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M Kohli

Publications and source records attributed to M Kohli.

At least 19 recordsLinked to original sources
PubMed2006

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK.

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites.

Calibration↗
PubMed2003

Prospective study of circulating angiogenic markers in prostate-specific antigen (PSA)-stable and PSA-progressive hormone-sensitive advanced prostate cancer.

OBJECTIVES: To prospectively describe and compare circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in two groups of advanced prostate cancer patients undergoing androgen deprivation. The first patient group (n = 21) consisted of patients with stable serum prostate-specific antigen (PSA) and the second group (n = 20) consisted of patients with a rising serum PSA during androgen deprivation. METHODS: Patients with diabetes or active heart disease or those receiving anticoagulants were excluded. Circulating VEGF and bFGF were measured in platelet-poor plasma. bFGF was also measured in urine. Platelet factor 4 protein (PF4) assays were performed to evaluate platelet activity in platelet-poor plasma samples. Commercially available enzyme-linked immunosorbent assay kits were used for all assays, and all tests were performed in duplicate. RESULTS: The median age of this study population was 75 years (range 58 to 85). Median plasma VEGF measured in the PSA-stable group was 801.5 pg/mL and in the PSA-rising group was 655.5 pg/mL (P = 0.464). Circulating bFGF was undetectable in plasma, but 4 patients in the PSA-stable group had measurable urine levels. Platelet-poor plasma PF4 assays in all patients were less than 3 IU/mL (normal range 0 to 10). CONCLUSIONS: Our pilot study suggests elevated plasma VEGF levels in advanced prostate cancer do not increase during failure of androgen deprivation therapy. Most of the advanced cancer patients in this study expressed plasma VEGF. This suggests its potential role as a surrogate marker for response assessment during antiangiogenic therapy in this stage.

Aged↗
PubMed2003

Characterization of SrgA, a Salmonella enterica serovar Typhimurium virulence plasmid-encoded paralogue of the disulfide oxidoreductase DsbA, essential for biogenesis of plasmid-encoded fimbriae.

Disulfide oxidoreductases are viewed as foldases that help to maintain proteins on productive folding pathways by enhancing the rate of protein folding through the catalytic incorporation of disulfide bonds. SrgA, encoded on the virulence plasmid pStSR100 of Salmonella enterica serovar Typhimurium and located downstream of the plasmid-borne fimbrial operon, is a disulfide oxidoreductase. Sequence analysis indicates that SrgA is similar to DsbA from, for example, Escherichia coli, but not as highly conserved as most of the chromosomally encoded disulfide oxidoreductases from members of the family Enterobacteriaceae. SrgA is localized to the periplasm, and its disulfide oxidoreductase activity is dependent upon the presence of functional DsbB, the protein that is also responsible for reoxidation of the major disulfide oxidoreductase, DsbA. A quantitative analysis of the disulfide oxidoreductase activity of SrgA showed that SrgA was less efficient than DsbA at introducing disulfide bonds into the substrate alkaline phosphatase, suggesting that SrgA is more substrate specific than DsbA. It was also demonstrated that the disulfide oxidoreductase activity of SrgA is necessary for the production of plasmid-encoded fimbriae. The major structural subunit of the plasmid-encoded fimbriae, PefA, contains a disulfide bond that must be oxidized in order for PefA stability to be maintained and for plasmid-encoded fimbriae to be assembled. SrgA efficiently oxidizes the disulfide bond of PefA, while the S. enterica serovar Typhimurium chromosomally encoded disulfide oxidoreductase DsbA does not. pefA and srgA were also specifically expressed at pH 5.1 but not at pH 7.0, suggesting that the regulatory mechanisms involved in pef gene expression are also involved in srgA expression. SrgA therefore appears to be a substrate-specific disulfide oxidoreductase, thus explaining the requirement for an additional catalyst of disulfide bond formation in addition to DsbA of S. enterica serovar Typhimurium.

Amino Acid Sequence↗
PubMed2002

[Intergenerational equity is more than pension financing].

Public old age pensions--often termed the "generational contract"--are part of a broader system of exchange among generations which must be assessed in its entirety when issues of generational equity are at stake. The paper discusses the elements of this exchange system on the basis of the German Aging Survey, a large representative survey of the German population aged 40-85. Its empirical foci are two domains that are usually neglected in the public discourse on generational equity: the productive activities of the elderly and the transfers between generations in the family. The results demonstrate that the elderly contribute substantially more to societal welfare than has become visible so far.

Adult↗
PubMed2002

Advanced prostate cancer activates coagulation: a controlled study of activation markers of coagulation in ambulatory patients with localized and advanced prostate cancer.

Cancer and increased age are risk factors for coagulation activation. Patients with advanced prostate cancer, which usually presents in the seventh to eighth decade of life, are likely to be at increased risk for thrombosis. We report results of a controlled study of changes in specific and sensitive markers of coagulation activation in patients with prostate cancer. Complete blood count, prothrombin time, partial thromboplastin time, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT) and quantitative D-dimers (DD) were measured in 30 patients of advanced prostate cancer (androgen ablated), in 30 newly diagnosed localized prostate cancer patients, in 30 healthy age-matched volunteers, and in 20 healthy young volunteers. Plasma F1 + 2 (P < 0.05) and DD (P < 0.05), but not TAT, were significantly elevated in healthy elderly males (mean age, 77 years) when compared with healthy young volunteers (mean age, 35 years). F1 + 2, TAT and DD were significantly elevated in advanced prostate cancer when compared with healthy age-matched controls (P < 0.001). In conclusion, advanced prostate cancer patients have significantly increased levels of sensitive markers of coagulation activation compared with healthy age-matched controls. This data can be used to plan studies to determine the risk of clinically significant coagulopathy and the role of primary prophylaxis in patients with advanced prostate cancer.

Adult↗
PubMed2001

A novel method for the evaluation of the severity of nausea and vomiting of pregnancy.

UNLABELLED: The symptomatology of nausea and vomiting of pregnancy (NVP) ranges from mild to very severe. The most advanced method to measure the burden of NVP, the Rhode's scores, incorporates physical signs (length and number of episodes of nausea, number and volume of vomits, and number of retching) with measures of distress caused by these symptoms. However, this system has been validated only for symptoms that occurred in the past 12 h, thus obviating its wide clinical use, and particularly its retrospective use. OBJECTIVE: To examine whether the severity of the physical symptoms of NVP correlate with the degree of stress caused by them, and to develop simple scores that can be used clinically. METHODS AND RESULTS: We prospectively scored 283 women with NVP using the Rhode's system. There was excellent and highly significant correlation between the physical symptoms and their degrees of distress. Subsequently, we examined two simple scoring systems, one with three and one with five physical symptoms. Both yielded distribution of severity of NVP not different from the one found with the use of the full Rhode's score. CONCLUSION: A scoring system based on all five physical symptoms, or only on three (length of nausea, number of episodes of nausea and number of vomits) yielded accurate estimates of severity and changes in severity of NVP. Unlike the Rhode's score, this simple method can be used clinically to evaluate the severity and changes in NVP.

Adolescent↗
PubMed2000

[Age boundaries as social regulation of individual life organization: an anachronism?].

As part of the modern institutionalization of the life course, chronological age boundaries have become highly salient even though they seem to contradict many of the values and systemic requirements of modern societies. During the past few decades, strict age boundaries have been increasingly criticized, and empirically they have become somewhat more fluid. Are they today an anachronism? I treat this question by focusing on the age boundary between work and retirement, and distinguish two levels: its weight for structuring behavior and its meaning for the actors. On both levels, the age boundary is still highly effective. As a last step, I discuss whether the age boundary is (still) "reasonable", especially with regard to the functional conditions of labor markets and social security systems.

Activities of Daily Living↗
PubMed2000

Use of HFE mutation analysis for hereditary hemochromatosis: the need for physician education in the translation of basic science to clinical practice.

BACKGROUND: Hereditary hemochromatosis (HH) is a common hereditary disorder of iron metabolism causing iron overload, organ failure, and malignancy. Preclinical diagnosis using HFE gene analysis followed by prophylactic phlebotomy can completely prevent the disease. METHODS: We conducted a mail survey of all registered primary care physicians, gastroenterologists, and hematologists in Arkansas (n = 860) to determine utilization of HFE mutation analysis in clinical medicine a year after the new molecular test first became available. RESULTS: Of 346 responding physicians (40%), 71 (21%) were aware of the test, 36 (10%) knew that the test was available in Arkansas, and 10 (3%) had used the test. One physician had used the test to screen first-degree relatives of a homozygous HH proband. CONCLUSIONS: Because of poor utilization of the test, the discovery of the role of HFE mutations in HH has had minimal impact on clinical care in Arkansas.

Arkansas↗
PubMed1999

Lack of dependence on p53 for DNA double strand break repair of episomal vectors in human lymphoblasts.

The p53 tumor suppressor gene has been shown to be involved in a variety of repair processes, and recent findings have suggested that p53 may be involved in DNA double strand break repair in irradiated cells. The role of p53 in DNA double strand break repair, however, has not been fully investigated. In this study, we have constructed a novel Epstein-Barr virus (EBV)-based shuttle vector, designated as pZEBNA, to explore the influence of p53 on DNA strand break repair in human lymphoblasts, since EBV-based vectors do not inactivate the p53 pathway. We have compared plasmid survival of irradiated, restriction enzyme linearized, and calf intestinal alkaline phosphatase (CIP)-treated pZEBNA with a Simian virus 40 (SV40)-based shuttle vector, pZ189, in TK6 (wild-type p53) and WTK1 (mutant p53) lymphoblasts and determined that p53 does not modulate DNA double strand break repair in these cell lines.

Cell Line↗
PubMed1999

Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate.

Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

Base Sequence↗
PubMed1999

The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses.

The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses.

Antigens, Polyomavirus Transforming↗
PubMed1999

Inhibition of luteinizing hormone secretion by delta9-tetrahydrocannabinol in the ovariectomized rat: effect of pretreatment with neurotransmitter or neuropeptide receptor antagonists.

Acute treatment with delta9-tetrahydrocannabinol [delta9-THC; 0.5 or 1.0 mg/kg b.w. intravenously (i.v.)], the major psychoactive constituent of marijuana, produces a dose-related suppression of pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. To determine whether delta9-THC produces this response by altering neurotransmitter and/or neuropeptide systems involved in the regulation of LH secretion, ovariectomized rats were pretreated with antagonists for dopamine, norepinephrine, serotonin, or opioid receptors, and the effect of delta9-THC on LH release was determined. Pretreatment with the D2 receptor antagonists butaclamol (1.0 mg/kg b.w., intraperitoneally) or pimozide [0.63 mg/kg, subcutaneously (s.c.)], the opioid receptor antagonists naloxone (1-4 mg/kg, i.v.) or naltrexone (2 mg/kg, i.v.), the noradrenergic alpha2-receptor antagonist idazoxan (10 microg/kg, i.v.), or the serotonin 5-HT(1C/2) receptor antagonist ritanserin (1 or 5 mg/kg b.w., i.p.), did not alter delta9-THC-induced inhibition of pulsatile LH secretion. Pretreatment with a relatively high dose of the beta-adrenergic receptor blocker propranolol (6 mg/kg, i.v.) attenuated the ability of the low THC dose to inhibit LH release; however, lower doses of propranolol were without effect. Furthermore, the ability of a relatively nonspecific serotonin 5-HT(1A/1B) receptor antagonist pindolol (4 mg/kg, s.c.) or the specific 5-HT1A receptor antagonist WAY-100635 (1 mg/kg, s.c.) to significantly attenuate THC-induced LH suppression indicates that activation of serotonergic 5-HT1A receptors may be an important mode by which THC causes inhibition of LH release in the ovariectomized rat.

Adrenergic Antagonists↗
PubMed1998

High occurrence of HBV among STD clinic attenders in Bombay, India.

The pattern of sexually transmitted disease (STD) is the basis for designing surveillance of specific STD, their trends and syndromic management protocols. Two hundred and fifteen consecutive first-time STD clinic attenders at a teaching hospital in Bombay were recruited for the study in October 1995. Thorough clinical examination and the following investigations were done: wet mount, Gram stain, Giemsa stain, modified Thayer-Martin (MTM) medium culture, Fontana stain, Venereal Disease Research Laboratory (VDRL), Treponema pallidium haemagglutination test (TPHA), HBsAg and HIV. Ulcerative STD constituted 73.5% of total STD while 15.8% were discharges and 10.2% were genital growths. Ulcers in decreasing order of frequency were chancroid (51.9%), genital herpes (29.1%) and syphilis (14.5). 76.5% of genital discharges were due to gonococcal infection. The high rate of ulcerative STD is possibly an important co-factor for the high HIV prevalence of 31.2% in Bombay. Of 182 patients tested for HBV, 16 (8.8%) were reactive for HBsAg, revealing a high prevalence among STD attenders. A high co-relation of HBsAg positive with either HIV or VDRL requires urgent attention for HBV intervention strategies in this population.

Adolescent↗
PubMed1997

Bhorugram (India): revisited. A 4 year follow-up of a computer-based information system for distributed MCH services.

Impact of a health informatics research project on the management and delivery of primary health care, focusing on maternal and child health care (MCH), was reported earlier in 1992, with encouraging results in terms of increased antenatal care coverage and decrease in Immunisation drop-outs. The software (MCHS) was based on essential data sets (EDS) to assist the care providers in information management for MCH care. The site was revisited after four years to evaluate the status of the project and to ascertain whether computers were still in use and was the dispensary staff using the MCHS package or not? The results are presented in this paper to demonstrate that 'information is a difference that makes a difference'. Information generated by the MCHS acted as a catalyst for behavioural change in the community from indifferent users to active users of the health care services. This is reflected by the increased acceptance of antenatal care, 80% fully immunised child (FIC) and participation in other primary health care activities.

Adolescent↗
PubMed1997

Primary care informatics: Bhorugram, India: revisited.

A Primary Health Care Informatics project was initiated in 1990 at Bhorugram, Rajasthan, India. It was reported in MIE91 with initial, encouraging results. The evaluation of the information system has been successful in all operational terms, and the Fully Immunised Child (FIC) could be used as a local cardinal index to monitor and evaluate the quality of care, cost-effectiveness and community participation. Health Systems and Health Economy Research alike have long searched for apt quality and performance markers that in themselves could embrace and express a number of aspects and factors. The FIC index is shown to well meet the criteria of such a cardinal measure in the MCHC services. We, also, demonstrate an implementation strategy for establishing Information Systems in Primary Health Care Centres in Developing countries.

Child↗
PubMed1995

Raynaud's phenomenon as a presenting sign of ovarian adenocarcinoma.

We describe a 53-year-old white woman whose first manifestation of ovarian adenocarcinoma was a sudden onset of severe Raynaud's phenomenon, which rapidly progressed to fixed ischemic changes in her thumb. After surgical removal of the tumor and chemotherapy, the vasospastic features regressed. To our knowledge this is only the 2nd such reported case.

Adenocarcinoma↗
PubMed1994

Local proliferation of fibroblast-like synoviocytes contributes to synovial hyperplasia. Results of proliferating cell nuclear antigen/cyclin, c-myc, and nucleolar organizer region staining.

OBJECTIVE: To test the hypothesis that local proliferation contributes significantly to the hyperplasia of rheumatoid synovium. METHODS: Immunohistologic and chemical staining was used to identify 3 markers of cell proliferation: proliferating cell nuclear antigen, c-myc proto-oncogene, and nucleolar organizer regions. Synovium from 21 patients with rheumatoid arthritis, 34 with degenerative joint disease, and 7 with joint trauma was examined. RESULTS: All 3 markers indicated substantial, active proliferation of synovial lining cells in synovium with hyperplasia. Proliferating cells showed type I procollagen immunoreactivity but were negative for CD68, a monocyte/macrophage marker. Proliferation was greater in rheumatoid arthritis than in the other conditions evaluated. CONCLUSION: In situ proliferation of fibroblast-like synoviocytes in the synovium lining contributes considerably to the increase in cell numbers in rheumatoid synovium.

Adult↗