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Biomedical subjects

V Alexander

Publications and source records attributed to V Alexander.

At least 19 recordsLinked to original sources
PubMed2005

Synthesis and relaxivity studies of a tetranuclear gadolinium(III) complex of DO3A as a contrast-enhancing agent for MRI.

A tetranuclear gadolinium(III) complex, [Gd4(H2O)8], of DO3A appended onto the pentaerythrityl framework was synthesized to improve the water proton relaxivity for MRI application. The longitudinal relaxivity of [Gd4(H2O)8] is 28.13 mM-1 s-1 (24 MHz, 35+/-0.1 degrees C, pH 5.6) which is 5.86 times higher than that of [Gd(DO3A)(H2O)2]. The relaxivity is based on "molecular" relaxivity of the tetramer and the r1p value is "7 per Gd". The high relaxivity of the tetramer is the result of the decrease in the rotational correlation (tauR) and the presence of eight inner-sphere water molecules (q=8). The complex exhibits pH-dependent longitudinal relaxivity, and the high relaxivity both at low and high pH (r1p=28.13 mM-1 s-1 at pH 5.6 and 16.52 mM-1 s-1 at pH 9.5) indicates that it could be used as a pH-responsive MRI contrast agent. The transverse relaxivity of the tetramer is 129.97 mM-1 s-1 (24 MHz, 35+/-0.1 degrees C, pH 5.6), and the r2p/r1p ratio of 4.6 shows that it could be used as a T2-weighted contrast agent.

Chemical Phenomena↗
PubMed2001

Conditional epidermal expression of TGFbeta 1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia.

To study the role of transforming growth factor type beta1 (TGFbeta1) in epidermal growth control and disease, we have generated a conditional expression system by using the bovine keratin 5 promoter to drive expression of the tetracycline-regulated transactivators tTA and rTA, and a constitutively active mutant of TGFbeta1 linked to the tetO target sequence for the transactivator. This model allows for induction or suppression of exogenous TGFbeta1 with oral doxycycline. Maximal expression of TGFbeta1 during gestation caused embryonic lethality, whereas partial suppression allowed full-term development with neonatal lethality characterized by runting, epidermal hypoproliferation, and blocked hair follicle growth. With complete suppression, phenotypically normal double transgenic (DT) mice were born. Acute induction of TGFbeta1 in the epidermis of adult mice inhibited basal and follicular keratinocyte proliferation and reentry of telogen hair follicles into anagen. However, chronic expression of TGFbeta1 in adult DTs caused severe alopecia characterized by epidermal and follicular hyperproliferation, apoptosis, as well as dermal fibrosis and inflammation. Readministration of doxycycline to tTA DT mice caused hair regrowth within 14 days. The mRNA and protein for Smad7, an inhibitor of TGFbeta signaling, were up-regulated in the epidermis and hair follicles of alopecic skin and rapidly induced in rTA mice in parallel with the TGFbeta1 transgene, suggesting that the hyperproliferative phenotype may result in part from development of a sustained negative feedback loop. Thus, this conditional expression system provides an important model for understanding the role of TGFbeta1 during development, in normal skin biology, and in disease.

Alopecia↗
PubMed2000

Effect of hospital asthma nurse appointment on inpatient asthma care.

While asthma nurses are funded by many health authorities within the U.K. National Health Service, for the improvement of clinical management in both inpatient and outpatient settings in secondary care, the effect of asthma nurse appointment on acute asthma care in hospitalized children has been inadequately studied. Here, we test the hypothesis that the employment of a full-time hospital asthma nurse improves quality of care for children admitted to hospital with acute asthma. Prospective in design, the study compares analyses of indicators of good clinical practice for hospitalized asthmatic children (2-16 yrs) before and after the appointment of a hospital asthma nurse. Both management [oxygen saturation check (35/106 vs. 111/126, P<0.05)] and discharge planning [self management plan/asthma education (17/106 vs. 49/126, P<0.05), follow-up arrangements with general practice (8/106 vs. 25/126, P<0.05)] improved. There was, however, no significant change in oral steroid administration, peak flow check, inhaler technique assessment, inhaled drug prophylaxis or arrangements for hospital follow-up at discharge. Employment of a hospital-based children's asthma nurse leads to significant improvement in aspects of routine in-patient asthma management. However, other important areas of in-patient asthma care did not improve following nurse-led interventions. A clearer evidence base may improve compliance with asthma management guidelines, and could make the role of hospital asthma nurse more effective.

Adolescent↗
PubMed1999

Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes.

Genetic inactivation of the transforming growth factor-beta (TGF-beta) signaling pathway can accelerate tumor progression in the mouse epidermal model of multistage carcinogenesis. By using an in vitro model of keratinocyte transformation that parallels in vivo malignant conversion to squamous cell carcinoma, we show that v-ras(Ha) transduced primary TGF-beta1-/- keratinocytes and keratinocytes expressing a TGF-beta type II dominant-negative receptor transgene have significantly higher frequencies of spontaneous transformation than control genotypes. Malignant transformation in the TGF-beta1-/- keratinocytes is preceded by aneuploidy and accumulation of chromosomal aberrations. Similarly, transient inactivation of TGF-beta signaling with a type II dominant-negative receptor adenovirus causes rapid changes in ploidy. Exogenous TGF-beta1 can suppress aneuploidy, chromosome breaks, and malignant transformation of the TGF-beta1-/- keratinocytes at concentrations that do not significantly arrest cell proliferation. These results point to genomic instability as a mechanism by which defects in TGF-beta signaling could accelerate tumor progression in mouse multistage carcinogenesis.

Aneuploidy↗
PubMed1995

Concurrent outbreaks of pertussis and Mycoplasma pneumoniae infection: clinical and epidemiological characteristics of illnesses manifested by cough.

Concurrent outbreaks of illnesses that were manifested by cough and that were suspected to be due to Bordetella pertussis and Mycoplasma pneumoniae infection were investigated in a midwestern town in Illinois. Three studies were conducted: questionnaires on the clinical and epidemiological characteristics of illness were administered to patients; serological tests were performed to confirm the presence of each pathogen and to develop case definitions for each illness; and case definitions were applied to responses to a mail-in questionnaire for estimating the magnitude of both outbreaks. In 135 cases of suspected pertussis and 42 cases of suspected mycoplasmal infection, subjects had a cough for > or = 14 days (the pertussis outbreak case definition). Among 20 laboratory-confirmed cases, a cough for > or = 14 days had a specificity of 20% for pertussis, and a cough for > or = 28 days plus whoop and/or vomiting had a specificity of 90% for pertussis. Six hundred-seventeen pertussis cases per 100,000 population and 1,179 cases of M. pneumoniae infection per 100,000 population occurred. In this setting, the standard outbreak case definition for pertussis lacked adequate specificity to distinguish pertussis from mycoplasmal infection. The magnitude of each outbreak was greater than the number of reported cases suggested.

Adolescent↗
PubMed1993

Dissolved Nitrogen Uptake by a Cyanobacterial Bloom (Anabaena flos-aquae) in a Subarctic Lake.

Uptake of dissolved nitrogen (NH(4) + NO(3) + urea + N(2)) by a cyanobacterial [Anabaena flos-aquae (Lyngb.)] De Brèb population in Smith Lake, Alaska, was measured every 2 to 4 days during the spring of 1990. Total dissolved nitrogen uptake ranged from 0.34 to 24.75 mumol liter h, with a mean of 5.75 mumol liter h; the euphotic zone accounted for 91% of the uptake. The mean turnover time for dissolved combined nitrogen (NH(4) + NO(3) + urea) in the euphotic zone was less than 14 h, and that for NH(4) was only 3.6 h. The mean relative preference indices for NH(4) (2.4), NO(3) (0.4), and urea (0.5) established NH(4) as the preferred nitrogenous nutrient. The uptake rates were apparently dependent on biomass, temperature, and light. Regeneration, probably due to zooplankton excretion and bacterial remineralization of dissolved organic nitrogen, was the main source of NH(4) for the cyanobacterial growth. The high half-saturation constant for NH(4) with low ambient NH(4) concentration nevertheless resulted in the simultaneous utilization of several forms of nitrogen.

Journal Article↗
PubMed1992

Audit of the quality of hospital discharge data.

An audit of the quality of computerised hospital discharge data, in General Medicine and Paediatrics in Dundee, showed that the national data set was often inaccurate. Structured discharge summaries checked by senior medical staff are recommended.

Abstracting and Indexing↗
PubMed1991

Medical and judicial perceptions of the risks associated with use of antipsychotic medication.

To determine whether occupational perspective influences the decision to prescribe antipsychotic medications, we presented a group of psychiatrists and judges with a hypothetical case involving a potentially psychotic patient. The subjects were asked what probability of drug-induced tardive dyskinesia they would accept in order to prevent psychotic decompensation. The subjects were then asked to estimate the actual probability that tardive dyskinesia would occur if the patient received antipsychotic medications. From the responses to these questions we inferred their treatment decisions. Although the psychiatrists and judges agreed on an acceptable level of risk, they differed significantly in their estimates of the actual risk involved and, by inference, their decisions concerning treatment. Our findings have several implications for adjudication of cases involving treatment decisions and the right to refuse treatment.

Antipsychotic Agents↗
PubMed1987

Measurement of branched-chain ketoacids in plasma by high-performance liquid chromatography.

Branched-chain ketoacids were isolated from plasma or serum samples by acidification, passage through a cationic exchange resin, ether extraction, and extraction of the ether layer with phosphate buffer. The recovery of 2-[1-14C]ketoisocaproate taken through these procedures averaged 95 +/- 3%. Branched-chain ketoacids were measured by high-performance liquid chromatography using a single mobile phase (sodium phosphate:acetonitrile). In normal human subjects, mean +/- SD fasting levels of 2-ketoisocaproate, 2-keto-3-methylvalerate, and 2-ketoisovalerate were 29 +/- 8, 18 +/- 4, and 12 +/- 3 microM, respectively. In normal rats, slightly different results were found: 24 +/- 10, 19 +/- 7 and 17 +/- 6 microM, respectively. In both species, levels of each ketoacid expressed as fractions of total branched-chain ketoacids were much less variable.

Animals↗
PubMed1983

Sediment nitrification, denitrification, and nitrous oxide production in a deep arctic lake.

We used a combination of N tracer methods and a C(2)H(2) blockage technique to determine the role of sediment nitrification and denitrification in a deep oligotrophic arctic lake. Inorganic nitrogen concentrations ranged between 40 and 600 nmol . cm, increasing with depth below the sediment-water interface. Nitrate concentrations were at least 10 times lower, and nitrate was only detectable within the top 0 to 6 cm of sediment. Eh and pH profiles showed an oxidized surface zone underlain by more reduced conditions. The lake water never became anoxic. Sediment Eh values ranged from -7 to 484 mV, decreasing with depth, whereas pH ranged from 6.0 to 7.3, usually increasing with depth. The average nitrification rate (49 ng of N . cm . day) was similar to the average denitrification rate (44 ng of N . cm . day). In situ N(2)O production from nitrification and denitrification ranged from 0 to 25 ng of N . cm . day. Denitrification appears to depend on the supply of nitrate by nitrification, such that the two processes are coupled functionally in this sediment system. However, the low rates result in only a small nitrogen loss.

Journal Article↗
PubMed1983

Mortality from brain tumor and other causes in a cohort of petrochemical workers.

To evaluate a suspected excess of deaths due to brain tumor (BT) among petrochemical workers, a retrospective cohort mortality study was conducted among 7,595 men ever employed at a plant in Texas City, Texas, between 1941 and 1977. Among hourly employees, overall mortality was lower than expected from U.S. national rates [standardized mortality ratio (SMR) = 79]. However, 19 BT deaths (International Classification of Diseases, seventh revision, codes 193, 223, and 237) among hourly employees were observed as against 9.6 expected (SMR = 198), and with extension of the analysis to include BT deaths occurring in 1978 and 1979, 22 deaths were observed versus 10.7 expected (SMR = 206). Fifteen years or more after being hired, 19 of these workers died from BT versus 7.2 expected (SMR = 263), and the standardized mortality ratios increased with duration of employment to 377 for hourly workers who had worked over 20 years. Although nonoccupational etiologies cannot be dismissed, these data suggest an occupational etiology for certain BT deaths in petrochemical workers.

Brain Neoplasms↗
PubMed1982

A progress report: the investigation of brain tumors at the Texas Division of Dow Chemical.

During the six-month period since this investigation was initiated, an increased risk of death due to brain tumor was linked with employment at the Texas Division of Dow Chemical by the results of a case-control study based on county death certificates. Specifically, the county-based case-control study yielded an odds ratio of 2.54 with a 90% confidence interval of the odds ratio extending from 1.23 to 6.80. Additional investigations were initiated which resulted in the ascertainment of 25 brain tumor deaths among former Dow employees. Of these cases, 84% were initially employed between 1940 and 1946 and 64% can be described as glioblastomas or astrocytomas grade III and IV. Detailed protocols have been developed for a sample-based cohort study and a series of in-plant case-control studies. The sample-based cohort study is nearing completion and the in-plant case-control studies are anticipated to begin in the near future. The study design serving as the framework of this investigation represents a modest departure from the traditional epidemiologic study designs. This sample-based approach was designed to circumvent or minimize the usual problems associated with the use of massive collections of data that have been partially automated, if at all. The anticipated benefits will be conservation of limited staff resources and a reduction of the time necessary to complete a large-scale epidemiologic investigation.

Adult↗
PubMed1980

Brain cancer in petrochemical workers: a case series report.

Eighteen primary brain cancer deaths among male workers at one Texas petrochemical plant from 1965-1980 are reported. Federal officials from OSHA and NIOSH are performing with company cooperation an historical prospective cohort mortality study, a case-control study, and neuropathological case confirmation. Average age at death was 53 (range 30-66). Median employment was 21 years and median latency was 24 years. 15/18 tumors were glioblastoma multiforme, an unusual histologic distribution. A preliminary estimate reveals a plant-wide excess brain cancer risk twice expected among 6,800 white males at the plant since 1941. Brain cancer mortality rates in surrounding counties are in the median range for US counties from 1950-1969. Ten recognized or suspected carcinogens are present in quantities greater than 10(6) lbs/yr. To date no common chemical exposures or work assignments have been identified among the cases. Data on 26 experimental brain carcinogens and relevant epidemiological studies are provided.

Adult↗