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Biomedical subjects

K Kelly

Publications and source records attributed to K Kelly.

At least 19 recordsLinked to original sources
PubMed1992

Risk factor correlates of coronary calcium as evaluated by ultrafast computed tomography.

Coronary artery calcium is invariably associated with atherosclerosis and has been linked to an increased risk of coronary events. Ultrafast computed tomography (CT) was recently used to document the presence and relative quantity of coronary calcium. The use of the self-reported coronary risk factors to identify persons with coronary calcium as documented by ultrafast CT screening was examined in 458 men and 139 women aged 26 to 81 years (88% asymptomatic). All subjects underwent ultrafast CT scanning, and received a questionnaire and underwent an interview regarding medical and risk factor history. Total calcium score was calculated as the sum of lesion-specific scores, each calculated as the product of density > or = 130 Hounsfield units and area > or = 0.51 mm2. The prevalence of coronary calcium increased significantly (p < 0.01) by age group, and the greater the number of risk factors present, the greater the likelihood of calcium. From multiple logistic regression, age (p < 0.01), male sex (relative risk [RR] 3.03; p < 0.01), and history of smoking (RR 1.85; p < 0.01) and hypertension (RR 1.65; p < 0.05) were independently associated with the probability of detectable calcium. Among asymptomatic subjects, an association with hypercholesterolemia was also seen (RR 1.56; p < 0.05). The results demonstrate that cardiovascular risk factors can help in identifying the likelihood of coronary calcium.

Age Factors↗
PubMed1992

The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B-mediated inhibition.

The candidate oncogene bcl-3 was discovered as a translocation into the immunoglobulin alpha-locus in some cases of B-cell chronic lymphocytic leukaemias. The protein Bcl-3 contains seven so-called ankyrin repeats. Similar repeat motifs are found in a number of diverse regulatory proteins but the motifs of Bcl-3 are most closely related to those found in I kappa B proteins in which the ankyrin repeat domain is thought to be directly involved in inhibition of NF-kappa B activity. No biological function has yet been described for Bcl-3, but it was noted recently that Bcl-3 interferes with DNA-binding of the p50 subunit of NF-kappa B in vitro. Here we demonstrate that Bcl-3 can aid kappa B site-dependent transcription in vivo by counteracting the inhibitory effects of p50/NF-kappa B homodimers. Bcl-3 may therefore aid activation of select NF-kappa B-regulated genes, including those of the human immunodeficiency virus.

Animals↗
PubMed1992

Immediate and long-term results of delayed recanalization of occluded acute myocardial infarction-related arteries using coronary angioplasty.

Recent evidence suggests that late reperfusion of an occluded infarct-related artery after acute myocardial infarction (AMI) may convey a better prognosis. The clinical outcome of percutaneous transluminal coronary angioplasty (PTCA) as a means of mechanical reperfusion in this particular setting has not been clearly delineated. Ninety-seven patients with AMI underwent PTCA of the occluded infarct-related artery after the acute phase of the AMI (48 hours to 2 weeks, mean 8 +/- 4 days). The study consisted of 72 men (74%) (mean age 56.5 +/- 12 years) and 25 women. Seventy-seven patients (79%) had a Q-wave AMI and 20 patients (21%) a non-Q-wave AMI. Seventy-six patients (79%) had angina after AMI and 4 had previously undergone coronary bypass surgery. Clinical success was achieved in 85 patients (87%). Angiographic success was obtained in 90 of the 97 occluded arteries (93%) and was similar for all 3 major vessels: right coronary 97%, left anterior descending 93% and circumflex 85% (p = not significant). Major complications (AMI, emergency bypass and death) occurred in 3 patients (3.1%). Long-term follow up (3.7 +/- 0.8 years) revealed symptomatic recurrence in 20 (23%), whereas 51 (58%) remained asymptomatic. Most recurrences (16 of 20) were in the form of restenosis rather than reocclusion, with a high success rate for repeat dilation (93%). These results indicate that mechanical reperfusion of an occluded infarct artery, performing PTCA 48 hours to 2 weeks after AMI, has a high success rate, a low complication rate and low symptomatic restenosis.

Adult↗
PubMed1992

Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. The Medical Research Council Working Party for Leukaemia in Adults.

Both melphalan and cyclophosphamide increase life expectancy in patients with myelomatosis, but few large randomised studies have compared combination chemotherapy regimens with these single agents. In the Vth MRC myelomatosis trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU, cyclophosphamide, and melphalan) as first-line treatment was significantly longer than that of 316 patients given intermittent melphalan (M7) (p = 0.0003). The 75%, median, and 25% survivals were 7, 24, and 42 months, respectively, with M7 and 10, 32, and 56 months, respectively, with ABCM. Stable disease with few symptoms (plateau) was achieved by 61% of patients given ABCM and 49% of those given M7 (p = 0.004). Myelotoxicity was comparable between regimens. Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed. The results indicate that ABCM is an acceptable regimen that is more effective than melphalan, with or without prednisone, for first-line treatment of myelomatosis.

Aged↗
PubMed1992

Is stage I epithelial ovarian cancer overtreated both surgically and systemically? Results of a five-year cancer registry review.

OBJECTIVE: To review the incidence of Stage I epithelial ovarian carcinoma in the West Midlands region and to identify prognostic factors that have a significant effect on survival. DESIGN: A retrospective review of all Stage I ovarian cancer patients registered from 1.1.80 to 31.12.84. SETTING: West Midlands Regional Cancer Registry. POPULATION: 457 patients with Stage I ovarian cancer--373 with epithelial ovarian carcinoma. MAIN OUTCOME MEASURES: Survival at censor date of 30.6.89. RESULTS: 28% developed recurrent disease, and the overall 5-year survival of the group was 70%. Univariate analysis of all possible prognostic factors showed that stage, adjuvant chemotherapy, histological grade and type, surgical rupture of the tumour, intact capsule histologically, clinical finding of ascites and the performance of peritoneal washings were significantly associated with survival. Adequate surgical staging as defined by FIGO was not significantly associated with survival. A multivariate analysis based on the Cox proportional hazard model identified histological grade, adjuvant chemotherapy, patient age and peritoneal washings as having independent prognostic effects. Surprisingly adjuvant chemotherapy and peritoneal washings had negative effects on survival. CONCLUSIONS: Although a retrospective review has limitations, it would appear that adequate surgical staging and adjuvant chemotherapy confer no benefit in terms of survival in Stage I disease.

Adolescent↗
PubMed1992

The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients.

We evaluated the predictive value of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in 32 depressed outpatients completing a double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe), which failed to show any significant difference between SAMe and placebo. Treatment response was defined as the change in Hamilton Rating Scale for Depression (HRSD-24) score between baseline and the end of the six-week trial. Subjects with TSH response outside the normal range (7-25 uU/ml) had a significantly greater response than patients with a normal response. There was also a significant correlation between absolute deviations from the mean TSH response (16 uU/ml) and changes in HRSD-24 scores.

Adolescent↗
PubMed1992

A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site.

A Rel-related, mitogen-inducible, kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells. The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein. This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B. Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats. In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa B sites. We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97. p50B is able to form heteromeric kappa B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa B. Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site. The data imply the existence of a complex family of NF-kappa B-like transcription factors.

Amino Acid Sequence↗
PubMed1992

Employment of antipeptide antisera to distinguish two closely related cytokines induced in human T cells.

AT464 and AT744 are two cytokines encoded by mitogen-induced genes from human T lymphocytes. These proteins belong to a family of structurally related chemotactic proteins associated with inflammation. By expression of their full length cDNAs in COS cells and in baculovirus-infected Sf9 cells, we found that pAT464 and pAT744 cDNAs represent secreted polypeptides of a molecular mass of about 8,000 and 11,000 Da, respectively. Biochemical characterization of these proteins has been persued through polyclonal antisera, which were derived to synthetic peptides. Using these sera for Western blotting analyses the recombinant AT464 and AT744 proteins could be detected as secreted products from transfected COS cells and from baculovirus-infected Sf9 cells. Similarly the native proteins could be detected in the supernatants of activated human peripheral blood T cells. The recombinant and the T cell-secreted AT464 and AT744 proteins appear to be identical as judged by their mobility by SDS-PAGE and by their reactivity with the rabbit polyclonal antisera.

Animals↗
PubMed1992

Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group.

We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage.

Alleles↗
PubMed1992

A high proportion of early response genes are constitutively activated in T cells by HTLV-I.

Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an 'early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX-encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation.

Blotting, Northern↗
PubMed1991

Growth factors in lung cancer: possible etiologic role and clinical target.

Growth factors play an important role in the pathogenesis and progression of all histologic types of lung cancer. Ideas for the exploitation of growth factors in lung cancer management are growing. The inhibition of the interaction between growth factors and their receptors, utilization of negative growth factors, interruption of the signal transduction pathways, or effecting decreased growth factor and/or receptor expression, could result in cell death, and all seem logical possibilities for new and specific treatment approaches. There can be no question that observations of the abnormal expression of growth factors have made a startling impact in every aspect of cancer research. The elucidation of their role in cell proliferation, coupled with our growing knowledge of the functions of oncogenes, has given birth to a unifying concept for the etiology of malignant transformation, which hopefully will translate into new, less toxic, more effective, and desperately needed lung cancer treatment.

Amino Acid Sequence↗
PubMed1991

Coronary angioplasty of diffuse coronary artery disease.

From January 1983 through December 1987, 98 patients underwent angioplasty of at least one diffusely diseased coronary artery. Diffuse coronary disease was described as: group I, narrowing greater than or equal to 50% that involved the entire vessel (40 patients), group II, long lesions greater than or equal to 2 cm in length (39 patients), group III, three or more lesions in the same vessel (19 patients). There were 65 men and 33 women, with a mean age of 60 years; 64 patients (65%) had unstable angina, 23 patients (23%) were diabetic, 31 (32%) had prior myocardial infarctions, and 12 had prior bypass surgery. Multivessel disease was present in 89% of patients. Angioplasty of only the diffusely diseased vessel was performed in 41 patients, and additional vessels were dilated in 57 patients. Overall, of 396 lesions (four per patient) and 197 vessels (two per patient) attempted, success was achieved in 382 lesions (96%) and 187 vessels (95%); angiographic success was achieved in 112 of 120 diffusely diseased vessels (93%). Clinical success was achieved in 91 patients (93%). The overall complication rate (death, myocardial infarction, urgent bypass surgery) was 8% (8 of 98): six patients (6%) had myocardial infarction (one Q wave, five non-Q wave), one patient (1%) had urgent bypass surgery, and two patients (2%) died (one during bypass surgery). The majority of complications (7 of 8 or 87%), including the two deaths, occurred in group I patients, with a 17.5% rate, versus 2.5% in group II and 0% in group III, p less than 0.002.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Placental teratoma.

The rare teratoma of the placenta has been compared to the fetus amorphus, two distinguishing characteristics being the teratoma's lack of structural organization and lack of large vessels entering the tumor. A case of placental teratoma and theories of origin are discussed.

Adult↗
PubMed1991

Contrasts between symptoms of summer depression and winter depression.

Epidemiological studies and studies of clinical populations suggest that there are primarily two opposite patterns of seasonally recurring depressions: summer depression and winter depression. In addition, there is preliminary evidence that the two seasonal types of depression may have opposite types of vegetative symptoms. In the present study, we prospectively monitored symptoms of depression in 30 patients with recurrent summer depression and 30 sex-matched patients with recurrent winter depression and compared the symptom profiles of the two groups. Consistent with predictions based on the earlier reports, we found that winter depressives were more likely to have atypical vegetative symptoms, with increased appetite, carbohydrate craving, weight gain and hypersomnia, and that summer depressives were more likely to have endogenous vegetative symptoms, with decreased appetite and insomnia. A cluster analysis performed on the patients' symptom profiles without reference to season of occurrence of their episodes separated 78% of the summer depressives and winter depressives from each other on the basis of their symptoms (chi 2 = 19.29, P less than 0.001).

Adult↗
PubMed1991

Retrospective analysis of 318 cases of uterine sarcoma.

A study of data from 318 cases of uterine sarcoma presenting during a 10-year period (1967-1976) is reported. All but 6 of the patients had at least a 5-year follow-up (98% 5-year follow-up). Overall 5-year survival was 31%, with the major prognostic indicator being tumour stage. Despite the tendency for mixed mesodermal tumours to present in older women with more advanced disease, survival was not statistically different to those patients with leiomyosarcomas. Thus, the propensity for tumour dissemination in leiomyosarcomas should not be underestimated. Leiomyosarcomas are less likely to present with abnormal symptoms than are other sarcomas, and their occurrence as an incidental finding on histological examination underlines the need for an adequate inspection of the intra-abdominal contents at hysterectomy. The tendency to treat all sarcomas as if they were endometrial tumours may be fallacious, and an alternative classification (such as the TNM system) may be required. Recurrence of tumour tended to be at distant sites (distant:pelvic recurrence rate 3:1). Adjuvant radiotherapy is unlikely to alter distant disease foci, and thus the development of combination chemotherapeutic regimens using agents which have shown to result in tumour response seem warranted. Such trials will need to be organised on a multicentre basis to attain statistically evaluable numbers of patients.

Adult↗
PubMed1991

Interstitial IR-192 implants of the oral cavity: the planning and construction of volume implants.

The success of radioactive implant therapy for head and neck carcinomas depends critically on careful planning and execution of the implant procedure. In this paper we discuss our experience with oral tongue and floor of mouth implants, and some innovations introduced to facilitate these procedures. Implants were carried out using standard angiocatheters modified with magnetic caps at the open end and terminated with Teflon spacers and lead shot at the closed end. The importance of accurate source placement and careful determination of the target dose rate is discussed with numerical examples. Differential hot-loading of sources is clearly indicated in cases of extension of the lesion to the dorsal or lateral tongue surface. For dorsal surface extension the use of Teflon spacers at the closed ends of the catheters helps to ensure adequate coverage of the target volume with the higher dose region enclosing the demonstrable tumor. All 10 patients implanted with this technique are controlled without recurrence at a median follow-up of 38 months. The two complications observed appeared to be associated with excessive hot-loading of edge plane sources.

Brachytherapy↗