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Biomedical subjects

W G Wood

Publications and source records attributed to W G Wood.

At least 19 recordsLinked to original sources

Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells.

Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.

Adenine Phosphoribosyltransferase

[C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation].

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

Adult

Analysis of the human alpha globin upstream regulatory element (HS-40) in transgenic mice.

We have analysed the effect of a 1.4 kb segment of DNA containing the upstream alpha globin regulatory element (HS-40) on human alpha globin gene expression in fetal mice and lines of transgenic mice. High levels of tissue-specific, human alpha mRNA expression were seen in all transgenic animals and in this sense expression was position independent. However, the level of human alpha mRNA expression per integrated gene copy decreased during development and was inversely related to copy number. The limitation in expression with increasing gene copy number was shown to be in cis since homozygotes for the transgene produced twice as much human alpha mRNA as hemizygotes. In many respects HS -40 appears similar to single elements within the previously described beta globin locus control region and in cross breeding experiments we have shown that HS -40 behaves in a similar manner to such elements in transgenic mice.

Animals

Elastase alpha 1-proteinase inhibitor and lactoferrin concentrations in endotracheal aspirates of ventilated newborns.

Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections

Na pump and plasma membrane structure in L-cell fibroblasts expressing rat liver fatty acid binding protein.

Although the intracellular fatty acid binding proteins have been investigated for nearly two decades and purified proteins are now available, little is known regarding the function of these proteins in intact cells. Therefore, L-cell fibroblasts transfected with cDNA encoding for rat liver fatty acid binding protein (L-FABP) were examined as to whether L-FABP expression in intact cells modifies plasma membrane enzyme activities, fluidity, and lipids. Plasma membrane Na/K-ATPase activity was 65.9 +/- 18.7 and 38.6 +/- 22.8 (P less than 0.001) nmol/mg protein x min for control and high-expression transfected cells, respectively. Consistent with this observation, [3H] ouabain binding to whole cells was significantly decreased from 3.7 +/- 0.3 to 2.0 +/- 0.8 pmol ouabain bound/mg cell protein in control and high-expression cells, respectively, whereas the cell's affinity for ouabain was not significantly altered. Unexpectedly, Western blot analysis indicated that transfected cells had higher levels of Na+, K(+)-ATPase protein; in contrast, the activities of 5'-nucleotidase and Mg-ATPase were unaltered. The effects of L-FABP expression on plasma membrane Na/K-ATPase function appeared to be mediated through alterations in plasma membrane lipids and/or structure. The plasma membrane cholesterol/phospholipid ratio decreased and the bulk plasma membrane fluidity increased in the high-expression cells. In conclusion, plasma membrane Na/K-ATPase activity in L cells may be regulated in part through expression of cytosolic L-FABP.

Animals

A single beta-globin locus control region element (5' hypersensitive site 2) is sufficient for developmental regulation of human globin genes in transgenic mice.

The beta-globin gene complex is regulated by an upstream locus control region (LCR) which is responsible for high-level, position-independent, erythroid-cell-specific expression of the genes in the cluster. Its role in the developmental regulation of beta-like globin gene transcription remains to be established. We have examined the effect of a single LCR element, hypersensitive site 2 (HS2), on the developmental regulation of the human fetal gamma and adult beta genes in transgenic mice. In mice bearing HS2A gamma beta and HS2G gamma A gamma-117 delta beta human globin gene constructs, switching from gamma- to beta-gene expression begins at about day 13.5 of gestation and is largely completed shortly after birth. The larger construct also demonstrates a switch in G gamma- to A gamma-gene expression during the gamma-to-beta switch similar to that observed during normal human development. We conclude that HS2 alone is sufficient for developmental regulation of the human beta-globin genes.

Aging

Towards an understanding of the mode of action of Bacillus Calmette-Guérin-therapy in bladder cancer treatment, especially with regard to the role of fibronectin.

The interaction between Bacillus Calmette-Guérin (BCG) and the host was investigated after repeated intravesicular BCG-therapy for superficial bladder cancer. Studies were performed on (a) the local reaction in the bladder, (b) the systemic reaction, and (c) short and long term interactions in both the bladder and the serum/plasma. The analytes measured included anti-BCG IgA and IgG, fibronectin, lactoferrin, elastase-alpha 1-proteinase inhibitor, myeloperoxidase and alpha 2-proteinase inhibitor. All analytes, with the exception of alpha 2-proteinase inhibitor, were measured in both serum/plasma and urine. An additional group of 94 patients undergoing bronchoalveolar lavage was used for comparison with other diseases affecting mucous membranes. In vitro studies on human bladder in culture were also carried out to study the relationship between BCG, elastase and fibronectin. The results revealed a normal defence reaction, in which IgA and IgG antibodies specific to BCG were produced by the host. Maximal concentrations of all analytes in urine were found about 4 h after BCG instillation. Immunoglobulins, soluble fibronectin, and granulocyte markers all appeared in urine after instillation and all showed a similar time course. The in vitro study showed the synergistic effect of elastase and BCG in stimulating the host defence reaction. The relationship between BCG and fibronectin can be seen as fortuitous but not indicative of the efficacy of BCG-therapy in patients with superficial bladder cancer.

Administration, Intravesical

[Myeloperoxidase, lactoferrin and elastase in bronchoalveolar lavage and plasma in pneumonia].

Neutrophilic granulocytes in the lower respiratory tract are of decisive importance for the elimination of pathogenic germs in bacterial pneumonia. On the other hand, the liberation of phagocyte products (e.g. elastase) can result in tissue damage in the parenchyma of the lungs. For this reason, we determined in patients suffering from acute pneumonia (n = 21), in patients with acute pneumonia associated with immunosuppression (n = 12), in patients who had overcome their pneumonia (n = 9) and in controls (n = 17) in bronchoalveolar lavage (BALF) and in plasma, the concentration of the locally produced granulocyte products myeloperoxidase (MPO), lactoferrin (LF) and elastase-alpha 1 proteinase complex (ELA) as well as of the alpha 1 proteinase inhibitor (alpha 1 Pi) and alpha 2 proteinase inhibitor (alpha 2 Pi) via chemoluminescence immunoassay, and compared the same with the differential cell count in the BALF. The protein concentrations were referred to the albumin concentration (Alb) for standardisation. This concentration did not differ significantly between the various patients and control groups. The BALF concentration of ELA in the group with pneumonia (median: 86.3 micrograms/l or 8.5 micrograms/mg Alb) was about eight times higher than in the group of patients suffering from pneumonia with immunosuppression (median: 16 micrograms/l or 1.0 micrograms/l Alb, p less than 0.001) or in whom the pneumonia was no longer present (17.6 micrograms/l or 0.5 micrograms/mg), and approximately 40 times higher than in the control group (3 micrograms/l or 0.2 micrograms/mg, respectively). Similar results were obtained for LF (61 micrograms/mg Alb vs. 11.3; 16.8 and 5.9 micrograms/mg; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cellular origins of the fetal-haemoglobin-containing cells of normal adults.

The origin of the small population of adult red cells which contain Hb F (F-cells) has been studied in a clonal disorder of haemopoiesis, polycythaemia rubra vera (P.R.V.). In eleven patients who had not received cytotoxic therapy F-cells comprised less than 0.1% to 11.9% of the circulating red cells, compared with 0.34% to 4.6% in 21 haematologically normal controls. Two additional patients were glucose-6-phosphate-dehydrogenase heterozygotes in whom the clonal nature of the P.R.V. could be demonstrated directly; they had F-cell values of 2.1% and 8.3%. These observations indicate that F-cells arise from the same population of stem cells as other adult cells and not from a separate stem-cell pool.

Aged

Anxiety and depression in young and middle aged hypertensive and normotensive subjects.

This study examined the effects of essential hypertension on measures of anxiety and depression for two age groups of hypertensive (free from hypertension-related pathology and/or cardiovascular disease) and normotensive subjects. Hypertensive subjects had significantly higher State Anxiety scores and Zung Depression scores than did normotensive subjects. These differences between the blood pressure groups were due largely to the scores of the younger hypertensive subjects. The results of the present study are consistent with previous results from our laboratory that have found that younger hypertensives differed (relative to controls) from middle aged hypertensives on measures, such as, symptoms reported on the Cornell Medical Index and WAIS Performance scores. The results of the present study were discussed within the context of age associated differences in response to hypertension and factors that might account for these differences.

Adult

Relationship of age and hypertension to neuropsychological test performance.

Young adult (X- = 29) and middle aged (X- =50) hypertensive and normotensive subjects were compared with respect to seven neuropsychological test scores derived from tests on the Halstead-Reitan battery. Age main effects, with inferior performance for the middle aged subjects, were observed for the localization and time portions of the Tactile Performance Test (TPT) and for the Trail Making A test. The multivariate age effect was significant for the composite of seven scores. A multivariate blood pressure main effect was obtained and main effect blood pressure was significant for the category test; hypertensives made more errors than normotensives. A blood pressure by age interaction was observed for finger tapping scores and the TPT-Memory scores with larger differences between hypertensives and normotensives for the younger than for the middle aged group. Results were discussed in terms of previous studies of age and hypertension with the WAIS, the Primary Mental Abilities Test and serial reaction time measures. The poor prediction of hypertensive status from individual neuropsychological test scores was emphasized and readers were cautioned not to conclude that essential hypertensives, as a group, can be characterized as brain damaged.

Adult

Nephropathy in angioimmunoblastic lymphadenopathy.

Two elderly men who had fulminating systemic illnesses typical of angioimmunoblastic lymphadenopathy died in acute oliguric renal failure. In both, glomerular lesions were present. In one patient mild diffuse proliferative glomerulonephritis associated with necrotizing arteritis was seen, and in the other, minimal change was observed by light microscopy. In both, immunoglobulin-containing dense deposits within glomeruli were observed by fluorescence and electron microscopy, suggesting that the renal disease was mediated, at least partly, by deposition of immunoglobulin.

Acute Kidney Injury

WAIS performance for different age groups of hypertensive and control subjects during the administration of a diuretic.

This study examined the effects of age and hypertension on WAIS performance. Previous studies have reported that hypertension adversely affects cognitive functioning, but few have considered the influence of hypertension on discrete age groups. Hypertension was found to be negatively associated with WAIS Verbal scores for younger (21 to 39 years) but not older (45 to 65 years) subjects. Further, younger subjects attained higher WAIS Performance scores than did older subjects. Medication history was not associated with performance levels for hypertensives, nor was performance of controls influenced by whether or not they were tested while on a diuretic. When WAIS Performance scores were analyzed for subjects matched on WAIS Verbal scores across age (21 to 39 vs 45 to 65 years) and blood pressure (normotensive vs hypertensive), a significant age by blood pressure interaction was found. The effect of blood pressure on Performance scores was found to be greater for younger than for older subjects. The association between plasma renin activity (PRA) level and WAIS Performance scores was also examined. Contrary to previous findings PRA was not related to Performance scores. The results are discussed in the context of previous hypertension research and their implications for comparisons across age levels.

Adult

Nonspecific ulcers of the colon: a case presentation of ulceration of the transverse colon.

This paper describes a patient with nonspecific discrete ulcer of the transverse colon. The lesion was responsible for diarrhea which was cured by conservative resection. These uncommon ulcers, which mimic carcinoma radiographically and were previously thought to be uniformly fatal, may occasionally heal spontaneously. The patient has taken several drugs, some of which may have played a role in the pathogenesis of the ulcer, but the etiology of nonspecific colon ulcer remains uncertain.

Colonic Diseases

Acute renal failure in McArdle's disease.

A case of reversible acute renal failure in an adult with myophosphorylase deficiency (McArdle's disease) is described. Myoglobinuria, possibly abetted by intravenous urography, was incriminated as the cause of impairment of renal function.A muscle biopsy specimen contained necrotic fibers and no histochemically demonstrable phosphorylase activity. Ultrastructurally, nonspecific degenerative changes were observed.

Acute Kidney Injury