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Biomedical subjects

J L Hall

Publications and source records attributed to J L Hall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antibiotic prophylaxis for patients undergoing breast surgery.

Some groups of patients undergoing clean surgery benefit from the provision of antibiotic prophylaxis against wound infection. Breast surgery may belong to this category because several substantial studies have reported that it is accompanied by an unacceptably high rate of wound infection. However, only two clinical trials have addressed this issue and both produced equivocal results. Resolution of this problem is important because, aside from the usual advantages obtained by preventing such complications, wound infection diminishes the proportion of patients with breast cancer who start adjuvant regimens within an optimum time after surgery.

Antibiotic Prophylaxis↗
PubMed2000

Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin.

We determined the effect of insulin on the fate of glucose and contractile function in isolated working hypertrophied hearts from rats with an aortic constriction (n = 27) and control hearts from sham-operated rats (n = 27). Insulin increased glycolysis and glycogen in control and hypertrophied hearts. The change in glycogen was brought about by increased glycogen synthesis and decreased glycogenolysis in both groups. However, the magnitude of change in glycolysis, glycogen synthesis, and glycogenolysis caused by insulin was lower in hypertrophied hearts than in control hearts. Insulin also increased glucose oxidation and contractile function in control hearts but not in hypertrophied hearts. Protein content of glucose transporters, protein kinase B, and phosphatidylinositol 3-kinase was not different between the two groups. Thus hypertrophied hearts are less responsive to the metabolic and functional effects of insulin. The reduced responsiveness involves multiple aspects of glucose metabolism, including glycolysis, glucose oxidation, and glycogen metabolism. The absence of changes in content of key regulatory molecules indicates that other sites, pathways, or factors regulating glucose utilization are responsible for these findings.

Animals↗
PubMed1999

Identification and localization of G protein subunits in human spermatozoa.

Antibodies to alpha and beta subunits of guanine nucleotide regulatory proteins (G proteins) were used to identify which G proteins are present in mature human spermatozoa and to determine their subcellular localization. Immunoblots of membranes from spermatozoa demonstrate the presence of Galphai2, Galphai3, Galphaq/11 and Gbeta35 and the absence of Galphai1, Galpha0, Galphas, Galpha12, Galpha13, Galpha16, Galpha and Gbeta36. Indirect immunofluorescence demonstrates the presence of Galphaq/11 in the acrosome, with the highest proportion in the equatorial segment. Galphai2 is present in the acrosome, midpiece and tailpiece and Galphai3 in the postnuclear cap, midpiece and tailpiece. The Gbeta35 subunit is found mostly in the midpiece, with marginal labelling of the head, tailpiece and the equatorial segment of the acrosome. The distinct pattern of distribution of G proteins suggests that they may couple to receptors or effectors which also have discrete regions of localization in spermatozoa. These highly localized signal transduction pathways may regulate discrete functions, such as activation of the acrosome reaction, fusion with the oocyte and motility.

Adult↗
PubMed1999

Functional characterization and expression analysis of the amino acid permease RcAAP3 from castor bean.

A polymerase chain reaction-based library screening procedure was used to isolate RcAAP3, an amino acid permease cDNA from castor bean (Ricinus communis). RcAAP3 is 1.7 kb in length, with an open reading frame that encodes a protein with a calculated molecular mass of 51 kD. Hydropathy analysis indicates that the RcAAP3 protein is highly hydrophobic in nature with nine to 11 putative transmembrane domains. RcAAP3-mediated uptake of citrulline in a yeast transport mutant showed saturable kinetics with a K(m) of 0.4 mM. Transport was higher at acidic pH and was inhibited by the protonophore carbonylcyanide-m-chlorophenylhydrazone, suggesting a proton-coupled transport mechanism. Citrulline uptake was strongly inhibited (72%) by the permeable sulfydryl reagent N-ethylmaleimide, but showed lower sensitivity (30% inhibition) to the nonpermeable reagent p-chloromercuribenzenesulfonic acid. Diethylpyrocarbonate, a histidine modifier, inhibited citrulline uptake by 80%. A range of amino acids inhibited citrulline uptake, suggesting that RcAAP3 may be a broad substrate permease that can transport neutral and basic amino acids with a lower affinity for acidic amino acids. Northern analysis indicated that RcAAP3 is widely expressed in source and sink tissues of castor bean, and that the pattern of expression is distinct from RcAAP1 and RcAAP2.

Amino Acid Sequence↗
PubMed1998

Cloning of a cDNA coding for an amino acid carrier from Ricinus communis (RcAAP1) by functional complementation in yeast: kinetic analysis, inhibitor sensitivity and substrate specificity.

A cDNA for the amino acid permease gene RcAAP1 has been isolated from Ricinus communis by yeast complementation and subjected to a detailed kinetic analysis. RcAAP1 cDNA is 1.5 kb with an open reading frame that codes for a protein with 486 amino acids and a calculated molecular mass of 53.1 kDa. RcAAP1-mediated histidine uptake was pH dependent with highest transport rates at acidic pH; it was sensitive to protonophores and uncouplers and the Km for histidine uptake was 96 microM. The substrate specificity was investigated by measuring the levels of inhibition of histidine uptake by a range of amino acids. The basic amino acids (histidine, lysine and arginine) showed strongest inhibition of uptake whereas acidic amino acids competed less effectively. Alanine was the most efficient competitor of the neutral amino acids. Glutamine, serine, asparagine, methionine and cysteine showed moderate inhibition whereas threonine, isoleucine, leucine, phenylalanine, tyrosine and tryptophan showed only low levels of inhibition. Glycine, proline and citrulline caused slight stimulation. More detailed competition kinetics indicated that both lysine and arginine showed simple competitive inhibition of histidine uptake. When direct uptake measurements were carried out, both lysine and arginine were found to be effective substrates for RcAAP1.

Amino Acid Sequence↗
PubMed1998

Duration of antimicrobial prophylaxis in vascular surgery.

BACKGROUND: This randomized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen (until the lines/drain tubes were removed, but not for more than 5 days). METHODS: Each of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g (Timentin) intravenously immediately after the induction of anesthesia. Patients randomized to the multiple-dose group received an average of 14.3 doses (range 9 to 20). RESULTS: The incidence of wound infections was 18% (28 of 153) for patients in the single-dose group and 10% (15 of 149) for patients in the multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence interval = -1.02 to 3.92). CONCLUSIONS: A multiple-dose antibiotic regimen, rather than single-dose therapy, provides optimal prophylaxis against wound infection for patients undergoing vascular surgery.

Aged↗
PubMed1998

Amino acid carriers of Ricinus communis expressed during seedling development: molecular cloning and expression analysis of two putative amino acid transporters, RcAAP1 and RcAAP2.

This study reports on the isolation of two putative amino acid carrier cDNAs, RcAAP1 and RcAAP2, from Ricinus communis. Northern analysis shows that RcAAP1 and RcAAP2 are expressed abundantly in the cotyledon and root tissues of developing seedlings and at lower levels in the endosperm and hypocotyl. In the mature plant low expression was observed in the source and sink leaves. We have further characterized the expression of RcAAP1 in Ricinus roots by in situ hybridization. The transcripts are localized in many cell types of the root tip region, including the epidermal and cortical cells, but the highest expression was observed in the cells of the stele situated adjacent to the xylem poles. This is the first report describing the cellular expression of an amino acid transporter in roots, and the results are discussed in relation to the physiological role of this transporter.

Amino Acid Sequence↗
PubMed1998

Expression analysis of a sucrose carrier in the germinating seedling of Ricinus communis.

This study describes the expression of a sucrose carrier at various developmental stages in Ricinus communis. A partial-length cDNA clone, RcSUT1, was isolated by RT-PCR from Ricinus seedling RNA. This is almost identical to a sucrose carrier cDNA, Rscr1, which has previously been isolated by library screening. However, we have observed a very different expression pattern in the seedling to that previously reported. Northern analysis, with RcSUT1 as a probe, revealed high expression of a 2 kb transcript in the cotyledons of the germinating seedling; transcript levels were similar in cotyledons harvested 3-6 days after germination. A much lower level of this transcript was detected in the root, hypocotyl and endosperm RNA of the seedling and very low levels were also present in the sink and source leaves of the mature plant. This pattern of expression was also reflected at the protein level with an antipeptide antibody raised to part of the RcSUT1 deduced amino acid sequence. Tissue print hybridisation analysis of the hypocotyl revealed that the sucrose carrier transcripts were localised to the phloem cells of the vascular bundles. A more detailed analysis of sucrose carrier gene expression in the cotyledons of the germinating seedling was carried out by in situ hybridisation; the strongest signals were observed from the lower epidermal layer and the phloem, consistent with an active loading role for these cells. An ultrastructural study of the cells in the lower epidermis showed that they have wall ingrowths which are characteristic of transfer cells. The results are discussed in relation to the physiological role of the sucrose carrier in the Ricinus seedling and to the pathways of sucrose movement from endosperm to the sieve elements in the cotyledons.

Amino Acid Sequence↗
PubMed1998

Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease.

We postulated that activation of a genetic program that tonically inhibits intimal cell death is a necessary condition for the pathogenesis of vascular disease. Studies of vascular lesions in humans and animal models documented increased expression of the anti-apoptotic gene product Bcl-xL within intimal cells. Downregulation of intimal cell bcl-xL expression with the use of antisense oligonucleotides induced apoptosis and acute regression of vascular lesions. These findings indicate that apoptosis regulatory genes such as bcl-xL are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.

Animals↗
PubMed1998

The time of presentation of wound infection after cardiac surgery.

Clinical experience indicates that many wound infections present relatively late after cardiac surgery. Hence, timing may be an important issue in using this outcome as a clinical indicator. A database of 1000 patients who underwent cardiac surgery was accessed to ascertain baseline characteristics, the type of surgery, and the time of presentation of wound infections. The overall incidence of wound infection was 5.9% (59/1000). Only 36% (21/59) of the wound infections presented while the patient was in hospital. Diabetics were more likely to have a late presentation of a wound infection (the median time of presentation of wound infections (more than 17 days), i.e. 10/29 (33.4%) versus 98/971 (10.1%), Fisher's exact test P < 0.01). Wound infection can only be regarded as a reliable clinical indicator after cardiac surgery if patients are reviewed with care for 6 weeks after surgery.

Aged↗
PubMed1998

Surgery on trial: an account of clinical trials evaluating operations.

BACKGROUND: The objective of this study was to review published clinical trials to determine the level of compliance with issues relevant to operations. METHODS: We evaluated 10 methodologic criteria in 186 trials that were published in 10 prestigious journals between January 1986 and December 1995. RESULTS: One quarter of the trials failed to provide a clear account of the operative technique, 34% of the trials did not adequately detail the adverse events that occurred after operation, and 40% of the trials neglected to declare the nature and success of the follow-up of patients after the operation. Only 35% of the trials indicated that there was an attempt to standardize either the surgical procedure or perioperative care. In addition, less than 20% of the trials declared a method for assessing compliance with the surgical protocol or commented on the use of resources during the perioperative period. CONCLUSIONS: Greater attention needs to be paid to the specific issues that arise when operations are evaluated in clinical trials.

Authorship↗
PubMed1997

Effect of multifactorial genetic liability to exencephaly on the teratogenic effect of valproic acid in mice.

The present study shows that the multifactorial genetic liability to spontaneous exencephaly in the SELH/Bc mouse strain (10-20% of embryos) also confers an elevated risk of exencephaly induced by valproic acid. Treatment of pregnant dams (600 mg/kg sodium valproate in distilled water, i.p.) during the critical period on day 8 (D8) of gestation resulted in D14 exencephaly frequencies of 69% in SELH/Bc contrasted with 39% in each of the SWV/Bc and ICR/Bc strains. Analysis of these data under the assumptions of the threshold model indicated that the valproic acid-induced-shift in mean liability was similar for all three strains, and therefore the effects of genotype and teratogen were additive, not synergistic. A similar exencephaly response pattern for the same three strains was observed previously with retinoic acid [Tom et al. (1991) Teratology 43:27-40], a pattern that, combined with the data of Finnell et al. [(1988) Teratology 38:313-320], argues that strain differences in exencephaly response are not due to strain differences in teratogen metabolism. SWV/Bc and ICR/Bc embryos differ in location of the Closure 2 initiation site of cranial neural tube closure [Juriloff et al. (1991) Teratology 44:225-233], but the observation that they do not differ in risk of exencephaly produced by either valproic acid or retinoic acid contradicts the hypothesis that this particular morphological difference underlies strain differences in exencephaly risk. The high exencephaly response of SELH/Bc to two teratogens predicts that human conceptuses with a genetically determined elevated risk for neural tube defects could be easily tipped into high risk by mild teratogens.

Abnormalities, Drug-Induced↗
PubMed1997

Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions.

It is now clear that the availability of different metabolic substrates can have a profound influence on the extent of damage incurred during episodes of cardiac ischaemia, and on cardiac functional recovery on reperfusion following ischaemia. In particular, increases in fatty acid availability and oxidation, compared to glucose oxidation, under such conditions leads to a worsening of outcome. Therefore metabolic interventions aimed at enhancing glucose utilisation and pyruvate oxidation at the expense of fatty acid oxidation is a valid therapeutic approach to the treatment of myocardial ischaemia. In particular, the development of agents which will promote full glucose oxidation as opposed to glycolysis alone, offer clear advantages. This can be accomplished by different means, including direct or indirect inhibition of CPT-I or inhibition of fatty acid beta-oxidation, or by direct or indirect activation of PDH. It is not yet clear which of these approaches offers the best treatment of cardiac ischaemia. To date, trimetazidine and carnitine have received limited approval in Europe for the treatment of angina; large scale clinical trials with the other agents mentioned above have not been completed. The increasing availability of agents affecting these specific sites, and the increasingly sophisticated techniques for assessing myocardial metabolism, should allow elucidation of the optimum metabolic targets and development of novel pharmacological agents for the treatment of ischaemic heart disease.

Animals↗
PubMed1997

Decreased myocardial glucose uptake during ischemia in diabetic swine.

The purpose of the study was to assess myocardial glucose uptake in nondiabetic (n = 5) and streptozotocin-diabetic (n = 6) Yucatan miniature swine under matched hyperglycemic and hypoinsulinemic conditions. Fasting conscious diabetic swine had significantly higher plasma glucose levels (20.9 +/- 2.6 v 5.2 +/- 0.3 mmol/L) and lower insulin levels (6 +/- 1 v 14 +/- 4 microU/mL) than nondiabetic animals. Myocardial glucose uptake was measured in open-chest anesthetized animals under aerobic and ischemic conditions 12 weeks after streptozotocin treatment. Coronary blood flow was controlled by an extracorporeal perfusion circuit. Ischemia was induced by reducing left anterior descending (LAD) coronary artery blood flow by 60% for 40 minutes. Animals were treated with somatostatin to suppress insulin secretion, and nondiabetic swine received intravenous (IV) glucose to match the hyperglycemia in the diabetic animals. The rate of glucose uptake by the myocardium was not statistically different under aerobic conditions, but was significantly lower in diabetic swine during ischemia (0.20 +/- 0.08 v 0.63 +/- 0.14 micromol x g(-1) x min(-1), P < .01). Myocardial glucose transporter (GLUT4) protein concentration was decreased by 31% in diabetic swine. In conclusion, 12 weeks of streptozotocin diabetes in swine caused a significant decrease in myocardial GLUT4 protein and a decrease in myocardial glucose uptake during ischemia.

Animals↗
PubMed1997

Aqueous hyaluronic acid concentration: comparison in pediatric and adult patients.

PURPOSE: To determine if there is an age-related increase in human aqueous hyaluronic acid (HA) concentration. METHODS: HA concentrations were measured in 102 specimens of human aqueous humour obtained during intraocular surgery. Patient age ranged from one month to 93 years. Measurement of the HA concentration in the specimens was performed by a modified ELISA-like assay using a biotinylated HA-binding peptide. RESULTS: An approximate five-fold increase in the mean aqueous HA concentration was observed between the pediatric (0.33 microgram/ml, n = 5) and the adult patients (1.72 micrograms/ml, n = 97, p < 0.0002). Among the adult patients, however, there was a poor correlation between age and aqueous HA concentration. CONCLUSIONS: Adult aqueous humor has a significantly higher HA concentration than aqueous obtained from pediatric patients. The source of this increase is unclear, but may be from anterior segment production of HA, or alternatively, from anterior diffusion of vitreous HA.

Adult↗
PubMed1997

Sympathetic stimulation elicits increased or decreased VO2 in the perfused rat hindlimb via alpha 1-adrenoceptors.

The effects of lumbar sympathetic nerve stimulation on oxygen uptake (VO2) in curarized muscle of the perfused rat hindlimb were investigated. Stimulation of sympathetic nerves elicited vasoconstriction at all frequencies. Importantly, this was associated with changes in VO2 that were generally stimulatory at low frequencies (0.5-2 Hz) and inhibitory at high frequencies (5-10 Hz). Both the pressor response and the changes in VO2 were almost completely blocked by the alpha 1/alpha 2-blocker phentolamine (1.0 microM) but were not affected by the beta 1/beta 2-blocker DL-propranolol (2.0 microM). The alpha 2-blocker yohimbine (0.1 microM) did not significantly affect either the pressor or VO2 response. The alpha 1-antagonist prazosin (0.1 microM) abolished the vasoconstriction with low-frequency stimulation and inhibited > 90% of the vasoconstriction with high-frequency stimulation. Intra-arterial infusion of phenylephrine (alpha 1-agonist), but not of UK-14304 (alpha 2-agonist), also elicited a similar biphasic response in VO2 during vasoconstriction. The changes in VO2 at both low- and high-frequency stimulation were fully reversed by prazosin. The vasodilator sodium nitroprusside also showed similar effects to prazosin in blocking both VO2 and vasoconstriction. Thus sympathetic control of VO2 in the perfused rat hindlimb appears to be initiated by activation of predominantly vascular alpha 1-adrenoceptors.

Adrenergic alpha-1 Receptor Agonists↗