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Biomedical subjects

J J McCarthy

Publications and source records attributed to J J McCarthy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Segregation-driven organization in chaotic granular flows.

An important industrial problem that provides fascinating puzzles in pattern formation is the tendency for granular mixtures to de-mix or segregate. Small differences in either size or density lead to flow-induced segregation. Similar to fluids, noncohesive granular materials can display chaotic advection; when this happens chaos and segregation compete with each other, giving rise to a wealth of experimental outcomes. Segregated structures, obtained experimentally, display organization in the presence of disorder and are captured by a continuum flow model incorporating collisional diffusion and density-driven segregation. Under certain conditions, structures never settle into a steady shape. This may be the simplest experimental example of a system displaying competition between chaos and order.

Journal Article↗
PubMed1999

Segregated regulatory elements direct beta-myosin heavy chain expression in response to altered muscle activity.

Our previous transgenic analyses revealed that a 600-base pair beta-myosin heavy chain (betaMyHC) promoter conferred mechanical overload (MOV) and non-weight-bearing (NWB) responsiveness to a chloramphenicol acetyltransferase reporter gene. Whether the same DNA regulatory element(s) direct betaMyHC expression following MOV or NWB activity in vivo remains unknown. We now show that a 293-base pair betaMyHC promoter fused to chloramphenicol acetyltransferase (beta293) responds to MOV, but not NWB activity, indicating a segregation of these two diverse elements. Inclusion of the betaMyHC negative regulatory element (-332 to -300; betaNRE) within transgene beta350 repressed expression in all transgenic lines. Electrophoretic mobility shift assays showed highly enriched binding activity only in NWB soleus nuclear extracts that was specific to the distal region of the betaNRE sense strand (dbetaNRE-S; -332 to -311). Supershift electrophoretic mobility shift assay revealed that the binding at the distal region of the betaNRE sense strand was antigenically distinct from cellular nucleic acid-binding protein and Y-box-binding factor 1, two proteins shown to bind this element. Two-dimensional UV cross-linking and shift Southwestern blotting analyses detected two proteins (50 and 52 kDa) that bind to this element. These in vivo results demonstrate that segregated betaMyHC promoter elements transcriptionally regulate betaMyHC transgene expression in response to two diverse modes of neuromuscular activity.

Animals↗
PubMed1999

Surgery-associated factor VIII inhibitors in patients without hemophilia.

The acquisition of antibodies to factor VIII (ie, factor VIII protein) by patients without hemophilia is associated with conditions such as pregnancy, lymphoma, and autoimmune disorders. We present three patients who acquired factor VIII antibodies in the postoperative setting. Preoperatively, none gave a history of bleeding even with past surgeries and all had normal coagulation tests. Within days of surgery (bowel resection, cholecystectomy, coronary bypass), a bleeding diathesis emerged with prolonged partial thromboplastin time, decreased factor VIII levels, and demonstrable factor VIII antibodies. All patients required multiple blood transfusions and urgent reexploration for hemostatic control. All were treated with high dose human factor VIII infusions, corticosteroids, and various forms of immunosuppression. We wish to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, dramatic bleeding, subsequent persistence, but potential reversal by immunosuppression.

Aged↗
PubMed1999

Children's and parents' visual perception of physicians.

The purpose of this study is to evaluate the child's and parents' visual perception of physicians. To do this, 50 children and their parents were asked which physician they preferred, when shown eight pairs of photographs. Four characteristics were tested twice, white coat versus no white coat, smile versus stern face, cartoon posters versus no posters, and standing versus stooping. We found that both children and parents preferred the smiling physician and the physician with cartoon posters on the wall. Surprisingly 54% of children preferred the physician in the white coat, whereas only 35% of parents preferred the white coat. Sixty-eight percent of children also preferred the standing physician compared with only 41% of parents. There was little correlation between the parent's and child's answers. The results did not differ significantly with age, gender, or number of hospitalizations. In conclusion our study did not confirm the popular belief that children are afraid of physicians in white coats, although children did strongly prefer physicians who smiled and those with cartoon posters on the wall.

Adult↗
PubMed1997

beta-MHC transgene expression in suspended and mechanically overloaded/suspended soleus muscle of transgenic mice.

Non-weight-bearing (NWB) activity [space flight and hindlimb suspension (HS)] results in the loss of soleus muscle mass, a slow-to-fast fiber-type conversion, and decreased beta-myosin heavy chain (beta-MHC) protein and mRNA expression. To identify beta-MHC promoter sequences required for decreased beta-MHC expression in response to HS, we have modified an existing noninvasive hindlimb unweighting model to accommodate the use of (transgenic) mice. After 2 wk of HS, body and muscle (soleus > gastrocnemius > plantaris) weights were decreased as was the proportion of histochemically classified type I fibers in HS soleus muscle. Northern blot analysis revealed decreases in endogenous mRNA representing beta-MHC, slow myosin light chain 1 and 2, and cardiac/slow troponin C, whereas those representing skeletal troponin C, muscle creatine kinase, and glyceraldehyde-3-phosphate dehydrogenase increased. Protein extracts prepared from HS soleus (SS) muscle of mice harboring transgenes comprised of 5.6 or 0.6 kilobase of wild type (wt) mouse beta-MHC promoter (beta 5.6 wt, beta 0.6wt) and those carrying the simultaneous mutation (mut) of the MCAT, C-rich, and beta e3 subregions (beta 5.6mut3, beta 0.6mut3) revealed decreases in chloramphenicol acetyltransferase (CAT) specific activity relative to respective controls. Decreased CAT mRNA was observed for transgene beta 5.6mut3, line 85. Two weeks of the simultaneous imposition of mechanical overload (synergist ablation) and HS (MOV/HS) countermanded the loss in absolute and normalized SS weight but did not decrease beta 0.6wt transgene expression. These transgenic results demonstrate that regulatory sequences within a 600-base pair beta-MHC promoter are sufficient to direct decreased transcription of beta-MHC transgenes after 2 wk of HS.

Animals↗
PubMed1997

Outpatient evaluation of hematuria: locating the source of bleeding.

Hematuria can have many causes, ranging from minor to serious. Urinalysis can usually differentiate a renal from a urologic source of bleeding. Most often the cause is found to be in the lower urinary tract. In patients with normal renal function and no significant proteinuria, red blood cell casts, or dysmorphic red blood cells, a urologic workup is indicated. When hematuria is thought to be of renal origin and associated with proteinuria and hypertension, renal biopsy may help to pinpoint the diagnosis.

Age Factors↗
PubMed1996

Arthroscopic reduction and internal fixation of a displaced intraarticular lateral femoral condyle fracture of the knee.

Anatomic reduction, typically obtained by direct visualization through an arthrotomy and internal fixation (open reduction and internal fixation), is the traditional treatment method for displaced intraarticular condylar fractures of the distal femur. We present a case report describing an alternative treatment method, namely, arthroscopic reduction and internal fixation, of a displaced, malrotated intraarticular lateral femoral condyle fracture of the knee. The potential benefits of decreased blood loss, shortened operative time, excellent intraarticular visualization, decreased soft tissue dissection, and shortened postoperative recovery are outlined.

Adult↗
PubMed1996

Induction of beta-MHC transgene in overloaded skeletal muscle is not eliminated by mutation of conserved elements.

Mechanical overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in overloaded plantaris muscles of transgenic mice. Protein extract from mechanically overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by mechanical overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.

Animals↗
PubMed1996

Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice.

The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences that are required for mechanical overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by mechanical overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by mechanical overload in fast- and slow-twitch muscles.

Adenosine Triphosphatases↗
PubMed1996

Innominate osteotomy in adolescents and adults who have acetabular dysplasia.

The results were evaluated for twenty-eight adolescents and adults (thirty-one hips) who had had a Salter innominate osteotomy because of acetabular dysplasia and pain in the hip. The mean age at the time of the index operation was twenty-two years, and the mean duration of radiographic follow-up was seventy-one months. Radiographs were available for twenty-five patients (twenty-eight hips) at the most recent follow-up evaluation. The radiographic evaluation included determination of the acetabular angle, the center-edge angle, the coverage of the femoral head, the height of the joint space, and the Shenton line. Compared with the preoperative measurements, the acetabular angle had decreased by a mean of 10.0 degrees, the center-edge angle had increased by a mean of 13.2 degrees, and the coverage of the femoral head had increased by a mean of 15 per cent (p < 0.001 for all three values). The height of the joint space had decreased but, with the numbers available, this change was not significant. The Harris hip scores, determined for twenty patients (twenty-one hips), improved from a mean of 71.2 points preoperatively to a mean of 88.3 points at the latest follow-up evaluation (p < 0.001). A questionnaire, completed by twenty-seven patients (thirty hips), revealed that twenty-one patients (78 per cent) were satisfied with the result of the operation; twenty-two patients (81 per cent) said that they would recommend this procedure to others who had a similar condition. The pain score (with 1 point indicating mild pain and 5 points indicating severe pain) improved from a mean of 3.7 points preoperatively to a mean of 2.5 points at the latest follow-up evaluation (p < 0.001). There were six postoperative complications. One patient had a non-union; one, an infection; one, heterotopic bone; and three, numbness. Two of these patients subsequently had a total hip arthroplasty at ninety-eight and 150 months, and one patient had a Chiari osteotomy at twenty-two months. Our findings demonstrate that the Salter innominate osteotomy provides notable clinical improvement as well as improvements in the radiographic measurements of the hip in patients who have acetabular dysplasia.

Acetabulum↗
PubMed1995

Acute effects of amiodarone on membrane properties, refractoriness, and conduction in guinea pig papillary muscles.

Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 microM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (Vmax) of the fast action potential (i.e., [K]e = 5.4-9.0 mM) as well as that of the slow action potential (i.e., [K]e = 15.0 mM in the presence of 1.0 microM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]e-dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD90), disclosing post-repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug.

Action Potentials↗
PubMed1994

An instrument for the measurement of rapid reaction kinetics.

Two versions of an inexpensive mixing device capable of measuring reaction kinetics with millisecond resolution are described. The instruments deliver reactants via microsyringes controlled by nitrogen pressure at time intervals that are either mechanically or software controlled. In addition, an optical system for calibration of the time required to deliver the reactants as well as the intervals between syringe firing is given. Data illustrating the effect of variations in volume and syringe size on the accuracy and reproducibility of these time measurements as well as the volume of fluid delivered are presented. Examples of kinetic measurements of several reactions illustrating the capabilities of the instrument are also presented.

Enzymes↗
PubMed1994

Can heparin cause adult respiratory distress syndrome by a similar mechanism as heparin-associated thrombocytopenia?

A 62-year-old woman who underwent an aortic valve replacement for severe aortic valve stenosis developed postoperative thrombocytopenia and adult respiratory distress syndrome, simultaneously. Both complications resolved promptly after discontinuing heparin therapy. The presence of a heparin-related antiplatelet antibody was detected by in vitro testing. The time course of clinical events suggests the possibility of a heparin-induced, immune-mediated injury to both the pulmonary vascular endothelium and the platelet membrane as an underlying pathophysiologic mechanism.

Antibodies↗
PubMed1991

Identification of false positive exercise tests with use of electrocardiographic criteria: a possible role for atrial repolarization waves.

Atrial repolarization waves are opposite in direction to P waves, may have a magnitude of 100 to 200 mu V and may extend into the ST segment and T wave. It was postulated that exaggerated atrial repolarization waves during exercise could produce ST segment depression mimicking myocardial ischemia. The P waves, PR segments and ST segments were studied in leads II, III, aVF and V4 to V6 in 69 patients whose exercise electrocardiogram (ECG) suggested ischemia (100 mu V horizontal or 150 mu V upsloping ST depression 80 ms after the J point). All had a normal ECG at rest. The exercise test in 25 patients (52% male, mean age 53 years) was deemed false positive because of normal coronary arteriograms and left ventricular function (5 patients) or normal stress single photon emission computed tomographic thallium or gated blood pool scans (16 patients), or both (4 patients). Forty-four patients with a similar age and gender distribution, anginal chest pain and at least one coronary stenosis greater than or equal to 80% served as a true positive control group. The false positive group was characterized by 1) markedly downsloping PR segments at peak exercise, 2) longer exercise time and more rapid peak exercise heart rate than those of the true positive group, and 3) absence of exercise-induced chest pain. The false positive group also displayed significantly greater absolute P wave amplitudes at peak exercise and greater augmentation of P wave amplitude by exercise in all six ECG leads than were observed in the true positive group.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function↗