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Biomedical subjects

T White

Publications and source records attributed to T White.

At least 19 recordsLinked to original sources
PubMed1995

The signal modulator protein 14-3-3 is a target of sphingosine- or N,N-dimethylsphingosine-dependent kinase in 3T3(A31) cells.

Phosphorylation of a 28 kDa protein in 3T3(A31) cells upon addition of semi-purified kinase was induced only by sphingosine (Sph) or N,N-dimethylsphingosine (DMS), but not by 17 other lipids tested. The 28 kDa protein, a major target of Sph- or DMS-dependent kinase, is now identified as 14-3-3 protein, which modulates a number of key protein kinases involved in regulation of intracellular signaling (Aitken A, Trends Biochem Sci 20:95-97, 1995; Morrison D, Science 266:56-57, 1994). Thus, Sph and DMS modulate the function of a versatile modulator controlling a number of signaling molecules.

14-3-3 Proteins↗
PubMed1995

Purification and cDNA cloning of a human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase.

A UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase (GalNAc-transferase) from human placenta was purified to apparent homogeneity using a synthetic acceptor peptide as affinity ligand. The purified GalNAc-transferase migrated as a single band with an approximate molecular weight of 52,000 by reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based on a partial amino acid sequence, the cDNA encoding the transferase was cloned and sequenced from a cDNA library of a human cancer cell line. The cDNA sequence has a 571-amino acid coding region indicating a protein of 64.7 kDa with a type II domain structure. The deduced protein sequence showed significant similarity to a recently cloned bovine polypeptide GalNAc-transferase (Homa, F.L., Hollanders, T., Lehman, D.J., Thomsen, D.R., and Elhammer, A.P. (1993) J. Biol. Chem. 268, 12609-12616). A polymerase chain reaction construct was expressed in insect cells using a baculovirus vector. Northern analysis of eight human tissues differed clearly from that of the bovine GalNAc-transferase. Polymerase chain reaction cloning and sequencing of the human version of the bovine transferase are presented, and 98% similarity at the amino acid level was found. The data suggest that the purified human GalNAc-transferase is a novel member of a family of polypeptide GalNAc-transferases, and a nomenclature GalNAc-T1 and GalNAc-T2 is introduced to distinguish the members.

Amino Acid Sequence↗
PubMed1995

UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Identification and separation of two distinct transferase activities.

Using a defined acceptor substrate peptide as an affinity chromatography ligand we have developed a purification scheme for a unique human polypeptide, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) (White, T., Bennett, E.P., Takio, K., Sørensen, T., Bonding, N., and Clausen, H. (1995) J. Biol. Chem. 270, 24156-24165). Here we report detailed studies of the acceptor substrate specificity of GalNAc-transferase purified by this scheme as well as the Gal-NAc-transferase activity, which, upon repeated affinity chromatography, evaded purification by this affinity ligand. Using a panel of acceptor peptides, a qualitative difference in specificity between these separated transferase activities in four rat organs and two human organs also revealed qualitative differences in specificity. The results support the existence of multiple Gal-NAc-transferase activities and suggest that these are differentially expressed in different organs. As the number of GalNAc-transferases existing is unknown, as is the specificity of the until now cloned and expressed GalNAc-transferases (T1 and T2), it is as yet impossible to relate the results obtained to specific enzyme proteins. The identification of acceptor peptides that can be used to discriminate GalNAc-transferase activities is an important step toward understanding the molecular basis of GalNAc O-linked glycosylation in cells and organs and in pathological conditions.

Amino Acid Sequence↗
PubMed1995

Familial aggregation of adolescent personality disorders.

OBJECTIVE: A family study of DSM-III-R personality disorders was conducted in the families of 66 clinically referred adolescents to examine the validity of personality disorder diagnoses in adolescents. METHOD: Semistructured interviews of Axis I and II disorders, including the Structured Clinical Interview for DSM-III-R Personality Disorders, were used to directly interview 66 clinically referred adolescents and their adult first-degree family members, combining family study and family history data. RESULTS: The relatives of adolescents with avoidant personality disorder had an increased prevalence of avoidant and cluster A (schizoid, schizotypal, and paranoid) personality disorders. The relatives of adolescents with borderline personality disorder demonstrated increased rates of borderline and avoidant personality disorders, even after adjusting for comorbidity. CONCLUSIONS: The results of this study support the validity of Axis II diagnoses, particularly avoidant and borderline disorders, in adolescents.

Adolescent↗
PubMed1992

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.

ABO Blood-Group System↗
PubMed1992

Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils.

Human neutrophil protein kinase C (PKC) activity is inhibited by an endogenous protein found primarily in the pellet fraction from homogenized specific granules, which was both heat- and proteinase-sensitive [Balazovich, Smolen & Boxer (1986) J. Immunol. 137, 1665-1673]. We now report that two PKC isoenzymes and the endogenous PKC inhibitor, which we named PKC-I, were purified from human neutrophils. A neutrophil soluble fraction that was subjected to DEAE-Sephacel chromatography yielded highly enriched PKC because, by definition, enzymic activity was strictly dependent on Ca2+ and phosphatidylserine. Hydroxyapatite chromatography resolved two peaks of PKC activity. Type II and Type III PKC isoenzymes were each identified on Western blots by using isoenzyme-specific monoclonal antibodies. Unlike rat brain, from which PKC isoenzymes were also purified, Type I PKC was not detected in human neutrophils. Western blots indicated that both Type II and Type III PKC isoenzymes had molecular masses near 80 kDa. In agreement with other reports, PKC was autophosphorylated in vitro. PKC-I, an endogenous neutrophil inhibitor of PKC, was purified to apparent homogeneity by DEAE-Sephacel and S-400 Sephacel chromatography. PKC-I had a molecular mass of 41 kDa. PKC-I inhibited purified PKC activity stimulated by 1,2-diacylglycerols in a concentration-dependent manner, and inhibited PKC-dependent phosphorylation of proteins present in neutrophil cytosol.

Animals↗
PubMed1992

Screening and confirmation of drugs in urine: interference of hordenine with the immunoassays and thin layer chromatography methods.

Hordenine cross-reacted with various enzyme linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) kits used for the screening of urine samples. Morphine-ELISA kit was most sensitive, whereas etorphine- and buprenorphine-ELISA kits were least sensitive to hordenine cross-reactivity. Hordenine also interfered with the thin layer chromatography of oxymorphone, hydromorphone and apomorphine. The major source of hordenine in humans is beer brewed from barley, whereas the major source of hordenine in horses is canary grass or barley. Therefore, the presence of hordenine in the urine of humans consuming beer or in the urine of horses consuming canary grass may give false positive values when the immunoassay and TLC methods are used for the screening of the urine sample. In order to distinguish hordenine from the opiate drugs, simple and sensitive gas chromatographic/mass spectrometric (GC/MS) and high performance liquid chromatographic (HPLC) methods have been developed in this study.

Alkaloids↗
PubMed1992

A computerized method for measurement and analysis of blood pressure in small animals.

A method is described for computerized measurement of blood pressure (BP) in small animals. As described, the system measures BP in up to four experimental animals at one time by sequential sampling but can be expanded to take data from up to 10. It requires an Apple II computer, and is run from a Grass pen-recording system. Pulse rate and systolic and diastolic BP are measured, and these variables are used to calculate mean arterial pressure (MAP) and the time integral of MAP minute by minute. The data are displayed in real time and stored hourly on floppy disc for further analysis.

Animals↗
PubMed1992

Sub-syndromes of tardive dyskinesia and some clinical correlates.

Syndromes of dyskinetic movements in subjects (N = 70) with chronic schizophrenia were investigated, using principal components analysis of AIMS ratings. Consonant with previous research, three discrete groupings were found, namely dyskinetic movements of lips-jaw-tongue, limb-truncal and facial movements. These were then related to demographic, psychological and movement disorder variables. The limb-truncal, but neither the lips-jaw-tongue nor facial movements components, were associated with negative symptoms and cognitive impairment.

Aged↗
PubMed1992

Renal parenchymal function evaluated by scintillation camera renography before and after pyeloplasty for hydronephrosis.

Scintillation camera renography with Tc-DTPA was performed before and after pyeloplasty on 16 kidneys with urographic signs of pelviureteric obstruction causing hydronephrosis. Regional parenchymal renograms were generated, and the passage of Tc-DTPA through the parenchyma was measured and correlated to the change in separate glomerular filtration rate. Preoperative parenchymal passage of DTPA was significantly slower (p = 0.02) in kidneys with improved glomerular filtration rate after pyeloplasty than in those without such improvement. Postoperative passage of DTPA in parenchyma was almost identical with that in a reference series. This method seems to be clinically useful for evaluating cases of hydronephrosis and for predicting the outcome of pyeloplasty.

Adult↗
PubMed1992

Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin's disease.

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long-term effects of mantle radiotherapy on pulmonary function were observed.

Adult↗
PubMed1992

A case of right coronary artery occlusion, caused by blunt chest trauma and treated with acute coronary artery bypass surgery.

A 37-year-old man sustained occlusion of the right coronary artery after a bicycle accident with blunt chest trauma over the left scapula. Acute coronary angiography was performed because of chest pain and ST-segment elevation. Despite surgically successful acute revascularization the patient developed a transmural inferior wall infarction. Coronary artery occlusion after blunt chest trauma is rare, especially occlusion of the right coronary artery. When it occurs, the impact is usually frontal (car accidents), and not dorsal as in this case. Coronary artery bypass surgery has been reported in a few cases but to the best of our knowledge this is the first report of bypass surgery at the stage of acute transmural ischaemia.

Adult↗