India.

A total of 2337 mother-baby paired sera were screened for the presence of hepatitis B surface antigen. Fifty eight mothers (2.48 per cent) were positive for HBsAg. Six babies (10.3 per cent) were positive for HBsAg at birth. The risk of the babies acquiring the infection during the first year of life varied with the serological status of the mothers. In HBeAg positive mothers the babies were at the greatest risk, with 11/15 (73.3 per cent) babies acquiring the infection by twelve months. If the mothers were only HBsAg positive the risk was lower (17.3 per cent), and if the mother was anti-HBe positive also then the baby had the least chance of becoming infected (9 per cent).

Carrier State↗

Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.

The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.

Carrier State↗

Heterodimerization with c-Fos is not required for cell transformation of chicken embryo fibroblasts by Jun.

c-Jun belongs to a family of proteins that require dimerization for activity. Dimerization occurs through a leucine-rich region near the carboxy terminus called the leucine zipper. Jun can form dimeric complexes with other Jun family as well as Fos family members. The relative proportion of these different dimeric complexes is determined by the relative abundance of each family member at a particular time. Overexpression of v-Jun or c-Jun alone will lead to cell transformation of chicken embryo fibroblasts, albeit with varying efficiencies. Upon overexpression, v-Jun or c-Jun presumably becomes the predominant AP-1 component in the cell. Theoretically, this should lead to a larger proportion of homodimers than heterodimers. It is not clear what role, if any, the other Jun and Fos family proteins play during cell transformation. We have examined the ability of Jun to induce cell transformation in chicken embryo fibroblasts in the absence of interaction with other Jun or Fos family proteins. To this end, we have constructed a chicken v-Jun mutant that is incapable of heterodimerization. This was accomplished by replacing the leucine zipper region of Jun with that of the yeast transcription factor GCN4. This chimeric protein, VJ-GLZ, retains all of the DNA binding and transcriptional activation domains of v-Jun. As expected, in vitro translated VJ-GLZ was found to be incapable of forming heterodimers with c-Fos, FosB, and JunD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Screening for cervical cancer by direct inspection.

Since cytology-based screening programmes for cervical cancer cannot be provided on a large scale in developing countries, an alternative approach is needed. To find out whether visual inspection of the cervix is an adequate alternative, women with cytological evidence of dysplasia were followed up cytologically and colposcopically until cancer was detected, and the gross appearance of the cervix was recorded at each stage. Although only 40-50% of cancers were accompanied by abnormal-looking cervices, whereas 71% were detectable on cytology and 87% on colposcopy, visual inspection may be useful in areas where cytological screening programmes are not available.

Adult↗