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Biomedical subjects

A McCormick

Publications and source records attributed to A McCormick.

At least 37 records · Page 2Linked to original sources
PubMed1998

Depressed ventilatory response to hypoxia in hypothermic newborn piglets: role of glutamate.

To evaluate whether changes in extracellular glutamate (Glu) levels in the central nervous system could explain the depressed hypoxic ventilatory response in hypothermic neonates, 12 anesthetized, paralyzed, and mechanically ventilated piglets <7 days old were studied. The Glu levels in the nucleus tractus solitarius obtained by microdialysis, minute phrenic output (MPO), O2 consumption, arterial blood pressure, heart rate, and arterial blood gases were measured in room air and during 15 min of isocapnic hypoxia (inspired O2 fraction = 0.10) at brain temperatures of 39.0 +/- 0.5 degrees C [normothermia (NT)] and 35.0 +/- 0.5 degrees C [hypothermia (HT)]. During NT, MPO increased significantly during hypoxia and remained above baseline. However, during HT, there was a marked decrease in MPO during hypoxia (NT vs. HT, P < 0.03). Glu levels increased significantly in hypoxia during NT; however, this increase was eliminated during HT (P < 0.02). A significant linear correlation was observed between the changes in MPO and Glu levels during hypoxia (r = 0.61, P < 0.0001). Changes in pH, arterial PO2, O2 consumption, arterial blood pressure, and heart rate during hypoxia were not different between the NT and HT groups. These results suggest that the depressed ventilatory response to hypoxia observed during HT is centrally mediated and in part related to a decrease in Glu concentration in the nucleus tractus solitarius.

Acid-Base Equilibrium↗
PubMed1997

Transcriptional regulation of the Drosophila homeotic gene teashirt by the homeodomain protein Fushi tarazu.

The Drosophila melanogaster gene teashirt (tsh) is essential for segment identity of the embryonic thorax and abdomen. A deletion 3' to the tsh transcription unit causes the loss of tsh early expression in the even-numbered parasegments, and the corresponding larval cuticular patterns are disrupted. tsh function in the odd-numbered parasegments in these mutants is normal by both criteria. The in vivo activities of genomic fragments from the deleted region were tested in transgenic embryos. A 2.0 kb enhancer from the 3' region acts mainly in the even-numbered parasegments and is dependent on fushi tarazu (ftz) activity, which encodes a homeodomain protein required for the development of even-numbered parasegments. Ftz protein binds in vitro to four distinct sequences in a 220 bp sub-fragment; these and neighboring sequences are conserved in the equivalent enhancer isolated from Drosophila virilis. Tsh protein produced under the control of the 220 bp enhancer partially rescues a null tsh mutation, with its strongest effect in the even-numbered parasegments. Mutation of the Ftz binding sites partially abrogates the capacity for rescue. These results suggest a composite mechanism for regulation of tsh, with different activators such as ftz contributing to the overall pattern of expression of this key regulator.

Animals↗
PubMed1996

Distribution of blood viscosity values and biochemical correlates in healthy adults.

Increases in the viscosity of blood and plasma predict clinical manifestations of atherothrombotic vascular disease. The clinical utility of viscosity measurements in cardiovascular risk factor analysis requires reference values established from a healthy disease-free population. A cohort of 126 (71 men, 55 women) healthy nonsmoking adults had fasting blood analysis after a 12-14-h fast. Viscosity measurements were made on samples of whole blood, plasma, and serum at 37 degrees C with a coaxial cylinder microviscometer. The mean blood viscosity at shear rates of 100, 50, and 1 s-1 were 3.26 +/- 0.43, 4.37 +/- 0.60, and 5.46 +/- 0.84 mPa.s, respectively. Men had significantly higher blood viscosity values than women at each shear rate. The differences in blood viscosity did not remain significant after blood viscosity values were normalized to a hematocrit of 45%, except at 100 s-1. For the entire group, normalized blood viscosity values at each measured rate correlated inversely with HDL cholesterol and positively with fibrinogen. The mean plasma viscosity was 1.39 +/- 0.08 mPa.s and the mean serum viscosity was 1.27 +/- 0.06 mPa.s. Plasma viscosity correlated with fibrinogen (r = 0.51, P < 0.0001), total serum protein (r = 0.33, P < 0.0001), and triglyceride concentrations (r = 0.33, P < 0.0015). Serum viscosity correlated with total serum protein (r = 0.50, P < 0.0001) and LDL cholesterol (r = 0.24, P = 0.0065). This study provides reference values for the viscosity of blood, plasma, and serum that may assist in evaluating hemorheological profiles.

Adult↗
PubMed1996

The capture of socioeconomic data in general practice.

BACKGROUND: It is common practice to record the reasons why patients have an encounter with the practice, but the collection of socioeconomic data with which to link this morbidity data is less easy to achieve. AIM: To describe the social enquiry used in the Fourth National General Practice-based morbidity study (1991-1992) and to consider its effectiveness for use in practice. METHOD: Socioeconomic data were collected suing a structured questionnaire administered by a trained interviewer. Data were provided by both consulting and non-consulting registered patients. RESULTS: The interview technique proved to be acceptable to patients, interviewers and general practitioners, simple to administer, and inexpensive to collect. Eighty-three per cent of the 502,000 people included in the study provided social and occupational data. Less than 1.5% of patients refused to be interviewed. Fifty-four of the 60 practices achieved the target level of 90% of registered patients being successfully interviewed. CONCLUSION: A method of socioeconomic data collection based on that used in the 1991-1992 study would be of benefit for health care planning, allocation of resources, design of performance indicators and epidemiological research.

England↗
PubMed1995

Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate.

Although methotrexate (MTX) is one of the most clinically effective therapies employed to treat psoriasis, the mechanism by which low-dose MTX acts to modulate the hyperplasia of psoriasis, leading to the restoration of clinically normal skin, is only partially understood. MTX has been considered a cytotoxic agent that mediates its effect primarily on proliferating or cycling epidermal cells. Recently, proliferating lymphoid cells have been identified in psoriatic lesions, raising the possibility that proliferating lymphoid cells could be another target cell that is killed by MTX. In this study, we examined the growth-inhibitory and cytotoxic effects of MTX on proliferating lymphoid cells [THP-1 (macrophage), and MOLT-4 (T cell)], epithelial cells (HeLa, and HaCat), and normal human keratinocytes (NHK) in vitro. The proliferating cells were exposed to MTX for 24 h, and placed in fresh media to mimic the transient MTX blood levels that result from once-weekly therapy. THP-1 and MOLT-4 were found to be 10-100 times more sensitive to the cytotoxic effects of MTX than were HeLa and HaCat, and more than 1000 times more sensitive than primary human keratinocytes. At MTX concentrations that would be expected to occur in vivo during once-weekly therapy, a large percentage (> 95%) of proliferating lymphoid targets would be killed, and only a small percentage (< 10%) of proliferating epidermal cells would be affected. This in vitro data suggests that in psoriasis proliferating lymphoid cells are more likely than epithelial cells to be a major cellular target of MTX in vivo.

Cell Division↗
PubMed1995

Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene.

Along the anterior-posterior axis of animal embryos, the choice of cell fates, and the organization of morphogenesis, is regulated by transcription factors encoded by clustered homeotic or 'Hox' genes. Hox genes function in both epidermis and internal tissues by regulating the transcription of target genes in a position- and tissue-specific manner. Hox proteins can have distinct targets in different tissues; the mechanisms underlying tissue and homeotic protein specificity are unknown. Light may be shed by studying the organization of target gene enhancers. In flies, one of the target genes is teashirt (tsh), which encodes a zinc finger protein. tsh itself is a homeotic gene that controls trunk versus head development. We identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm. Sites where Antennapedia (Antp) and Ultrabithorax (Ubx) proteins bind in vitro were mapped within evolutionarily conserved sequences. Although Antp and Ubx bind to identical sites in vitro, Antp activates the tsh enhancer only in epidermis while Ubx activates the tsh enhancer in both epidermis and in somatic mesoderm. We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable. Next to the homeotic protein-binding sites are extensive conserved sequences likely to control tissue activation by different homeodomain proteins. We propose that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.

Animals↗
PubMed1994

Altered prostacyclin synthesis by aortae from hepatic portal vein-constricted rats: evidence for effects on protein kinase C and calcium.

To investigate the mechanisms causing reduced systemic vascular reactivity to vasoconstrictor agents in portal hypertension, we studied receptor- and signal-transduction-linked PGI2 (a vasodilator) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) in the aorta (ex vivo) of portal vein-constricted rats. PGI2 synthesis was stimulated by adrenaline (via heterogeneous alpha-adrenoceptors), phorbol ester dibutyrate (a protein kinase C activator), arachidonic acid (the substrate for PGI2 synthesis) and the Ca2+ ionophore A23187 (A23187) and thapsigargin (both of which elevate intracellular Ca2+, which in turn elicits the release of arachidonic acid). The release of PGI2 by the aortae of rats with portal hypertension in comparison to sham-operated controls was: 1) enhanced in response to adrenaline, 2) reduced in response to phorbol ester dibutyrate, A23187 and thapsigargin and 3) unchanged in response to arichidonic acid. These data indicate that in aortae from rats with experimental portal hypertension: i) there are no changes in the enzymes involved in PGI2 synthesis (cyclooxygenase, PGI2 synthase), ii) there is a specific increase in adrenoceptor-linked PGI2 synthesis in aortae which may contribute to arterial vasodilation in this experimental model and 3) the diminished response of PGI2 synthesis to A23187, phorbol ester dibutyrate and thapsigargin indicates that there is a generalised attenuation of protein kinase C activator activity and of Ca2+. Since Ca2+ is a key component of excitation-contraction coupling and protein kinase C activator has been implicated in mediating this event, attenuation of these systems may also explain, at least in part, the known reduced vasoactivity of aortae from rats with portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chemistry of zirconia and its use in chromatography.

The purpose of this review is to shed some light on the complex properties of zirconia's surface chemistry in order to better understand its behaviour under chromatographic conditions. We emphasize the great differences between the much better known chemistry of a silica surface and the chemistry of zirconia's surface. The review describes both the physical and chemical properties of zirconium dioxide from a chromatographic point of view. The chemistry of monoclinic zirconia surface is developed from its underlying crystalline structure. The paper describes the dependence of the specific surface area, pore volume, porosity and mechanical strength on thermal treatment. Methods of synthesis of chromatographically useful zirconia are outlined. The review also covers the adsorption properties of zirconia at both gas-solid and liquid-solid interfaces. Adsorption of water, carbon dioxide, carbon monoxide and ammonia are described and the controversies concerning the surface concentration of adsorption sites are presented. The complex chemistry of a zirconia surface is pointed out and the importance of ligand exchange reactions is emphasized. In contrast to a silica surface, ligand exchange plays an important role in liquid chromatographic applications of zirconia. Strong, hard Lewis acid sites, present on a zirconia surface, can interact with hard Lewis bases and these interactions, sometimes troublesome, can be successfully exploited even for protein separations. Zirconia's surface can be modified in many ways: dynamically, by addition of competing Lewis bases to the mobile phase, or permanently, by covering its surface with polymers or by depositing carbon. The review also shows that the main difficulty in achieving a wider variety of applications is probably our lack of knowledge and poor understanding of zirconia's surface chemistry.

Chromatography↗
PubMed1993

The notification of infectious diseases in England and Wales.

For nearly a hundred years, it has been a statutory requirement for doctors to notify a Proper Officer of the local authority (now, usually, the Consultant in Communicable Disease Control) of cases of certain infectious diseases. This prompts local investigation and appropriate action to control the disease. These data are also used for the analysis of local and national trends. This article describes how the notification system has evolved, its legal basis, and some of its strengths and weaknesses, and suggests how improvements could be achieved. Trends in notification data are presented for several diseases and compared with data derived from other sources.

Communicable Disease Control↗
PubMed1993

Photoaging and the skin. The effects of tretinoin.

The appearance of photoaged skin is cosmetically unacceptable to many in our society. Ostensibly, avoidance of ultraviolet light and sunlight from early childhood is most desirable but not likely to happen in our culture. Tretinoin is the only pharmacologic compound shown to partially reverse some signs of photoaging. Improvement with tretinoin therapy has been quantified clinically and histologically. A major degree of improvement occurs in 6 to 12 months, and maintenance treatment one to three times per week may continue this response. Tretinoin therapy should optimally be used with daily moisturizer and sunscreen applications. Psychosocial benefits of tretinoin therapy, use of tretinoin for intrinsically aged or non-Caucasian skin, and higher-strength tretinoin therapy for severely photoaged skin need to be further explored. It is possible that some subsets of patients with photoaged skin may respond better than others.

Animals↗
PubMed1992

Cyclosporine therapy for psoriasis: a cell cycle-derived dosing schedule.

BACKGROUND: Cyclosporine is effective in the treatment of psoriasis; however, potentially serious side effects limit its long-term use. On the basis of the 36-hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated. OBJECTIVE: The purpose of this study was to evaluate a 36-hour weekly dosing schedule with cyclosporine for the treatment of psoriasis, in an attempt to decrease side effects while maintaining efficacy. METHODS: Fifteen patients were studied by means of oral doses of cyclosporine taken at 12-hour intervals for three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10 mg/kg/dose. RESULTS: The average improvement as assessed by the Psoriasis Area and Severity Index for all 15 patients was 61%. Six patients had a more than 75% improvement, three patients improved 50% to 74%, and six patients improved less than 50%. Three patients dropped out because of adverse side effects, and three others completed the study at a reduced dose. CONCLUSION: It is concluded that, although effective, this dosing regimen may not have an advantage over daily dosing, given its side effect profile and the need to go to relatively high doses every 24 hours.

Adult↗
PubMed1991

Unrecognised HIV related deaths.

OBJECTIVES: To establish whether follow up of deaths from selected HIV related causes could increase the number of cases of HIV infection reported to the Public Health Laboratory Service Communicable Disease Surveillance Centre (CDSC), and to estimate the proportion of deaths among HIV positive men that occurred in men who were not known to be HIV positive at the time of death by the person who signed the death certificate. DESIGN: Follow up of draft death entries received by the Office of Population Censuses and Surveys on which one of 11 medical or external causes likely to be related to HIV was stated; letters were sent to the people who signed the certificates. The respondents were invited to report men known to have been HIV positive who were not already on the CDSC register. SETTING: England and Wales. SUBJECTS: Men aged 15-54 who died in February 1989 to July 1989 with one of the 11 selected HIV related diseases as cause of death on their death certificates. MAIN OUTCOME MEASURES: Number of men reported to the CDSC as a result of this follow up; estimate of excess deaths due to an HIV related cause; estimate of the proportion of excess deaths that occurred in those who were not known to be HIV positive at the time of death. RESULTS: Replies were received for 473 deaths (86%). Forty were for men known to have been HIV positive, 31 of whom had been reported to CDSC by the time they died; six were subsequently reported. The respondent did not know that the decreased was HIV positive for 20 (35%) of the 57 excess deaths in men for whom one of the medical causes was stated and 41 (93%) of the 44 excess deaths in men for whom one of the external causes was stated. CONCLUSION: Follow up of death registrations is not an efficient way of increasing the number of cases of HIV infection reported to CDSC. Between 35% and 60% of HIV positive people for whom certain causes are stated may be dying without HIV positivity having been diagnosed. There may be implications for those caring for people with these conditions and those who carry out postmortem examinations.

Adolescent↗
PubMed1991

Cellular aging and senescence.

Differentiated eukaryotic cells have only a finite capacity for cell division. This limitation is thought to be a cellular manifestation of organismal aging, and a restraint to tumor progression. The molecular basis for cellular senescence is not known, but a molecular framework for understanding this phenomenon has recently been established.

Animals↗
PubMed1991

The pituitary-specific regulatory gene GHF1 contains a minimal cell type-specific promoter centered around its TATA box.

GHF-1 is a pituitary-specific transcription factor responsible for activation of the growth hormone (GH) gene. The GHF1 gene is expressed exclusively in cells of the somatotrophic lineage, and its transcription is extinguished in somatic cell hybrids. The minimal sequences required for differential transcription of GHF1 in GH-expressing and -nonexpressing cell lines and somatic cell hybrids were localized to a 15-bp region surrounding and including its TATA box. This 15-bp fragment acts as a cell type-specific promoter element and is recognized by a transcription factor present in GH-expressing cell lines. Hence, in addition to enhancers and upstream promoter elements, the TATA element (TATA box plus surrounding sequences) can be, in certain cases, an important determinant of cell-type-specific transcription.

Animals↗
PubMed1991

Urinary hydroxyproline: relationship to growth, bone mineral content, and serum alkaline phosphatase level in premature infants.

There is little information on urinary hydroxyproline (UHP) excretion in premature infants. We hypothesized that UHP excretion would positively correlate with growth in premature infants, and that there would be correlations between UHP excretion and serum alkaline phosphatase concentration as well as bone mineral content (BMC). Twenty-six premature infants (birth weight, less than 1,300 g; gestational age, less than or equal to 32 weeks) received one of four oral feedings. Seven received mother's own milk (HM), and eight received mothers own milk fortified with 0.85 g/dl of bovine whey, 90 mg/dl of Ca, and 45 mg/dl of P. Six and five infants received Similac, 20 cal/oz (SIM) and Similac Special Care, 20 cal/oz, respectively. Measurements of UHP, serum alkaline phosphatase, BMC (photon absorptiometry), and growth were made during the 1st 7 weeks of life. The lowest UHP excretion was in the HM group. For all infants, there was a significant correlation between UHP excretion (mg/day) and absolute weight (r = 0.64, p less than 0.001), as well as rate of weight gain (r = 0.50, p less than 0.01). The UHP excretion (milligrams per day) also correlated with absolute length (r = 0.41, p less than 0.01) and rate of gain in length (centimeters per week) (r = 0.70, p less than 0.001). The UHP excretion did not correlate significantly with BMC or serum alkaline phosphatase concentration. We conclude that UHP excretion is increased in the growing premature infant compared to older infants and adults and is a good marker for somatic growth in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗