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Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 163 records · Page 9Linked to original sources

Human glandular Kallikrein genes: genetic and physical mapping of the KLK1 locus using a highly polymorphic microsatellite PCR marker.

We describe a highly polymorphic microsatellite repeat sequence, KLK1 AC, which is located 3' to the human glandular kallikrein gene (KLK1) at 19q13.3-13.4. A multiplex PCR was developed to simultaneously genotype the KLK1 AC repeat length polymorphism and a similar repeat at the adjacent APOC2 locus at 19q13.2. Genotypes from these two loci in the 40 large kindred pedigrees from the Centre d'Etude du Polymorphisme Humain were used in conjunction with the background genetic map to establish a multipoint linkage map. The KLK1 locus was also localized physically using somatic cell hybrid DNA templates for polymerase chain reaction analysis. Both genetic and physical mapping studies are consistent with the assignment cen-APOC2-KLK1-D19522-qter. The linkage map places KLK1 approximately 10 cM distal to APOC2. These markers therefore flank the myotonic dystrophy gene and may be useful for diagnosis.

Alleles↗

NADH measurements in adult rat myocytes during simulated ischemia.

In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content, and contractile performance in single cells under several conditions analogous to myocardial ischemia, with and without reperfusion. Myocytes were paced at 1 Hz while cell contraction and NADH fluorescence were determined simultaneously for single cells at 37 degrees C. Cells were exposed to cyanide and 2-deoxy-D-glucose (metabolic inhibition) or to metabolic inhibition plus 12 mM KCl and 20 mM lactate at pH 6.5 (simulated ischemia). Pyridine nucleotide fluorescence signals from single cells studied in this fashion could be modulated by metabolic inhibitors in a manner similar to that classically described for isolated mitochondria. Metabolic inhibition or simulated ischemia quickly produced maximal reduction of NAD+ to NADH. When cells were exposed to simulated ischemia for 10 min, then superfused with glucose-containing control buffer, 28% of cells exposed to conditions of simulated ischemia developed hypercontracture on reperfusion. Hypercontracture developed despite mitochondrial electron transport being reestablished. When myocyte suspensions in a cuvette were studied spectrofluorimetrically, the pyridine nucleotide fluorescence response to metabolic inhibitors was similar to that for a single cell. This permitted correlation of ATP determinations on cells in suspension with contractile and fluorescence measurements from single myocytes. In the absence of glycolysis there is correspondence among loss of electron transport, decline in high-energy phosphate concentration, and decline in contraction. Irreversible disruption of the electron transport process does not appear to be an early event in ischemic injury.

Adenine Nucleotides↗

Coliform septicemia and pulmonary disease associated with canine parvoviral enteritis: 88 cases (1987-1988).

Parvovirus infection was confirmed by fluorescent antibody staining or viral culturing in 137 (22%) of 615 necropsy accessions from dogs at the Missouri Veterinary Medical Diagnostic Laboratory from Jan 1, 1987 through Sept 30, 1988. Septicemic colibacillosis was diagnosed in 88 (90%) of the 98 canine parvovirus-positive accessions in which liver or lung was cultured bacteriologically. Pulmonary edema or alveolitis similar to that seen in the human adult respiratory distress syndrome was observed in 63 (69%) of the 91 canine parvovirus-positive accessions in which the lungs were examined histologically.

Animals↗

Norepinephrine in acute exacerbations of chronic schizophrenia. Negative symptoms revisited.

In recent years the dopamine hypothesis has failed to explain the complexities of schizophrenia. Because both negative symptoms and noradrenergic activity appear to increase with psychotic relapse, we studied negative symptoms, psychosis, cerebrospinal fluid norepinephrine, and cerebrospinal fluid monoamine metabolites in 32 male patients with a DSM-III diagnosis of schizophrenia while both receiving and not receiving long-term haloperidol treatment. Drug-free cerebrospinal fluid norepinephrine and 3-methoxy-4-hydroxyphenylglycol levels correlated significantly with the severity of negative symptoms and psychosis ratings. When the patients were divided into those who did and did not relapse while not receiving the drug, significant positive correlations between negative symptoms and cerebrospinal fluid norepinephrine and 3-methoxy-4-hydroxyphenylglycol were observed only in the patients who relapsed. Non significant but negative correlations were observed between the same variables in the nonrelapsers. Thus, increased norepinephrine activity in drug-free patients is associated with intensification of schizophrenic symptoms without necessarily causing the symptoms.

Acute Disease↗

Metastatic neuroblastoma: new abnormalities on bone scintigraphy may not indicate tumour recurrence.

Neuroblastoma is a potentially curable childhood malignancy with survival rates of 20% reported even in advanced disease. Technetium-labelled methylene diphosphonate (Tc99m-MDP) scanning is well established as a method of assessing bone disease. We report four patients, with advanced neuroblastoma in complete or partial remission, in whom new abnormalities on bone scintigraphy were due to benign lesions. Correct management depends on the precise diagnosis of such lesions.

Bone Diseases↗

The initial effects on workload and outcome of a public education campaign on early diagnosis and treatment of malignant melanoma in Leicestershire.

We report our experience of the initial effects of a publicity campaign directed at early presentation of malignant melanoma in Leicestershire. The campaign resulted in a dramatic increase in workload and, at the pigmented lesion clinic, the numbers of new patients rose from 12.3 to 54.5 per clinic. There was a large rise in the number of new melanomas presenting in Leicestershire: from 1.02 per week before the campaign to 1.88 per week in the immediate post-publicity period. This was statistically significant (P less than 0.001). Although there was also an apparently encouraging rise in the percentage of thinner 'good prognosis' tumours, it was not possible to isolate this statistically from a pre-existing trend.

Dermatology↗

Cerebral blood flow velocity recordings and the prediction of intracranial haemorrhage and ischaemia.

Doppler ultrasound was used to study prospectively cerebral and cardiovascular hemodynamics in a cohort of 120 preterm infants to see whether it was possible to predict infants at increased risk of developing cerebral pathology. The infants were divided into four outcome groups: Group I (n = 65, median gestation = 30 weeks) did not develop periventricular haemorrhage (PVH) nor periventricular leukomalacia (PVL) Group II (n = 43, median gestation = 28 weeks) developed PVH as the first or only cerebral lesion Group III (n = 7, median gestation = 29 weeks) developed PVL as the first or only cerebral lesion Group IV (n = 5, median gestation = 28 weeks) developed PVH and PVL simultaneously. Cerebral blood flow velocity (CBFV) and aorta blood flow velocity (ABFV) recordings made before the onset of PVH or PVL were compared between the four groups on each postnatal day but it was not possible to demonstrate a statistically significant difference between these variables in the four outcome groups. We conclude, therefore, that it is not possible to identify the infants who will go on to develop haemorrhage or ischaemic lesions on the basis of Doppler cerebral haemodynamic studies.

Aorta↗

[Pathogenesis and treatment of Zencker's diverticulum].

The aims of this study were: 1) To measure pharyngeal and upper oesophageal function manometrically at the same time as recording video images of the patient swallowing barium, in normal controls and patients with Zenker's diverticulum, and, 2) In those patients who progressed to surgery to biopsy the cricopharyngeus and compare the findings with biopsies from normal controls. Subjects were seated in front of a fluoroscope and video images of a barium swallow were synchronised with a multichannel recording catheter which contained 3 perfused side holes 1 cm apart (situated in the pharynx) and a 4 cm long perfused sleeve pressure sensor (positioned across the upper oesophageal sphincter). The coordination of the upper sphincter with swallowing, its relaxation, the pressures generated in the distal pharynx and the maximum luminal area of the open upper sphincter, were calculated for different volumes of barium swallowed in 11 patients with a Zenker's diverticulum (mean age 71 years, range 50-99) and 9 normal controls (mean age 65 years, range 55-86). Seven patients progressed to cricopharyngeal myotomy and their biopsies were compared with biopsies from 9 normal controls. In patients with Zenker's diverticulum intrapharyngeal pressures during barium swallows were significantly greater (p less than .05) and maximal luminal areas of the open sphincter were significantly less (p less than .05) than in control patients. In patients having a cricopharyngeal myotomy, intrapharyngeal pressures and maximum luminal areas returned to normal after surgery. The cricopharyngeus muscle of patients with a Zenker's diverticulum showed significantly increased fibrosis compared with normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Efficacy of zinc citrate ascorbate for treatment of canine cataracts.

Efficacy of zinc citrate ascorbate was evaluated in 146 dogs (265 eyes) that had various lens opacities. Zinc citrate ascorbate or saline placebo drops were applied topically once or twice daily for 4 to 31 weeks. Of 138 eyes treated with zinc citrate ascorbate, 86 eyes (62.3%) had no change, 48 eyes (34.8%) had increased lens opacity, and 4 eyes (2.9%) had decreased lens opacity. Of 127 eyes treated with a saline placebo, 99 eyes (77.9%) had no change, 25 eyes (19.7%) had increased lens opacity, and 3 eyes (2.4%) had decreased lens opacity. Zinc citrate ascorbate drops were not significantly (P = less than 0.05) more effective in clearing cataracts than were saline drops. Seemingly, zinc citrate ascorbate drops may have caused lens opacities to increase in area and density.

Animals↗

The fidelity of response by 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene in time-resolved fluorescence anisotropy measurements on lipid vesicles. Effects of unsaturation, headgroup and cholesterol on orientational order and reorientational dynamics.

Time-resolved fluorescence anisotropy measurements on 1-[4-(tri-methylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) molecules in lipid vesicles of palmitoyloleoylphosphatidylcholine (POPC), PC extracted from egg yolk (EggPC), dioleoyl-PC (DOPC), dilinoleoyl-PC (DLPC), phosphatidylglycerol extracted from egg yolk (EggPG), dioleoyl-PG (DOPG), sulfoquinovosyldiacylglycerol (SQDG) and digalactosyl-DG (DGDG) with and without cholesterol are presented. The observed intensity decay curves are analyzed simultaneously in terms of the Brownian rotational diffusion model. The analysis thus yields the isotropic fluorescence decay, the initial anisotropy r (0), the order parameters mean value of P2 and mean value of P4 as well as the diffusion coefficient of the long molecular axis. It is shown that increasing unsaturation in the acyl chains of the PC lipids results in an increase in the rotational diffusion rates of the probes and a decrease in the order parameter mean value of P2. However, the value of mean value of P4 remains unchanged. The corresponding orientational distribution function of the probes is bimodal, with fractions lying preferentially parallel and perpendicular to the local vesicle surface. Surprisingly, the fraction of probe molecules lying with their long axes parallel to the bilayer surface increases with increasing unsaturation with a concomitant narrowing in the width of the distribution of the fraction lying perpendicular to it. As expected, cholesterol is found to increase the order parameters in all the systems and to suppress the tendency of the molecules to lie parallel to the bilayer surface. Furthermore, the rotational diffusion coefficients of the probes is found to increase in all the systems except for DLPC. Interestingly, the effects of unsaturation on the reorientational dynamics of TMA-DPH molecules in the vesicle systems are opposite to those found in the corresponding planar multibilayers (Deinum et al. 1988), whereas the same cholesterol effect is observed for the two systems. Nevertheless, the TMA-DPH molecules exhibit higher diffusion coefficients in the vesicle than in the planar multibilayer systems. In addition, a unimodal distribution of the probe molecules is found in the multibilayer systems. The differences between the two systems are ascribed to the differences in the radius of curvature and the hydration of the bilayers. Lastly we rationalize the bimodal distribution of the TMA-DPH molecules in the vesicles in terms of their observed partition between the lipid and aqueous phases.

Cholesterol↗

Computerized tomography appearances of pelvic haemangioma involving the large bowel in childhood.

The Computed Tomography (CT) appearance of a pelvic haemangioma involving the rectum in two children, one with the Vater association and one with Klippel-Trenaunay syndrome, is described. Both cases complained of painless rectal bleeding and the diagnosis was suggested by the presence of pelvic phleboliths on the plain abdominal radiograph. CT provides a simple, non-invasive method of diagnosing such lesions and assessing their extent.

Child↗

Florid radiological appearance of megakaryoblastic leukaemia--an aid to earlier diagnosis.

Accurate diagnosis of leukaemia is essential to enable appropriate treatment. The diagnosis is made by cytological and cytochemical techniques but radiology may, however, serve a very useful role in first suggesting a diagnosis. We present here four cases of megakaryoblastic leukaemia (AML FAB classification M7), three of which have strikingly similar unusual radiological changes. A review of the literature suggests this condition has previously been diagnosed as acute or malignant myelofibrosis, and the megakaryoblastic nature of the disease was not recognised. The presence of these radiological features may therefore prompt specific immunocytochemical testing, in a disease that is otherwise difficult to diagnose early.

Bone and Bones↗

Ventilatory compensation for changes in posture after human heart-lung transplantation.

We have studied the contribution of vagal pulmonary receptors to the stability of breathing during postural changes in humans. Quiet breathing was quantified in the seated and the supine postures in 10 patients with chronic pulmonary denervation due to heart-lung transplantation and 10 age and sex matched normal controls. In the vast majority of patients and normal subjects frequency histograms for tidal volume and mean inspiratory flow rate were virtually superimposed seated and supine. There were no significant differences in the mean levels of respiratory variables between postures in either group (except for mean inspiratory flow rate in the patients which was slightly greater seated than supine). Experiments performed on a tilt table in two additional patients showed that the ventilatory response to postural changes was immediate. In addition, the response was maintained after blockade of intact tracheal stretch receptors with aerosolized lidocaine. These results indicate that adequate ventilatory compensation during postural changes does not depend on vagal afferent information arising in intrapulmonary or tracheal airway stretch receptors. The appropriate receptors may be diaphragmatic Golgi tendon organs.

Adolescent↗

Inability of oral bovine transfer factor to eradicate cryptosporidial infection in a patient with congenital dysgammaglobulinemia.

A 31-year-old man with dysgammaglobulinemia Type I (deficient IgG, IgA, and elevated IgM) and persistent cryptosporidiosis was treated over a 13-week period with oral bovine transfer factor from calves immunized with cryptosporidia. Spiramycin was added toward the end of the treatment period. This patient failed to show clinical response although there was a decrease in the stool oocyst count from the value just prior to therapy. Bovine transfer factor alone and in combination with spiramycin failed to eradicate the infection in this man with well-documented stable cryptosporidiosis.

Administration, Oral↗

Isolation, partial sequence and asynchronous appearance during lactation of lysozyme and alpha-lactalbumin in the milk of a marsupial, the common ringtail possum (Pseudocheirus peregrinus).

1. Lysozyme and alpha-lactalbumin from the milk of the common ringtail possum have been purified and partially sequenced. 2. The lysozyme had similar enzymic activity to the c-type lysozyme of the domestic hen and 43% homology over the N-terminal 49 residues. 3. alpha-Lactalbumin was present in the milk in two biologically active forms; the more acidic form had 66% sequence homology with the N-terminal 35 residues of red-necked wallaby, 54% with human and 43% with bovine alpha-lactalbumin. 4. SDS polyacrylamide-gel electrophoresis of milk samples showed that alpha-lactalbumin was present in the milk throughout lactation but that lysozyme first appeared only in mid-lactation. The implications of this functional adaptation are discussed.

Amino Acid Sequence↗