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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 91 records · Page 5Linked to original sources

Effects of sodium monensin on reproductive performance of dairy cattle. II. Effects on metabolites in plasma, resumption of ovarian cyclicity and oestrus in lactating cows.

A randomised trial was conducted to determine the effects of sodium monensin on plasma metabolite concentrations, resumption of cyclicity and oestrus and milk production and milk composition of postparturient dairy cows. Cows treated with sodium monensin in a controlled-release capsule had significantly lower plasma beta-hydroxybutyrate (BHB) concentrations (P = 0.006) and tended (P = 0.07) to have significantly higher plasma glucose concentrations than untreated cows. Treatment did not significantly influence plasma free fatty acid, urea nitrogen or cholesterol concentrations. Despite higher plasma glucose concentrations and lower plasma BHB concentrations, periods from calving to first ovulation and oestrus were not reduced by treatment. This observation, with limited numbers of cows, is not consistent with a hypothesis that glucose or ketones are important metabolic regulators of pulsatile release of luteinising hormone and consequent resumption of cyclicity. While milk production and milk protein concentration did not significantly differ between groups, milk fat concentration was significantly lower for treated cows. Treated cows probably had lower dry matter intake than untreated cows as they produced 67 litres less milk per head and lost more weight than untreated cows during the study period, although weight and body condition score were not significantly affected by treatment. The lack of significance of these latter observations probably reflects the low statistical power of the study.

3-Hydroxybutyric Acid↗

Conservative treatment of plantar heel pain: long-term follow-up.

In order to evaluate the long-term results of patients treated conservatively for plantar heel pain, a telephone follow-up survey was conducted. After eliminating those patients with worker's compensation-related complaints and those with documented inflammatory arthritides, data on 100 patients (58 females and 42 males) were available for review. The average patients was 48 years old (range 20-85 years). The average follow-up was 47 months (24-132 months). Clinical results were classified as good (resolution of symptoms) for 82 patients, fair (continued symptoms but no limitation of activity or work) for 15 patients, and poor (continued symptoms limiting activity or changing work status) in 3 patients. The average duration of symptoms before medical attention was sought was 6.1, 18.9, and 10 months for the three groups, respectively. The three patients with poor results all had bilateral complaints, but had no other obvious risk factors predictive of their poor result. Thirty-one patients stated that, even with the understanding that surgical treatment carries significant risk, they would have seriously considered it at the time medical attention was sought; twenty-two of these patients eventually had resolution of symptoms. Although the treatment of heel pain can be frustrating due to its indolent course, a given patient with plantar fasciitis has a very good chance of complete resolution of symptoms. There is a higher risk for continued symptoms in over-weight patients, patients with bilateral symptoms, and those who have symptoms for a prolonged period before seeking medical attention.

Adult↗

Commentary: recent reforms in the British National Health Service--lessons for the United States.

President Clinton recently announced his reform plan for health care in the United States. The United Kingdom, along with other countries, has already enacted reforms in an effort to overcome the basic problem of having insufficient funds to provide a health service to meet modern demands. This paper briefly describes the recent health reforms in the United Kingdom and highlights some lessons for the United States, which include the need to choose procedures that should be universally provided. Health reforms that involve some fundamental restructuring need to be evaluated everywhere and agreed to by the staff in advance.

Health Care Reform↗

Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss.

Women with anticardiolipin antibodies (ACLA) are at increased risk for fetal loss. One potential explanation for this outcome is that sera from these individuals contain antibodies reactive with trophoblast cells, which are involved in the establishment of the uteroplacental vasculature and maintenance of placental blood fluidity. To examine this hypothesis, we compared the incidence of trophoblast-reactive antibodies in 27 patients with ACLA and a history of fetal loss with that in 29 normal pregnant women. Sera from 20 patients, but only one control, contained trophoblast-reactive antibodies (P < .001). These antibodies were not directed against major histocompatibility class I antigens, and reacted with both term and first-trimester trophoblast cells. In most cases, sera from which ACLA were adsorbed by cardiolipin-containing liposomes maintained reactivity against cells. In addition, patient Ig fractions immunoprecipitated an approximately 62-kD protein from the trophoblast cell surface, stimulated the release of arachidonic acid and thromboxane A2 by trophoblasts, and inhibited the binding of prourokinase to trophoblast urokinase receptors. These observations show that sera from women with ACLA and a history of fetal loss contain antitrophoblast antibodies. These antibodies may be serologically distinct from ACLA, and may contribute to the pathogenesis of fetal demise.

Abortion, Spontaneous↗

A mutation in CFTR produces different phenotypes depending on chromosomal background.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene but the association between mutation (genotype) and disease presentation (phenotype) is not straightforward. We have been investigating whether variants in the CFTR gene that alter splicing efficiency of exon 9 can affect the phenotype produced by a mutation. A missense mutation, R117H, which has been observed in three phenotypes, was found to occur on two chromosome backgrounds with intron 8 variants that have profoundly different effects upon splicing efficiency. A close association is shown between chromosome background of the R117H mutation and phenotype. These findings demonstrate that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced.

Base Sequence↗

The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E.

The adenovirus E1A proteins form complexes with a group of cellular proteins, including a protein of 130 kD. E1A-associated p130 was purified through coimmunoprecipitation with E1A, and sequence data from four tryptic peptides was obtained. Oligonucleotides derived from the peptide sequences were used to clone a 4.85-kb cDNA. The cDNA contained an 1139-amino-acid open reading frame with homology to the retinoblastoma protein and E1A-associated p107 but was more closely related to p107. In vitro-translated p130 bound to E1A, and anti-p130 antibodies detected p130 in immunoblots of E1A immunoprecipitates. p130 was also detected in immunoprecipitates of cyclins A and E and was an efficient substrate in vitro for kinase activities associated with these cyclins. The p130 gene mapped to chromosome 16q12.2-13, a region that undergoes allelic loss in several types of tumors, including hepatocellular, prostate, and breast carcinomas.

Adenovirus E1A Proteins↗

ELF exposure facility for human testing.

A laboratory facility specifically designed for controlled human exposure to 60-Hz electric (0 to 16 kV/m) and magnetic (0 to 32 A/m, B = 0 to 40 microT) fields has been constructed. The facility presents uniform fields under controlled temperature and humidity. Special control systems allow collection of physiological data during, as well as before and after, exposure to electric fields at strengths to 16 kV/m under verified double-blind control. Exposure to continuous or intermittent fields is possible in the facility. The capability of obtaining physiological data during actual exposure to constant or intermittent, 60-Hz fields, and of doing so without either the subject or the experimenter being aware of actual field conditions, is a critical factor in valid experimentation.

Electromagnetic Fields↗

A replication study of human exposure to 60-Hz fields: effects on neurobehavioral measures.

The purpose of this study was to reproduce and extend an earlier investigation of the effects of human exposure to combined, 60-Hz electric and magnetic fields. This paper presents the neurobehavioral results. Thirty men participated in one training session and four testing sessions. Subjects were randomly assigned to two groups. The 18 subjects in Group I were exposed (9 kV/m, 20 microT) and sham exposed in two counterbalanced orders. In Group II, half of 12 subjects were exposed (9 kV/m, 20 microT) every session, and the remaining half were sham exposed every session. The study was doubly blinded. Measures of cardiac interbeat interval, event-related brain potentials, and performance were obtained before, during, and after exposures. As in the earlier study, exposure to the combined field resulted in a statistically significant slowing of heart rate, in changes in late components of event-related brain potentials, and in decreased errors on a choice reaction-time task. In addition, field effects on several other measures approached statistical significance. The physiological measures obtained during exposure indicated that effects were greatest soon after the field was switched on, and again when it was switched off. The data indicate that changes in exposure level may be more important than duration of exposure for producing effects in human beings.

Adult↗

Influences of exogenous epinephrine on two reproductive parameters in female mice: disruption of receptivity but not implantation.

Diverse stressors impede female receptivity and fertility. Since epinephrine is released from the adrenal during stress, it might play a role in stress-induced disruptions of female reproductive parameters. Experiment 1 examined whether exogenous epinephrine would disrupt lordosis behavior in estrogen- and progesterone-treated ovariectomized female mice. Single dosages of 20 and 40 micrograms almost eliminated sexual receptivity. Experiments 2 and 3 examined whether chronic dosages of epinephrine shortly after insemination would lead to a failure of implantation of mouse embryos. Results indicated that epinephrine had little effect on the number of dams delivering pups, the number of pups born, litter weight, or the number of stillbirths.

Aggression↗

A study of coroner's records of suicide in young people, 1986-88 in Western Australia.

Coroner's records of 25 consecutive suicides aged 15-19 years and 43 aged 20-24 years were compared with 68 suicides aged 45-59 years to identify associated clinical and psychosocial factors. Male: female ratios were 2.6:1, 5.1:1 and 3.5:1 respectively. The most common method of suicide in males in all three age groups was CO poisoning using motor vehicles. In females the teenage group used mainly active methods, whilst in the 20-24 and 45-49 years age groups the most common method was overdosage. Over 90% of each age group had some identifiable psychiatric symptomatology. In each age group the commonest symptoms were minor affective symptoms. In each group the pattern was mainly of associated multiple rather than single psychosocial factors. In each group disruption of interpersonal relationships (boy-girlfriend, de facto, marital, family) was the predominant stressor. Compared with the 45-59 year group the following associated factors were significantly greater in (a) 15-19 years: personality/conduct disorders, unemployment and legal/disciplinary problems, and (b) 20-24 years: drug abuse and unemployment. Although the two younger groups had significantly more unemployment than the older group, only the 20-24 years group had significantly more unemployment compared with community age norms. Preventive implications of the findings are discussed.

Adolescent↗

Analysis of four diverse population groups indicates that a subset of cystic fibrosis mutations occur in common among Caucasians.

To determine the nature and frequency of non-delta F508 cystic fibrosis (CF) mutations among diverse populations, we have sequenced exons 9-12 and 19-23 of the CF transmembrane conductance regulator (CFTR) gene from 128 CF chromosomes (39 U.S. Caucasian, 27 African-American, 42 Northern Irish, and 20 Israeli chromosomes). These regions were chosen because they encode the two putative ATP-binding folds of CFTR, domains which appear to have functional significance. In addition, CFTR exons 1 and 2 were analyzed in the American patients. Mutations were found on 49 of the 128 CF chromosomes. Nineteen different mutations were observed; six were novel, while the remaining 13 had been reported previously by our group or by other investigators. Six of nine different mutations found in African-American patients were unique to that population. However, the vast majority of the mutations found in U.S. Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians. A survey of mutation frequencies in other Caucasian groups confirmed this observation. Unfortunately, this subset accounts for less than half of non-delta F508 CF mutations in most groups. These data suggest that screening for delta F508 and this select group of mutations will efficiently and economically maximize the number of CF mutations identified in Caucasian groups. However, it will be difficult to detect more than 90% of mutant CFTR alleles except in ethnically and geographically discrete populations where CF is the result of founder effect.

Amino Acid Sequence↗

Characterization of the aldose reductase-encoding gene family in rat.

Although the enzyme aldose reductase (AR) is implicated in the development of tissue pathology in diabetes, the exact mechanism of this involvement remains unclear. To better understand the role that expression of the aldose reductase-encoding gene (ALR) may play in diabetic complications, we have begun to analyze the gene and its regulatory regions, and we present here the sequence of four ALR genes in the rat. The putative functional gene is 14.1 kb long, has ten exons which show perfect sequence identity to the rat lens AR RNA sequence, and nine introns with classical splice-site consensus sequences. Potential regulatory elements in the 5'-flanking region of this gene include a TATA box and two CCAAT boxes. Probing rat genomic Southern blots with a fragment from the first intron indicates that there is probably only one copy of this gene in the rat genome. The other three genes are processed pseudogenes which show approx. 90% identity to the rat lens AR RNA sequence, contain no introns, and have poly(A) regions at their 3' ends. Chromosomal localization studies show the presence of ALR genes on chromosomes 3, 4 and 6 in the rat with the putative functional gene mapped on chromosome 4.

Aldehyde Reductase↗

Effects of methanol vapor on human neurobehavioral measures.

Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes.

Aldose reductase (AR) is implicated in some of the disabling complications of diabetes, including neuropathy, retinopathy and cataracts. Our studies are aimed at further clarifying the role of AR in diabetes and facilitating the design of new classes of potent, specific AR inhibitors by gaining an understanding of the protein structure of AR. To this end, we have determined the complete protein sequence of rat lens AR using cDNA analysis and primer extension of mRNA. By comparing protein sequences, we have found that the structural relatedness (41% to 57%) among the vertebrate proteins, aldose reductase, aldehyde reductase, prostaglandin F synthase and the frog lens protein rho-crystallin can now be extended to prokaryotes by the inclusion of Corynebacterium 2,5-diketo-D-gluconate reductase. This more distantly related protein shares 30-40% identity with the vertebrate enzymes. Sequence alignments reveal that 18% of the amino acids are completely conserved in all members of the superfamily, many of them in clusters, suggesting that they mark important structural features such as the nucleotide binding site and substrate binding site. rho-Crystallin, which is structurally related to this superfamily of NADPH-dependent reductases, does not appear to reduce PGH2, PGD2, xylose or glyceraldehyde to any appreciable extent. It does, however, bind NADPH.

Aldehyde Oxidoreductases↗

Small bowel obstruction in the elderly.

The records of 56 consecutive patients, age 70 years or older, who were operated on for mechanical small bowel obstruction were reviewed to determine the effect of early operation versus delayed operation. Delayed operation was defined as a laparotomy performed more than 48 hours after admission. Excluding the 13 patients with hernias, there were no significant differences between the early operation and delayed operation groups in regard to age, cause of small bowel obstruction, duration of prehospitalization symptoms, degree of underlying disease, or physical findings on presentation--with the exception of a significantly higher number of patients in the early operation group who had abdominal tenderness. There were no differences between mortality and small bowel infarction rates in the two groups. There was an increase in the complication rate (60 vs 24%, P less than .05) and the mean length of stay (29.6 vs 20.0 days, P less than 0.05) in the delayed operation group. This increased mean length of stay was directly related to the higher number of complications caused by delay in operation. Advanced age in a patient with complete small bowel obstruction should not stay the surgeon's hand because delay only leads to a prohibitive increase in complications and length of hospitalization.

Aged↗

Characterization of mRNA and genes for aldose reductase in rat.

Aldose reductase (AR; E.C. 1. 1. 1. 21) has been implicated in a variety of diabetic complications. To investigate the expression of this enzyme in target tissues susceptible to such complications, mRNA encoding AR was characterized by Northern blot hybridization in various tissues and cultured cell preparations. The size of mRNA for AR (approximately 1500 bases) was in good agreement with the size determined by sequence analysis. A cDNA probe for AR from rat lens hybridized to the same size species of RNA isolated from cultured dog lens epithelial cells, cultured human retinal capillary pericytes (mural cells), and Y 79 human retinoblastoma cells. In rat tissues, a substantial amount of mRNA was expressed not only in lens, but also in retina, sciatic nerve and kidney medulla. AR mRNA seemed to be less abundant in rat skeletal muscle and brain, and was scarcely present in liver. Furthermore, Southern blot analysis of rat genomic DNA indicated that there are multiple sequences related to that for AR, probably indicating the existence of a multi-gene family.

Aldehyde Reductase↗