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Biomedical subjects

S Ismail

Publications and source records attributed to S Ismail.

At least 73 records · Page 4Linked to original sources

Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study.

3-Cyano-imipramine (cianopramine) is a potent and selective inhibitor of serotonin uptake into synaptosomes. In a double-blind trial, 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine (n = 20, mean daily dose 3.3 +/- 0.6 mg) amitriptyline (n = 20, mean daily dose 86.4 +/- 21 mg) or placebo (n = 20) orally. According to the ratings of the Hamilton Scale of Depression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P less than 0.02). The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group. The findings suggest that cianopramine is a promising new antidepressant.

Adjustment Disorders↗

Chromosomal deletion and plasmid complementation of the photosynthetic reaction center and light-harvesting genes from Rhodopseudomonas capsulata.

Using in vitro interposon mutagenesis, Rhodopseudomonas capsulata strains have been constructed wherein all or part of the reaction center (RC), light-harvesting I (LHI), and light-harvesting II (LHII) structural genes have been deleted. In one series of strains, the 2778-bp ApaI fragment bearing more than 90% of the rxcA operon (promoter and structural genes coding for LHI beta, LHI alpha, RC-L and RC-M) has been deleted from the chromosome. When the rxcA operon is deleted, resultant strains possess only LHII and are photosynthetically defective. The rxcA deletion in an LHII- background results in a strain lacking all LH antennae and RC subunits. As expected this strain has no near-infrared absorption characteristic of LH or RC bacteriochlorophyll. The rxcA deletion may be complemented by a pBR322 derivative carrying the entire rxcA operon (pU21). In a second series of deletion mutants, the 2500-bp BstEII-StuI fragment, including the beta and alpha structural genes coding for LHII has been deleted from the chromosome. In the wild-type background, functional RC and LHI are synthesized. LHII may be restored in the deletion strain by conjugal transfer of the plasmid pU2 which carries the LHII operon.

Chromosome Deletion↗

Structure of the SAD mutation and the location of control sites at silent mating type genes in Saccharomyces cerevisiae.

The SAD mutation, an extra mating type cassette, has been shown to arise from an unequal mitotic crossover between the MAT and HMR loci, resulting in the formation of a hybrid cassette and a duplication of the MAT-HMR interval. The SAD cassette contains the "a" information and left-hand flanking regions from the parental HMRa cassette and the right-hand flanking sequences of the parental MAT cassette. This arrangement of flanking sequences causes a leaky but reproducible mating phenotype correlated with a low-level expression of the cassette as measured by RNA blotting. This weak expression is attributed to the loss of one flanking control site normally present at the silent HM storage loci.

Alleles↗

Therapeutic efficacy and tolerance of diclofensine in psychoreactive depression--a double-blind comparison with placebo.

Diclofensine increases the availability of the three neurotransmitters dopamine, noradrenaline and serotonin by inhibiting their re-uptake into synaptosomes. In a randomized double-blind parallel-group comparative study, a total of 40 patients, some hospitalized (n = 11) and some ambulatory (n = 29), mean age of 39.6 years +/- 12 S.D., with psychoreactive depression were treated for 30 days with 2 X 25 mg/day of diclofensine or with placebo. The assessments of efficacy indicated superiority of diclofensine over placebo. The number of "improved" patients (reduction in the overall depression scores by 50% or better) relative to that of "not improved" patients, was found to be statistically significant (p less than 0.025) on day 10 of treatment. With respect to individual symptoms, anxiety showed a significantly (p less than 0.05) better improvement under diclofensine than under placebo. Side effects were observed in one patient in each group. One patient (diclofensine group) reported a transient slight somnolence, the other (placebo group) reported episodes of transient dizziness. Based on these data it can be concluded that diclofensine is a well tolerated and effective drug for the treatment of symptoms associated with reactive depressions.

Adjustment Disorders↗

Antigen shared by human hemopoietic precursor cells and T and B lineage cells.

In this study, we investigated antigens present at the surface of acute myeloblastic leukemia (AML) cells by using the monoclonal antibody (MAb) approach. The MAb AGF43 reacted with acute myeloid and lymphoid leukemia cells and chronic lymphocytic leukemia cells and was unreactive against chronic myeloid leukemia cells. A large proportion of AML blasts showing minimal or no differentiation (AML-M1) were intensely labeled by AGF43 in contrast to a smaller percentage of blasts showing partial differentiation (AML-M2 and acute myelomonocytic leukemia). The AGF43 antigen is expressed by bone marrow lymphoid (TdT+) and myeloid (CFU-GM) progenitor cells, 95% of B cells and 65% of T cells in the blood and absent from monocytes. Only 17% of normal myeloblasts were weakly stained by AGF43. Sections of tonsil and spleen were used to confirm that, unlike antibodies to MHC class II antigens, AGF43 stained a majority of T cells and macrophages were unreactive. In conclusion, the MAb AGF43 identifies a new precursor cell antigen. The distribution of this antigen during normal myelopoiesis and on AML cells support the suggestion that acute myeloid leukemias originate in pluripotent or closely related myeloid stem cells.

Antibodies, Monoclonal↗

Changing concepts in the presentation, diagnosis and management of the Zollinger-Ellison syndrome.

Nine patients with the Zollinger-Ellison syndrome seen at a single referral centre between 1976 and 1981 are presented to highlight changes in the recognition, diagnosis and management of the condition. Less well recognized manifestations such as diarrhoea and features of the multiple endocrine neoplasia (MEN) type I syndrome are described, and the simplification of the pre-operative diagnosis by the use of both the serum gastrin estimation and the secretin provocation test considered. The problem of tumour localization is discussed with special reference to the newer techniques such as ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) and CAT scanning, and the value of arteriography confirmed. The striking advances in management during the past few years are stressed with special reference to the role of the H2-receptor blocking drugs. Despite their profound inhibitory effect on both acid secretion and symptoms, all patients with the exception of those with proven metastases or the MEN type I syndrome underwent laparotomy to exclude a resectable lesion. If no resectable lesion was found truncal vagotomy was performed to facilitate acid secretory control post-operatively and H2-receptor blocking drugs continued in a dose necessary to maintain basal acid secretion under 5 mmol/hr.

Adolescent↗

Sgd 101/75: a sympathomimetic that can be used to identify a new subtype of alpha-adrenoceptor, the alpha 1s-adrenoceptor.

When Sgd 101/75 was compared with clonidine in a number of tests for CNS activity, Sgd 101/75 exhibited little activity in any test. Sgd 101/75 raised BP without affecting HR in several species of anaesthetised animals. The rise in BP was subject to tachyphylaxis, could be antagonised by alpha 1-adrenoceptor antagonists, and was obtainable in reserpinised animals. The vasopressor effect of NA was antagonised by Sgd 101/75. Thus Sgd 101/75 is a directly acting partial agonist for vascular alpha 1-adrenoceptors. On the coaxially stimulated guinea-pig ileum and field stimulated rat vas deferens, the twitch response to single pulse stimulation was reduced by NA or clonidine stimulating prejunctional alpha 2-adrenoceptors. Sgd 101/75 antagonised these inhibitory effects competitively (pA2 for antagonism of clonidine on the vas = 6.12). Sgd 101/75 acted as a specific partial agonist on the alpha 1-adrenoceptors of the guinea-pig taenia caecum that subserve relaxation of this tissue. Sgd 101/75 was a full agonist on the alpha 1-adrenoceptors of the rat anococcygeus in vitro. Phenoxybenzamine (300 pM for 30 min, followed by 20 washes over the next 30 min) reduced contractions of the anococcygeus to Sgd 101/75, but produced little inhibition of NA-induced contractions. In phenoxybenzamine-pretreated preparations, Sgd 101/75 (400 microM) did not antagonise NA (maximal effect and EC50 values not changed significantly), so it was concluded that Sgd 101/75 and NA interact with different alpha 1-adrenoceptor subtypes in this tissue. The subtype specifically activated by Sgd 101/75 was designated the alpha 1s-adrenoceptor. The mouse anococcygeus contained alpha 1s-adrenoceptors, whereas this receptor was absent from the rabbit anococcygeus.

Adrenergic alpha-Agonists↗

Pharmacological and toxicological studies of binodaline hydrochloride.

It has been shown, in extensive animal experiments, that 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline HCl, Sgd-Scha 1059), can be regarded as an antidepressant with novel characteristics. With anticholinergic and histamine-antagonistic effects almost completely lacking, the main effects of binodaline HCl are to increase noradrenergic influences and to produce CNS depression. The acute toxicity of binodaline HCl is comparatively low, and the good tolerance has been demonstrated in long-term studies in laboratory animals.

Animals↗

Pharmacological studies with beclobrate, a new hypolipidemic agent.

A new diphenylmethane derivative with potent hypolipidemic activity, ethyl-(+/-)-2-[[alpha-(p-chlorophenyl)-p-tolyl]-oxy]-2-methylbutyrate (Sgd 24774, beclobrate) has been investigated in animals. From a comparison of the ED25 values of beclobrate and clofibrate, the new drug is 11 times more potent with respect to its hypocholesterolemic activity and 36 times more hypotriglyceridemic in normally fed rats, and lowers fructose-induced hypertriglyceridemia in rats 20 times as effectively as does clofibrate. On a similar basis of comparison, the hepatomegalic effect of beclobrate in rats is 22 times that of clofibrate. High doses of beclobrate did not reveal any other peripheral or central effects in a wide range of pharmacological tests, indicating a high specificity of the action of the drug on blood lipids. On the basis of the results of interaction studies performed with beclobrate in animals, administration of the substance in man should be largely free from risk.

Animals↗

Response to the central and peripheral airways to cigarette smoking in human and rats.

The effects of tobacco smoke on the central nd peripheral airways were assessed in humans and rats by direct and indirect methods. In both species tobacco smoke affected the central and peripheral airways. In humans there were apparent decreases in the 1-second forced expiratory volume, peak expiratory flow rate and significant increases in closing volume and closing capacity (P less than 0.001). In rats significant changes were seen in specific airway resistance from the 6th week of exposure onwards. Similarly, airway luminal diameter decreased markedly in tobacco-exposed animals to subthreshold concentrations of acetylcholine (10(-8) M). This decrease was also exposure time dependent. The increased responsiveness of the respiratory system has been attributed to inter alia: (1) increased vagal activity; (2) increased mucus production leading to decreased airway lumen; (3) mucosal swelling due to changed ionic constellation; (4) disturbance of the lungs' defense mechanism; (5) imbalance in and easy accessibility to the adrenoceptors.

Adult↗

Bronchomotor tone in protein-energy malnutrition.

The study examined the reactivity of the tracheobronchial tree of rats maintained on low protein and tryptophan-deficient diets. It was found that: (1) Rats maintained on 5% protein or tryptophan-deficient diets showed little or no weight gain. A 15% protein diet was adequate for normal growth of female rats, but not of male rats. (2) Airways of malnourished rats showed significant bronchoconstriction when treated to an acetylcholine (AcCh) concentration of 10(-11) M. The threshold concentration of AcCh for normal rats was 10(-5) M. Airways of malnourished rats were also more sensitive to cold. (3) Rehabilitation of the malnourished rats attenuated the response to AcCh. Recovery, however, was not complete. (4) Prior application of phentolamine and atropine markedly reduced the sensitivity of the airways of malnourished rats to AcCh. The results seem to indicate that alpha-adrenoceptors and the vagus nerve may be involved in the observed increased reactivity of airways of malnourished rats.

Acetylcholine↗

Tracheobronchial function in health and disease. Effect of mucolytic substances.

The effect of mucolytic and expectorant substances on ciliary beat frequency, mucus transport velocity and mucus production, was investigated in normal and bronchitic rats. The results showed that: (i) N-acetylcysteine and S-carboxymethylcysteine were mildly cilioexcitatory at low and ciliodepressive at higher concentrations in both normal and bronchitic rats. A similar pattern was seen in mucus transport velocity. (ii) Bisolvon enhanced all aspects of mucociliary activity in both groups of animals. Sobrepin was less effective than Bisolvon and more effective than Tachoquilin. (iii) Geleomyrtol, Ozothin and prostaglandin E1 were all cilioexcitatory in rats with bronchitis. Mucus transport velocity was similarly stimulated by both Geleomyrtol and Ozothin. (iv) Ammonium chloride and potassium iodide enhanced mucociliary activity in normal and bronchitic rats. (v) All substances stimulated mucus production, however, the most potent was prostaglandin E1. The mechanisms for increased mucociliary activity involve inter alia the probable cleaving of disulfide bridges, decreased mucosal swelling, altered rheological characteristics and stimulation of adenylate cyclase.

Animals↗

Direct determination of luminal diameter changes in intrapulmonary airways.

A method is described for the direct measurement of changes in luminal diameter at all levels of the airway. Using this method it was found that (i) abrupt bronchiolar collapse occurred in the preterminal and terminal bronchioles once the luminal diameter was reduced to a critical level: (ii) decreased temperatures resulted in airway narrowing which was reversed by increasing the temperature to above 25 degrees C; as a rule, airway narrowing followed a cranial to caudal direction, and higher concentration of a drug being required to close the peripheral airways; (iii) bronchodilators except Carbuterol had no effect on resting bronchial tone or on acetylcholine-induced constriction in the absence of alpha-adrenoceptor blockade; (iv) at 35 degrees C rhythmic waves (frequency 6--20/min) were observed; these waves travelled from the periphery in a cranial direction.

Action Potentials↗

Lactate dehydrogenase and transaminase activities in the cerebrospinal fluid of protein-energy malnourished children.

The present study is aiming to assess whether there are variations in the activities of the enzymes glutamic-oxalacetic transaminase (GOT) and lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) of children suffering from protein-energy malnutrition (PEM). In this respect, serum and CSF activities of GOT and LDH were assayed in thirteen cases suffering from kwashiorkor and ten normal cases serving as controls. Increased activities of both enzymes in sera and CSF of PEM children compared with normals were observed. The significance of these variations was discussed.

Child↗

Studies of tryptophan metabolism in protein-energy malnutrition (PEM).

Studies on tryptophan metabolism in PEM were performed. In this respect, the basal excretion of tryptophan and some of its metabolites, namely, kynurenine, 3 OH-anthranilic, anthramilic, indol-3-acetic, 5 OH-indol acetic and xanthurenic acids were determined. The response of these metabolites to oral tryptophan load, singly and in combination, with pyridoxine, were performed in kwashiorkor cases compared to normal controls. The study revealed that kynurenine leads to niacine pathway is hindered, Indole-3-acetic acid levels are lower and respond poorly to tryptophan loading in PEM. Increased levels of 5 OH-indol acetic were found in kwashiorkor compared to marasmus, although lower response to tryptophan was noted. Xanthurenic acid excretion is much higher in PEM and poorly responds to tryptophan load either singly or in combination with pyridoxine. These errors of tryptophan metabolism in PEM are suggested to be due to defects in the enzyme systems involved rather than to vitamin B6 deficiency.

Child, Preschool↗