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Biomedical subjects

M McBride

Publications and source records attributed to M McBride.

At least 19 recordsLinked to original sources

Characterization of two novel sublines established from a human megakaryoblastic leukemia cell line transfected with p210(BCR-ABL).

Disease progression in chronic myelogenous leukemia (CML) is usually accompanied by chromosomal abnormalities such as an additional Ph chromosome, trisomies of chromosome 8 or 19, or i(17) in addition to the standard translocation t(9;22) (q34;q11). However, detailed studies of the various steps involved during this evolution are difficult to perform, thereby making the study of cell lines that contain the transposed genes BCR-ABL, especially those of human origin, an important focus. In this analysis we investigated the human megakaryoblastic cell line MO7e and its subline transfected with BCR-ABL, MO7e/p210. Initial studies demonstrated that the phenotype of the MO7e line was consistent with a megakaryocytic lineage as originally described and was growth factor dependent in liquid culture. The MO7e/p210 subline, however, was growth factor independent and could be further separated into two distinct sublines based on expression of glycophorin A using the monoclonal antibody R10. The subline R10 negative (R10-) was similar to the parent line MO7e but R10 positive (R10+) cells had a distinct erythroid phenotype. In addition, the R10- and R10+ sublines demonstrated strikingly different colony morphology when cultured in semisolid medium. Furthermore, R10+ cells had additional chromosomal abnormalities not detected in the R10- population. These results demonstrate that the insertion of the BCR-ABL in this human leukemia cell line resulted in two distinct subpopulations of cells, each now growth factor independent, but one with a phenotype and karyotype identical to the parent cell line and the other with a different phenotype and additional chromosomal abnormalities. These two subpopulations derived from the MO7e/p210 transfected cell line may prove useful in further understanding the multistep events that occur in the progression of this disease.

Chromosome Aberrations

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

Acquired Immunodeficiency Syndrome

Copper speciation and microbial activity in long-term contaminated soils.

Most soil quality guidelines do not distinguish among the various forms of metals in soils; insoluble, nonreactive, and nonbioavailable forms are deemed as hazardous as highly soluble, reactive, and toxic forms. The objective of this study was to better understand the long-term effects of copper on microorganisms in relation to its chemical speciation in the soil environment. Carbon mineralization processes and the global structure of different microbial communities (fungi, eubacteria, actinomycetes) are still affected after more than 50 years of copper contamination in 20 soils sampled from two different agricultural sites. The microbial respiration lag period (LP) preceding the beginning of mineralization process increases with the level of soil copper contamination and is not significantly affected by other environmental factors such as soil pH and soil organic matter (SOM) content. The total copper concentration showed the best correlation with the LP when each site is considered separately. However, when considering the whole set of data, soil solution free Cu2+ activity (pCu2+) is the best predictor of Cu toxicity determined by LP (quite likely because pCu2+ integrates the soil physicochemical variability). The maximum mineralization rate (MMR), even if well correlated with the pCu2+, appears not to be a good biomonitor of copper contamination in soils since it is highly sensitive to soil characteristics such as SOM content. This study emphasizes the importance of the physicochemical properties of the environment on soil heavy metal toxicity and on soil toxicological measurements. These properties must be characterized in soil toxicological studies with respect to (1) their interactions with heavy metals, and (2) their direct impact on the selected biological test. The measurement of pCu2+ to characterize the level of soil contamination and of lag period as a bioindicator of metal effects in the soil are recognized as useful tools for the evaluation of the biological quality of soils.

Copper

A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada.

Myelodysplastic syndrome (MDS) is considered to be very rare in children. However, the only two published population-based studies reported widely divergent incidence figures. To further explore the epidemiology of childhood MDS and to evaluate the accuracy of cancer registry and treatment trial data, we conducted a population-based study of children aged 0-14 years in British Columbia (BC), Canada, between 1982 and 1996. MDS was diagnosed in 31 cases corresponding to an annual incidence of 3.2 per million children or 6% of all leukaemias, compared with an incidence of 6.0/million for acute myeloid leukaemia (AML), and of 0.5/million for chronic myeloid leukaemia. There was a non-significant (P = 0.19) trend toward an increase in MDS incidence with time, the increase was partly explained by an increasing number of patients with Down syndrome. Associated abnormalities were found in 48% of the MDS cases with Down syndrome as the most common (seven cases). Only one third of the MDS cases were correctly registered in the Cancer Registry and less than half of the eligible MDS patients were enrolled on a cooperative group study. Data on MDS from treatment-based studies and cancer registries were inaccurate and seemed to significantly underestimate the incidence of MDS in children.

Adolescent

A prospective study of internal carotid artery plication during carotid endarterectomy: early clinical and duplex outcome.

OBJECTIVE: internal carotid artery (ICA) plication prevents kinking and secures the distal intimal step following carotid endarterectomy (CEA). The aims of this prospective study were to quantify the proportion of patients in whom plication might be beneficial and determine whether plication is associated with an increased incidence of early restenosis and a reduction in postoperative thromboembolic complications. METHODS: analysis of a prospectively gathered computerised database. RESULTS: between 1 November 1992 and 31 December 1997, 228 consecutive CEAs were performed in 213 patients, of which 84 (37%) in 79 patients were plicated. Sixty endarterectomy sites have been examined by duplex ultrasonography at a median of 5 (range 1-44) months postoperatively. No abnormality was detected in 52 (87%), six (10%) had restenosis of <50% and two (3%) restenosis of 50-75%. All were asymptomatic. Three patients (3. 6%), one of whom died, had an intraoperative neurological event and one patient (1.2%) had a postoperative cerebral haemorrhage. No patient suffered ICA thromboembolism. During the same time period 144 non-plicated CEAs were performed in 134 patients. Of these, one (0.7%) had an intraoperative and five (3.5%) had a postoperative neurological event. Five of these six complications were due to ICA thromboembolism. There was no mortality in the non-plicated group. CONCLUSION: ICA plication can be used to prevent kinking, secure the distal intimal step, has not, to date, been associated with increased early restenosis rate and has avoided postoperative ICA thromboembolism.

Aged

Decreasing hospitalization rates for older home care patients with symptoms of depression.

OBJECTIVE: To target medically ill older home care patients with symptoms of depression in order to reduce their rate of hospitalization. DESIGN: A case-control study. SETTING: A private, nonprofit home care organization, the Visiting Nurse Association of St. Louis. PARTICIPANTS: Home care patients 65 years of age and older with symptoms of depression who were participants of a Total Quality Management (TQM) intervention (n = 81) were compared with an historical control of home care patients 65 years of age and older with symptoms of depression (n = 69). INTERVENTION: Utilization of TQM principles to develop a plan including: (a) an educational seminar on depression for home care staff involved in the project; (b) letters to physicians introducing the TQM project; (c) use of the Geriatric Depression Scale (GDS) for screening; (d) recommendation to the primary physician of a home social service (SS) consultation for patients with a GDS of 10 to 14; (e) recommendation to the primary physician of three interventions for patients with a GDS > or = 15: home SS consultation + mental health (MH), or gerontological nurse (GN) consultation + antidepressant medication (a pharmacotherapeutic algorithm sent by facsimile to the primary physician upon request). OUTCOME MEASURES: Hospitalization rates of the control group compared with the TQM intervention group, the degree to which part (e) of the plan was implemented, and the effect this had on hospitalization rates. RESULTS: The TQM intervention patients had a higher mean age than the historical control patients but were not different in percent female, percent white race, percent with a caregiver in the home, functional status, and in 15 of 16 diagnostic categories. Overall, the TQM intervention group had a hospitalization rate of 23.5% (19/81) compared with a rate of 40.6% (28/69) for the historical control group (P = .024). For part (e) of the plan (56/81 patients had a GDS > or = 15), 29/56 (52%) received the recommended SS consultation, 50/56 (89%) received the recommended MH or GN consultation, and 32/56 (57%) received antidepressant medication. One type of intervention did not seem to lower hospitalization rates more than another although having received the MH or GN visits approached significance (12/50, 24%; P = .052) when compared with the control group. CONCLUSIONS: Utilization of TQM principles and the development of an intervention such as the one described here can decrease hospitalization rates for medically ill older home care patients with symptoms of depression.

Aged

Hepatorenal syndrome: combined liver kidney transplants versus isolated liver transplant.

BACKGROUND: As many as 38% of combined liver-kidney transplant (LKTx) procedures performed nationally may be done for the renal diagnosis of hepatorenal syndrome (HRS). This study was designed to compare the national results with those at our medical center and to determine if combined LKTx provides any benefit over isolated liver transplant (LTx) to HRS patients. METHODS: Data on 29 combined LKTx and 79 HRS patients at our center were collected and compared with the national data on 414 LKTx and 2442 patients with serum creatinine >2.0 mg/dl receiving isolated LTx from 1988 to 1995. RESULTS: United Network of Organ Sharing data revealed 5-year patient survival of 62.2% for LKTx recipients and 50.4% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P=0.0001). Our center results demonstrated 5-year patient survival of 48.1% for LKTx patients, 67.1% for HRS patients receiving isolated LTx, and 70.1% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P not significant comparing all groups). Intensive care unit status and preoperative dialysis rates were similar in those HRS patients who did and those who did not need future KTx. CONCLUSION: National data would suggest a survival benefit of combined LKTx over isolated LTx for those patients with poor renal function, specifically those with HRS, whereas our center's results suggest otherwise. Unfortunately, we could not identify any preoperative risk factors in the HRS patients, or in the broader group of patients with renal insufficiency at our center, that would indicate the need for future renal transplantation. We believe that HRS patients can be successfully managed with isolated LTx.

Hepatorenal Syndrome

Sequence of the bovine HDL-receptor (SR-BI) cDNA and changes in receptor mRNA expression during granulosa cell luteinization in vivo and in vitro.

Steroidogenic activity in the mature corpus luteum of most mammals depends upon provision of cholesterol from the circulating lipoproteins. In cattle, as in many species, high-density lipoprotein (HDL) is the major lipoprotein involved. The recent identification of the scavenger receptor SR-BI as an HDL-receptor allows control of this process to be investigated more closely. In this study, we have sequenced the bovine SR-BI HDL-receptor and examined changes in expression of the receptor mRNA during corpus luteum development in vivo and granulosa cell luteinization in vitro. Sequencing of the bovine HDL-receptor showed that it codes for a protein of 509 amino acids with close identity to hamster, mouse, rat and human sequences. Examination of the tissue distribution of the HDL-receptor mRNA showed high levels in adrenal cortex and corpus luteum and lower levels in spleen and liver. Using a semi-quantitative, reverse transcription-polymerase chain reaction technique levels of HDL-receptor mRNA were measured in corpora lutea from cattle at known stages of the oestrus cycle and in bovine granulosa cells luteinized in culture. Levels of HDL-receptor mRNA were low in isolated bovine granulosa cells, but increased 7-fold during corpus luteum development in vivo and 5-fold during granulosa cell luteinization in culture. Results show that luteinization of granulosa cells is associated with an increase in HDL-receptor RNA levels which, along with changes in steroidogenic enzyme activity, is likely to explain the marked increase in steroidogenic capacity which occurs during corpus luteum formation.

Amino Acid Sequence

Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.

OBJECTIVES: This study examined the association between exposure to chlorophenates and the risk of soft tissue sarcoma; non-Hodgkin's lymphoma; Hodgkin's disease; and cancers of the lung, nose, and nasopharynx. METHODS: A retrospective cohort study was conducted of 26487 workers employed for at least 1 year between 1950 and 1985 in 11 chlorophenate-using and 3 non-using sawmills in British Columbia, Canada. Exposures by job were ascertained with interviews of senior employees. RESULTS: Probabilistic record linkage to the Canadian Mortality Data Base and the British Columbia Cancer Registry found 4710 deaths between 1950 and 1990, and 1547 incident cases of cancer between 1969 and 1989. None of the cancers of interest had elevated mortality related to chlorophenate exposure. Non-Hodgkin's lymphoma incidence (n = 65) increased with increasing chlorophenate exposure hours, yielding the following standardized incidence ratios: less than 120 hours 0.68; 120 to 1999 hours, 0.59; 2000 to 3999 hours, 1.04; 4000 to 9999 hours, 1.02; and 10000 or more hours, 1.30. CONCLUSIONS: These results are consistent with the borderline positive associations seen in other recently reported studies of chlorophenate-exposed workforces.

British Columbia

Who gets a heart? Rationing and rationalizing in heart transplantation.

National policy on organ transplantation is made by the United Network for Organ Sharing (UNOS), a representative body composed of health care professionals and patients. Standardized criteria for determining when a patient should be placed on the waiting list for heart transplantation are now in effect nationwide. Current and future directions to maximize the utilization of available donated organs are explored.

Guidelines as Topic

Reversible AIDS-related sclerosing cholangitis.

Although hepatobiliary involvement is common in the acquired immunodeficiency syndrome, it infrequently leads to biliary tract abnormalities. We describe a 39-year-old man with human immunodeficiency virus infection and no previous acquired immunodeficiency syndrome-defining illnesses, who presented with malaise, right upper quadrant pain, lymphadenopathy and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated sclerosing cholangitis due to disseminated B-cell nonHodgkin's lymphoma. Following chemotherapy, his symptoms and signs rapidly improved, so that 1 month later his endoscopic retrograde cholangiopancreatography had returned entirely to normal.

Adult