An RFLP associated with insulinoma amyloid polypeptide locus (IAPP).
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Amyloid↗
Biomedical subjects
P Patel
Publications and source records attributed to P Patel.
Brain metabolites as 1H NMR markers of neuronal and glial disorders.
1H NMR spectroscopy of human brain in vivo can be used to detect a number of cerebral metabolites including N-acetylaspartate, creatine + phosphocreatine and choline-containing compounds. We have used 1H NMR spectroscopy to analyse these signals in (i) biopsy material from both normal human brain and astrocytomas, and (ii) primary astrocyte cultures. On the basis of this analysis, we conclude that in vivo 1H NMR spectroscopy could play an important clinical role in the non-invasive assessment of neuronal degeneration and proliferation of non-neuronal cells.
Animals↗
Analysis of the HepG2/erythrocyte glucose transporter locus in a family with type 2 (non-insulin-dependent) diabetes and obesity.
A recent report has shown an association between a specific Xba1 restriction fragment of the human HepG2-Erythrocyte glucose transporter gene and Type 2 (non-insulin dependent) diabetes. To further examine the significance of this finding we have studied Type 2 diabetic pedigrees for linkage between the Xba1 alleles of this glucose transporter gene and diabetes. One large pedigree, in which the diabetic phenotype was associated with obesity and insulin resistance, was informative. In this family the disease did not co-segregate with the glucose transporter locus. Formal linkage analysis was performed assuming autosomal dominant inheritance with age-dependent penetrance. At putative gene frequencies of 0.01 and 0.001 the logarithm of the odds for linkage versus non-linkage at a recombination fraction of 0.001 was -1.84 and -3.32 respectively (a value of less than -2 indicates definite non-linkage). Genetic variations in the HepG2-Erythrocyte glucose transporter gene are unlikely to be responsible for the development of diabetes in this pedigree.
Adult↗
Minimal neuropsychological sequelae following prophylactic treatment of the central nervous system in adult leukaemia and lymphoma.
The potential long-term toxicity of central nervous system prophylaxis (CNS-P) in adult acute lymphoblastic leukaemia (ALL, n = 17) and non-Hodgkin's lymphoma (NHL, n = 7) was investigated in a multidisciplinary study. At least 4 years had elapsed from CNS-P (mean 11.5 years) for all patients. Neurological history and physical examination were unremarkable; minor signs were commoner in older patients (P less than 0.02). Psychometry yielded normal results, but individual verbal IQ generally exceeded performance IQ, with a trend to more marked differences in younger adults (P = 0.06). EEG was scored and differed significantly from that of controls, with a tendency to more marked (but still minor) abnormalities in younger patients (P = 0.06). Brainstem auditory evoked potentials demonstrated significant but generally minor abnormality in 24% of patients. CT brain scan revealed widening of cerebral hemisphere sulci to greater than 3 mm in 38% of patients; cerebral atrophy was commoner in the older group (P less than 0.02) and those with neurological signs (P less than 0.02). MRI brain scans were normal in all patients tested. Thus, following standard CNS-P for ALL at this hospital, there is a 5% primary CNS relapse rate, and only minimal, mainly subclinical, long-term neuropsychological toxicity.
Adult↗
A host-encoded DNA-binding protein promotes termination of plasmid replication at a sequence-specific replication terminus.
We have purified approximately 6600-fold an approximately 40-kDa protein (Ter protein) encoded by Escherichia coli that specifically binds to two sites at the 216-base-pair replication terminus (tau) of the plasmid R6K. Chemical footprinting experiments have shown that the Ter protein binds to two 14- to 16-base-pair sequences that exist as inverted repeats in the tau fragment. Site-directed mutagenesis of one of the terminus sequences (tau R) resulted in a mutant tau R that failed to bind to the Ter protein. The same mutant terminus also failed to terminate DNA replication in vivo. These experiments strongly suggest that the interaction of the Ter protein with tau sequences plays an essential role in the termination of DNA replication, specifically at tau.
Base Sequence↗
Postmortem metabolic indices of antemortem adrenergic stimulation.
Tissue lactate concentration has been reported to be a useful postmortem indicator of antemortem awareness of mortal danger. The purpose of this study was to determine further whether selected tissue metabolites could be used as postmortem markers of antemortem adrenergic stress. Sprague-Dawley albino rats were anesthetized with pentobarbital and then injected with 2.0 mg kg-1 i.p. epinephrine hydrochloride to induce experimentally a severe sympathetic response that may be associated with the awareness of mortal danger; 20 min after the injection of epinephrine, when the metabolic response was at its peak, the animals were killed by exsanguination. Samples of the following tissues were removed immediately prior to death (0 h) and 48 h postmortem: soleus, plantaris, kidney medulla, kidney cortex, liver, and heart. These samples were analyzed for glycogen, lactate, ATP, creatine phosphate, pH, and total protein concentration. Significant differences in lactate concentration were observed in all tissues except soleus at 0 h in the epinephrine-injected animals. Specific tissues also had significant reductions in glycogen, ATP, and creatine phosphate concentrations at 0 h. At 48 h postmortem, however, only the liver and soleus lactate concentrations were significantly different from the 48-h control samples. It is unlikely that these small differences found in some tissues at 48 h postmortem would be detected in an uncontrolled accident situation. We concluded from these findings that these selected tissue metabolites are not useful as long-term postmortem indicators of antemortem adrenergically induced hypermetabolism.
Adenosine Triphosphate↗
Stem-cell depletion and grid therapy.
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Animals↗
A micro-method for measuring total protein in cerebrospinal fluid by using benzethonium chloride in microtiter plate wells.
By using a benzethonium chloride concentration 12-fold that described originally (Clin Chem 1979;25:1317-9), we developed a reliable method suitable for routine measurement of total protein in cerebrospinal fluid. Only 10 microL of sample is required. Reactivity to immunoglobulin G (IgG) and to albumin (Alb) is similar, as is necessary for specimens that can have very varied IgG/Alb ratios. The assay, performed in a microtiter plate for ease of use, has a between-batch coefficient of variation of 3.4% for a protein concentration of 450 mg/L. This contrasts with a dye-binding technique with Ponceau S, for which the CV was 9% at the same concentration.
Albumins↗
Osteoradionecrosis of the jaw bones at the University of Kentucky Medical Center.
There is disagreement over the management of teeth in irradiated head and neck cancer patients. Some oral surgeons support preirradiation extraction; others favor maintaining teeth. Before 1974, The University of Kentucky Department of Radiation Medicine found osteoradionecrosis (ORN) of the jaw in 10.9% of 220 irradiated cancer patients. After a program of oral care was instituted, the incidence declined to 2.7%. Of 109 patients who received radiotherapy between 1976 and 1985, only three (2.7%) developed ORN of the mandible. There was also a reduction in patients treated with interstitial therapy during this time. A review of the most recent experiences shows that, with present management methods at the University of Kentucky, ORN is not a significant problem. Of 30 patients treated in 1986, only one had ORN, and this was of the maxilla. Post-irradiation extractions were not identified as a significant risk for necrosis. Hyperbaric oxygen is used as a treatment for persistent ORN.
Head and Neck Neoplasms↗
Contractile actions of epidermal growth factor-urogastrone in isolated smooth muscle preparations from guinea pig stomach: structure-activity relationships and comparison with the effects of human transforming growth factor-alpha.
In two distinct isolated guinea pig stomach smooth muscle preparations, we have studied the contractile effects of intact human epidermal growth factor-urogastrone (mEGF-URO) and murine epidermal growth factor-urogastrone (mEGF-URO), along with the actions of derivatives (hEGF-URO1-47; mEGF-URO1-47) lacking the C-terminal pentapeptide. The effects of these polypeptides were compared with the actions of human transforming growth factor-alpha (TGF-alpha). In the longitudinal muscle preparation, wherein the contractile actions of agonists were abolished by 1 microM indomethacin, the order of potency was: hEGF-URO = mEGF-URO greater than TGF-alpha greater than hEGF-URO1-47 greater than or equal to mEGF-URO1-47. In this longitudinal muscle preparation, reproducible contractions could be obtained by rinsing the preparation free of agonist and by maintaining intermittent dose intervals of 1 hr or more. In contrast, in the circular muscle preparation, all agonists elicited a contractile effect that was present in the presence of 1 microM indomethacin. In this indomethacin-treated preparation, when an intermittent dosing regimen was used, repeated exposure to either human or murine EGF-URO caused a persistent desensitization. However, in the indomethacin-treated circular muscle preparation, repeated exposure to TGF-alpha and hEGF-URO1-47 during an intermittent dosing schedule caused only a low degree of persistent desensitization. In the indomethacin-treated circular muscle preparation, the order of potency for the contractile effect was: TGF-alpha = hEGF-URO1-47 greater than or equal to hEGF-URO.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Analysis of the pro-opiomelanocortin gene in non-insulin dependent diabetic families.
Products of the pro-opiomelanocortin gene have been shown to have marked effects on insulin secretion. Selective antagonists of beta-endorphin have been reported to correct the impaired insulin secretory response to glucose seen in non-insulin dependent diabetes. Families with an autosomal dominant pattern of inheritance of diabetes were studied for possible linkage between diabetes and the pro-opiomelanocortin locus by examining the inheritance of a Rsa 1 restriction fragment length polymorphism. In two families with classical Type 2 diabetes there were recombinants between the disease and the pro-opiomelanocortin locus. In a family with maturity-onset diabetes of the young there were only two informative meoises, but there was a crossover between the disease and the pro-opiomelanocortin gene locus. Inherited defects in or near the pro-opiomelanocortin gene locus are unlikely to be directly involved in the aetiology of non-insulin dependent diabetes.
Alleles↗
Measurement of the distribution coefficients of several classes of drug using reversed-phase thin-layer chromatography.
Using reversed-phase thin-layer chromatography, with octan-1-ol as stationary phase and phosphate buffer (pH 7.4) as mobile phase, the behaviour of different drugs at 37 degrees C was studied. Three classes of drug were examined: beta-adrenoceptor antagonists, non-steroidal anti-inflammatory agents and dihydropyridine calcium antagonists. As well as ranking these compounds in terms of their distribution coefficients, an attempt was also made to assign a quantitative value to each. For the beta-adrenoceptor antagonists this was done by using a series of published values obtained using the shake-flask technique: for the non-steroidal anti-inflammatory agents a series of standard compounds was used. No good calibration data were available for the dihydropyridine calcium antagonists, but approximate values were assigned. The results obtained were compared with other published data and the applicability of the method discussed.
Adrenergic beta-Antagonists↗
Intoxication from vitamin A in an asthmatic child.
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Asthma↗
A new Sst 1 RFLP associated with human insulin receptor locus.
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Chromosomes, Human, Pair 19↗
Feasibility study of Californium-252 for the therapy of stage IV cervical cancer.
Twenty patients with Stage IVA and IVB cervic cancers were treated with Californium-252 (Cf) neutron brachytherapy (NT) in a feasibility trial between 1976 and 1986. Eleven patients had Stage IVA disease; nine patients had Stage IVB disease. Patient compliance with therapy was poor in four of nine patients with Stage IVB disease, and the 50% survival time was 6 months. In Stage IVA disease there were 18% 3-year survivals. For those that failed, the 50% survival time was 7.5 months. Because of the frequency of disseminated metastases, effective adjuvant therapy needs to be developed to use after the tumor debulking therapy, especially for Stage IVB disease. A single early Cf-NT implant followed by 6000 cGy of whole-pelvis fractionated radiation would accomplish this adequately for local tumor control and palliation.
Adult↗
Linkage analysis of the human insulin receptor gene in type 2 (non-insulin-dependent) diabetic families and a family with maturity onset diabetes of the young.
The possibility of linkage between the human insulin receptor gene locus and diabetes was examined in three Type 2 (non-insulin-dependent) diabetic families and one family with maturity onset diabetes of the young. Insulin receptor gene haplotypes were established using BglII, Rsal and Sstl restriction enzyme digests of genomic DNA from all available family members. The digested DNA was subjected to agarose gel electrophoresis, Southern blotted, and hybridised to 32P-labelled human insulin receptor gene cDNA. In the pedigree with maturity onset diabetes of the young, formal linkage analysis allowed exclusion of close linkage between the insulin receptor locus and diabetes (logarithm of the odds for linkage versus non-linkage was -5.35 at recombination fraction of 0.01). This confirms the absence of linkage between insulin receptor and diabetes which has been reported in two similar pedigrees. In the three Type 2 diabetic families there were a minimum of 4 recombinants between the insulin receptor locus and diabetes, which makes a direct role for insulin receptor defects unlikely. The importance of using realistic estimates of penetrance when performing linkage analysis in a disease with a late age of onset is emphasised. In contrast to the one previous linkage analysis study of the insulin receptor gene, no specific association of diabetes with the rare Sst1 S1(-) allele was observed in either the maturity onset diabetes of the young or the Type 2 diabetic families.
Adolescent↗
Increased natural resistance to Listeria monocytogenes in senescent mice correlates with enhanced macrophage bactericidal activity.
Natural resistance to Listeria monocytogenes is increased in aging (18-22-month-old) AB6F1 mice when compared to their younger counterparts. We have investigated several parameters of macrophage function of old AB6F1 mice to establish what macrophage characteristics determine their enhanced resistance to Listeria. Senescent mice had an increased number of macrophages present in unstimulated peritoneal cavity. These macrophages exhibited enhanced bactericidal activity and H2O2 production. Old mice showed a diminished subcutaneous inflammatory response. Kupffer cells obtained from normal uninfected old mice had good levels of listericidal activity, but Kupffer cells obtained from normal young mice could not kill Listeria. The increased natural resistance to Listeria monocytogenes seen in old AB6F1 mice could be the result of enhanced macrophage bactericidal activities in the liver prior to the infection.
Aging↗