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Biomedical subjects

C Goodman

Publications and source records attributed to C Goodman.

At least 19 recordsLinked to original sources

Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila.

Mutations in the dachsous gene of Drosophila lead to striking defects in the morphogenesis of the thorax, legs, and wings. The dachsous gene has been cloned and shown to encode a huge transmembrane protein that is a member of the cadherin superfamily, similar to the fat gene reported previously. Both the Dachsous and Fat proteins contain large tandem arrays of cadherin domains--27 and 34, respectively--as compared with 4 cadherin domains in classic vertebrate cadherins. In addition, Dachsous and Fat each has a cytoplasmic domain with sequence similarity to the cytoplasmic beta-catenin-binding domain of classic vertebrate cadherins. The dachsous gene is expressed in the ectoderm of embryos, whereas its expression in larvae is restricted to imaginal discs and specific regions of the brain. The phenotypes of, and genetic interactions between dachsous and fat are consistent with a model in which cell proliferation and morphogenesis of imaginal structures depends on the coupled equilibria between homo- and heterophilic interactions of the Dachsous and Fat cadherin proteins.

Alleles

The haematological, biochemical and immunological profile of athletes suffering from the overtraining syndrome.

To help clarify the overtraining syndrome (OTS), a combination of parameters were measured in ten athletes who were suffering from OTS. Blood samples were obtained at rest and a range of haematological, biochemical and immunological tests were carried out on the samples. For each parameter, the mean value for the group was compared to an established normal range amongst age-matched controls. The subjects were also asked to complete a questionnaire to establish the severity of their condition. The data indicated that the debilitating fatigue experienced by the OTS sufferers was not related to any of the blood parameters traditionally associated with chronic exercise stress, since levels were normal in OTS. The only parameter measured which deviated significantly from the normal range for both the sedentary controls and the athletes was the plasma concentration of glutamine. Although the data in this study would suggest that plasma glutamine concentrations represented an objective, measurable difference between OTS subjects and normal controls, it remains to be shown that there is any correlation between glutamine concentrations and other clinical symptoms of OTS such as physical capability.

Adult

Systemic CD56+ cells can predict pregnancy outcome.

PROBLEM: To evaluate differences in circulating CD56+ cells between successful and unsuccessful pregnancies, 114 pregnant women were studied prospectively. METHOD: Seventy women had a history of infertility (INF) and 44 had two or more previous spontaneous abortions (RSA). Among the infertile women, 12 were donor egg recipients (DER) and 15 underwent intracytoplasmic sperm injection (ICSI) for treatment of male factor infertility. Nineteen women were carrying multiple gestations (MG) and 55 had singleton gestations (SG). Thirteen additional women were receiving intravenous immunoglobulin (IVIg). RESULTS: The percentage of CD56+ cells was determined in 310 blood samples from 114 pregnant women by flow cytometry. The prevalence of women with persistent elevation of percent of 56+ cells (> 12%) was 58% among DER, 73% among ICSI, 37% among MG, 22% among SG, 18% among RSA, and 39% among INF. Thirteen women with SG received IVIG, 10 had CD56+ cells greater than 12% and all 13 experienced live births. Women with percentage CD56+ cells persistently greater than 12% who were not DER, not ICSI, not receiving IVIg, and not carrying MG had a live birth rate of 11%. Women with greater than 12% CD56+ cells had normal karyotype in 78% of concepti studied in contrast to women less than 12% CD56+ cells who had 68% abnormal karyotypes (P = 0.04). CONCLUSION: Elevated CD56+ cells in pregnant women who are not DER, not ICSI, not receiving IVIg, and not carrying MG predicts loss of a karyotypically normal conceptus with a specificity of 87% and positive predictive value of 78%. While the specificity value of this test is high in both infertile and RSA populations, the sensitivity is 86% in RSA and only 54% in INF suggesting this test does not identify all losses among INF. It may identify a subset of pregnancies at risk for loss of a karyotypically normal embryo that may respond to treatment with IVIg.

Abortion, Habitual

Comparison of maximal oxygen consumption with oral and nasal breathing.

The major cause of exercise-induced asthma (EIA) is thought to be the drying and cooling of the airways during the 'conditioning' of the inspired air. Nasal breathing increases the respiratory system's ability to warm and humidity the inspired air compared to oral breathing and reduces the drying and cooling effects of the increased ventilation during exercise. This will reduce the severity of EIA provoked by a given intensity and duration of exercise. The purpose of the study was to determine the exercise intensity (%VO2 max) at which healthy subjects, free from respiratory disease, could perform while breathing through the nose-only and to compare this with mouth-only and mouth plus nose breathing. Twenty subjects (11 males and 9 females) ranging from 18-55 years acted as subjects in this study. They were all non-smokers and non-asthmatic. At the time of the study, all subjects were involved in regular physical activity and were classified, by a physician, as free from nasal polyps or other nasal obstruction. The percentage decrease in maximal ventilation with nose-only breathing compare to mouth and mouth plus nose breathing was three times the percentage decrease in maximal oxygen consumption. The pattern of nose-only breathing at maximal work showed a small reduction in tidal volume and large reduction in breathing frequency. Nasal breathing resulted in a reduction in FEO2 and an increase in FECO2. While breathing through the nose-only, all subjects could attain a work intensity great enough to produce an aerobic training effect (based on heart rate and percentage of VO2 max).

Adolescent

Effects of oral creatine loading on single and repeated maximal short sprints.

This investigation determined whether oral creatine (Cr) loading could enhance single and repeated short sprint performance. A 1 x 10 s cycle sprint (Study One) and 6 x 6 s (departing every 30 s) repeated cycle sprints (Study two) were the performance tests used. Separate groups of subjects, randomly assigned to either a Cr or placebo (P) group, were used in each study in a double blind design. After performing a familiarization and two baseline tests subjects loaded with 5g of Cr or P four times per day for five days before repeating the tests one and three days post-loading. In Study One (n = 9 in each group), work completed (kJ) at 2, 4, 6, 8 and 10 s and peak power (W) were greater than baseline values in each of the post-loading trials in both the Cr and P groups. There were no between group performance differences. In Study Two (n = 11 in each group) after loading, the Cr group recorded significantly greater scores than the P group in total work (kJ) completed over the 6 sprints, work completed in sprint 1, and peak power (W). Post-exercise blood lactate and pH responses were not different between the Cr and P groups after loading in either study. Although Study One results are equivocal, Study Two results suggest that Cr supplementation can enhance both single (if sprint 1 results are considered in isolation) and repeated short sprint performance.

Administration, Oral

Y-intercept of the maximal work-duration relationship and anaerobic capacity in cyclists.

The degree to which the y-intercept (Y-int) of the linear regression of maximal work output on exercise duration represented anaerobic capacity was determined in ten well-trained male cyclists [peak oxygen uptake (VO2peak) = 69.8 (SD 4.2) ml.kg-1.min-1]. Each cyclist performed three exhausting cycle sessions on separate occasions; the mean exercise durations were 312, 243 and 141 s for the low (approximately 104% VO2peak), medium (approximately 108% VO2peak) and high (approximately 113% VO2peak) intensities respectively, and Y-int (kilojoules; joules per kilogram) was derived from the regression of work output on exercise duration. The muscle anaerobic adenosine 5'-triphosphate (ATP) yield (sigma ATP) and anaerobic capacity (AC) were estimated from changes in metabolites in the vastus lateralis muscle and blood lactate concentration during the high intensity cycling session. The activities of glycogen phosphorylase, phosphofructokinase and citrate synthase, as well as muscle buffer value (in vitro beta) were also determined. The Y-int (kilojoules) was positively correlated (P < or = 0.05) with AC (r = 0.73), sigma ATP (r = 0.70) and in vitro beta (r = 0.71); similar correlations (P < or = 0.05) were observed for Y-int (joules per kilogram). The Y-int was not correlated (P > 0.05) with any enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Prompting the clinical care of non-insulin dependent (type II) diabetic patients in an inner city area: one model of community care.

OBJECTIVE: To evaluate the effectiveness and acceptability of centrally organised prompting for coordinating community care of non-insulin dependent diabetic patients. DESIGN: Randomised single centre trial. Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic (controls). Median follow up two years. SETTING: Two hospital outpatient clinics, 38 general practices, and 11 optometrists in the catchment area of a district general hospital in Islington. PATIENTS: 181 patients attending hospital outpatient clinics. NULL HYPOTHESIS: There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care. RESULTS: 14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group (chi 2 = 6.1, df = 1; p = 0.013). Follow up for retinal screening was better in prompted patients than in controls; two prompted patients defaulted as against 12 controls (chi 2 = 6.9, df = 1; p = 0.008). Three measures per patient yearly were more frequent in prompted patients: tests for albuminuria (median 3.0 v 2.3; p = 0.03), plasma glucose estimations (3.1 v 2.5; p = 0.003), and glycated haemoglobin estimations (2.4 v 0.9; p < 0.001). Continuity of care was better in the prompted group (3.2 v 2.2 reviews by each doctor seen; p < 0.001). The study ended with no significant differences between the groups in last recorded random plasma glucose concentration, glycated haemoglobin value, numbers admitted to hospital for a diabetes related reason, and number of deaths. Questionnaires revealed a high level of patient, general practitioner, and optometrist satisfaction. CONCLUSIONS: Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable.

Ambulatory Care

Services for persons with dementia and their families: a survey of information and referral agencies in Michigan.

In planning a statewide Dementia Program, Michigan agencies (N = 244) providing geriatric information and referral (I&R) were surveyed to determine service availability, families' needs, and problems providing I&R for persons with dementia and their families. Home-delivered meals, nursing and social work assessments were considered more available. Medical assessment, however, was considered "very available" by only 60%. Respite and adult day care were least available and most needed. Least was known about autopsy and financial services. For several services, non-urban areas reported less availability than urban areas. With additional information and training, existing agencies could provide more available and extensive I&R for persons with dementia and their families, forming a statewide network.

Data Collection

It's time to rethink health care technology assessment.

Health care technology assessment is broadly and ambiguously interpreted, diluting its role. It is time to recast the field. We must elucidate it in the contemporary context of health inquiry, explicitly relating it to such pursuits as quality assurance, health services research, effectiveness research, medical informatics, and technological innovation.

Health Policy

Muscle creatine kinase isoenzyme expression in adult human brain.

Previous studies have suggested that MM creatine kinase is a muscle-specific protein and is not present in adult brain tissue. We have isolated a protein from human brain with an apparent molecular weight of 43,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis which is identical to the muscle M creatine kinase isoenzyme subunit at all 30 sequenced amino acid residues and possesses creatine kinase enzymatic activity following nondenaturing agarose-gel electrophoresis. Immunohistochemistry localizes M creatine kinase to discrete areas of adult human brain. Northern blot analysis of both total and poly(A)-selected RNA isolated from brain did not detect M creatine kinase mRNA. However, polymerase chain reaction amplification of cDNA synthesized from human placenta, heart, and brain mRNA detected M creatine kinase message in both heart and brain but not placenta which contains no detectable M creatine kinase protein. N1E115 and NS20Y, mouse neuroblastoma cell lines which have been used as models of neural cell differentiation, were found also to express MM creatine kinase. Moreover, a transiently transfected reporter gene with 4,800 base pairs of M creatine kinase upstream region fused to chloramphenicol acetyltransferase was expressed during differentiation of these neural cell lines. In summary, MM creatine kinase is present in human brain and we suggest the M creatine kinase upstream region is sufficient to modulate M creatine kinase expression in certain neuronal cells and may be regulated independently from other muscle genes.

Adult

Evaluation of a model self-help telephone program: impact on natural networks.

A study of a model telephone network program for caregivers of Alzheimer's disease victims considered its impact on caregivers' use of informal supports as well as perceived social supports, mental health, burden, and information about Alzheimer's disease. Participants were randomly assigned to a peer telephone network or an informational lecture series accessed over the telephone, and then they were reassigned to the alternative component after three months. Time series analysis of variance group-by-time interactions showed that participants learned more while listening to informational tapes and contacted family and friends more while waiting to enter a peer network. Program benefits seen after the first three months (reduced psychological distress, increased support satisfaction, and perceived social support) leveled off or declined during the second three months. Additionally, caregiver burden and social conflict increased during the second three months. This erosion of benefits suggests that program entry may be the period of maximum program receptivity or that overload of family networks created conflict.

Alzheimer Disease

Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease.

We transplanted autologous adrenal medullary tissue into the caudate nucleus of 3 patients with advanced Parkinson's disease. The 1st patient, a 59-year-old man with parkinsonian symptoms for 15 years, had mild improvement in his motor functioning after the operation. However, his postoperative course was characterized by prolonged drowsiness and complex visual hallucinations. The patient died suddenly 8 months after the transplant, and an autopsy revealed coronary atherosclerosis. Examination of the graft site showed necrotic adrenal medullary tissue surrounded by inflammatory cells. The 2nd patient, a 50-year-old man with a 21-year history of parkinsonian symptoms, improved the most after the procedure. The 3rd patient, a 43-year-old man with 12 years of parkinsonian symptoms, had mild improvement in his motor functioning. CSF homovanillic acid increased postoperatively in the 3 patients, but then returned to preoperative levels in all except the 2nd patient. The anatomic, neurochemical, and physiologic basis for the modest clinical improvement shown in these patients is not yet understood.

Activities of Daily Living

Burns after spinal cord injury.

The problem of burns after spinal cord injury is described. Chart review was performed on thirty-five known cases. All burns occurred below the level of the lesion (p less than .001). Causes included bathing and showering, food and beverage, and therapeutic and environmental heating devices. We conclude that spinal cord injured patients should be educated about the risk of burn injury and the situations in which burns can occur.

Adolescent

Effects of angiotensin converting enzyme inhibition and beta-blockade on exercise responses in hypertensive patients.

We compared exercise responses in two groups of hypertensive patients treated with an angiotensin converting enzyme (ACE) inhibitor (lisinopril, 20-80 mg/day, n = 17) or a cardioselective beta-blocker (atenolol, 50-200 mg/day, n = 9). Measurements were made at rest and during exercise at 25 W (2.7 mets) and at 50 W (3.8 mets) on a bicycle ergometer (where mets is exercising oxygen consumption/resting oxygen consumption) after 4 weeks of placebo, and again after 12 weeks of drug administration. Both drugs reduced (P less than 0.05) mean arterial pressure. Atenolol caused significant decreases in the heart rate (approximately 25%) and cardiac output (approximately 26%; Defares CO2 rebreathing), and significant increases in total peripheral resistance (approximately 30%) and arteriovenous O2 content (approximately 20%). Lisinopril decreased (P less than 0.05) stroke volume. At the same exercise intensity systolic blood pressure, arteriovenous O2 and total peripheral resistance were lower (P less than 0.05) and the heart rate was higher (P less than 0.05) after lisinopril than after atenolol. After the treatment of hypertension with the ACE inhibitor the responses to exercise were less restrictive than those after treatment with the cardioselective beta-blocker.

Atenolol

polyhomeotic: a gene required for the embryonic development of axon pathways in the central nervous system of Drosophila.

Hypomorphic alleles of the locus polyhomeotic (ph) produce multiple, homeotic-like transformations in adult flies that mimic dominant mutations in the Antennapedia and Bithorax complexes. Analysis of null alleles of ph has revealed a complex, embryonically lethal phenotype that includes cell death of the ventral epidermis and abnormalities in the patterns of expression of homeotic and segmentation genes. There is also a dramatic alteration in the pattern of axon pathways in the central nervous system, such that the wild-type array of segmentally repeated commissures and connectives is replaced by bundles of axons confined to the hemiganglia of origin. It is possible that this axonal phenotype is the result of loss of neuronal identity caused by abnormal homeotic and segmentation gene expression.

Animals

Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise.

This study was undertaken to gain insight into the mechanisms responsible for the hypoferremia occurring after severe exercise. To this end, 18 athletes who were competing in a 160-km triathlon involving canoeing, cycling, and running were evaluated before the race, immediately after the finish, and thereafter at 30 min, 24 h, and 48 h. The evaluation included plasma iron, total iron-binding capacity, lactoferrin, ferritin, haptoglobin, cortisol, various enzymes, and white cell count. The cortisol, white cell count, and lactoferrin were significantly increased immediately after the race, while the plasma iron and transferrin saturation were significantly decreased. There was a 40% but nonsignificant rise in the plasma ferritin at the completion of the race, while the C-reactive protein was raised by nearly 300% at 24 h. In contrast, haptoglobin declined significantly by 24 h but was normal again 24 h later. Quantitative considerations suggested that the lactoferrin was not responsible for removing transferrin iron from circulation and hence causing the hypoferremia. Instead, it seemed more likely that the iron-related changes were occurring as part of an acute phase response initiated by muscle injury.

Acute-Phase Proteins

Labeling in vivo of serotonin uptake sites in rat brain after administration of [3H]cyanoimipramine.

The properties of sites in rat brain labeled in vivo after administration of [3H]cyanoimipramine ([3H]CN-IMI) have been studied. The radioactivity in hypothalamus and cortex 20 min to 2 hr after [3H]CN-IMI administration was reduced in rats pretreated with chlorimipramine (10 mg/kg) 5 min before [3H]CN-IMI. No effect of chlorimipramine pretreatment was seen in the cerebellum; levels of radioactivity in this tissue were subtracted from total levels in hypothalamus and cortex to define specific binding. This represented approximately 50 and 30% of total binding in hypothalamus and cortex, respectively. Specific binding in hypothalamus and cortex was reduced by a number of drugs which are potent blockers of serotonin uptake and the binding was inhibited in a stereoselective manner by the stereoisomers of norzimelidine. In contrast, pretreatment with drugs which are weak inhibitors of serotonin uptake had no effect on specific binding. Experiments using increasing doses of [3H]CN-IMI showed that the binding in vivo was saturable. Lesioning rats with the serotonin neurotoxin 5,7-dihydroxytryptamine resulted in an 80% decrease in the specific binding in hypothalamus and a 35% decrease in cortex. The potencies of drugs to inhibit the specific binding of [3H]CN-IMI in vivo were highly correlated with their previously published potencies for inhibiting serotonin uptake in human blood platelets in vitro and for preventing the serotonin depletion induced by 4-methyl-alpha-ethyl-metatyramine in vivo. These results indicate that [3H]CN-IMI can be given to rats to provide a measure of serotonin uptake sites in the central nervous system in vivo.

5,7-Dihydroxytryptamine