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Biomedical subjects

C Wells

Publications and source records attributed to C Wells.

At least 73 records · Page 4Linked to original sources
PubMed1996

Telomerase activity in human breast cancer and benign breast lesions: diagnostic applications in clinical specimens, including fine needle aspirates.

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, 10 microns thick, from each breast biopsy. This method was used to obtain effective extraction from small samples and to confirm the histological identity of the specimen by microscopical examination of serial sections. Fifty-two of 71 breast carcinomas were positive for telomerase activity, and the intensity of this was strong in most cases, whereas all 6 samples of normal breast tissue and 17 of fibrocystic disease were negative and only 1 of 15 fibroadenomas was positive. Invasive ductal carcinomas were more frequently positive than invasive lobular carcinomas. There was no correlation of telomerase activity with tumour size or the occurrence of lymph node metastasis. Evaluation of our assay system showed that a signal of telomerase activity was detectable in extracts from single cryostat sections (< 1 mm2) of a cancer specimen and from as few as 4 cells of a human breast cancer cell line. On the basis of the above data, we applied this assay to fine needle aspirates of breast lesions. Ten of 15 aspirates which had been cytopathologically diagnosed as cancer were strongly positive, while 26 of 29 benign aspirates were totally negative and the remaining 3 showed only borderline activity. In 3 cases, the telomerase result could have helped establish a diagnosis when the cytological observations were inconclusive. Our results indicate that this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue biopsies and fine needle aspirates.

Autoradiography↗
PubMed1996

Comparison of the transmission of Theileria parva between different instars of Rhipicephalus appendiculatus.

The transmission of Theileria parva by nymphal and adult Rhipicephalus appendiculatus was compared by the assessment of salivary gland infections in tick batches fed on the same group of infected cattle at the same time. When larval and nymphal R. appendiculatus Muguga ticks were fed concurrently on cattle undergoing acute infection with T. parva Muguga, the resultant nymphae developed a slightly lower prevalence of infection than did the adult ticks. The abundance of infection was 5-20 times higher in the adult ticks than in the nymphae. When larval and nymphal R. appendiculatus Muguga and R. appendiculatus McIlwaine were fed to repletion on cattle infected with T. parva Boleni, a parasite causing subacute infection, resultant adult tick batches had a relatively high prevalence of infection, but infection was not detected in resultant nymphal batches. When cattle that were carriers of 2 stocks of T. parva, Marikebuni and Kiambu 5, were used as the source of infection, the infections developing in adult R. appendiculatus Muguga ticks were much higher than those developing in nymphae. The structure of salivary glands differed between nymphal ticks, adult males and adult females, and this is considered to be an important factor affecting the infection levels. The morphology of the type III acini, the target acini for sporogony, was similar, but the mean numbers of type III acini were different, with 87 in nymphae, 1346 in males and 1736 in females. This difference was correlated with the different tick instars and sexes was similar, the rate of sporogony was fastest in feeding nymphae, taking on average 2-3 days. compared to 3-4 days in females and an irregular period in the males. These results are discussed in relation to the epidemiology of T. parva.

Animals↗
PubMed1996

Impaired absorption of zidovudine in patients with AIDS-related small intestinal disease.

OBJECTIVES: To investigate the effect of small intestinal disease (SID) on the absorption of zidovudine (ZDV) in patients with AIDS. METHODS: Fourteen fasted homosexual men with AIDS received a single oral dose of ZDV (5 mg/kg). Nine subjects had clinical evidence of intestinal disease (chronic diarrhoea with wasting) confirmed by reduced fat absorption measured indirectly using the 14C-triolein test. Five subjects had AIDS-related symptoms other than those affecting the gastrointestinal tract with normal fat absorption. Sequential measurements of plasma ZDV including its glucuronide metabolite (GZDV) were obtained using radio-immunoassay and ZDV/GZDV concentrations-time profiles of both groups of subjects were compared. Comparisons were also made for each of the following computed variables: the maximum plasma concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-6 h), the elimination half-life (t 1/2), and apparent oral clearance (CL0). RESULTS: In patients with SID, Cmax ZDV was reduced (6.39 +/- 3.39 versus 11.51 +/- 5.01 mumol/l; P < 0.05) and Tmax ZDV prolonged (0.81 +/- 0.51 versus 0.40 +/- 0.14 h; P < 0.05) but AUC0-6 h ZDV was no different from the non-SID group (8.03 +/- 2.73 versus 14.56 +/- 9.0 mumol/l-1xh; P = 0.06). There were no differences in t 1/2 ZDV (1.22 +/- 0.20 versus 1.13 +/- 0.30 h) or CL0 ZDV (3017 +/- 1158 versus 1700 +/- 889 ml/min; P > 0.05) between SID and non-SID groups, respectively, and GZDV values were comparable between the two groups. CONCLUSIONS: These data suggest delayed absorption rather than altered metabolism of ZDV in AIDS-related SID and raise the possibility of drug malabsorption. The clinical efficacy of orally administered low-dose ZDV regimens may require further evaluation in patients with chronic diarrhoea and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Pulmonary fibrosis and lung cancer in the United States: analysis of the multiple cause of death mortality data, 1979 through 1991.

We determined the relationship between pulmonary fibrosis and lung cancer in the United States from 1979 through 1991 by analyzing death certificate reports compiled by the National Center for Health Statistics. Of the 26,866,600 people who died during the study period, 107,312 died with pulmonary fibrosis, 1,739,725 died with lung cancer, 2,040,634 died with chronic obstructive pulmonary disease, and 7,807 died with asbestosis. Lung cancer occurred less frequently among decedents with pulmonary fibrosis (4.81%) and more frequently among decedents with chronic obstructive pulmonary disease (10.06%) and decedents with asbestosis (26.60%) than among decedents in the general population (6.48%). We conclude that the prevalence of lung cancer among people who died with a diagnosis of pulmonary fibrosis is lower than the 10% to 40% prevalence that has been reported in case series of pulmonary fibrosis.

Adolescent↗
PubMed1996

Ethnic differences in women with HIV infection in Britain and Ireland. The study group for the mrc collaborative study of HIV infection in women.

OBJECTIVE: To examine ethnic differences in the socio-epidemiological and clinical characteristics of a cohort of women with HIV infection in Britain and Ireland. DESIGN AND METHODS: Analysis of baseline data (ethnic group, sexual history, likely route of HIV infection, reasons for HIV testing and first AIDS-defining disease) from 400 women with HIV infection recruited into a cohort study from 15 genitourinary medicine/HIV clinics in Britain and Ireland. RESULTS: Sixty-five per cent of women were white and 29% black African. Their median number of lifetime sexual partners was seven and three, respectively (P < 0.001). Ninety-three per cent of black African and 43% of white women were probably infected through sexual intercourse. Injecting drug use was the most likely route of infection in 55% of white women, but none of the black African women. Perceived risk (33%) or investigation of symptoms (26%) were the most common reasons for HIV testing. Seven per cent of white women and 16% of black African women (P < 0.001) had AIDS when HIV infection was diagnosed. The distribution of first AIDS-defining diagnoses differed (P = 0.001) by ethnic group. For white women, the most common disease was Pneumocystis carinii pneumonia; for black African women it was pulmonary tuberculosis. CONCLUSION: There are important differences between black African and white women in sexual history and route of transmission, disease stage at diagnosis and pattern of AIDS-defining diseases.

AIDS Serodiagnosis↗
PubMed1995

Early responses of trans-activating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-beta (C/EBP beta) and C/EBP delta.

Using the 3T3-F442A preadipocyte line as a model of GH-dependent differentiation, early changes in the DNA-binding affinity of transcription factors in response to GH addition were investigated. Addition of 50 ng/ml human GH to cells in chemically defined medium led to a rapid increase in binding activity of activator protein 1 (AP-1) and CCAAT enhancer-binding protein (C/EBP), which was significant at 30 min and reached maximal induction by 2 h (3-fold for AP-1, 2.5-fold for C/EBP). Induction in AP-1 DNA binding correlates with a concomitant GH trans-activation of c-jun and c-fos genes described previously. Using specific antibodies in electrophoretic mobility shift assays and Western blots, it was shown that the increase in activity of C/EBP is the result of an increase in synthesis of two alternatively translated forms of C/EBP beta: 40-C/EBP beta and 23-C/EBP beta. This increase in protein was not accompanied by alteration in mRNA level and could be blocked by a Janus kinase 2 tyrosine kinase inhibitor and a C kinase inhibitor at concentrations shown to inhibit GH-dependent activation of microtubule-associated protein (MAP) kinases. Concomitant with the translationally activated increase in C/EBP beta, a GH-dependent increase was observed in C/EBP delta transcription. This was accompanied by an increase in mRNA for C/EBP delta, which was superinduced by cycloheximide and, unlike the increase in C/EBP beta protein, was not observed with insulin. Thus GH exerts its effects on C/EBP isoforms at two levels: transcriptional activation of C/EBP delta and translational activation of C/EBP beta. It is proposed that GH-dependent phosphorylation results in the efficient translation of 40-C/EBP beta and 23-C/EBP beta (the mouse homolog of the inhibitor liver-enriched inhibitory protein), and that together with the induction of C/EBP delta, these may be involved in initiating the adipocyte differentiation program.

3T3 Cells↗
PubMed1995

Isolation of the insecticidal components of Tagetes minuta (Compositae) against mosquito larvae and adults.

Application of Tagetes minuta floral extract to silica gel column chromatography produced 2 fractions with the hydrogenate part 20-30 times more toxic to larvae and 12-13 times more toxic to adults of Aedes aegypti and Anopheles stephensi, respectively, than the oxygenate part. Further fractionation by column chromatography of the hydrogenate fraction produced 4 thiophenes, 5-(but-3-ene-1-ynyl)-2,2'-bithiophene, 5-(but-3-ene-1-ynyl)-5'-methyl-2,2'-bithiophene, 2,2',5',2"-terthiophene, and 5-methyl-2,2',5',2"-terthiophene. These compounds in Tagetes minuta are largely responsible for the toxicity exhibited against the tested mosquitoes.

Aedes↗
PubMed1994

Toxicity of extracts from three Tagetes against adults and larvae of yellow fever mosquito and Anopheles stephensi (Diptera: Culicidae).

Whole-plant Soxhlet extractions for the three Tagetes species showed that T. minuta had the greatest biocidal effect on the larvae and adults of Aedes aegypti (L.) and Anopheles stephensi Liston. Bioassays of simultaneous steam distillation extractions of the various parts of T. minuta found extracts from the flowers provided LD90s of 4 and 8 ppm against the larvae and 0.4 and 0.45% against the adults of A. aegypti and A. stephensi, respectively. Further research on T. minuta floral extracts as new biorational insecticides are discussed.

Animals↗
PubMed1994

A study of the cumulus-corona cell complex in in-vitro fertilization and embryo transfer; a prognostic indicator of the failure of implantation.

In-vitro morphological changes and proliferation of cells of the cumulus oophorus, in particular cells of the corona radiata, were seen to differ between individuals and between oocytes of the same cohort in an unselected series of 159 IVF cycles. Cell proliferation did not relate to indications for treatment, type and length of ovarian stimulation, age of patient, ovarian response and quality of oocyte, fertilization rate or embryo morphology. A direct relationship, however, was demonstrated between the proliferative capacity of these cells and the incidence of clinical pregnancy. No pregnancies resulted when there was an absence of morphological change or proliferation of these cells. In cycles where the proliferative capacity of these cells varied between oocytes of a single cohort the pregnancy rate was 40% per cycle, and in cycles where cells associated with all oocytes underwent extensive proliferation the pregnancy rate was 49% (P < 0.001). Thus, regardless of the apparent quality of gametes or embryo, no pregnancies arose if the cumulus-corona complex was incapable of replication. We have, therefore, identified two populations of oocytes based on the proliferative capacity of cumulus-corona cells in vitro, one being associated with a failure of implantation.

Adult↗
PubMed1994

Caring for people with human immunodeficiency virus. Incorporating the patient's perspective.

The interdisciplinary HIV work team meets to improve care for people with the human immunodeficiency virus (HIV). Through its efforts, including patient and provider focus groups, the team identified what is done well in caring for patients with HIV, the obstacles that patients encounter in accessing care, and how to prepare for the future. The work team has been instrumental in developing ideas and implementing changes by serving as a vehicle for communication and enhancing a spirit of collaboration.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Menstrual symptoms in women infected by the human immunodeficiency virus.

OBJECTIVE: To determine whether there is a higher prevalence of menstrual symptoms in women seropositive for the human immunodeficiency virus (HIV) compared to a matched control group and to examine the relation between menstrual symptomatology and immunosuppression. METHODS: In a cross-sectional study, 55 HIV-seropositive women and a matched control group underwent detailed gynecologic assessment. The prevalence of regular cycles, oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, and dyspareunia was assessed in the two groups. Any association with clinical disease or CD4 lymphocyte count was sought. RESULTS: There were no significant differences in the prevalence of oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, or dyspareunia between the groups. Furthermore, no differences were demonstrated between symptomatic and asymptomatic women infected by HIV, nor was any correlation found between CD4 lymphocyte count and menstrual loss or dysmenorrhea. CONCLUSION: Infection with HIV and related immunosuppression do not seem to have a clinically significant effect on menstruation.

Adult↗
PubMed1993

Pressure changes in the eye due to an injection of inert gases: a theoretical model.

In the repair of retinal tears and detachments, the vitreous humor is often completely replaced with a temporary mixture of gases, one of which is not normally found in the bloodstream. The resulting bubble can then support the healing retina. There is diffusion of gases, however, from the bubble into the bloodstream and vice versa. This alters the intraocular pressure, with possible adverse consequences, as the intraocular pressure must be maintained within a certain range for the procedure to be successful. A simple model has been developed to predict the evolution of intraocular pressure over time, given a certain initial mixture of injected gases. This model could be useful in determining what mixture to use to support effectively and safely a healing retina.

Capillaries↗
PubMed1993

Growth characteristics of human herpesvirus-6: comparison of antigen production in two cell lines.

In order to optimize viral antigen production, the growth characteristics of human herpesvirus-6 (HHV-6) (strain AJ) were studied in two cell lines: HSB-2 and JJHAN. The cells were infected with different multiplicities of infection (moi) and viral growth was monitored by appearance of cytopathic effect (CPE), total and viable cell count, immunofluorescence test, immunoblotting, and electron microscopy. Although > or = 70% of JJHAN cells showed CPE when infected at high moi, only 5% of the cells contained viral antigens when tested with immunofluorescence. In contrast the percentage of cells showing fluorescence in HSB-2 cells reached > or = 30% when infected at > or = 1:50. More than 10 polypeptides of molecular weight ranging between 31-140 kD appeared in the HSB-2 cultures by immunoblotting while only 3 polypeptides were detected in the JJHAN cultures at high moi. Different stages of virus maturation were seen in the HSB-2 cells by electron microscopy but the replication of the virus in JJHAN cells appeared to be restricted. For the purpose of antigen production the optimal conditions for the AJ strain of HHV-6 were found to be culturing in HSB-2 cells at a concentration of 1:25-1:50 infected to uninfected cells and harvesting after 7 days.

Antigens, Viral↗