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Biomedical subjects

V Patel

Publications and source records attributed to V Patel.

At least 181 records · Page 10Linked to original sources

Autocrine production of TGF-alpha and TGF-beta during tumour progression of rat oral keratinocytes.

This study describes a new technique to separate transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta) from culture supernatants using ion exchange chromatography; assays of competitive inhibition of ligand binding were used to quantify the amount of growth factor. The method was simple, inexpensive and did not require large volumes of culture medium. The autocrine production of TGF-alpha and TGF-beta was examined in oral keratinocyte cell lines derived from the palatal and lingual mucosa of rats painted with the carcinogen 4-nitroquinoline N-oxide (4NQO). Escape from cellular senescence (immortality) was associated with a marked increase in TGF-alpha production (cell line R2P) but tumour progression, as reflected by the development of anchorage independence in agarose gels and tumorigenicity in athymic mice, did not result in a consistent increase or decrease of TGF-alpha production compared to normals. Four cell lines (R8AP, R1T, R3T, R1P), with different functional cellular phenotypes, produced two to three times more TGF-alpha than normals. TGF-alpha production was inversely correlated to epidermal growth factor cell surface receptor expression. The autocrine production of TGF-beta was variable with the majority of cell lines producing markedly little TGF-beta; three cell lines (R4T, R8BP, R9T) produced more TGF-beta than normals. The production of TGF-beta was unrelated to tumour progression, the expression of TGF-beta cell surface receptors or TGF-alpha production. The results indicate that the autocrine production of TGF-alpha and TGF-beta are not accurate markers of tumour progression in the rat 4NQO model of oral carcinogenesis.

4-Nitroquinoline-1-oxide↗

Role of first exon/intron sequences in the regulation of myc family oncogenic potency.

cis-Acting sequence elements that participate in the regulation of myc family gene expression in normal tissues and that serve as potential targets for the deregulation of expression in tumors have been localized to the first exon/intron region of all three myc family genes. To test directly the importance of these cis elements in the tumor-associated deregulation of myc family gene expression, we have compared the oncogenic activities of complete (exons 1, 2 and 3) and truncated (exons 2 and 3 only) c-, N- and L-myc expression constructs in the rat embryo fibroblast (REF) cooperation assay. Removal of the first exon/intron region from each construct was associated with a dramatic increase in oncogenic potency by several criteria. Analysis of N-myc/ras-transformed cell lines demonstrated (i) fewer transfected N-myc gene copies and an overall higher level of steady-state N-myc mRNA with the truncated N-myc expression construct and (ii) the presence of a significant block to transcriptional elongation in the first exon of the complete N-myc expression construct. These results indicate that the first exon of N-myc plays an important role in governing oncogenic potency, possibly through transcriptional control mechanisms.

Animals↗

Progressive abrogation of TGF-beta 1 and EGF growth control is associated with tumour progression in ras-transfected human keratinocytes.

This study examined the response of human keratinocytes in different stages of transformation to exogenous TGF-beta 1 and EGF as well as their receptor and growth-factor expression. Cells of the spontaneously immortalized HaCaT cell line and c-Ha-ras transfected clones (I-6, I-7, II-3, II-4) exhibited different tumorigenic potentials when transplanted to athymic mice. HaCaT- and I-6 cells were non-tumorigenic, I-7 cells formed persisting epidermal cysts (benign tumours) and II-3 and II-4 cells developed into invasive squamous-cell carcinomas. TGF-beta 1 inhibited thymidine uptake in a dose-dependent manner, a progressive decrease in response being associated with an increasing malignant potential (HaCaT greater than I-6 greater than I-7 = II-4). HaCaT-cells and ras-clones expressed TGF-beta 1 mRNA at similar levels, but cells of increasing malignant potential secreted markedly less receptor-binding TGF-beta (HaCaT greater than I-6 = I-7 greater than II-3 greater than II-4) into the culture medium. Whilst ras-transfected cells expressed fewer TGF-beta receptors than HaCaT cells, there was little difference between TGF-beta receptor number or affinity between the 4 transfected cell clones. The same was true for the TGF-beta receptor types, but Type-II receptors were expressed at lower levels by the malignant clones II-3 and II-4. When HaCaT and ras-transfected cells were investigated for their response to exogenous EGF, cells were refractory (I-7, II-4), partially stimulated (I-6) or fully stimulated (HaCaT). Cells with increasing malignant potential produced increasing amounts of endogenous TGF-alpha (II-4 = II-3 greater than I-7 = I-6 greater than HaCaT). All tumorigenic ras clones expressed higher mRNA levels than HaCaT-cells. Ras-transfected clones expressed fewer high- and low-affinity EGF receptors than HaCaT cells with a tendency toward increased numbers of high-affinity EGF receptors associated with increasing malignant potential (II-4 = II-3 greater than I-7 greater than I-6) but these changes were associated with a progressive decrease in receptor affinity. The results indicate that tumour progression in human epidermal keratinocytes transfected with c-Ha-ras is associated with a progressive abrogation of TGF-beta 1 and EGF growth control. They suggest that the increased autonomous growth potential associated with advanced stages of epithelial tumour progression can be defined more closely using a cellular profile of TGF-beta and EGF.

Cell Division↗

Retinal blood flow in diabetic retinopathy.

OBJECTIVES: (a) To report on the basic parameters of retinal blood flow in a population of diabetic patients with and without retinopathy and non-diabetic controls; (b) to formulate a haemodynamic model for the pathogenesis of diabetic retinopathy from this and other studies. DESIGN: Laser-Doppler velocimetry and computerised image analysis to determine retinal blood flow in a large cross sectional study. SETTING: Diabetic retinopathy outpatient clinic. SUBJECTS: 24 non-diabetic controls and 76 diabetic subjects were studied (63 patients with insulin dependent diabetes, 13 with non-insulin dependent diabetes). Of the diabetic subjects, 12 had no diabetic retinopathy, 27 had background retinopathy, 13 had pre-proliferative retinopathy, 12 had proliferative retinopathy, and 12 had had pan-retinal photocoagulation for proliferative retinopathy. MAIN OUTCOME MEASURES: Retinal blood flow (microliters/min) and conductance (rate of flow per unit of perfusion pressure). RESULTS: In comparison with non-diabetic controls (9.52 microliters/min) and diabetic patients with no diabetic retinopathy (9.12 microliters/min) retinal blood flow was significantly increased in all grades of untreated diabetic retinopathy (background 12.13 microliters/min, pre-proliferative 15.27 microliters/min, proliferative 13.88 microliters/min). There was a significant decrease in flow after pan-retinal photocoagulation in comparison with all the other groups studied (4.48 microliters/min). Conductance of the retinal circulation was higher in the untreated diabetic retinopathy groups. These results were independent of age, sex, type of diabetes, duration of diabetes, glycated haemoglobin concentration, blood glucose concentration, blood pressure, and intraocular pressure. CONCLUSIONS: Retinal blood flow is significantly increased in diabetic retinopathy in comparison with non-diabetic controls and diabetic subjects with no retinopathy. This has implications for controlling hypertension and hyperglycaemia as a strategy in reducing morbidity from diabetic retinopathy.

Adolescent↗

Effect of mixture of surfactants and adsorbents on anaerobic digestion of water hyacinth-cattle dung.

In an effort to improve the anaerobic digestion of water hyacinth-cattle dung with enriched methane content, the effects of mixtures of surfactant-surfactant, adsorbent-adsorbent and surfactant-adsorbent have been studied in various combinations. Among the combinations tested, bentonite and gelatin, gelatin and Tegoprens 43, sodium lauryl sulfate and Tegoprens 42, and Tegoprens 47 and Tegoprens 63 showed more than a 100% increase in gas production with higher methane yield.

Adsorption↗

Spinal oxygenation, blood supply localization, cooling, and function with aortic clamping.

Similar to other methods of organ preservation, "spinoplegia" may protect the spinal cord from the effects of oxygen desaturation during aortic cross-clamping. In porcine experiments, spinal cord O2 saturation was studied during intraoperative localization of the blood supply to the spinal cord using hydrogen; division of arteries not supplying the spinal cord; aortic cross-clamping for 60 minutes; and 60 minutes after unclamping. In 5 animals, 120 mL of cold saline solution with lidocaine (100 mg/dL) was infused into the aorta during aortic cross-clamping. During sequential localization, O2 saturation dropped by 40.02% (standard deviation, 20.16%) for T-14 artery testing versus a decrease of 17.27% (standard deviation, 11.88%; p = 0.0075) for L-5 artery segment testing in the control animals and returned to baseline thereafter. During aortic cross-clamping maximal O2 desaturation was 5% of baseline (15.7%; p less than 0.0001), which improved slightly by 30 minutes after clamping (48% of baseline +/- 37.37%; p = 0.048 versus maximum) and then returned to baseline (97.1% of baseline +/- 41%) with unclamping; 5 minutes later, hyperoxygenation occurred with a progressive decline thereafter (68% of baseline +/- 29.3%; p = 0.025, 45 minutes after unclamping versus baseline). The decrease in spinal motor evoked potentials was significantly less (p less than 0.02) in the treated group. Intraoperative hydrogen testing in 8 patients was demonstrated to be safe. It accurately localized reattached arteries, and O2 saturation of the spinal cord fell by 56% (standard deviation, 29%; p = 0.0025) with aortic cross-clamping. We conclude that spinal cord ischemia occurs with aortic cross-clamping in both animals and humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A rating scale for aggressive behaviour in the elderly--the RAGE.

A 21-item rating scale for measuring aggressive behaviour in psychogeriatric in-patients is described. This scale is designed to be completed by ward staff. It should prove valuable in treatment studies and in studies which aim to investigate the correlates of aggressive behaviour. Studies using the scale demonstrate that when used in conjunction with a ward check list the scale has high reliability and validity.

Aged↗

Aggressive behaviour in elderly psychiatric inpatients.

We describe the types of aggressive behaviour and determine their prevalence in a sample of hospitalized elderly psychiatric patients. Data were obtained by nurse ratings of aggressive behaviour using the recently developed Rating Scale for Aggressive Behaviour in the Elderly; 90 patients were rated over a 3-d period. Nearly half the sample were at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries and the use of restraints and medication for aggressive behaviour were low. Some correlates of the aggressive behaviour were also analysed.

Aged↗

Non-completion of active orthodontic treatment.

This paper reports a retrospective study of patient factors which might be associated with failure to complete orthodontic treatment in a hospital and in a specialist practice. Case records of patients commencing treatment were examined and targeted for further investigation by mailed questionnaires. There was a statistically significant difference in the discontinuation rate between the two groups of patients. Precise reasons for the differences could not be isolated, but did not appear to be related to the age of the patient at the start of treatment.

Adolescent↗

The effect of anticonvulsants on cognitive functioning following a probable encephalitic illness.

A 54-year-old man developed an acute encephalitic illness and subsequently suffered from marked memory difficulties. Considerable improvement with anticonvulsant therapy was demonstrated using a ward-based observation programme and serial neuropsychological assessments. The case report highlights the prominent role played by epileptic activity in determining the severity of the patient's amnesia.

Carbamazepine↗

Incarceration of existing inguinal hernia as a complication of pulmonary function testing.

Pulmonary function testing (PFT) has not been listed as a risk for development of incarceration in an existing inguinal hernia. We report two patients who developed this complication after routine preoperative PFT. We also present data of our retrospective review of eight patients with inguinal hernia who were referred for preoperative PFT. Two out of eight patients suffered incarceration of an existing inguinal hernia. We found no significant difference in mean age, weight, smoking habits, number of forced expiratory maneuvers, time of sustained forced expiratory maneuver, or any PFT data between the groups with and without incarceration. Thus, incarceration of inguinal hernia could not have been predicted prior to PFT and was not related to other factors such as obesity or more severe airway obstruction.

Aged↗

General medicine and ophthalmology: common interests.

A conference entitled 'General Medicine and Ophthalmology' was held at the Royal College of Physicians on 1 June, 1992. Eye diseases are frequently a manifestation of systemic conditions; it is therefore in the patient's best interest for ophthalmologists and physicians to co-operate in their management. Without such co-operation there is the risk that patients fall between stools and neither condition is adequately treated. Medical specialties in which eye conditions are particularly prominent include dermatology, endocrinology, neurology, rheumatology, and cardiovascular diseases. The advantages of joint clinics in medicine and ophthalmology were demonstrated by Professors Alex Crombie and Pat Kendall-Taylor for Graves' disease, by Mr Philip Murray and Dr David Young for uveitis, and by Professor Eva Kohner for diabetes. These included more expert assessments of patients leading to quicker and more complete diagnoses, earlier recognition of complications, and access to a wider range of investigations and treatments, opportunities for collaborative research, improved education for patients and doctors, increased patient convenience, and a stimulus for better control of factors which can worsen the disease.

Ambulatory Care Facilities↗

Diagonal earlobe creases and atheromatous disease: a postmortem study.

The association between the grade of earlobe creases and degree of atheromatous disease was investigated in 376 postmortem examinations. Each earlobe crease was individually graded from 0 to 3. The risk of atherosclerosis as a cause of death was nearly doubled in men with grade 3 creases in both earlobes, and more than trebled in women with bilateral high-grade creases. The risk of death from myocardial infarction was 2.50 in men with high-grade creases and 3.70 in women. The earlobe crease is an important sign of atheromatous disease and it may be useful to include it in the clinical examination of patients.

Aged↗

Phosphorylation occurs in the amino terminus of the Raf-1 protein.

The ability of the Raf-1 protein to morphologically transform murine fibroblasts can be activated by amino-terminal deletions or substitutions. We have compared the phosphorylation states of full-length and representative transforming and non-transforming amino-terminal deletion mutants of the Raf-1 protein using phosphoamino acid analysis and tryptic phosphopeptide mapping. Several [32P]orthophosphate-labeled tryptic phosphopeptides that were present in the full-length Raf-1 protein were absent from the highly transforming 22W Raf-1 mutant (lacking 305 amino-terminal residues). Peptide-specific antisera localized Raf-1 phosphorylation sites to several amino-terminal cyanogen bromide and tryptic peptides that are deleted from the 22W protein. A major phosphorylated tryptic peptide of the Raf-1 protein was immunoprecipitated by antiserum directed against amino acid residues 257-275, a highly conserved region of the raf family. This tryptic peptide is entirely deleted from the highly transforming 22W protein. Subtractive Edman degradation and electrophoretic analysis of the immunoprecipitated tryptic peptide indicated that phosphorylation of the Raf-1 protein occurs at serine 259. Multiple phosphorylated tryptic peptide forms were immunoprecipitated by antiserum directed against Raf-1 residues 283-309. The majority of this tryptic peptide is also deleted from the highly transforming Raf-1 mutant 22W.

3T3 Cells↗

Disopyramide analysis using REMEDi: comparison with EMIT and conventional high performance liquid chromatographic methods.

REMEDi (Rapid EMErgency Drug identification; Bio-Rad) is an automated high performance liquid chromatographic (HPLC) system designed to detect, identify and measure a range of basic and neutral drugs in 0.5-1.0 mL of urine or plasma/serum. We have evaluated REMEDi in the analysis of the antiarrhythmic drug disopyramide in patient samples. The specimens were also analysed by a conventional HPLC method, based on solvent extraction and UV detection (254 nm), and by EMIT. There were good correlations between the results obtained with each method (r = 0.91 or greater). REMEDi gave a lower mean result than EMIT [means +/- SD (mg/L): REMEDi 2.64 +/- 1.10, EMIT 3.14 +/- 1.51; t = 4.0, p less than 0.01; n = 25], but there were no other significant differences in mean results. The principal disopyramide metabolite, mono-N-desalkyldisopyramide, did not interfere in any method. Clearly REMEDi can be used for therapeutic drug monitoring of disopyramide provided enough sample is available.

Autoanalysis↗

Multicenter randomized clinical trial of home uterine activity monitoring for detection of preterm labor.

Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.

Birth Weight↗