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Biomedical subjects

J Kennedy

Publications and source records attributed to J Kennedy.

At least 19 recordsLinked to original sources
PubMed1992

Multiple dopamine D4 receptor variants in the human population.

The dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4 receptor. A 48-base-pair sequence in the putative third cytoplasmic loop of this receptor exists either as a direct-repeat sequence (D4.2), as a fourfold repeat (D4.4) or as a sevenfold repeat (D4.7). Two more variant alleles were detected in humans. Expression of the complementary DNA for the three cloned receptor variants showed different properties for the long form (D4.7) and the shorter forms (D4.2, D4.4) with respect to clozapine and spiperone binding. To our knowledge, this is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population. Such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.

Base Sequence↗
PubMed1992

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Aged↗
PubMed1992

Pancytopenia caused by unsuspected pernicious anemia complicating sickle cell beta-thalassemia.

We have described a a 23-year-old black woman with sickle cell beta-thalassemia who had a urinary tract infection and who was incidentally found to be pancytopenic. Although her anemia was categorized as "normocytic, normochromic" by an electronic particle counter, evaluation of the pancytopenia confirmed unsuspected pernicious anemia. Greater vigilance and a higher index of suspicion are crucial for early diagnosis of pernicious anemia in patients with other known hemoglobinopathies.

Adult↗
PubMed1992

Effects of pinealectomy on wool growth and wool follicle density in merino sheep.

There is evidence to indicate that pinealectomy may enhance wool growth in the sheep. The aim of this study was to determine the effect of pinealectomy on wool growth and wool follicle density in Merino sheep. Castrated Merino rams (4 months old) were either pinealectomized (P), sham-pinealectomized (S) or not treated (C). Wool growth on mid-side patches was measured every 4 weeks and follicle density was monitored in skin biopsies collected before treatment and at regular intervals for 60 weeks. Venous blood samples were taken on each of these occasions for prolactin analysis. Melatonin concentrations were determined in venous blood collected pre- and posttreatment from samples taken over a 24-hr period during the winter solstice. Pre- and posttreatment plasma melatonin levels (mean +/- SEM) 65 +/- 17 and < 13 pg/ml for P, 86 +/- 21 and 69 +/- 20 pg/ml for S, and 94 +/- 41 and 122 +/- 37 pg/ml for C, respectively, indicated that the pineal glands had been successfully removed. Wool growth, total follicle density and liveweight (mean +/- SEM) did not differ between treatment groups. Measurements at week 60 were 3.9 +/- 0.3, 4.1 +/- 0.2, and 3.8 +/- 0.3 gm clean wool/100 cm2; 66 +/- 6, 69 +/- 7, and 64 +/- 3 follicles/mm2; and 50.4 +/- 1.3, 50.8 +/- 1.4, and 52.6 +/- 1.1 kg liveweight for groups P, S, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moiré topographic analysis.

Qualitative visual inspection and manual muscle testing are traditional methods of evaluation that may overlook subtle weakness of the axioscapular musculature. A modification of the standard technique of Moiré topographic analysis of spinal deformity was applied to assess axioscapular muscle function in 51 subjects: 22 asymptomatic individuals, 22 with shoulder instability, and seven with impingement syndrome. Static Moiré evaluation demonstrated scapulothoracic asymmetry or increased topography in 14% of asymptomatic subjects, compared with 32% and 57% in the instability and impingement groups, respectively. The dynamic Moiré test demonstrated an abnormal Moiré pattern in 18% of asymptomatic individuals, compared with 64% and 100% in the instability and impingement groups, respectively. Axioscapular muscle dysfunction is common with both instability and impingement syndrome of the shoulder, although it remains to be determined whether this represents a primary or secondary phenomenon.

Adult↗
PubMed1991

Tests of EEG localization accuracy using implanted sources in the human brain.

The accuracy with which electrical sources in the brain can be localized by using electroencephalograms measured on the scalp is not well known. In this study, tests of localization accuracy were performed by using implanted dipolar sources in the human brain. These dipoles are created by passing a weak (subthreshold) current through intracerebral electrodes implanted in the brains of epileptic patients for seizure monitoring. The locations of these dipoles are accurately known from roentgenographs. First, 16 electroencephalograms produced by these dipoles were recorded, then inverse solutions were calculated for the apparent sources of these electroencephalograms. Finally, the locations of the apparent sources were compared with the known locations of the implanted dipoles to determine localization error. The average localization error for a total of 28 dipoles in 3 subjects was 1.1 cm. These results indicate that good localization accuracy for focal sources in the brain can be provided by scalp electroencephalograms.

Brain↗
PubMed1991

A rapid visual test for predicting fetal lung maturity.

A rapid bedside test has been devised that enables an untrained observer to predict (p less than 0.001) when amniotic fluid will be greater than or equal to 0.15 at an optical density of 650 nm, lecithin/sphingomyelin ratio will be greater than or equal to 2.0, or when phosphatidylglycerol will be present. By a visual comparison of the turbidity of unspun amniotic fluid against positive (mature) or negative (immature) controls, technicians and resident physicians who had had no special training were able to classify correctly 87.2% (82/94) of unknown amniotic fluid samples. The sensitivity of the new test is 90.8% (58/65); the specificity is 70.3% (23/29). Thus, when more sophisticated methods are not readily available, we believe that this easily performed and accurate test can provide supplemental or preliminary data for patient management. In remote geographic areas our method could serve as the primary source of information about fetal lung maturity.

Amniotic Fluid↗
PubMed1991

Long term use of neuroleptics by schizophrenic patients.

1. Use of antipsychotic medications by schizophrenic patients. 2. Side effects of typical neuroleptics. 3. Dosage strategies for treating schizophrenia. Evidence that high dosage treatment and rapid neuroleptization concepts should be abandoned. 4. Minimal effective dosage in maintenance treatment. Studies attempting to define this regimen. 5. Blood levels of antipsychotics and their clinical relevance. 6. New research strategies, focusing on a) case definition, b) target symptoms, c) clinically stable patients, d) dosage reduction studies.

Antipsychotic Agents↗
PubMed1991

Stimulation of frog ciliated cells in culture by acetylcholine and substance P.

1. Ciliary beat frequency in epithelial outgrowths from cultured explants of Rana pipiens palate changed markedly from second to second. 2. Acetylcholine (10(-8) to 10(-3) M) and substance P (1.35 x 10(-7) to 1.35 x 10(-5) M) increased and stabilized ciliary beat frequency. The effect of acetylcholine and part of the effect of substance P were blocked by atropine (10(-4) M). 3. Acetylcholine appears to act directly and substance P both directly and indirectly through the release of acetylcholine.

Acetylcholine↗
PubMed1991

Long term results of cyclophosphamide, adriamycin and platinum chemotherapy in advanced epithelial ovarian cancer.

Between January 1980 and December 1983, 57 consecutive patients with advanced epithelial ovarian cancer (FIGO Stage IIc n = 5; III n = 45; IV n = 7) were treated with 6 cycles of cyclophosphamide 600 mg/m2, adriamycin 30-45 mg/m2 and platinum 50 mg/m2 (CAP) at 3 weekly intervals. Pathological complete remission (CR) was documented in 10 (18%) and 4 with no residual disease after primary cytoreductive surgery were free from progression (FFP). There were 19 partial remissions (PR) giving a 51% overall response rate. The median duration of CR was 33 months from second look surgery. Median survival (MS) for all patients was 22 months. Multivariate analysis indicated that response to chemotherapy was the most important prognostic factor, with MS for CR of 53 months, PR 23 months and stable or progressive disease 11 months (p = 0.001). Most CR (8 of 10) occurred in patients with minimal residual disease (no single lesion greater than 2.0 cm), but extent of disease, though significant in univariate analysis of prognostic factors was not an independent predictor of survival. Six patients (11%) are alive and tumour free with a minimum follow-up of 7 years. All had FIGO Stage III disease at presentation and four had no residual tumour after primary surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

Adolescent↗
PubMed1990

Actin and myosin isoforms in aneural and malformed chick hearts.

Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiovascular system, by removing various regions of the neural crest from early embryos. The neural crest provides both neural (sympathetic and parasympathetic) and ectomesenchymal components to the heart, and selective removal of various areas results in embryos with sympathetically aneural hearts, or persistent truncus arteriosus with or without parasympathetic denervation. Myosin isoform expression was studied in each of these types of hearts using an array of myosin antibodies specific for atrium, ventricle or the conduction system. Myosin expression in experimental hearts was found to follow the normal pattern of development using these antibodies. Actin expression was studied using cDNA probes for the 3' untranslated region of actin mRNA of the alpha-skeletal, alpha-cardiac and beta-actin isoforms. Using slot-blot hybridization analysis, the pattern of actin expression in atrium and ventricle was followed throughout the period of incubation in normal hearts. The pattern of actin expression was found to be abnormal in hearts which were sympathetically aneural and those which had persistent truncus arteriosus combined with parasympathetic denervation. ATPase activity was increased only in atria of hearts with persistent truncus arteriosus. It appears from these experiments that actin isoform expression is influenced in the chick heart by autonomic innervation.

Actins↗
PubMed1990

The chest radiograph in acute bronchiolitis.

The relationship between clinical severity, as judged by a clinical scoring method, and the degree of radiological change on a chest X-ray, was assessed in 153 children with acute bronchiolitis. There was no statistical correlation between clinical severity and the degree of radiological change. The majority of radiographs were requested on the assumption that it was a useful routine investigation. We suggest that the request for a chest X-ray in acute bronchiolitis should be made only when the need for intensive care is being considered, where there has been an unexpected deterioration in the child's condition or the child has an underlying cardiac or pulmonary disorder.

Acute Disease↗
PubMed1990

Risk factors in progression beyond stage 2 retinopathy of prematurity.

Of the 96 babies born at less than 30 weeks gestation at Westmead Hospital between January 1986 and December 1987, 91 were studied. Of these 37 developed some form of retinopathy of prematurity (ROP), with eight babies having stage 3 or worse. We compared the clinical features of these eight babies to a control group of eight babies with stage 2 ROP, having matched for gestational age. Factors of statistical significance in progression beyond stage 2 were male sex and number of days of assisted ventilation. The presence of a patent ductus arteriosus, although not statistically significant, is a factor which we consider to be clinically important. The development of Plus disease is associated with a poor prognosis.

Australia↗