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Biomedical subjects

K McCabe

Publications and source records attributed to K McCabe.

At least 19 recordsLinked to original sources
PubMed2001

A functional imaging study of cooperation in two-person reciprocal exchange.

Cooperation between individuals requires the ability to infer each other's mental states to form shared expectations over mutual gains and make cooperative choices that realize these gains. From evidence that the ability for mental state attribution involves the use of prefrontal cortex, we hypothesize that this area is involved in integrating theory-of-mind processing with cooperative actions. We report data from a functional MRI experiment designed to test this hypothesis. Subjects in a scanner played standard two-person "trust and reciprocity" games with both human and computer counterparts for cash rewards. Behavioral data shows that seven subjects consistently attempted cooperation with their human counterpart. Within this group prefrontal regions are more active when subjects are playing a human than when they are playing a computer following a fixed (and known) probabilistic strategy. Within the group of five noncooperators, there are no significant differences in prefrontal activation between computer and human conditions.

Adaptation, Physiological↗
PubMed2000

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Adjuvants, Immunologic↗
PubMed2000

L-Pipecolic acid oxidase, a human enzyme essential for the degradation of L-pipecolic acid, is most similar to the monomeric sarcosine oxidases.

L-Pipecolic acid oxidase activity is deficient in patients with peroxisome biogenesis disorders (PBDs). Because its role, if any, in these disorders is unknown, we cloned the associated human gene and expressed its protein product. The cDNA was cloned with the use of a reverse genetics approach based on the amino acid sequence obtained from purified L-pipecolic acid oxidase from monkey. The complete cDNA, obtained by conventional library screening and 5' rapid amplification of cDNA ends, encompassed an open reading frame of 1170 bases, translating to a 390-residue protein. The translated protein terminated with the sequence AHL, a peroxisomal targeting signal 1. Indirect immunofluorescence studies showed that the protein product was expressed in human fibroblasts in a punctate pattern that co-localized with the peroxisomal enzyme catalase. A BLAST search with the amino acid sequence showed 31% identity and 53% similarity with Bacillus sp. NS-129 monomeric sarcosine oxidase, as well as similarity to all sarcosine oxidases and dehydrogenases. No similarity was found to the peroxisomal D-amino acid oxidases. The recombinant enzyme oxidized both L-pipecolic acid and sarcosine. However, PBD patients who lack the enzyme activity accumulate only L-pipecolic acid, suggesting that in humans in vivo, this enzyme is involved mainly in the degradation of L-pipecolic acid.

Amino Acid Sequence↗
PubMed2000

The human L-pipecolic acid oxidase is similar to bacterial monomeric sarcosine oxidases rather than D-amino acid oxidases.

L-Pipecolic acid oxidase activity is deficient in patients with peroxisome biogenesis disorders (PBDs). Because its role, if any, in these disorders is unknown, the authors cloned the human gene to order to further study its functions. BLAST search of the translated sequence showed greatest homology to Bacillus sp. NS-129 monomeric sarcosine oxidase. The purified enzyme could use either L-pipecolic acid or sarcosine as a substrate. No homology was found to the peroxisomal D-amino acid oxidases. A further comparison of L-pipecolic acid oxidase to the two D-amino acid oxidases in peroxisomes showed that the proteins differed in many ways. First, both D-amino acid oxidase and L-pipecolic acid oxidase showed no enzyme activity in liver from Zellweger syndrome patients; D-aspartate oxidase activity was unchanged from control levels. Although all were targeted to peroxisomes, their targeting signals differed. No L-pipecolic acid oxidase was found in brain or other tissues outside of liver and kidney. The D-amino acid oxidases were similarly and more widely distributed. Finally, although D-amino acid degradation is limited to peroxisomes in mammals, L-pipecolic acid can be oxidized in either mitochondria or peroxisomes, or both.

Bacillus↗
PubMed1999

Are decisions under risk malleable?

Human decision making under risk and uncertainty may depend on individual involvement in the outcome-generating process. Expected utility theory is silent on this issue. Prospect theory in its current form offers little, if any, prediction of how or why involvement in a process should matter, although it may offer ex post interpretations of empirical findings. Well-known findings in psychology demonstrate that when subjects exercise more involvement or choice in lottery procedures, they value their lottery tickets more highly. This often is interpreted as an "illusion of control," meaning that when subjects are more involved in a lottery, they may believe they are more likely to win, perhaps because they perceive that they have more control over the outcome. Our experimental design eliminates several possible alternative explanations for the results of previous studies in an experiment that varies the degree and type of involvement in lottery procedures. We find that in treatments with more involvement subjects on average place less rather than more value on their lottery tickets. One possible explanation for this is that involvement interacts with loss aversion by causing subjects to weigh losses more heavily than they would otherwise. One implication of our study is that involvement, either independently or in interaction with myopic loss aversion, may help explain the extreme risk aversion of bond investors.

Behavior↗
PubMed1999

Driver distance from the steering wheel: perception and objective measurement.

OBJECTIVES: This study assessed the accuracy of driver perceptions of the distance between the driver's nose and the steering wheel of the vehicle as a factor in considering driver disconnection of an airbag contained in the steering wheel for preventing injury to the driver in an accident. METHODS: A cross-sectional survey of 1000 drivers was done to obtain perceived and objective measurements of the distance between the driver's nose and the steering wheel of the vehicle. RESULTS: Of 234 drivers who believed that they sat within 12 inches of the steering wheel, only 8 (3%) actually did so, whereas of 658 drivers who did not believe that they sat within 12 inches of the wheel, 14 (2%) did so. Shorter drivers were more likely than taller ones to both underestimate and overestimate their seating distance. CONCLUSIONS: Considerable misperception of drivers' distance from the wheel indicates that drivers should objectively measure this distance.

Adolescent↗
PubMed1999

TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible.

The objective of this study was to investigate the incidence of overexpression of TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit mandibles with high-dose external-beam radiation. As part of a protocol investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New Zealand-White rabbits underwent mandibular radiation treatments with a total dose of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation, leaving 90 animals at risk for tumor development. These animals were divided into one control group and 12 other groups each treated with different schedules of postirradiation hyperbaric oxygen. All animals were sacrificed after the hyperbaric oxygen treatment, approximately 8 months after completion of irradiation. Seventeen of the 90 animals that survived after irradiation developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected a 59% overall incidence of TP53 overexpression. There was no correlation between the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The high incidence and short interval of development of osteosarcoma suggest that the study animals may have had a genetic predisposition to radiation-induced osteosarcoma. Additionally, our data provide further evidence that TP53 mutations may play an important role in radiation-induced osteosarcoma.

Animals↗
PubMed1998

Prostate rebiopsy is a poor surrogate of treatment efficacy in localized prostate cancer.

PURPOSE: Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk. MATERIALS AND METHODS: A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status. RESULTS: Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy. CONCLUSIONS: This series demonstrates that the risk of a false-negative sextant biopsy in the presence of documented prostate cancer is high and is affected by several factors, including PSA and hormonal status. These data suggest that prostate sextant rebiopsy is an inaccurate method of assessing the therapeutic efficacy of treatments for carcinoma of the prostate in which the gland remains in situ following therapy.

Adenocarcinoma↗
PubMed1998

D-lactate production and [14C]succinic acid uptake by adherent and nonadherent Escherichia coli.

Escherichia coli isolates of different adherence phenotypes produced different amounts of D-lactate. Alterations of culture conditions did not influence the amount of D-lactate produced. The observed pH decreases in tissue culture medium corresponded with increases in D-lactate concentration. Very little [14C]succinic acid was incorporated into cells during the in vitro incubation of adherent and nonadherent E. coli with HeLa cells, but the amounts of tracer removed from the culture medium by adherent and nonadherent strains differed. The results are further evidence of a difference in the metabolic behavior of adherent and nonadherent E. coli.

Bacterial Adhesion↗
PubMed1996

Growth factors in the treatment of degenerative retinal disorders.

There are currently a number of degenerative conditions, both inherited and acquired, that affect the retina and lead to blindness. Retinal photoreceptors degenerate from inherited conditions, such as retinitis pigmentosa or as a result of light damage or normal ageing; retinal ganglion cells degenerate from optic nerve injury or glaucoma. Current research in this field includes the use of growth factors to: (1) inhibit the degenerative processes; (2) promote regeneration of the retina from the pigmented epithelium; and (3) improve the conditions for transplantation of new cells to the retina by expanding the photoreceptor cell populations in vitro. The results to date have shown that a number of different growth factors promote survival of retinal cells in vitro and in vivo. In addition, some of the same factors can stimulate regeneration in the developing retina and act as mitogens for the retinal progenitor cells. It is likely that a combination of these approaches will ultimately be important for the treatment of the various retinal degenerations.

Animals↗
PubMed1991

Flurbiprofen-associated acute tubulointerstitial nephritis.

We report a case of biopsy-proven acute tubulointerstitial nephritis associated with a second course of flurbiprofen, a nonsteroidal anti-inflammatory drug of the propionic acid class. The clinical presentation and course was consistent with acute tubulointerstitial nephritis due to these agents.

Adult↗
PubMed1987

Guaifenesin alone or in combination with ketamine or sodium pentobarbital as an anesthetic in rabbits.

Guaifenesin was administered alone and in combination with ketamine or sodium pentobarbital to adult New Zealand white rabbits. A solution of 5% guaifenesin in 5% dextrose given intravenously at a dosage of 200 mg/kg, abolished the pedal, palpebral and corneal reflexes for up to 15 minutes with little influence on cardiopulmonary function. Guaifenesin (200 mg/kg, intravenously) and ketamine (50 mg/kg, intramuscularly) produced effective and safe surgical anesthesia for over 30 minutes. This combination mildly depressed respiratory rate but heart rate and arterial blood pressure were not significantly affected. Guaifenesin (200 mg/kg, intravenously) was combined with sodium pentobarbital (20 mg/kg, intravenously) to produce surgical anesthesia for a period of more than 30 minutes. This combination depressed respiratory rate, produced a tachycardia and decreased arterial blood pressure.

Anesthesia, Intravenous↗
PubMed1986

Anesthesia in the Richardson's ground squirrel: comparison of ketamine, ketamine and xylazine, droperidol and fentanyl, and sodium pentobarbital.

A combination of ketamine and xylazine (88.9 mg of ketamine/ml and 11.1 mg of xylazine/ml) given IM (85.5 +/- 3.4 mg of ketamine/kg of body weight and 10.6 +/- 0.5 mg of xylazine/kg) or subcutaneously (85.6 +/- 4.0 mg of ketamine/kg and 10.7 +/- 0.7 mg of xylazine/kg) induced effective surgical anesthesia for 20 to 30 minutes in Richardson's ground squirrels. Use of ketamine alone (86 +/- 7 mg/kg, IM), a droperidol and fentanyl combination (2.6 +/- 0.4 mg of droperidol/kg and 52 +/- 8 micrograms of fentanyl/kg, IM), or sodium pentobarbital (50 +/- 2 mg/kg, intraperitoneally) did not induce surgical anesthesia, but did induce depressed respiratory rates in the squirrels.

Anesthesia↗
PubMed1984

A controlled trial of treatment of acquired immunodeficiency in severe measles with thymic humoral factor.

A randomized controlled trial of treatment with thymic humoral factor (THF) in 20 children with severe complicated acute measles infection, resulted in objective benefit as evidenced by improvement in the ESR and a fall in C-reactive protein, fewer complications and a reduced incidence of secondary herpes infection. An increased ratio of helper to suppressor T cells (OKT4/OKT8 ratio) and a greater lymphocyte transformation response to phytohaemagglutin was seen in those children receiving THF. We conclude that THF treatment helps to prevent the development of complications particularly secondary viral infections possibly by enhancing cell-mediated immune responses.

Child, Preschool↗