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Biomedical subjects

J G Davis

Publications and source records attributed to J G Davis.

At least 55 records · Page 3Linked to original sources

Expression of the neu proto-oncogene by Schwann cells during peripheral nerve development and Wallerian degeneration.

The neu gene, which encodes a putative tyrosine kinase growth factor receptor termed p185neu, was originally identified as a dominant transforming gene in neurogliomas and schwannomas induced by transplacental treatment of rat embryos with ethylnitrosourea. The present studies were undertaken to determine the expression pattern of the neu gene in peripheral nerve. Northern blot analysis of total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA expression on postnatal days 1 and 7, with substantially lower expression up to adulthood. Immunohistochemical studies confirmed expression of p185neu by Schwann cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in adult nerves. However, neu mRNA and p185neu protein progressively increased following sciatic nerve transection in adult animals. In addition, neu mRNA and p185neu were found in neonatal rat sciatic nerve SC and several SC-derived cell lines. In resting SC, neu mRNA was expressed at a low level, but was greatly increased by treatment with forskolin and glial growth factor. These studies demonstrate that the neu gene and its protein product, p185neu, are expressed by SC both in vivo and in vitro and suggest that p185neu plays a role in the regulation of SC proliferation or differentiation.

Animals↗

Neonatal alloimmune thrombocytopenia due to anti-HPA-5b (Br(a), Zav(a), Hca): the importance of third-generation platelet antibody detection techniques, a case report.

Investigation of the maternal serum in a case of suspected alloimmune neonatal thrombocytopenia by conventional, second-generation platelet serological assays (platelet radioactive antiglobulin test [PRAT], platelet suspension immunofluorescence test [PSIFT] and solid-phase adherence assay (SPAA, 'Capture-P') demonstrated only the presence of HLA class-I antibodies of limited specificities: no platelet-specific antibodies were detectable. The use of a third generation, glycoprotein capture assay (monoclonal antibody-specific immobilization of platelet antigens, MAIPA) revealed the additional presence of anti-HPA-5b with a titre of 1 in 32. Despite this relatively high titre, and the fact that it was able to induce a prolonged thrombocytopenia, this antibody was not detectable by conventional assays. In view of these findings we conclude that the use of MAIPA is essential when investigating cases of suspected alloimmune neonatal thrombocytopenia.

Abnormalities, Multiple↗

Fanconi anemia: a model for genetic causes of abnormal brain development.

Fanconi anemia is an autosomal recessive disease resulting in bone-marrow failure, phenotypical abnormalities and predisposition to malignancy. The authors reviewed 257 clinical and neuropathology results from the International Fanconi Anemia Registry at The Rockefeller University. Two patients had hydrocephalus and ventriculoperitoneal shunts. Of 15 neuropathology reports, 10 found CNS abnormalities, with the most common--ventriculomegaly--seen in six, two of whom required shunts. Aqueductal stenosis, agenesis of the corpus callosum and septum pellucidum, and holoprosencephaly were found. The authors conclude that neurological derangements are probably more common in Fanconi anemia than previously recognised. Fanconi anemia cells in culture are highly sensitive to oxidative stress and alkylating agents; Fanconi anemia may provide a model for a genetic disorder potentially predisposing to environmental insults.

Abnormalities, Multiple↗

Thrombocytopenia in malaria.

The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.

Adolescent↗

Characterization of a neu/c-erbB-2 protein-specific activating factor.

The neu oncogene encodes a tyrosine kinase with growth factor receptor-like properties. A neu protein-specific activating factor (NAF) was partially purified from medium conditioned by the transformed human T-cell line ATL-2. NAF was able to stimulate the tyrosine-specific kinase activity of the neu protein (p185neu), induce dimerization and internalization, and increase the growth of cells bearing the neu protein. The effects of NAF were mediated by an interaction with the p185neu extracellular domain. NAF had no effect on the epidermal growth factor receptor kinase activity and no effect on cells that express that receptor. Further analysis of NAF and of other recently described neu protein-activating activities should help clarify the role of the neu protein in cell growth and transformation.

Cell Division↗

Isolation and characterization of a neu protein-specific activating factor from human ATL-2 cell conditioned medium.

The rat neu gene product is a 185 kD membrane bound tyrosine kinase that is closely related to, yet distinct from the epidermal growth factor receptor. The biochemical and cellular effects of a neu protein-specific activating factor (NAF) detected in human ATL-2 cell conditioned medium were recently described (1). To further characterize NAF, some of its physicochemical properties were examined and a method for purifying this factor from ATL-2 cell conditioned medium was developed. In these studies NAF was found to be heat stable and sensitive to the protease chymotrypsin. In addition, a method for purifying this activity was developed using a quantifiable, in vitro autophosphorylation assay system to measure NAF activity in fractions following ion-exchange and then reverse-phase HPLC.

Cell Line↗

Marfan syndrome in adolescents and young adults: psychosocial functioning and knowledge.

Twenty-two subjects with Marfan syndrome (age range 11-24 years, mean 15.7 years) were studied to evaluate the impact of Marfan syndrome on their lives, level of psychosocial adaptation, concerns about their disorder, compliance with medical regimens, and knowledge of Marfan syndrome. Subjects were interviewed and then completed the Offer Self-Image Questionnaire and two questionnaires designed for the study. Parents also were interviewed. Subjects demonstrated normal psychosocial adaptation on the Offer Self-Image Questionnaire. Nevertheless, the subjects perceived that their lives would be significantly better without Marfan syndrome, especially in the areas of physical activities and self-image. They expressed concerns about their illness most often to their parents, less frequently to their doctors. Their compliance with medical regimens were suboptimal and similar to the published description of compliance among teenagers with other chronic illnesses. Their knowledge base was weakest in the areas pertaining to future childbearing. Thus, although these subjects showed normal psychosocial adaptation, doctors caring for them may foster better coping with Marfan syndrome by discussing self-image issues and Marfan syndrome-related concerns, and by encouraging compliance and imparting knowledge.

Activities of Daily Living↗

Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts.

The protein product of the rodent neu oncogene, p185neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c-erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c-neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c-neu. During efforts to characterize the interaction of p185c-neu with EGFR further, we created cell lines that simultaneously overexpress both p185c-neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.

Animals↗

A second case of neonatal alloimmune thrombocytopenia associated with anti-PlA2 (Zwb) antibodies.

A case of neonatal alloimmune thrombocytopenia due to fetomaternal incompatibility against the platelet specific antigen PlA2 (Zwb) is described. Anti-PlA2 antibodies were present in the maternal serum together with anti-HLA antibodies. Initial identification of the platelet-specific antibodies was achieved by using chloroquine-treated PlA1(+) and PlA1(-) platelets. Antibody specificity was later confirmed using a panel of platelets of known phenotype.

Adult↗

Human left main coronary artery blood flow: noninvasive Doppler echocardiography with sample volume tracking.

We developed sample volume tracking units that controlled the pulsed ultrasonic Doppler sample volume location in relation with the anterior-posterior movement of the human left main coronary artery (LMCA). Combined with noninvasive Doppler echocardiographic mechanical sector scanners (DS), the trackers controlled the axial location of the sample volume by range gate control. The Doppler angle was minimized with the long axis of the imaged LMCA. Both stored waveform, memory-driven (MD) and real-time (RT) trackers were developed. These devices were used to measure blood velocity spectral waveforms and lumen diameters, which were used to calculate flow. Using the RT tracker, we compared DS measurements with known flows (0-1000 ml/min) in a moving 4 mm tygon tubing phantom (r = 0.92, SEE = 32 ml/min). Using the MD tracker, we compared the DS with simultaneous invasive flow measurements in 11 patients with angiographically normal coronaries and ventricular function during cardiac catheterization. Using the RT tracker, we compared the DS measurements with subsequent nonsimultaneous, invasive flow data in 8 similar patients. Invasively determined flows were calculated from angiographic diameters and blood velocities which were obtained with a Doppler velocimeter catheter. Regression coefficients (r) were: (Table: see text). V = maximum velocity, D = diameter, Q = mean flow, *p less than .05 Interoperator and intraoperator variabilities in vivo of DS measurements with RT tracking were 21% and 15%, respectively. We conclude that Doppler echocardiography with either MD or RT sample volume tracking may be of limited clinical usefulness in the noninvasive measurement of phasic left main coronary artery blood flow in unselected patients.

Angiocardiography↗

Interstitial deletion of chromosome 2 (p23p25).

We report a patient with a de novo interstitial deletion of the short arm of chromosome 2 (p23p25). The patient had microcephaly with prominent forehead and occiput, narrow rectangular face, clinodactyly, failure to thrive, delayed psychomotor development, and seizures. Maternal serum alpha-fetoprotein was undetectable at 18 weeks of gestation. Heterozygosity at the red cell acid phosphatase locus (SRO-2p25) and normal levels of red cell malate dehydrogenase (SRO-2p23) are findings consistent with the presence of genetic material from bands 2p25 and 2p23.

Abnormalities, Multiple↗

Berry aneurysms, cirrhosis, pulmonary emphysema, and bilateral symmetrical cerebral calcifications: a new syndrome.

Familial idiopathic nonarteriosclerotic cerebral calcification (FINCC) constitutes a rare but pathologically well defined disorder. Thus far, central nervous system symptoms and signs have been the only recorded expression of this disease. Autosomal dominant and autosomal recessive inheritance have both been postulated as cause. We describe three sibs who had symmetrical cerebral calcifications, but three also had cirrhosis and pulmonary emphysema; two had congenital cerebral aneurysms. All were male and of short stature; they also had delayed development and seizures, and two had other neurologic deficits. One sib died at age 3 years of hepatic failure and portal hypertension. Ruptured cerebral aneurysms led to the death of the other two boys at ages 8 and 13 years. The cerebral calcifications symmetrically involved the basal ganglia and thalami, the dentate nucleus, and the cortical and subcortical areas of the cerebrum. The liver was studied by sequential biopsies in two of the children and in all three by autopsy. Fatty degeneration and portal fibrosis preceded a periportal and micronodular cirrhosis. Severe bilateral pulmonary emphysema was present in one sib at age 12 years, whereas all three had bullae and cysts at autopsy. Ruptured left middle cerebral artery aneurysms were demonstrated in two sibs, and one also had aneurysms of the anterior and posterior communicating arteries. We conclude that in this family FINCC is a complex pleiotropic mendelian mutation, either of autosomal or X-linked recessive nature, whose basic pathogenesis remains unknown but may involve a metabolic defect. This form of FINCC may be a previously undescribed syndrome or a form of FINCC in which extraneural manifestations were previously overlooked.

Adolescent↗

Pre-transfusion non-invasive quality assessment of stored platelet concentrates.

The Platelet Monitor System has been designed to assess routinely prepared platelet concentrates (P.C.) during storage. The system is based upon observations of changes in light transmission induced by platelets in intact packs. It is practical, provides constant gentle agitation for P.C., and non-invasively give continuous semi-quantitative evidence of the probable numbers of discoid platelets within each pack. The information yielded correlates both with established in vitro parameters of platelet behaviour, and with in vivo survival of platelets in normal healthy volunteers. The device safely provides the Blood Banker with the means to achieve on-going assessment of methods and improvements--or failings--in P.C. production. To the clinician it offers information throughout and even beyond present arbitrary storage limits, about which P.C. are likely to be of least or greatest value to a thrombocytopenic patient.

Adult↗

Rapid average-flow velocity measurement by NMR.

We describe an NMR method to make a quick determination of average fluid velocity by monitoring the change in phase of the magnetization during a transient signal. We give an example utilizing the second Carr-Purcell-Meiboom-Gill echo in which we measured the velocity of water up to 54 cm/s where each velocity was determined by data taken over 2.5 ms.

Humans↗

A new method for flow velocity measurement: frequency encoded NMR.

We demonstrate a new rapid NMR method to measure the average velocity and the velocity distribution of a flowing fluid. We use a truncated Carr-Purcel-Meiboom-Gill pulse sequence, pi/2-T-pi-2T-pi-T-echo, in the presence of a static magnetic field gradient. The pi/2 pulse is selective and tags a narrow slice of nuclei. The second echo from the tagged nuclei is Fourier transformed after the nuclei have evolved for a time 4T to give the velocity distribution modified by the initial slice selection profile. In this way, average velocities up to 54 cm/s were measured for water flowing in a plastic tube with either a plug or a developed velocity distribution. Each measurement required about 20 ms but this could be reduced with larger field gradients. Thus, this method is fast enough to apply to such problems as measuring pulsatile flow in arteries.

Animals↗

Use of the ultrasound aspiration transducer in midtrimester amniocentesis.

Midtrimester amniocentesis was performed on 2,100 consecutive patients over a four-year period. A specially designed ultrasonic aspiration transducer was used to guide the needle into the amniotic cavity under direct vision by following the path of the needle tip ultrasonically as it entered the fluid. This technique has made the aspiration of amniotic fluid relatively simple and safe. We obtained an adequate amount of amniotic fluid in 99.2% of the patients at their initial visits. The incidence of grossly bloody taps was 0.8%, and the total number of bloody amniotic fluid specimens was 2.37%. The rate of primary culture failure was 0.53%. The total fetal loss within eight weeks after amniocentesis was 0.9% as compared with 0.52% in a control population composed of pregnant women between 16 and 24 weeks of gestation. The estimated amniocentesis-related fetal loss was 0.38%.

Amniocentesis↗