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Biomedical subjects

J Rowe

Publications and source records attributed to J Rowe.

At least 55 records · Page 3Linked to original sources
PubMed1999

Potential biochemical growth markers in premature infants.

Identification of a biochemical marker of growth in low birth weight (LBW) infants would be of benefit to rapidly assess the effects of illness and/or therapeutic intervention. The aims of the present study were (1) to measure serially the C-terminal fragment of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) in LBW infants during the first 6 weeks of life; (2) to correlate the changes in PICP, BSAP, and OC with the changes in weight; and (3) to evaluate PICP levels as a marker for bronchopulmonary dysplasia (BPD). Premature neonates (< or =36 weeks of gestation) had cord blood and then weekly blood samples taken from up to 6 weeks after birth. Daily changes in weight were recorded. Measurements of serum PICP, BSAP, and OC were done in duplicate by immunoassay. In a subset population (25-30 weeks), PICP levels in the first 4 weeks of life were evaluated as a marker for subsequent development of BPD. A total of 77 infants had serum PICP and BSAP measured. The mean (+/- SEM) gestational ages of all the infants were 30.4 (+/-0.3) weeks and birth weights 1477 (+/-55) g. Fifteen infants also had measurements of OC done. In these 15 infants, change in weight was correlated significantly with PICP (p<0.0001), but not with either BSAP (p = 0.8) or OC measurements (p = 0.9). In appropriate for gestational age (AGA) infants (n = 66), the PICP values decreased from the cord blood values to the week 1 measurement, coinciding with the fall in weight over the same time period. BSAP values, on the other hand, continued to increase from birth onwards. Over the first 6 weeks of postnatal life in these infants, change in weight had a stronger positive correlation with PICP (R2 = 0.43, p<0.0001) than BSAP (R2 = 0.03, p<0.01). In the subset population, PICP levels at week 4 were significantly lower (p<0.04) in those infants who subsequently developed BPD. PICP measurements are correlated with somatic growth in premature infants and could be used as a biochemical marker in infants who develop BPD.

Alkaline Phosphatase↗
PubMed1999

The humoral immune response to human T-cell lymphotropic virus type 1 envelope glycoprotein gp46 is directed primarily against conformational epitopes.

Individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) develop a robust immune response to the surface envelope glycoprotein gp46 that is partially protective. The relative contribution of antibodies to conformation-dependent epitopes, including those mediating virus neutralization as part of the humoral immune response, is not well defined. We assess in this report the relationship between defined linear and conformational epitopes and the antibodies elicited to these domains. First, five monoclonal antibodies to linear epitopes within gp46 were evaluated for their ability to abrogate binding of three human monoclonal antibodies that inhibit HTLV-1-mediated syncytia formation and recognize conformational epitopes. Binding of antibodies to conformational epitopes was unaffected by antibodies to linear epitopes throughout the carboxy-terminal half and central domain of HTLV-1 gp46. Second, an enzyme-linked immunoadsorbent assay was developed and used to measure serum antibodies to native and denatured gp46 from HTLV-1-infected individuals. In sera from infected individuals, reactivity to denatured gp46 had an average of 15% of the reactivity observed to native gp46. Third, serum antibodies from 24 of 25 of HTLV-1-infected individuals inhibited binding of a neutralizing human monoclonal antibody, PRH-7A, to a conformational epitope on gp46 that is common to HTLV-1 and -2. Thus, antibodies to conformational epitopes comprise the majority of the immune response to HTLV-1 gp46, and the epitopes recognized by these antibodies do not appear to involve sequences in previously described immunodominant linear epitopes.

Animals↗
PubMed1999

Prostacyclin concentrations and transitional circulation in preterm infants requiring mechanical ventilation.

AIM: To describe the association between early postnatal prostacyclin concentrations in preterm infants; echocardiographic measurements of ductal diameter and ventricular output and clinical outcomes of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA). METHODS: Forty nine preterm infants born before 30 weeks of gestational age (median birthweight 980 g, median gestational age 27 weeks) underwent echocardiographic studies at 5, 12, 24 and 48 hours of postnatal age. Measurements included ventricular outputs and the ductal shunt diameter as a measure of the shunt size. Simultaneous measurements of blood pressures, mean airway pressure and inspired fraction of oxygen (FIO2) were recorded. A blood sample for the prostacyclin metabolite 6-ketoprostaglandin F1-alpha (6KPGF1 alpha) was taken at the 5 and 24 hour echocardiogram. RESULTS: The mean 6KPGF1 alpha concentrations were higher than adult concentrations at 5 (515 pg/ml) and 24 (255 pg/ml) hours. There was no association with gestational age. Raised 6KPGF1 alpha concentrations were related to increased need for mechanical ventilation and severity of respiratory disease. At 5 hours, increased 6KPGF1 alpha concentrations were associated with larger PDA and at 24 hours with larger PDA and higher left ventricular output. Infants with higher 6KPGF1 alpha concentrations were more likely to develop clinically significant PDA. There was no association between early measurements of 6KPGF1 alpha and IVH. CONCLUSIONS: Early postnatal prostacyclin concentrations are markedly raised in preterm infants, particularly in those with more severe lung disease. Raised 6KPGF1 alpha concentrations were associated with an increased ductal diameter and subsequent PDA, but not IVH.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Blockade of membrane transport and disassembly of the Golgi complex by expression of syntaxin 1A in neurosecretion-incompetent cells: prevention by rbSEC1.

The t-SNAREs syntaxin1A and SNAP-25, i.e. the members of the complex involved in regulated exocytosis at synapses and neurosecretory cells, are delivered to their physiological site, the plasma membrane, when transfected into neurosecretion-competent cells, such as PC12 and AtT20. In contrast, when transfection is made into cells incompetent for neurosecretion, such as those of a defective PC12 clone and the NRK fibroblasts, which have no endogenous expression of these t-SNAREs, syntaxin1A (but neither two other syntaxin family members nor SNAP-25) remains stuck in the Golgi-TGN area with profound consequences to the cell: blockade of both membrane (SNAP-25, GAT-1) and secretory (chromogranin B) protein transport to the cell surface; progressive disassembly of the Golgi complex and TGN; ultimate disappearance of the latter structures, with intermixing of their markers (mannosidase II; TGN-38) with those of the endoplasmic reticulum (calreticulin) and with syntaxin1A itself. When, however, syntaxin 1A is transfected together with rbSec1, a protein known to participate in neurosecretory exocytosis via its dynamic interaction with the t-SNARE, neither the blockade nor the alterations of the Golgi complex take place. Our results demonstrate that syntaxin1A, in addition to its role in exocytosis at the cell surface, possesses a specific potential to interfere with intracellular membrane transport and that its interaction with rbSec1 is instrumental to its physiological function not only at the plasma membrane but also within the cell. At the latter site, the rbSec1-induced conversion of syntaxin1A into a form that can be transported and protects the cell from the development of severe structural and membrane traffic alterations.

Animals↗
PubMed1999

In vitro human decidual endothelial cell thromboxane secretion in preeclampsia is not abnormal.

OBJECTIVES: The aims of this study were to describe levels of thromboxane secretion by decidual endothelial cells from normal pregnancies and to determine whether decidual endothelial cell secretion of thromboxane, implicated in the causation of the hypertension and vasoconstriction of preeclampsia, is increased in this disorder. METHODS: We measured thromboxane generation by cultured decidual endothelial cells from 13 normal pregnancies (NDEC) and 13 pregnancies complicated by preeclampsia (PEDEC), compared with a control population of 6 normal human umbilical vein endothelial cells (HUVEC). Responses to stimulation by bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were examined. MAIN OUTCOME MEASURES: Thromboxane B2 levels in supernatants of cultured endothelial cells. RESULTS: The level of secretion over 24 h in culture by NDEC [14 (7-26) pg/10(6) cells] was approximately 25% that of HUVEC [63 (49-70) pg/10(6) cells]. Levels achieved in response to all stimuli examined were consistently lower in NDEC than in HUVEC (p < 0.01). Proportional stimulation by LPS and TNF-alpha was comparable in HUVEC and NDEC, whereas NDEC displayed a greater increase (25-fold) than HUVEC (10-fold) in response to IL-1 beta (p < 0.01). There were no significant differences between decidual endothelial cells from normotensive and preeclamptic women in basal secretion of thromboxane or in responses to the stimuli examined. CONCLUSIONS: In vitro thromboxane secretion by decidual endothelial cells is lower than that of HUVEC, and responsiveness to specific stimuli may be quantitatively different. These findings emphasize the importance of examining endothelial cells from the involved maternal vascular bed if intrauterine vascular pathophysiological events are to be clarified. No significant differences were noted in decidual endothelial cell thromboxane secretion between normal and preeclamptic subjects.

Cells, Cultured↗
PubMed1998

Use of recombinant herpes simplex virus type 1 vectors for gene transfer into tumour and normal anterior pituitary cells.

In this paper we demonstrate the use of recombinant viral vectors derived from herpes simplex virus type 1 (HSV1) to transfer reporter genes in vitro into rat anterior pituitary cells grown in primary cultures and the anterior pituitary tumour cell lines GH3 and AtT20. The three vectors used were, tsK/beta-galactosidase (beta-gal), tsK/CRH and tsK/TIMP, the corresponding transgene products respectively being E. coli beta-gal, pre-procorticotropin releasing hormone (ppCRH), and the chimeric protein TIMP/Thy1 (tissue inhibitor of metalloproteinases (TIMP)/linked to the carboxy terminus of Thy1 which confers the addition of a glycolipid glycosyl-phosphatidylinositol anchor in the ER). Double labelling immunofluorescence experiments to detect reporter proteins and transduced cell types indicated that the three vectors could transfer and express the reporter genes in normal and tumour anterior pituitary cells. Virus infection of pituitary cells was characterised, and it was shown that infection with tsK/beta-gal at multiplicities of infection (MOI)=10, 100% of tumour and non-endocrine anterior pituitary cells expressed beta-gal, whereas 75% endocrine anterior pituitary cells expressed the transgene. Long-term expression studies after infection with tsK/beta-gal indicated that anterior pituitary cells in primary cultures expressed the transgene for significant longer periods than tumour anterior pituitary cells. Growth arrest by serum starvation markedly decreased the frequency of transgene expression in anterior pituitary cells following infection with tsK/beta-gal. Transgenic products expressed from tsK were targeted to their correct intracellular domain in both anterior pituitary cells in primary cultures and in pituitary tumour cell lines. We conclude that transgenes can be delivered into anterior pituitary cells in primary culture and pituitary tumour cell lines using tsK derived HSV1 vectors. The prospect of employing viral vectors to transfer genes into endocrine cells opens up the potential exploration of various molecular aspects of pituitary cell function both in vitro and in vivo, as well as the use of gene transfer into the pituitary for potentially therapeutic applications, such as the treatment of pituitary tumours.

Animals↗
PubMed1998

Risk-factor assessment for falls: from a written checklist to the penless clinic.

OBJECTIVE: to audit risk-factor identification of fallers before and after an education programme and the insertion of a written checklist in medical notes. Risk-factor identification in a dedicated, computerized falls clinic was then examined. METHODS: documentation of risk factors for falls was studied on wards and a self-auditing 'penless' clinic for fallers subsequently set up to generate reports for medical notes and letters for general practitioners. RESULTS: risk-factor identification improved after the insertion of the checklist but remained relatively poor. A dedicated clinic allowed almost complete identification of risk factors. Of the first 112 patients (median age 82) seen in the clinic, 75 (67%) were housebound. Remediable risk factors--e.g. inappropriate medication (67%), unsatisfactory footwear (59%) and postural hypotension (17%)--were found in most. Thirty-three patients (29%) had difficulty with alarm raising. CONCLUSION: ward-based intervention showed limited capacity to identify risk factors for falls: a dedicated clinic was more successful. The use of a portable computer with a programme to screen fallers for risk factors is worthy of consideration.

Accidental Falls↗
PubMed1998

Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson's disease. A consecutive series of eight simultaneous bilateral and twelve unilateral procedures.

Intellectual, psychological and functional outcomes were evaluated in a consecutive series of 20 Parkinsonian patients who had unilateral (UPVP) or simultaneous bilateral posteroventral pallidotomy (BPVP) using Image Fusion and Stereoplan (Radionics Inc., Boston, Mass., USA) with stimulation for lesion localization. Comprehensive baseline and 3-month postoperative neuropsychological and neurological assessment protocols were administered together with questionnaire measures of functional disability, quality of life and psychological symptomatology. Changes in patients' clinical presentation and scores on psychometric tests, questionnaires and observational rating scales were then examined. We observed no new neuropsychiatric sequelae directly related to pallidotomy. Cognitive sequelae were restricted to selective reductions in categorical verbal fluency following UPVP (P < 0.001) and BPVP (P < 0.01) and a reduction in phonemic verbal fluency following BPVP (P < 0.01); these changes were not reported subjectively. A fall in diadochokinetic rates (P < 0.01) and some subjective reports of a worsening in pre-existing dysarthria, hypophonia and hypersalivation/drooling following BPVP also suggested changes in speech motor apparatus; however, these changes did not have significant functional consequences. There was one case of more generalized cognitive impairment following BPVP. We also observed significant symptomatic improvement on neurological rating scales; following UPVP, Total Unified Parkinson's Disease Rating Scale (UPDRS) scores improved by 27% (P < 0.01) and following BPVP the improvement was 53% (P < 0.05). Patients' perceptions of reduced postoperative functional disability and improvements in 'quality of life' also achieved statistical significance on a number of both physical and psychosocial questionnaire subscales.

Activities of Daily Living↗
PubMed1998

Discrepancies between cerebral perfusion and metabolism after subarachnoid haemorrhage: a magnetic resonance approach.

INTRODUCTION: There is a variable relation between angiographic vasospasm and delayed ischaemic neurological deficit (DIND). Magnetic resonance (MR) techniques have the potential to investigate the haemodynamic, metabolic, and structural changes occurring with these complications. These techniques have been applied to study DIND in patients recovering from subarachnoid haemorrhage. METHODS: Fifteen studies were performed on 11 patients, 10 with DIND. Vasospasm was diagnosed angiographically or with transcranial Doppler. The MR protocol consisted of T2 weighted imaging, contrast enhanced dynamic perfusion scanning, TI weighted imaging, and two dimensional localised proton spectroscopy. Relative cerebral blood volume maps were generated from perfusion scans. Metabolite ratios were calculated from proton spectra. RESULTS: All patients had cortical oedema on T2 weighted images, significantly more pronounced in patients of poor clinical grade (p<0.01). Spectra were normal in good grade patients. Lactate was increased and N-acetyl aspartate decreased in the poor grades, significantly worse in grade 4 compared with grade 3 patients (p<0.05). Spectral changes also correlated with the severity of oedema (p<0.05). Relative blood volumes were significantly higher in oedematous regions of poor compared with good grade patients (p<0.05). Lactate was seen in regions of the brain with increased relative blood volume. CONCLUSIONS: Despite the paramagnetic effects of haemorrhage, or of the coils and clips used to treat aneurysms, this study demonstrates that patients recovering from subarachnoid haemorrhage can undergo complex MR studies. Oedema, lactate, and increased relative blood volume correlate well with each other and with DIND and poor clinical grade.

Adult↗
PubMed1997

Serum from women with preeclampsia partially corrects the abnormal in vitro prostacyclin secretion of preeclamptic villous cytotrophoblasts but not that of prostaglandin E2 or endothelin-1.

OBJECTIVE: This study was conducted (1) to determine in vitro placental villous cytotrophoblast secretion of prostacyclin, prostaglandin E2, and endothelin-1, (2) to examine the effect of serum from normal and preeclamptic women on secretion of these vasoactive substances, and (3) to determine whether responses to these sera by cytotrophoblasts from preeclamptic pregnancies are different from those of normal pregnancies. STUDY DESIGN: Cytotrophoblasts isolated from human placentas collected at cesarean section from normal and preeclamptic women were incubated for 20 hours in 20% (vol/vol) sera from preeclamptic or gestational age-matched normal pregnant women. Levels of prostacyclin (measured as 6-keto-prostaglandin F1alpha), prostaglandin E2, and endothelin-1 were measured in cytotrophoblast supernatants. RESULTS: In normal pregnancy sera preeclamptic cytotrophoblasts secreted significantly lower amounts of prostacyclin and prostaglandin E2 but higher amounts of endothelin-1 than did normal cytotrophoblasts. In preeclamptic sera the abnormality of prostacyclin secretion by preeclamptic cytotrophoblasts was partially corrected, but there was no effect on prostaglandin E2 or endothelin-1 secretion. Preeclamptic sera had no effect on secretion by normal cytotrophoblasts. CONCLUSIONS: The differences between normal and preeclamptic cytotrophoblasts in prostacyclin, PGE2, and endothelin-1 secretion and in response to preeclamptic serum suggest altered arachidonic acid metabolism in preeclampsia.

Blood Physiological Phenomena↗
PubMed1997

Neutralizing human monoclonal antibodies to conformational epitopes of human T-cell lymphotropic virus type 1 and 2 gp46.

Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lymphotropic virus (HTLV)-associated myelopathy are described. One monoclonal antibody recognized a linear epitope within the carboxy-terminal 43 amino acids of HTLV gp21, and two monoclonal antibodies recognized linear epitopes within HTLV type 1 (HTLV-1) gp46. The remaining seven monoclonal antibodies recognized denaturation-sensitive epitopes within HTLV-1 gp46 that were expressed on the surfaces of infected cells. Two of these antibodies also bound to viable HTLV-2 infected cells and immunoprecipitated HTLV-2 gp46. Virus neutralization was determined by syncytium inhibition assays. Eight monoclonal antibodies, including all seven that recognized denaturation-sensitive epitopes within HTLV-1 gp46, possessed significant virus neutralization activity. By competitive inhibition analysis it was determined that these antibodies recognized at least four distinct conformational epitopes within HTLV-1 gp46. These findings indicate the importance of conformational epitopes within HTLV-1 gp46 in mediating a neutralizing antibody response to HTLV infection.

Antibodies, Monoclonal↗
PubMed1997

Abstract genetic representation of dynamical neural networks using Kauffman networks.

Abstract (developmental) genetic representations are schemes where each genotype encodes a program for the construction of a phenotype. A new method for contriving abstract genetic representations is presented, based upon Kauffman's ideas regarding biological development [13-16]. Phenogenesis is controlled by genotype via cell replication and differentiation. Comparison is made with the earlier published methods of Gruau [9] and Kitano [18]. It is argued that greater expressive power is obtained using Kauffman networks. The new method was tested in the artificial evolution of morphology and finally successfully applied to the synthesis of structure in dynamical neural networks.

Evolution, Molecular↗
PubMed1997

Inability of histamine to regulate TNF-alpha production by human alveolar macrophages.

Tumor necrosis factor alpha (TNF-alpha), a major product of alveolar macrophages (AM), has been implicated in many pulmonary diseases. Histamine, a mediator important in pulmonary inflammation, has been demonstrated to regulate the production of TNF-alpha by monocytes. In this study, we show that human AM and monocytes differ in their responses to histamine. Whereas histamine suppressed lipopolysaccharide (LPS)-stimulated TNF-alpha production by monocytes through a cAMP-dependent mechanism, it had no effect on either cAMP levels or TNF-alpha production by AM. In contrast, both PGE2 and IL-10 suppressed LPS-stimulated TNF-alpha production by AM and monocytes. The lack of response of AM to histamine appears unique, as histamine suppressed LPS-stimulated TNF-alpha production by mononuclear cells isolated from sites of acute and chronic inflammation, as well as from noninflammatory tissues, and by macrophages differentiated in vitro. In the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine, histamine increased cAMP levels in AM. Freshly isolated monocytes and AM did not differ in PDE activity. However, PDE activity in AM, but not in monocytes, was increased 15 min after culture with histamine and may, in part, be responsible for the inability of histamine to suppress TNF-alpha production by AM. However, this increase was small and we hypothesize that additional mechanisms may contribute to the unresponsiveness of AM to histamine. We suggest that the lack of response of AM to histamine may be important in the host defense function of AM in the distal lung.

Adult↗
PubMed1997

Validity of the McGill Quality of Life Questionnaire in the palliative care setting: a multi-centre Canadian study demonstrating the importance of the existential domain.

This study was carried out in eight palliative care services in four Canadian cities. A revised version of The McGill Quality of Life Questionnaire (MQOL) is compared to a single-item scale measuring overall quality of life (SIS), and the self-administered version of the Spitzer Quality of Life Index (SA-QLI), to obtain evidence of validity. MQOL total score predicts SIS better than does SA-QLI, although much of the variance remains to be explained. The results of principal components analysis of data using this revised version of MQOL are similar to those from previous MQOL studies with different patient populations. The MQOL subscales, constructed on the basis of principal components analysis, demonstrate acceptable internal consistency reliability. The MQOL measures reflecting physical well-being and existential well-being are important for predicting SIS.

Humans↗
PubMed1997

Expression of transgenes in normal and neoplastic anterior pituitary cells using recombinant adenoviruses: long term expression, cell cycle dependency, and effects on hormone secretion.

Adenovirus vectors have recently been used to transfer genes into a variety of cell types, including neurons, glial cells, Schwann cells, and epithelial cells. To evaluate the efficiency of gene transfer into pituitary cells using viral vectors, we used replication-deficient recombinant adenovirus vectors (RAds) encoding beta-galactosidase driven by various viral promoters. We tested the ability of RAds to infect and express beta-galactosidase within the different identified cell populations of the anterior pituitary anterior pituitary gland and also in tumor cells of anterior pituitary origin, i.e. GH3 and AtT20 cells. Our results demonstrate that transgenes encoded by RAds are expressed within all cell types of the adenohypophysis in vitro and also within AtT20 and GH3 endocrine tumor cells. Our long term expression studies indicate that long term expression with low cytotoxicity can be achieved, but that the longevity of transgene expression from RAds depends on the proliferative status of the target cells. Slowly dividing cells (endocrine population) express transgenes for longer than actively dividing cells (tumor cells and nonendocrine anterior pituitary cells). The ability of anterior pituitary cells to secrete ACTH or LH through the regulated secretory pathway decreased after infection with RAds at high multiplicity of infection (> or = 20 plaque-forming units/target cell), whereas cell viability was not affected. We also demonstrate that a higher percentage of cells expressed the transgene beta-galactosidase when we infected actively dividing GH3 cells compared with the infection of growth-arrested GH3 cells. This could reflect differential virus entry or differential activity of the individual promoters during different stages of the cell cycle. This work demonstrates that high efficiency gene transfer into all pituitary cell types can be achieved with RAds, and that this system can be exploited to characterize and experimentally manipulate pituitary-specific gene expression. The higher efficiency of infection and transgene expression in actively dividing cells compared to that in their growth-arrested counterparts could also be exploited for the treatment of pituitary adenomas that do not respond to classical treatment strategies, using suicide or cytotoxic gene therapy.

Adenoviridae↗