Search PubMed⌕ Search

Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 469 records · Page 26Linked to original sources
PubMed1988

Mild hemophilia A associated with a cryptic donor splice site mutation in intron 4 of the factor VIII gene.

Hemophilia A, an X-linked disease caused by deficiency of factor VIII, is characterized by variation in clinical severity and coagulation activity. This variation is though to reflect heterogeneity of mutations in the factor VIII gene. Here we describe a CG-to-CA mutation within a potential cryptic donor splice site in intron 4 of the factor VIII gene from a patient with mild disease. This mutation makes the cryptic sequence resemble more closely the consensus sequence for donor splice sites. We infer that the mutation activates the cryptic donor splice site, which in turn causes a defect in RNA processing.

Adult↗
PubMed1988

Endolaser treatment of the ciliary body for severe glaucoma.

Endolaser photocoagulation of the ciliary body was used to treat 42 eyes with severe glaucoma that could not be managed successfully by medical therapy and conventional glaucoma surgery. Follow-up ranged from 6 to 36 months (mean, 13 months). The preoperative intraocular pressure (IOP) ranged from 13 to 76 mmHg (mean, 37 mmHg). The postoperative IOP ranged from 1 to 44 mmHg (mean, 17 mmHg), representing an absolute decrease of 20 mmHg, and a mean decrease of 48%. After one or two (7 eyes) treatment sessions, 11 eyes (26%) had an IOP less than 21 mmHg without medications; 21 eyes (50%) had an IOP less than 21 mmHg with medications; 5 eyes (12%) had an IOP of 21 to 25 mmHg with or without medications; and 5 eyes (12%) had an IOP greater than 25 mmHg. Postoperatively, the number of antiglaucoma medications required was reduced from a mean of 2.8 +/- 0.13 to a mean of 1.4 +/- 0.19. Twenty-three (72%) of 32 patients were able to discontinue carbonic anhydrase inhibitors.

Adolescent↗
PubMed1988

125I-labeled 8-phenylxanthine derivatives: antagonist radioligands for adenosine A1 receptors.

A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 adenosine receptors of bovine and rat brain and A2 receptors of human platelets was examined. The addition of arylamine or photosensitive aryl azide groups to the 3-position of xanthine had little effect on A1 binding affinity with or without iodination, whereas substitutions at the 1-position caused greatly reduced A1 binding affinity. The addition of an aminobenzyl group to the 3-position of the xanthine had little effect on A2 binding affinity, but 3-aminophenethyl substitution decreased A2 binding affinity. Two acidic 3-(arylamino)-8-phenylxanthine derivatives were labeled with 125I and evaluated as A1 receptor radioligands. The new radioligands bound to A1 receptors with KD values of 1-1.25 nM. Specific binding represented over 80% of total binding. High concentrations of NaCl or other salts increased the binding affinity of acidic but not neutral antagonists, suggesting that interactions between ionized xanthines and receptors may be affected significantly by changes in ionic strength. On the basis of binding studies with these antagonists and isotope dilution with the agonist [125I]N6-(4-amino-3-iodobenzyl)adenosine, multiple agonist affinity states of A1 receptors have been identified.

Adenosine↗
PubMed1988

Photoaffinity labeling adenosine A1 receptors with an antagonist 125I-labeled aryl azide derivative of 8-phenylxanthine.

We have derivatized a series of 125I-labeled 8-phenylxanthines with photoactive aryl azide groups on the 1- or 3-position of the xanthine ring. A 3-azidophenethyl derivative was found to be optimal for use as an antagonist photoaffinity label for adenosine A1 receptors. Following photoactivation, radioactivity was covalently and specifically incorporated into a 34,000-dalton and, to a lesser extent, into a 24,000-dalton polypeptide of rat brain membranes. Photoincorporation into both polypeptides was competitively inhibited by adenosine analogues with a potency order typical of adenosine A1 receptors, but the 24,000-dalton polypeptide bound both agonists and antagonists with lower affinity than the 34,000-dalton polypeptide. Specific photolabeling of receptors in brain membranes of rat, guinea pig, dog, and cow did not show any variation in the 34,000-dalton adenosine receptor binding subunit. The adenosine agonist photoaffinity label [125I]N6-(4-azido-3-iodobenzyl)adenosine also specifically photolabeled the 34,000-dalton polypeptide, but photoincorporation of the agonist was less efficient than the antagonist and, unlike the antagonist, was greatly reduced by guanosine 5'-(beta,gamma-imidotriphosphate). The results indicate that the antagonist photoaffinity label may be more useful than agonists particularly for labeling uncoupled receptors.

Affinity Labels↗
PubMed1988

Do overlapping vessels protect against canine right ventricular infarction after right coronary artery occlusion?

The severity of ischaemia in the left ventricle from total coronary occlusion is modified by retrograde blood flow through collateral or overlapping vessels, but whether that is true for the right ventricle is not known. The consequences and extent of ischaemic damage from occlusion of the right coronary artery were studied in anaesthetised dogs. In group 1 (n = 9), the right coronary artery alone was occluded; in group 2 (n = 8), the right coronary artery and overlapping vessels from the left anterior descending and circumflex coronary arteries were occluded. Occlusion for 2 h caused right ventricular end diastolic pressure to increase by 2.8(SEM 0.4) mm Hg in group 1 (p less than 0.05) and by 1.9(0.5) mm Hg in group 2 (p less than 0.05). Fractional shortening in the ischaemic zone became akinetic in group 1: 12.0(1.4)% v 0.1(1.6)%; p less than 0.05; and dyskinetic in group 2: 12.1(2.1)% v -1.2(0.9)%; p less than 0.05. In both groups, fractional shortening remained depressed during the ensuing 2 h of reperfusion. The incidence of right ventricular free wall necrosis was 56% in group 1 but 100% in group 2 (p = 0.082). The area of necrosis, expressed as a percentage of the area at risk, was 13.9(6.6)% in group 1 in contrast to 66.9(4.5)% in group 2 (p less than 0.05). Both groups had equal involvement of the subendocardial and subepicardial layers. We conclude that ligating epicardial overlapping vessels in addition to the right coronary artery produces a larger area of right ventricular free wall necrosis.

Animals↗
PubMed1988

Characterization of the effects of neurokinins on canine antral muscle.

The excitation of longitudinal antral muscle by substance P (SP) involves both a myogenic and a cholinergic effect. To examine if these responses are mediated by different neurokinin receptors, we studied the mechanical response and the release of [3H]acetylcholine from antral muscle strips in response to SP, substance P methylester (SPME), neurokinin A (NKA), neurokinin B (NKB), and several non-mammalian tachykinins. All peptides studied showed a dose-dependent inotropic and chronotropic effect on spontaneous phasic contractions. This ionotropic effect in longitudinal muscle was partially atropine sensitive for SPME, SP, and NKB but not for NKA, whereas neither atropine nor tetrodotoxin had an effect in circular muscle. In longitudinal muscle, all three neurokinins were equipotent. In longitudinal muscle treated with atropine and in circular muscle, the rank order of potency for the inotropic response was NKA greater than NKB greater than SP greater than SPME. For the chronotropic response the rank order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP caused a dose-dependent, tetrodotoxin-sensitive increase in [3H]acetylcholine release from strips preincubated with [3H]choline. NKA was significantly more potent to release [3H]acetylcholine than either NKB or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine enkephalinamide and the SP antagonist, spantide. These results are consistent with the hypothesis that NKA is the natural ligand mediating the myogenic inotropic response in both muscle layers and the cholinergic response in longitudinal muscle.

Acetylcholine↗
PubMed1988

125I-BW-A844U, an antagonist radioligand with high affinity and selectivity for adenosine A1 receptors, and 125I-azido-BW-A844U, a photoaffinity label.

3-(4-Amino)phenethyl-1-propyl-8-cyclopentylxanthine (BW-A844U) has been synthesized and shown to bind with high affinity to adenosine A1 receptors of bovine brain membranes (KD = 0.23 nM). This compound is highly selective for A1 receptors; the KI for binding to A2 receptors of human platelet membranes is 2.0 microM (A2/A1 ratio = 8700). Radioiodination of the 3-aminophenethyl group resulted in 125I-BW-A844U, a radioligand that retains high affinity for A1 receptors in bovine brain membranes (KD = 0.14 nM) and to 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate-solubilized receptors (KD = 0.34 nM). Specific binding of 125I-BW-A844U represented greater than 90% of the total binding at the KD. From the association constant (K1 = 5.0 X 10(8) M-1min-1) and the dissociation constant (K-1 = 0.064 min-1), the kinetic KD (K-1/K1) in membranes was calculated to be 0.13 nM. NaCl (1 M) had little effect on the binding affinity of 125I-BW-A844U, in contrast to the large effect of salt on the binding affinity of acidic antagonist radioligands. 8-Sulfophenyltheophylline inhibited radioligand binding with a Hill coefficient of 1.0, indicative of a single affinity binding state for the antagonist. By comparison, two distinct agonist affinity states of A1 receptors for the agonist (R)-phenylisopropyladenosine could be resolved, a high affinity state (62%, KH = 74 pM) and a low affinity state (KL = 3.83 nM). The addition of 0.1 mM guanylylimidodiphosphate converted all receptors to the low affinity state. Addition of NaCl (0.5 M) decreased the fraction of receptors in the high affinity state and increased both KH and KL, suggesting that NaCl alters coupling of receptors to G proteins and influences the conformation of the receptor polypeptide, whether or not the receptor is coupled to a G protein. Conversion of the arylamine on the 3-position of 125I-BW-A844U to an aryl azide resulted in a photoaffinity label, 125I-azido-BW-A844U. Upon photoactivation, the photoaffinity label was specifically photoincorporated into the 34,000-dalton polypeptide of the adenosine A1 receptor.

Adenosine↗
PubMed1987

Measles immunity in children: the 1985 national immunisation survey.

In April 1985 a national immunisation survey was conducted, in the course of which blood samples were collected from approximately 3000 randomly selected children throughout the country. The study sample comprised approximately 1000 new school entrants, 1000 standard three pupils, and 1000 form four students. The sera were tested for morbilli antibody using an ELISA technique. Twenty-one percent of the five year olds lacked antibody, suggesting that an overall immunisation rate of about 80% is being achieved. Fourteen percent of the 15 year olds lacked antibody, suggesting that this rate of immunisation is partially interfering with the circulation of the wild virus. We conclude that a sizeable pool of susceptible adolescents is accumulating at a time when some wild virus activity still persists, and anticipate a shift in the peak age of measles infection from the 5-9 to the 10-15 age group. This unfortunate side effect of the national immunisation programme could be minimised by improving immunisation uptake in young childhood. Suggestions are made as to how this could be achieved.

Adolescent↗
PubMed1987

Synthesis and biodistribution of [125I]iodo- and [75Se]seleno-ergoline derivatives.

(8 beta)-8-([125]Iodomethyl)-6-propylergoline (125I-3) was prepared by refluxing the mesyl analog with Na125I in methyl-ethyl-ketone, followed by HPLC, in a radiochemical yield greater than 70%. [75Se]Selenopergolide (75Se-2) was prepared in 74% yield starting with H75(2) SeO3. The biodistribution studies of the two compounds in male rats show good uptake by the adrenals and the brain. Compound 75Se-2 had higher adrenal uptake and adrenal-to-blood ratios (4.2% dose/g and 70:1) than 125I-3 (3.6% dose/g and 23.8:1) at 15 min post injection. The two compounds had almost equal brain uptake (0.91% dose/g for 75Se-2 and 1.14% dose/g for 125I-3), but 75Se-2 showed higher brain-to-blood ratios (15.2:1 vs 7.3:1) at 15 min post injection. This study indicates that 75Se-2 and 123I-3 may be useful agents for imaging the adrenal and the brain.

Animals↗
PubMed1987

Relationship between Respiration and CAM-Cycling in Peperomia camptotricha.

Mature leaves of well-watered Peperomia camptotricha show Crassulacean acid metabolism (CAM). Young leaves show CAM-cycling in which CO(2) uptake occurs during the day concomitant with a marked diurnal fluctuation of organic acids as in CAM. Evidence is presented suggesting that respiration is the source of CO(2) for nocturnal acid synthesis in leaves exhibiting CAM-cycling. Respiratory quotients for these leaves were consistently much less than unity despite the fact that the leaves metabolize starch. The conservation of CO(2) by refixation into acids at night represents about 17% of the total photosynthetically fixed CO(2) and about 50% of the total respiratory CO(2).

Journal Article↗
PubMed1987

A comparison of two incubation temperatures for the isolation of gram-negative contaminants from raw materials and non-sterile pharmaceuticals.

Selective and non-selective broth enrichment techniques may be used in the isolation of microbial contaminants from pharmaceutical products. A non-selective method may give better recovery rates for damaged organisms. A trial was carried out to determine whether the recovery of Gram-negative contaminants could be improved by using an incubation temperature of 30 degrees C for 48 h, rather than the more widely used 37 degrees C for 24 h. Contaminants were isolated from 3.2% of samples incubated at the lower temperature compared with 0.8% at the higher temperature. The recovery rate from raw materials improved noticeably (9.0% compared with 0.9%).

Alcaligenes↗