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Biomedical subjects

M Said

Publications and source records attributed to M Said.

At least 19 recordsLinked to original sources

Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart.

Previous experiments have shown that acidosis enhances isoproterenol-induced phospholamban (PHL) phosphorylation (Mundiña-Weilenmann, C., Vittone, L., Cingolani, H. E., Orchard, C. H. (1996) Am. J. Physiol. 270, C107-C114). In the present experiments, performed in isolated Langendorff perfused rat hearts, phosphorylation site-specific antibodies to PHL combined with the quantitative measurement of 32P incorporation into PHL were used as experimental tools to gain further insight into the mechanism involved in this effect. At all isoproterenol concentrations tested (3-300 nM), phosphorylation of Thr17 of PHL was significantly higher at pHo 6.80 than at pHo 7.40, without significant changes in Ser16 phosphorylation. This increase in Thr17 phosphorylation was associated with an enhancement of the isoproterenol-induced relaxant effect. In the absence of isoproterenol, the increase in [Ca]o at pHo 6.80 (but not at pHo 7.40) evoked an increase in PHL phosphorylation that was exclusively due to an increase in Thr17 phosphorylation and that was also associated with a significant relaxant effect. This effect and the phosphorylation of Thr17 evoked by acidosis were both offset by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62. In the presence of isoproterenol, either the increase in [Ca]o or the addition of a 1 microM concentration of the phosphatase inhibitor okadaic acid was able to mimic the increase in isoproterenol-induced Thr17 phosphorylation produced by acidosis. In contrast, these two interventions have opposite effects on phosphorylation of Ser16. Whereas the increase in [Ca]o significantly decreased phosphorylation of Ser16, the addition of okadaic acid significantly increased the phosphorylation of this residue. The results are consistent with the hypothesis that the increase in phospholamban phosphorylation produced by acidosis in the presence of isoproterenol is the consequence of two different mechanisms triggered by acidosis: an increase in [Ca2+]i and an inhibition of phosphatases.

Acidosis

Mechanism of inhibition of rat liver bilirubin UDP-glucuronosyltransferase by triphenylalkyl derivatives.

A series of potent and competitive inhibitors of UDP-glucuronosyltransferase derived from 7,7,7-triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IX alpha. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (Ki 12 to 180 microM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive-type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated.

Animals

[Testicular microlithiasis].

Testicular microlithiasis is an uncommon condition in which calcified concretions fill the lamina of seminiferous tubules. It has a specific appearance on sonography with diffuse intra testicular echogenic foci without acoustic shadows. Testicular microlithiasis can be associated with various entities and frequently with primary testicular neoplasm. The authors report a new case of testicular microlithiasis diagnosed by sonography in a 14-year-old boy with epididymo-orchitis. Based on a review and discussion of the literature, the authors emphasize the importance of regular and protracted ultrasound follow-up and monitoring of serum tumour markers to allow early detection of primary testicular neoplasm.

Adolescent

[Imaging of meconium peritonitis of pseudotumor clinical presentation].

An unusual case of meconium peritonitis is reported. A neonate presented with a huge multiseptate effusion in the peritoneal cavity in relation with a small bowel perforation. No calcification was visible. Such a presentation cannot be included in one of the classical types of meconium peritonitis. It could be due to a bowel perforation occurring immediately before birth and could therefore be related to a mixed fibroadhesive and generalized form.

Diagnosis, Differential

The descending septal branch (Bonapace's branch). A case report and literature review of this often forgotten branch. First description in vivo.

We present a 51-year-old female with exertional angina pectoris and a normal coronary angiogram who had a prominent descending septal branch originating from the proximal right coronary artery. This branch was perfused in the antegrade direction and did not show the tortuosity typical of coronary collaterals. The branch was almost 1 mm in diameter and supplied the middle third and basal two-thirds of the interventricular septum. The right coronary artery and this branch were free of coronary obstructions. The descending septal branch, described in 1921 by Crainicianu in a postmortem study, occurs in 12 to 85% of human hearts, but is still widely unknown. A review of the literature is also provided with special consideration of the functional importance of the condition and its prevalence in human and animal hearts. As far as we are aware, such a well developed descending septal branch in human hearts has not been described before. This is also the first description of a descending septal branch in vivo.

Adult

Colonoscopic diagnosis and treatment of acute appendicitis.

An atypical case of acute appendicitis is reported, in which the initial presentation was not suggestive of this diagnosis. A routine work-up revealed elevated levels of inflammatory markers, an ultrasonographically normal abdomen and normal endoscopic findings in the upper gastrointestinal tract. During colonoscopy, performed 3 days after admission, the inflamed appendiceal orifice was localized and intubated using an endoscopic retrograde cholangio-pancreatography (ERCP) catheter; pus was aspirated. Elective appendectomy was carried out 5 months later on the asymptomatic patient. Histological analysis revealed fibrous thickening of the appendiceal wall, correlating with an old inflammatory process, along with changes typical for acute ulcerophlegmonous appendicitis. To the best of our knowledge, this is the first case of an endoscopically diagnosed and treated acute ulcero-phlegmonous appendicitis. We draw the following conclusions: (1) Acute appendicitis may present atypically, leading to an extensive clinical work-up including gastroscopy and colonoscopy. (2) This condition may be effectively treated, at least temporarily, by colonoscopic suction of appendiceal pus, provided that clinical urgency for laparotomy is absent. (3) Histological changes typically associated with acute ulcero-phlegmonous appendicitis may be present in asymptomatic patients and in patients without fever and with normal erythrocyte sedimentation rates and blood leucocyte counts. (4) Elective appendectomy should be considered in patients with conservatively healed acute appendicitis or periappendiceal abscess.

Acute Disease

The effects of exercise induced tachycardia on the maternal electrocardiogram.

OBJECTIVE: To determine whether pregnancy has an effect on the maternal electrocardiographic response to stress. DESIGN: Eight maternal ECG parameters were screened before, during and after exercise induced tachycardia at 29 and 37 weeks gestation and at 6 weeks post partum for each participant. SETTING: General Hospital in Safed, Israel. SUBJECTS: Fifteen healthy, pregnant women aged 22 to 34 years with singleton pregnancies volunteered from the peripheral antenatal clinics. INTERVENTION: Exercise stress tests were performed on a Quinton 3000 treadmill stress test system according to a Modified Bruce Protocol, producing a heart rate of 85% of age predicted maximum. MAIN OUTCOME MEASURES: The ST-segment, T-wave, QRS complex, axis, rhythm, disorders of impulse conduction, the P-Q and Q-T intervals were screened before, during and after the exercise test. RESULTS: The study results suggest an increase in the ST-segment changes induced by stress at 37 weeks of pregnancy compared to 29 weeks (ST-depression in 6 women out of 15 versus 2, P = 0.125, McNemar's Test for Correlated Proportions-Exact Test, two tailed; 95% CI, 0.042-0.492, 0.01 < P < 0.05) and to the post partum test (ST-depression in 6 women out of 15 versus 1, P = 0.125; 0.029-0.637, 0.01 < P < 0.05). No significant alteration of the other ECG parameters. No significant correlation between blood haemoglobin level, serum levels of sodium, potassium, calcium, glucose and 17 beta-oestradiol with the appearance of the ECG change. CONCLUSIONS: The increase in the exercise induced ST-segment abnormalities at 37 weeks of pregnancy may be another physiological effect of late pregnancy which has not been demonstrated previously.

Adult

Selective and potent inhibition of different hepatic UDP-glucuronosyltransferase activities by omega,omega,omega-triphenylalcohols and UDP derivatives.

A homologous series of omega,omega,omega-triphenylalcohols and corresponding omega,omega,omega-triphenylalkyl-UDP derivatives was synthesized and tested as inhibitors of UDP-glucuronosyltransferase (UGT) activity in rat liver microsomes, with 1-naphthol, testosterone and bilirubin as substrates. Introduction of the UDP moiety in the triphenylalcohols increased their inhibition potency markedly toward the isoforms which glucuronidate 1-naphthol and testosterone, but strongly decreased that toward bilirubin. The inhibiting potency of the UDP-derivatives increased as a function of the length of the hydrocarbon chain. The best inhibitor 7,7,7-triphenylheptyl-UDP showed an I50 of 30 and 10 microM for 1-naphthol and testosterone glucuronidation, respectively; even a 1 mM concentration of the compound had little, if any, effect on bilirubin glucuronidation. The inhibition by 7,7,7-triphenylheptyl-UDP was mixed-type toward 1-naphthol, and non competitive toward testosterone (apparent K(i) 30 microM and 1.7 microM, respectively); on the other hand, the inhibition was competitive toward the common substrate UDP-glucuronic acid (apparent K(i) 1.9-1.2 microM). In addition, 7,7,7-triphenylheptyl-UDP (0.25-0.50 mM) almost inhibited glucuronidation of 1-naphthol and testosterone catalyzed by the recombinant rat liver UGT-2B1 and human liver UGT-1A1, whose cDNA has been expressed in V79 cells. In conclusion, the data indicate that 7,7,7-triphenyheptyl-UDP interacted competitively with the UDP binding site of UGT. The results also indicate that it is possible to design transition state analogue inhibitors with specificity for different UGT forms.

Alcohols

[Peripelvic tumors: approach and management].

The peripelvic area consists of the bony pelvis, hip joints and adjacent mesenchymal soft tissues. Malignant lesions in this area present unique diagnostic and therapeutic problems, in particular when tumor removal is involved. Between 1986 and 1988 we treated 7 females and a male, aged 8-75 years, for malignant tumors of this area. Diagnoses (histologic) included 4 cases of malignant fibrous histiocytoma, a malignant schwannoma, a Ewing sarcoma, a chondrosarcoma, and an osteosarcoma. Operations included marginal resection (4 cases), radical resection and reconstruction (2), radical resection (1), and modified hemipelvectomy (2). Adjuvant therapy consisted of radiotherapy in 1 case, chemotherapy in 2, and a combination of both in another 2. A patient who underwent radical resection and reconstruction of his left hemipelvis and hip joint died of local infection that progressed to generalized sepsis 2 months after operation. 2 patients died of recurrent disease, 3 and 30 months, respectively, after primary therapy. 1 died of myocardial infarction 20 months after the first and 3 months after the last of a series of marginal resections. 3 patients are alive and well 3-24 months following their first operation, and the fourth is doing well 24 months following first operation and 23 months after resection of lung metastases. Soft tissue sarcomas and osteosarcomas are the most frequent malignant tumors encountered in the pelvis and peripelvic areas. Their varying grades of malignancy and metastatic potential influence the approach on the one hand, while invalidity and compromised quality of life associated with tumor resection, influence it on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Dot-ELISA, a potential immunoassay for the detection of Plasmodium falciparum antibodies.

The dot enzyme-linked immunosorbent assay (dot-ELISA) was compared to the indirect immunofluorescent assay (IIFA) and radioimmunoassay (RIA) for the detection of malaria antibodies. Of 281 sera tested by dot-ELISA, 220 were from Ethiopia, 11 from the Sudan, and 50 from Egypt. A close correlation between the dot-ELISA and RIA results was observed in 92% of the 220 Ethiopian cases. Of the remainder, 6% gave positive RIA and negative dot-ELISA results, and 2% gave positive dot-ELISA and negative RIA results. Antibody titres determined by dot-ELISA and RIA were positively correlated in 10 of the 11 Sudanese cases tested by direct microscopical examination. The eleventh case was positive by dot-ELISA at 1:1000 dilution, but negative by RIA and direct examination. With the 50 Egyptian sera, the dot-ELISA results showed close correspondence to the IIFA results, but the dot-ELISA was 20-40 fold more sensitive than the IIFA. To test specificity, 62 samples from patients with 11 different diseases and conditions were examined by dot-ELISA. No malaria antibodies were detected in any of these or in sera from healthy controls. Dot-ELISA is a potentially useful method for sero-epidemiological studies of malaria.

Animals

Ketotifen in the treatment of infants and young children with wheezy bronchitis and bronchial asthma.

Ketotifen, an orally-administered anti-anaphylactic and antihistamine compound, was given in a dose of 0.06 mg/kg to 142 infants and young children presenting either with non-infected wheezy bronchitis or bronchial asthma to an allergy out-patient department. Treatment continued for 12 weeks. At the end of this time, ketotifen was considered to be very effective or effective in 70% of the children. The effect was more marked in non-infected wheezy bronchitis (83.55% response) than in bronchial asthma (56.5% response), perhaps because factors such as leukotrienes, prostaglandins and thromboxanes tend to produce a sustained bronchoconstriction in the latter condition. Ketotifen was not associated with any adverse effects and did not cause behavioural problems. Patients found it palatable and acceptable. The main disadvantage was that symptoms recurred within days of stopping treatment. Especially in non-infected wheezy bronchitis, ketotifen should be given for a year or longer to older children (older than 30 months) who have shown an initial good response to the drug.

Asthma

Study of eosinophilia in relation to serum IgE level and cell mediated immunity (CMI) to soluble egg antigen (SEA) in human schistosomiasis mansoni.

Eosinophil count, delayed intradermal test and lymphoblast transformation test (LTT) using SEA, have been used to study the correlation of eosinophilia with CMI in patients with schistosomiasis mansoni. Only a weak positive correlation was found between the eosinophil count and both in vivo and in vitro manifestations of CMI. When IgE serum level was correlated with eosinophil count, a positive correlation was only found in cases with hepato-splenic disease (those with increased CMI).

Antigens, Helminth

Recent results of the German Thorotrast study--dose relevant physical and biological properties of Thorotrast equivalent colloids.

As a prerequisite for quantifying the non-radiation effect of Thorotrast, nonradioactive and radioactive aquasols with identical physicochemical properties and with biophysical behavior comparable to that of Thorotrast were developed and produced for a second long-term animal experiment. Comparative investigations with hafnium and zirconium (zirconotrast) dioxide aquasols showed the latter to be most appropriate considering the size of both the dispersoids and the aggregates in the liver tissue. The average particle diameters of ThO2, ZrO2 and HfO2 proved to be values of 9.3 nm, 15 nm and 45 nm, respectively. The size of the aggregates shows a slight dependence on the applied amount but no dependence on the duration of body burden of the colloid. The aggregate diameters in the 600 microliters group turned out to be 9.6 microns, 14.4 microns and 5.3 microns, respectively. Radioactive zirconotrast was prepared by radiochemical incorporation of 230Th and 228Th at dose rates which produce accumulated doses in the liver of rats equivalent to those of commercial 230Th enriched Thorotrast after 1.5 yr. Five different colloids were prepared with alpha-energy emission rates increased by factors of 1, 2.5, 5, 10 and 25 compared to Thorotrast and then injected into rats.

Animals