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Biomedical subjects

J M Wagner

Publications and source records attributed to J M Wagner.

At least 37 records · Page 2Linked to original sources

Allergen challenge in asthma: association of eosinophils and lymphocytes with interleukin-5.

To test whether eosinophil recruitment after pulmonary allergen challenge is associated with interleukin (IL)-5 in patients with asthma, we performed segmental bronchoprovocation (SBP) with saline, and with low and high dosages of ragweed extract in six patients with allergic asthma. Bronchoalveolar lavage (BAL) of the challenged segments was performed 5 min after challenge (immediate BAL fluid) and repeated 24 h later (late BAL fluid). Allergen challenge resulted in recruitment of eosinophils, and increased levels of eosinophil-active cytokines. A bioassay showed the predominant eosinophil-active cytokine in the late BAL fluids to be IL-5. Analysis of the late BAL fluids revealed that IL-5 levels correlated with the numbers of eosinophils and lymphocytes. This study provides evidence that IL-5 is a critical cytokine associated with eosinophil and lymphocyte recruitment into the airways of patients with asthma following exposure to allergen.

Adolescent↗

The behavioral response to stress is altered in adult rats exposed prenatally to cocaine.

The behaviors displayed during and following acute stress exposure were investigated in rats prenatally exposed to cocaine. Offspring from Sprague-Dawley rat dams given SC injections of 40 mg/kg/3 cc cocaine HCl (C40) daily from gestational days 8-20, pair-fed dams injected daily with saline (PF), and untreated control dams (LC) were examined. Adult male rats 60 days old (P60) from the three prenatal groups were given either a 5-min forced swim test (FS), 10 min of intermittent foot shock exposure, or were not exposed to either acute stressor. Amount of immobility or inactivity during acute stress exposure was recorded. One day later, all animals were given a 5-min open field test. During both of the acute stressors, C40 offspring exhibited significantly less immobility than PF and LC control offspring. Whereas prior foot shock experience enhanced the amount of immobility shown by LC and PF offspring in the open field, similar immobility scores were observed between shocked and nonstressed C40 rats. In contrast, prior foot shock experience reduced locomotion in all prenatal treatment groups. These findings suggest that prenatal cocaine exposure results in altered behavioral reactivity in terms of the immediate and delayed response to stressful experiences.

Animals↗

Pregnancy-associated major basic protein: deposition of protein and expression of mRNA at the maternal-fetal junction in early and late gestation.

Pregnancy-associated major basic protein (pMBP) has previously been isolated from human placenta and localized to the X cell. Here we used immunofluorescence staining and in situ hybridization to determine the distribution of pMBP and pMBP mRNA throughout the maternal-fetal junction in both early gestation tissues and at term. In early gestation tissues, pMBP was present only at the placental insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the extracellular space, in interstitial pools and inside endometrial glands) and (b) intracellularly within extravillous interstitial trophoblasts in the decidua, in the myometrium and surrounding but not within luminal cells of spiral arteries. At term, the placental bed showed intense extracellular pMBP staining with little intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in both the early and late gestational tissues. pMBP mRNA was present in cells in the decidua, at the decidual-myometrial junction and in cell islands. Quantitative image analysis showed statistically significant hybridization signals with the pMBP antisense probe as compared to the control/sense probe. These results indicate that pMBP mRNA is expressed and pMBP is extensively deposited at the maternal-fetal junction in early pregnancy and at term.

Adult↗

Internal medicine preceptorships: three successful programs.

Undergraduate medical education is evolving to include community physicians in the training of students in the outpatient setting. The task of designing and implementing such preceptorships can be hindered by financial, institutional, and logistic factors. Nonetheless, several institutions have successfully begun such preceptorships, even in the absence of major federal or philanthropic funding. In this article, three institutions offer suggestions for overcoming the factors hindering the development of a successful preceptorship.

Education, Medical, Undergraduate↗

Analyzing and adjusting for variables in a large-scale standardized-patient examination.

BACKGROUND: Structuring a clinical performance examination that uses standardized patients (SPs) for large groups of examinees often involves the use of two or more parallel forms of the examination with different SPs portraying the same case on the different forms. In addition, each form may be administered more than once on different days and/or in different locations. METHOD: To determine the effects of critical variables, such as day of examination, time of day (AM/PM), which of two simultaneous forms were taken, and sequencing effects, a univariate nested factorial analysis of variance was conducted for each of four annual SP examinations (1990-1993) at the University of Texas Southwestern Medical School. The examinations were given to approximately 200 second-year students per year at the end of their Introduction to Clinical Medicine course, and were graded on a pass/fail basis. RESULTS: Statistically significant differences were found for the following variables: (1) time of day (AM or PM) and day were significant but were inconsistent and of small magnitude; (2) sequencing for the first two stations was significant in each form of the examination and in all four years; and (3) form-within-case differences (i.e., differences between SPs) were significant between the two forms of the examination in each year of administration. To minimize the impacts of these variables, two mean equating formulas were applied to the scores. Few examinees' pass/fail status would have been affected by either adjustment. CONCLUSION: The parallel-forms examination format is minimally affected by the variables evaluated and is a fair pass/fail assessment of a student's performance. Mean equating is a valuable tool in minimizing the possibly unfair impact of variables on pass/fail decisions for homogeneous student populations.

Analysis of Variance↗

Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta.

BACKGROUND: The human eosinophil granule major basic protein (MBP), a 13.8 kilodalton cationic polypeptide constituting the core of the eosinophil granule, is cytotoxic to parasites and numerous mammalian cells. Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP mRNA has been localized to placental X cells by in situ hybridization. Eosinophil granule MBP is initially translated as a nontoxic precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is believed to neutralize MBP toxicity. Recent analyses of sera from pregnant women have revealed that pregnancy-associated plasma protein-A (PAPP-A), previously thought to be a homotetramer of PAPP-A subunits, is actually composed of PAPP-A subunits bound by disulfide bonds to equimolar amounts of proMBP molecules to form a complex, PAPP-A/proMBP. In addition, the PAPP-A subunit nucleotide and deduced amino acid sequence have been determined from cloned cDNA. The PAPP-A monomer found in plasma contains 1547 amino acid residues. EXPERIMENTAL DESIGN: Because of the new evidence that PAPP-A is complexed with proMBP, previous studies on the localization of PAPP-A using antibodies to PAPP-A must be questioned. To determine the localization of the PAPP-A subunit, immunofluorescence was performed on normal placental tissues using proMBP absorbed anti-PAPP-A antibody. Furthermore, the expression of PAPP-A mRNA was investigated by in situ hybridization. RESULTS: Immunofluorescence staining with proMBP absorbed anti-PAPP-A antibody showed that PAPP-A is localized to placental septa, anchoring villi, and the syncytia of chorionic villi, whereas MBP is localized only to septa and anchoring villi. By in situ hybridization, PAPP-A mRNA is detected in placental X cells and syncytiotrophoblasts, but MBP mRNA is localized only to placental X cells. CONCLUSIONS: The presence of PAPP-A mRNA and PAPP-A subunit protein in placental X cells and syncytiotrophoblasts indicates that both X cells and syncytiotrophoblasts synthesize the PAPP-A subunit, whereas only X cells synthesize proMBP.

Blood Proteins↗

Speaking for the dead to protect the living: the role of the coroner in Ontario.

This paper describes the historical origins, modern-day operations and complexities of the Ontario coroners system. Both the Office of the Chief Coroner and Statistics Canada publish death statistics for the province of Ontario. The time required by the coroner's office to produce accurate cause-of-death data may significantly exceed the time constraints faced by Statistics Canada in producing its own annual cause-of-death statistics. As a result, substantial discrepancies arise in the number of deaths attributed to accidents, suicides and homicides that are published by these two agencies.

Cause of Death↗

Length of postexercise assessment in the determination of exercise-induced bronchospasm.

Exercise challenges were performed on 397 middle and high school athletes to detect unrecognized exercise-induced bronchospasm. All challenges were completed by a standard treadmill protocol and spirometry was performed prior to exercise and at 1, 10, 20, and 30 minutes after completion of the treadmill regimen. Using FEV1 as the diagnostic standard, we compared the number of students who had initial decreases of > or = 10%, > or = 15%, or > or = 20% at each of the four postexercise spirometric evaluations. FEV1 thresholds of > or = 10%, > or = 15%, and > or = 20%, when analyzed, identified 187, 125, and 90 subjects respectively with a positive response. The majority of those with a positive response were identified soon after completion of the exercise provocation; however, a larger than expected number of athletes had their initial drop in FEV1 > or = 20 minutes after cessation of exercise. This represented 9% to 14% of the total number of responders to exercise challenge. Protocols for evaluation of exercise-induced bronchospasm may need to be designed to include data points up to or beyond 30 minutes after exercise to avoid missing the late appearance of bronchospasm.

Adolescent↗

Prevalence and significance of acanthosis nigricans in an adult obese population.

BACKGROUND AND DESIGN: Acanthosis nigricans develops commonly in obese individuals, yet its prevalence and significance in an unselected adult obese population has not been determined. To address these issues, 34 patients enrolled in the Adult Obesity Clinic at Parkland Memorial Hospital (Dallas, Tex) were chosen at random and examined. RESULTS: Acanthosis nigricans was observed in fully 74% of patients; its prevalence correlated positively with severity of obesity. Black obese patients demonstrated a greater propensity for manifesting the cutaneous disorder than did white obese individuals. Patients with acanthosis nigricans exhibited fasting plasma insulin levels that were markedly higher than those of nonacanthotic cohorts. CONCLUSIONS: Obesity is a significant risk factor for the development of acanthosis nigricans. Conversely, acanthosis nigricans is a reliable cutaneous marker of hyperinsulinemia in obese individuals.

Acanthosis Nigricans↗

Fibrous myopathy from butorphanol injections.

We describe an unusual, and probably underrecognized manifestation of intramuscular narcotic abuse. Fibrous myopathy is a deforming, fibrous infiltration of the muscles used for injection over a prolonged period. It is usually associated with pentazocine or meperidine injections, and to our knowledge, this is the first report of butorphanol causing the entity.

Adult↗

Severe tick-bite fever in young children. A report of 3 cases.

Tick-bite fever in young children is usually a mild illness with few complications and no mortality. That it may assume a severe form is illustrated by the occurrence of 3 cases admitted to Johannesburg Hospital within 1 week in which 2 patients, 3 and 5 years old respectively, had severe involvement of the central nervous system with epileptiform fits and deep coma and loss of power of speech on recovering consciousness. The third patient, aged 5 years, developed an incipient haemorrhagic state as well as serious involvement of the central nervous system. The severe form of the disease in these patients appears to have been due to unusually virulent strains of Rickettsia conorii, probably acquired from dog ticks in their homes. All patients recovered on appropriate treatment. Two regained their normal speech after many weeks while the third patient's incipient haemorrhagic state rapidly resolved.

Child↗

[An uncommon syndrome: the trapped popliteal vein. Apropos of a case].

A case of trapped popliteal vein, an exceptional syndrome, is reported in which the clinical appearance was that of a deep phlebothrombosis, compression being detected on phlebographic images. The etiology (combined congenital malformation and acquired muscle hypertrophy in this case) was revealed during exploratory surgery, which also allowed treatment by excision of the compressing agent without any direct vascular gesture.

Adolescent↗

Comparative effects of diltiazem, propranolol, and placebo on exercise performance using radionuclide ventriculography in patients with symptomatic coronary artery disease: results of a double-blind, randomized, crossover study.

The effects of oral diltiazem (120 mg), propranolol (100 mg), and placebo on exercise performance and left ventricular function were compared before and during symptom-limited supine bicycle exercise by means of multigated radionuclide ventriculography in 12 patients with documented, symptomatic coronary artery disease; a double-blind, randomized crossover protocol was used. Diltiazem increased ejection fraction (EF) at submaximal exercise (+7.0 absolute percentage points, p less than 0.02) and maximal exercise (+8.1 percentage points, p less than 0.01). Exercise EF was increased by 13.6 percentage points (p less than 0.02) in patients with decreased ventricular function (resting EF less than 50%). Propranolol had no effect on exercise EF at any stage, even when patients with EF less than 50% were excluded. The increase in total exercise time was significant after diltiazem (+27%, p less than 0.01) but not after propranolol (+16%, p = NS). As expected, propranolol decreased both resting (-9 bpm, p less than 0.01) and exercise heart rates (-27 bpm, p less than 0.001), whereas diltiazem had no significant effect. Propranolol decreased resting diastolic blood pressure (-8 mm Hg, p less than 0.02), exercise systolic (-27 mm Hg, p less than 0.001) and diastolic (-9 mm Hg, p less than 0.01) blood pressures, and rest (p less than 0.01) and exercise (p less than 0.001) double product. Diltiazem decreased resting systolic blood pressure (-9 mm Hg, p less than 0.01) and both resting (-8 mm Hg, p less than 0.001) and exercise (-9 mm Hg, p less than 0.01) diastolic blood pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The interaction of tumor localizing porphyrins with collagen and elastin.

The interaction of a series of tumor localizing porphyrins with collagen and elastin was determined. All the porphyrins studied bound to both acid soluble and insoluble collagen, but to differing extents, as well as to elastin. The extent of binding to acid soluble collagen was greater than that to insoluble collagen. The major consequence of this association was a marked decrease in the solubility of the acid soluble collagen suggesting stabilization of the fibrillar structure of the collagen had occurred. Evidence was also obtained indicating the porphyrins could bind to collagen alpha-chains. The relevance of these findings to porphyrin localization is discussed.

Chemical Phenomena↗

Terbutaline and maternal cardiac function.

The effect of terbutaline sulfate on left ventricular size and performance was studied by M-mode echocardiography in pregnant women with premature labor. Patients with uterine activity initiated during either oxytocin challenge testing or induction of labor served as a comparison group. During terbutaline therapy, heart rate, ejection fraction, and cardiac output increased significantly. End-diastolic volume and systolic blood pressure (BP) were unchanged, and diastolic BP and end-systolic volume fell. No changes in echocardiographic or hemodynamic parameters were present during oxytocin-induced uterine activity. Terbutaline, as currently used to prevent premature labor, is a potent inotropic and chronotropic agent. Pulmonary edema accompanying terbutaline treatment is probably not due to cardiac failure.

Adolescent↗

The binding of tumor localizing porphyrins to a fibrin matrix and their effects following photoirradiation.

The binding of two tumor localizing porphyrins, meso-tetra (4-carboxyphenyl) porphine (TCPP) and meso-tetra (4-sulfonatophenyl) porphine (TPPS4) to fibrin clots was determined in vitro. Both TCPP and TPPS4 were found to bind extensively, although weakly, to fibrin. No appreciable binding by Hematoporphyrin IX to the fibrin matrix was detectable. Similar results were obtained whether the clot was non-crosslinked or crosslinked with factor XIII. Photoirradiation of a porphyrin-impregnated non-crosslinked clot rendered it urea insoluble. Electrophoretic analysis indicated that the alpha chain of the fibrinogen molecule was most affected by photoirradiation. This was manifested as a loss of the alpha chain intensity and a concomitant increase of high molecular weight components, suggesting the formation of crosslinks. No substantial differences were noted in susceptibility to plasmin lysis between photoirradiated and non-irradiated clots. Photoirradiated clots were, however, significantly more resistant to lysis induced by the plasminogen activators urokinase and streptokinase, suggesting that inactivation of plasminogen within the clot matrix had occurred during photoirradiation. The relevance of porphyrin binding to fibrin with regard to tumor localization and destruction is also discussed.

Binding Sites↗

The effect of tumor localizing porphyrins on the conversion of fibrinogen to fibrin.

The interaction of hematoporphyrin IX and two synthetic porphyrin tumor localizers, meso-tetra (4-carboxyphenyl) porphine (TCPP) and mesotetra (4-sulfonatophenyl) porphine (TPPS4) with fibrinogen was investigated in the presence and absence of light. Both TPPS4 and TCPP were found to bind to fibrinogen in greater than a 1/1 mole ratio in the absence of light. Chromatographic analysis indicated that during illumination TPP4 bound to fibrinogen to a greater extent that did either TCPP or hematoporphyrin. Both TCPP and TPPS4 were found to exhibit a greater inhibitory effect on clotting in the presence of light than did hematoporphyrin. In the absence of light and added Ca2+, both TCPP and TPPS4 were found to stimulate clotting at very specific porphyrin/fibrinogen concentration ratios, with TPPS4 being the more potent stimulator of the two. Hematoporphyrin exhibited little or no effect on clotting times. Fibrinogen, photoirradiated in the presence of the porphyrins was found to inhibit the clotting of unirradiated fibrinogen. A comparison of the stimulatory effects on clotting times by either calcium or TCPP and TPPS4 indicated that the porphyrins were capable of eliciting a greater stimulatory response than did calcium. The magnitude of the stimulatory response caused by the porphyrins alone was substantially reduced in the presence of calcium although the overall stimulatory response was increased but not additive. This suggests some interaction between either the calcium and porphyrin molecules or similarities in the respective stimulatory mechanism(s) involved. A possible correlation between these observations and the porphyrins ability to localize in tumors is also discussed.

Blood Coagulation↗