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Biomedical subjects

M M Ashraf

Publications and source records attributed to M M Ashraf.

14 recordsLinked to original sources

Increased endogenous ascorbyl free radical formation with singlet oxygen scavengers in reperfusion injury: an EPR and functional recovery study in rat hearts.

The objective of this study was to investigate the effect of singlet oxygen ((1)O2) scavengers on functional recovery and ascorbyl free radical (AFR) formation in isolated ischemic rat hearts. Hearts were subjected to 40 min. of global ischemia followed by 30 min. of reperfusion. Hemodynamics were measured as heart rate (HR), coronary flow (CF), left ventricular developed pressure (LVDP) and contractility (dP/dt). Electron paramagnetic resonance (EPR) spectroscopy was used to measure AFR release in coronary perfusate during the first two min. of reperfusion as a function of ROS scavengers. Relative to ischemic controls the administration of the (1)O2 scavengers 2,2,6,6-tetramethyl-4-piperidone x HCl (4-oxo-TEMP), carnosine (beta-alanyl-L-histidine) or a combination of the two significantly improved functional recovery as measured by LVDP. While no AFR signal was detected in coronary perfusate collected during preischemic perfusion with and without (1)O2 scavengers, the AFR background signal due to ischemia was significantly increased with the (1)O2 and *O2- scavengers. No such increase was observed with the hydroxyl radical (*OH) scavenger mannitol. Besides the AFR increase with the (1)O2 and *O2- scavengers the functional recovery was only significantly improved with the (1)O2 scavengers. In contrast to previous AFR studies we found with endogenous AFR that an increased AFR formation is not necessarily only reflecting increased oxidative stress but can also report improved functional recovery. Combining the hemodynamic data with increased AFR formation in the presence of several different ROS scavengers gives supportive evidence for (1)O2 also being involved in reperfusion injury.

Animals↗

Type II phospholipase A2 is linked to cyclooxygenase-2-mediated delayed prostaglandin D2 generation by cultured mouse mast cells following FcepsilonRI- and cytokine-dependent activation.

Treatment of murine bone marrow-derived mast cells (BMMC) with interleukin (IL)-10 and IL-1beta increased the expression of type II secretory phospholipase A2 (sPLA2), but not cytosolic PLA2 (cPLA2), after culture for several hours. Further stimulation with IgE and antigen (IgE/Ag) increased cyclooxygenase (COX)-2 expression dramatically, accompanied by augmented delayed prostaglandin (PG) D2 generation over several hours. BMMC were also found to express type IIC PLA2 (PLA2-IIC), a recently described novel sPLA2 possessing 16 cysteine residues, expression of which changed minimally after BMMC activation. Delayed PGD2 generation was suppressed by approximately 80% by an antibody raised against recombinant murine type II sPLA2. These results suggest that, of the three PLA2s expressed in BMMC, type II sPLA2 is the critical enzyme that is coupled with COX-2-dependent PGD2 generation elicited by IgE/Ag in the presence of IL-10 + IL-1beta.

Animals↗

Thoracic surgery and the war against smoking: Richard H. Overholt, MD.

Richard H. Overholt was born at the beginning of the twentieth century when thoracic surgery hardly existed. During the first 20 years of his life progress in the field was slow. The next 20 years, which coincided with Overholt's surgical training and his early years as a thoracic surgeon, saw a rapid and almost explosive growth. Overholt's contributions were legion. They included the world's first successful right pneumonectomy, advancements in surgical treatment of tuberculosis, development of segmental resection, and introduction of the prone operative position. He was a bold and creative pioneer thoracic surgeon with consumate technical skills. Sixty years ago, when Overholt started his career as a thoracic surgeon, the hazards of smoking were not appreciated, the habit was fashionable, and consumption of tobacco was rapidly rising. In the early 1930s Overholt was among the very few physicians who recognized the perils of smoking and initiated a long but initially unrewarding antismoking crusade. By the early 1950s evidence about the ill effects of tobacco use began to accumulate. Organized medicine, voluntary health groups, and governmental agencies joined in a concerted effort to educate and to contain smoking. During the ensuing 30 years the antismoking movement achieved ever-increasing success. Today, it is widely recognized that smoking is a major health hazard and tobacco consumption is on the decline. Richard Overholt issued the first warning signals about the perils of tobacco and served as an indefatigable leader of the antismoking crusade throughout his professional career.

History, 20th Century↗

Potentials of Shigella flexneri Y strain TSF21 as a candidate vaccine against shigellosis: safety, immunogenicity and protective efficacy in Bonnet monkeys.

A thymine-requiring and temperature-sensitive mutant of Shigella flexneri Y was tested in Bonnet monkeys for safety, immunogenicity and protective efficacy. A dose of 10(11) cells when fed orally mimicked natural infection in having invaded epithelial cells, but was otherwise clinically non-reactogenic. Animals immunized with two oral doses, each dose consisting of 1 x 10(11) mutant bacteria, were fully protected when challenged, with respect to the lack of any clinical symptoms or detectable histological abnormalities in the intestinal mucosa. Unimmunized animals when similarly challenged developed frank dysentery and the intestinal mucosa showed severe histological abnormalities. Titres of serum antibodies increased by about 11-fold of the base level in animals immunized with a dose of 10(11) cells, but not with lower doses. The challenge bacteria appeared to be phagocytised by macrophages. In some monkeys of a particular group, congestive patches were seen in the stomach, but not in any other part of the gut, after the animals were fed with the virulent parent strain. The lesions were relatively severe in the immunized groups of animals.

Administration, Oral↗

Unusual association of a plasmid with nalidixic acid resistance in an epidemic strain of Shigella dysenteriae type 1 from Asia.

The association of a 20-MDa plasmid with nalidixic acid resistant (Nalr) strains of Shigella dysenteriae 1 has been examined. The plasmid, which is readily transferable, does not itself code for nalidixic acid resistance but offers a survival advantage to its host under nalidixic acid stress. The plasmid-containing cultures of S. dynsenteriae 1 produced Nalr mutants in vitro at a frequency 1000-fold higher than their plasmidless parent strains, after two exposures to nalidixic acid. Using a similar procedure, mutants resistant to other antibiotics such as chloramphenicol, tetracycline, or ciprofloxacin could not be isolated. The genome of S. dysenteriae 1 appears to carry a heavy load of the insertion sequence IS1. The propensity of the plasmid-containing strains to readily mutate to nalidixic acid resistance and its possible relevance to the observed association of the plasmid with Nalr clinical isolates is discussed.

Asia↗

A comparative study of surgical results with rotation-advancement and triangular flap techniques in unilateral cleft lip.

This paper presents a randomised comparative study of surgical results of unilateral cleft lip repair with 58 rotation-advancement and 50 triangular flap repairs, the two commonly used types of repair at present, carried out over a period of 6 years. The surgical results following both repairs were assessed on a scoring basis. No significant difference was found in overall postoperative appearance of lip and nose between the two types of repair. As a result, we recommend either technique for unilateral cleft of the lip.

Cleft Lip↗

Rupture of left ventricle following mitral valve replacement.

A survey of the English language literature revealed 125 cases of left ventricular rupture following mitral valve replacement. In ten larger series, the incidence averaged 1.2%. Most of the ruptures were attributed either to technical maneuvers in the operation or to stretch injury produced by the untethering of the left ventricle through removal of the mural leaflet of the mitral valve. Preventive measures include modifications in operative techniques, containing pressure-volume work by the left ventricle, and probably retention of the posterior mitral leaflet. Surgical repair of the rupture with and without the aid of cardiopulmonary bypass resulted in 50% and 7% survival, respectively. With the use of cardiopulmonary bypass, external repair was followed by a 67% survival and the internal approach, by a 27% survival.

Heart Rupture↗

Primary cancer of the lung. A 42-year experience.

Between April, 1932, and July, 1974, 3,808 patients with primary lung cancer were studied and 1,848 underwent resection. Among untreated patients, 95% were dead with a year. Unresected cancer of the lung is so lethal that efforts to streamline surgical management should not be neglected. In good-risk patients with isolated lesions the approach can be direct. If surgical excision is indicated, regardless of a positive or negative sputum cytology, bronchoscopic biopsy, or brush biopsy, such investigations become superfluous. Needle biopsy is also inconclusive and in addition is hazardous. Preoperative investigation should focus on cardiopulmonary reserve more than on ways to obtain tissue for verification. With the passage of time, the extent of resection has become more conservative. The value of palliative resection is now better appreciated in terms of quality of life, its prolongation, and, for some, a possibility for cure.

Humans↗

Resolution of an iatrogenic coronary artery thromboembolus.

A patient with an iatrogenic coronary thromboemboulus, sustained during selective left coronary catheterization is presented. The embolus was identified by angiography and its complete resolution was documented in the same manner three months later. Despite chest pain and elevation of the cardiac enzymes, the electrocardiogram showed only nonspecific changes and the absence of macroscopically identifiable infarction was demonstrated at thoracotomy. Thromboembolization may be a more common cause of complication with the Judkins technique than generally realized but may be compatible with complete recovery and be avoided by special catheterization practices.

Cardiac Catheterization↗