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Biomedical subjects

T White

Publications and source records attributed to T White.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

The influence of topography on the cognitive and psychopathological effects of tardive dyskinesia.

OBJECTIVE: The purpose of the study was to investigate the influence of the topography of dyskinetic movements on their effect on cognitive impairment and negative symptoms. METHOD: Eighty-four inpatients who satisfied DSM-III-R criteria for schizophrenia were rated for tardive dyskinesia, akathisia, and drug-induced parkinsonism, as well as negative symptoms, with the Scale for the Assessment of Negative Symptoms and for cognitive state with the Mini-Mental State examination. The subjects were then divided into those without tardive dyskinesia (N = 45), those with orofacial dyskinesia (N = 19), and those with limb-truncal dyskinesia (N = 20). Differences among the groups were assessed with multiple analysis of covariance (MANCOVA), with age, akathisia, and drug-induced parkinsonism ratings as the covariates. Post hoc Spjotvoll and Stoline tests were then undertaken. RESULTS: MANCOVA revealed a significant difference among the groups. Post hoc tests showed that the group with limb-truncal dyskinesia had significantly lower scores on the Mini-Mental State Examination and higher scores on the Scale for the Assessment of Negative Symptoms. The group with orofacial dyskinesia was significantly different from the nondyskinetic group only on the total score for the Scale for the Assessment of Negative Symptoms and the attention subscale. There were no significant differences between the dyskinetic groups. CONCLUSIONS: After correction for the important confounding variables of age, akathisia, and drug-induced parkinsonism scores, those with limb-truncal and, to a lesser degree, orofacial dyskinesia differed significantly from nondyskinetic comparison subjects in ratings of cognitive impairment and negative symptoms.

Akathisia, Drug-Induced

Syndromes of chronic schizophrenia and some clinical correlates.

Subtypes of the features of chronic schizophrenia were investigated. As in previous research, three discrete syndromes were found. These were then related to demographic, psychological, and movement-disorder variables. Possible pathophysiological mechanisms are discussed in terms of known neostriatal functions.

Akathisia, Drug-Induced

The association among negative symptoms, movement disorders, and frontal lobe psychological deficits in schizophrenic patients.

Neuropsychological tests of frontal lobe function were undertaken in 46 chronic schizophrenic patients who were also rated for movement disorders and negative symptoms. "High" and "low" SANS groups were formed by segregating around the median value. The "high" SANS group was found to differ significantly in terms of the severity of tardive dyskinesia (TD) and drug-induced parkinsonism, and frontal psychological tests. A possible mechanism is discussed within the context of known neostriatal psychological function.

Antipsychotic Agents

Immunochemical detection of a small cell lung cancer-associated ganglioside (FucGM1) antigen in serum.

Recently, the ganglioside FucGM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4[NeuAc alpha 2-3]-Gal beta 1-4Glc beta 1-1 Cer) was identified as a small cell lung cancer (SCLC) marker both in chemical and histochemical studies. In order to further determine whether the FucGM1 ganglioside is shed from the tumor site and consequently is present in the serum of SCLC patients, we produced a series of new monoclonal antibodies raised against FucGM1 and related glycolipids. Shedding of the FucGM1 ganglioside was studied both in vitro and in vivo using SCLC cell lines and nude mice xenografts of SCLC cells as model systems, and finally immunochemical analyses were performed on serum samples from patients with SCLC. High-performance thin-layer chromatography immunostaining demonstrated the presence of FucGM1 in conditioned culture media obtained from FucGM1-positive SCLC cell lines. Furthermore, tumor extracts of SCLC cell line xenografts in nude mice were positive for the FucGM1 marker, and more importantly the marker was also present in serum samples from these mice. Twenty serum samples were obtained from patients with histologically verified SCLC. Eight patients had localized disease, and the remaining patients had disseminated cancer involving metastases to other organ sites. Sera from 4 of these patients were clearly positive, and 2 additional cases were found to be weakly positive. The positive patient sera were all from patients with extensive disease. Sera from 12 patients with non-SCLC and 20 healthy individuals were all found to be negative. These results clearly establish the FucGM1 glycolipid as a potential serum marker of SCLC for which a sensitive immunoassay should be developed and tested using a larger series of serum samples.

Adult

The role of oil and agalactosyl IgG in the induction of arthritis in rodent models.

The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.

Animals