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Biomedical subjects

D Jacobson

Publications and source records attributed to D Jacobson.

At least 19 recordsLinked to original sources

Camalexin accumulation in Arabis lyrata.

Inoculation of leaves of Arabis lyrata with either a bacterial pathogen Pseudomonas syringae pv. maculicola strain ES4326 or Cochliobolus carbonum, a fungal nonpathogen of A. lyrata, resulted in the accumulation of a compound with similar chromatographic and fluorescent properties to that of camalexin (I), a phytoalexin produced by Arabidopsis thaliana. A. lyrata is closely related to A. thaliana. High resolution electron impact mass spectroscopic and proton NMR analysis confirmed that the compound produced by A. lyrata is camalexin.

Chromatography, High Pressure Liquid

Reference ranges for serum prostate-specific antigen in black and white men without cancer.

OBJECTIVES: To determine the age- and race-specific prostate-specific antigen (PSA) distributions in healthy men in central South Carolina and to compare these to data from other studies. METHODS: Two thousand ninety-two black men aged 40 to 69 years and white men aged 50 to 69 years from the general population in 11 counties of central South Carolina participated in a prostate cancer educational program. Seventy-two percent of the participants were black-about double the proportion in the general population-and 63% of the men (1319 of 2092) subsequently obtained a PSA determination from their own physician. The distribution of serum PSA was compared with distributions from the Olmsted County study and from the Walter Reed Army Medical Center/Center for Prostate Disease Research study. RESULTS: Older men without cancer had higher PSA levels. Regression analyses yielded an associated increase of about 3.3% per year. Reference ranges for normal PSA in men without cancer (based on their sample 95th percentiles) were zero to 1.9, 3.8, and 5.7 ng/mL in black men aged 40 to 49, 50 to 59, and 60 to 69 years, and zero to 2.7 and 4.9 mg/mL in white men aged 50 to 59 and 60 to 69 years, respectively. CONCLUSIONS: Reference ranges for normal serum PSA levels should take into account the population from which they are derived and to which they will be applied. Reference ranges that are useful in the general population can differ from those that are appropriate in a hospital setting. For the general population in central South Carolina, reference ranges for serum PSA levels are lower than previously published reference ranges, particularly among black men.

Adult

Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest.

Chromosome 3q alterations occur frequently in many types of tumours. In a genetic screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q [i(3q)], which inhibits muscle differentiation when transferred into myoblasts. The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype. Furthermore, the i(3q) induces a 'cut' phenotype, abnormal centrosome amplification, aneuploidy and loss of G1 arrest following gamma-irradiation. Testing candidate genes within this region reveals that forced expression of ataxia-telangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q). Thus, genetic alteration of ATR leads to loss of differentiation as well as cell-cycle abnormalities.

Aneuploidy

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

OBJECTIVE: The gastrointestinal tonometer, which allows measurement of gastrointestinal mucosal CO2 and subsequent derivation of gut intramucosal pH (pHi), has been demonstrated to be a sensitive predictor of outcome following major surgery. Current theory suggests that the origin of the low pH may be hypovolaemia. This study was designed to compare the temporal sequence of changes in tonometric readings with invasive blood pressure, stroke volume, heart rate, lactate and arterial blood gas measurements during progressive haemorrhage. DESIGN: Observational healthy volunteer study. SETTING: Intensive care unit at University College London Hospitals. SUBJECTS: Six healthy, medically qualified volunteers. INTERVENTIONS: After obtaining baseline measurements, the subjects were progressively bled 25% (range = 21-31%) of their blood volume over a period of 1 h in two approximately equal aliquots. Equilibration was allowed for 30 min following the bleed, after which further measurements were made and the blood was then retransfused over 30 min. MEASUREMENTS AND MAIN RESULTS: There was no consistent change in any of the haemodynamic variables other than gastric intramucosal CO2:arterial CO2 gap (PiCO2-PaCO2) after removal of the first aliquot of blood, although five of the six subjects also demonstrated a fall in pHi. After removal of the second aliquot of blood, PiCO2-PaCO2 gap and pHi continued to indicate a worsening gastric intramucosal acidosis; stroke volume, as measured by suprasternal Doppler, demonstrated a marked fall, while all other variables measured had not altered consistently or to such a degree as to elicit a clinical response or cause suspicion of a hypovolaemic state. On retransfusion, all variables returned towards baseline. CONCLUSIONS: This study demonstrates the value of tonometry as an early monitor of hypovolaemia and highlights the shortcomings of other more commonly measured clinical variables.

Adult

Evidence for reliability, validity and usefulness of the Medical Outcomes Study HIV Health Survey (MOS-HIV).

The Medical Outcomes Study HIV Health Survey (MOS-HIV) is a brief, comprehensive measure of health-related quality of life (HRQoL) used extensively in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The 35-item questionnaire includes ten dimensions (health perceptions, pain, physical, role, social and cognitive functioning, mental health, energy, health distress and quality of life (QoL) and takes approximately 5 minutes to complete. Subscales are scored on a 0-100 scale (a higher score indicates better health) and physical and mental health summary scores can be generated. The MOS-HIV has been shown to be internally consistent, correlate with concurrent measures of health, discriminate between distinct groups, predict future outcomes and be responsive to changes over time. Limited experience suggests acceptable reliability and validity in women, injecting drug users and African-American and lower socioeconomic status patients. The MOS-HIV is available in 14 languages and has been included as a secondary outcome measure in numerous clinical trials for all stages of disease. In several studies it has detected significant differences between treatments; in some cases concordant with conventional endpoints and, in others, discordant. The interpretation of scores is facilitated by an explanation in terms meaningful to the intended audience. Research is needed to compare the MOS-HIV to other strategies for HRQoL assessment in early HIV disease.

Female

Circannual variations in bear plasma albumin and its opioid-like effects on guinea pig ileum.

Previous studies suggest that hibernation is controlled by an opioid system. In this study we examined the effect of plasma albumin fractions drawn from black bears at timed intervals while in hibernation or during the awake state in fall and winter, on induced contractility of the guinea pig ileum. Four hundred nM morphine produced typical suppression of contractility and 400 or 1000 nM naloxone (an opiate antagonist) restored it. Twenty mg of lyophilized albumin fraction from the winter hibernating bear caused similar suppression, the effect being greater than that of either summer bear or winter-active bear plasma albumin. Naloxone reversed the suppression in all cases. Strong suppression of contractility was also demonstrated with 2.5 nM [D-Pen2.5]-enkephalin (DPDPE), a delta agonist, but only minor suppression with 2.5 nM dynorphin A, a kappa agonist. Results support the opioid nature of the albumin-bound hibernation-induction trigger substance, that it binds to the delta opiate receptor, and that delta agonist opioid production may increase during the hibernation season.

Analgesics

It's a knockout!

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Animals

Cardiorespiratory and tissue oxygen dose response to rat endotoxemia.

The dose response to endotoxin (Escherichia coli serotype 127:B8) was assessed in a spontaneously breathing, halothane-anesthetized, Sprague-Dawley rat model monitoring blood pressure, aortic and renal blood flows, blood gases, and bladder epithelial PO2, a marker of organ perfusion. The animals received either saline or endotoxin at doses of 1, 10 and 100 mg/kg body wt. Blood pressure changed significantly in all three endotoxin groups, though only the 100 mg/kg group showed significant changes in arterial PCO2, arterial PO2, and body temperature compared with controls. Whereas aortic and renal blood flow rose significantly in the two lower-dose groups, an approximate one-third fall occurred in the 100 mg/kg group (P < 0.001). Notwithstanding these macrocirculatory hemodynamic changes, both bladder epithelial PO2 and arterial base deficit rose significantly in all groups, though only the base deficit showed a progressive dose response. This model illustrates that responses to endotoxin are dose dependent but with changing patterns for different variables. The consistent finding of an elevated tissue PO2 in endotoxemia, regardless of dose, is suggestive of defective cellular oxygen metabolism.

Animals

Maintaining blood flow in the extracorporeal circuit: haemostasis and anticoagulation.

OBJECTIVES: To review the methods and developments in maintaining extracorporeal circuits in critically ill patients. DESIGN: The review includes details of the pathophysiological processes of haemostasis and coagulation in critically ill patients, methods of maintaining blood flow in the extracorporeal circuit and methods of monitoring anticoagulation agents used. SETTING: Information is relevant to the management of critically ill patients requiring extracorporeal renal and respiratory support and cardiopulmonary bypass. CONCLUSIONS: Heparin is the mainstay of anticoagulation for the extracorporeal circuit although the complex abnormalities of the coagulation system in critically ill patients are associated with a considerable risk of bleeding. Alternative therapeutic agents and physical strategies (prostacyclin, low molecular weight heparin, sodium citrate, regional anticoagulation, heparin bonding and attention to circuit design) may reduce the risk of bleeding but expense and difficulty in monitoring are disadvantages.

Anticoagulants

A comparison of temperament and maternal bother in infants with and without colic.

This descriptive, retrospective study compared the temperament styles of 25 4- to 8-month-old infants who had colic with the temperament styles of 30 infants of similar age without colic. Infant temperament style was characterized by the mother's ratings of her infant's behavioral style. The degree of bother that the mother experienced in relationship to her infant's temperament also was examined. Results indicated that mothers of infants with colic rated their infants' temperaments differently than mothers of infants without colic in the temperament dimensions of activity and mood. Mothers of infants with colic were more bothered by the infants' temperament dimension of mood than were mothers of infants without colic. More infants in the colic group were characterized as difficult than were infants in the noncolic group. Individual temperament characteristics should be considered in the differential diagnosis of primary excessive crying (colic) during the newborn and infant periods.

Adult

Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis.

The effect of endotoxin on tissue oxygen tension measured at the bladder epithelium was assessed in spontaneously breathing Sprague-Dawley rats anesthetized with halothane. Hyperdynamic (high cardiac output, group A, n = 6) and hypodynamic (low cardiac output, group B, n = 6) circulatory responses were achieved by intravenous administration of Escherichia coli lipopolysaccharide, 10 mg/kg over 30 min or 20 mg/kg over 1 min, respectively. Comparison was made against sham-operated control rats (group C, n = 6). Aortic and renal blood flows increased in group A and fell in group B (P < 0.001). However, in both groups, bladder epithelial oxygen tension rose significantly compared with control (P < 0.01), despite an increasing metabolic acidosis. This is in contradistinction to previous studies of nonseptic insults where bladder epithelial oxygen tension fell in line with an increasing arterial base deficit. If a raised tissue oxygen tension could be demonstrated in other organ beds, this would suggest that decreased utilization of oxygen rather than reduced tissue oxygen availability is responsible for the apparent anaerobic respiration seen in sepsis.

Animals

Morphometric analysis of heterozygote dancer mice predisposed to 6-aminonicotinamide-induced cleft lip.

Mid-facial development is an extremely complex process involving coordinated events and precise timing. Cleft lip (CL) may result from the failed fusion of the lateral and medial nasal processes in the developing embryo. It has been postulated that spontaneous CL in the A/J strain of mice may be due to a predisposing face shape (Trasler, '68). This hypothesis was examined in mutant mice susceptible to teratogen-induced CL. Mice carrying the dancer (Dc) mutation in the heterozygous state rarely develop CL, whereas 90% of homozygotes (Dc/Dc) develop CL. Outcrossed heterozygotes show elevated susceptibility to 6-aminonicotinamide (6AN)-induced CL (Trasler et al., '84) and these were used to investigate face shape as a predisposing factor. Dc/+ and +/+ males were mated to R stock females, and embryos were collected on day 10/21 hr, when the nasal placodes are approximately at the oblong or crescent stage. Total nasal process areas and volumes, medial and lateral process areas and volumes, and medial jut lengths were measured from histological sections, and comparisons made between the two populations. The results indicate that compared to +/+ control, heads of embryos from the Dc/+ cross have significantly smaller mean total process areas and volumes (P less than 0.005), mean lateral process areas and volumes (P less than 0.005), mean medial process area and volumes (P less than 0.01), mean maximum head diameter (P less than 0.02), but similarly sized medial juts and crown rump lengths. Correlations between maximum head diameter and process size indicate that the Dc mutation may hinder normal development of the nasal processes. These reduced nasal processes may explain the underlying predisposition to 6AN-induced CL.

6-Aminonicotinamide

Genes necessary for directed axonal elongation or fasciculation in C. elegans.

The outgrowth of single axons through different cellular environments requires distinct sets of genes in the nematode C. elegans. Three genes are required for the pioneering circumferential outgrowth of identified motor neuron axons between the lateral hypodermal cell membrane and the basal lamina. Three other genes are required for the longitudinal outgrowth of these axons along preexisting axon bundles as well as for the fasciculation of axons within these neuron bundles. Five additional genes are required for circumferential outgrowth, longitudinal outgrowth, and fasciculation; mutations in three of these genes disrupt axon ultrastructure, suggesting that they function in axon formation rather than in axon guidance.

Animals

Endocrine correlates of mating-induced reductions in estrous behaviour in an induced ovulator, the ferret.

Experiments were conducted to assess the time course of behavioral and endocrine changes which occur in female ferrets as they switch from estrus to the pseudopregnant state. Significant reductions in females' acceptance of neck gripping by a stimulus male (receptivity) and in their latency to approach a stimulus male in an L-maze (proceptivity) were first observed 3 days after receipt of an intromission; no such changes occurred in other females which were only neck gripped by stimulus males during the initial test session. Corpora lutea were later found only in the ovaries of females which received intromissions, confirming that ovulation had occurred in these animals. Plasma concentrations of prostaglandin E1, prostaglandin F2 alpha, and the 13,14-dihydro 15-keto metabolite of prostaglandin F2 alpha (PGFM) were unchanged in female ferrets for 4-5 days after receipt of an intromission. By contrast, plasma concentrations of progesterone were significantly elevated beginning 5 days after, whereas plasma estradiol was significantly reduced beginning 4 days after receipt of an intromission. Daily sc administration of the progesterone receptor antagonist. RU 38486, significantly retarded the lengthening in females' approach latencies to a stimulus male, suggesting that postcoital elevations in circulating progesterone normally contribute to the expected decline in proceptive responsiveness. By contrast, postcoital reductions in acceptance quotients occurred at equivalent rates in females treated with RU 38486 versus vehicle, leading us to infer that postcoital reductions in estrogenic stimulation may cause this decline in ferrets' receptive responsiveness.

Animals

Protein kinase C blockers and neutrophil receptors for leukotriene B4.

Three protein kinase C blockers (staurosporin, Cl, and sphinganine) acted temperature- and time-dependently on human neutrophils to lower the affinity and number of high affinity plasmalemma receptors available to leukotriene B4. The drugs did not alter the ligand's binding to isolated plasma membranes or reduce intact cell binding of platelet-activating factor. Thus, protein kinase C may regulate the expression of certain receptors in resting cells and blockers of this enzyme, by interfering with receptor expression, have secondary effects that complicate their use as pharmacological probes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Receptor-independent metabolism of platelet-activating factor by myelogenous cells.

Human neutrophils incorporate and metabolize platelet-activating factor (PAF). We dissociated these events from PAF binding to its receptors. Cells were pretreated with either pronase, a PAF antagonist (L652731), or excess PAF. This reduced PAF receptor numbers by 70 to almost 100% but had no comparable effect upon the neutrophil's ability to metabolize PAF. Furthermore, HL-60 cells efficiently metabolized, but did not specifically bind, PAF. Thus, PAF receptor availability did not correlate with PAF metabolic capacity and we conclude that myelogenous tissues can process this bioactive ligand by a receptor-independent pathway.

Humans