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Biomedical subjects

A Hasan

Publications and source records attributed to A Hasan.

At least 19 recordsLinked to original sources
PubMed1995

Effects of short term ischemia and reperfusion on coronary vascular reactivity and myocardial function.

Ischemia and reperfusion have been shown to cause damage to the endothelium as well as to the cardiac myocyte. Although the vasodilator response has been shown to be impaired following ischemia and reperfusion, the effect of a short period of global ischemia on the contractile response of the coronary vasculature is not clear. In the present study, coronary vasoconstriction in response to U46619, PGF2 alpha, 5-HT, and KCl was found to be depressed for at least 15 min following 15 min of in vitro global ischemia in rats hearts. Vasodilator blockers or inactivators were used in an effort to restore this depressed coronary response. Indomethacin (5 microM) was used to block production of vasodilator prostaglandins, L-NAME (30 microM) to block production of nitric oxide (NO), and adenosine deaminase (2.4 units/ml of coronary flow) to inactivate adenosine. None of these agents restored the normal coronary constrictor response following ischemia. When superoxide dismutase and catalase (both 20 micrograms/ml of coronary flow) were infused for 5 min before and after ischemia, the coronary response recovered more than 100% of its preischemic value by 15 min of reperfusion, but still remained depressed at 5 min reperfusion. These data suggest that free radicals produced during ischemia and/or reperfusion may be at least partly responsible for this temporary "stunning" of the coronary vasculature. Since the impaired contractile response was still present at 5 min reperfusion when the buffer was supplemented with oxygen radical scavengers, another mechanism must also be involved in this "stunning" process.

Adenosine Deaminase↗
PubMed1995

Flavonoid glycosides and an anthraquinone from Rumex chalepensis.

Besides rutin, quercetin 3-rhamnoside and kaempferol 3-rhamnosyl(1-->6) galactoside, a new flavonol glycoside, quercetin 3-glucosyl(1-->4)galactoside, and 1,6,8-trihydroxy-3-methyl anthraquinone (emodin) have been characterized from leaves of Rumex chalepensis. The structures were established on the basis of Rf values, acid hydrolysis to aglycone and sugar and UV, EI and FAB-mass spectra, 1H NMR, 13C DEPT NMR, NOE difference measurement, 1H-H COSY and 1H-13C COSY spectral data.

Anthraquinones↗
PubMed1995

Mechanical ventricular assistance for the failing right ventricle after cardiac transplantation.

Right ventricular failure secondary to elevated pulmonary vascular resistance (PVR) following orthotopic cardiac transplant is a complication with a high mortality; and patients with high resistance are often not accepted on transplant waiting lists. We describe six cases of right ventricular failure after cardiac transplant managed by right ventricular assist device (RVAD), four of whom died and two patients who survived following life-threatening complications.

Adult↗
PubMed1995

Pentoxifylline, pentifylline, and interferons decrease type I and III procollagen mRNA levels in dermal fibroblasts: evidence for mediation by nuclear factor 1 down-regulation.

Pentoxifylline (PTX) is a methylxanthine that exhibits multiple biologic activities, including the inhibition of collagen synthesis by dermal fibroblasts. Because some PTX activities have recently been linked to transcription factor-mediated regulation of gene transcription, we have investigated if PTX acts to inhibit collagen synthesis at a transcriptional locus by measuring procollagen mRNA levels by assaying for the presence of an activator of procollagen gene promoters, nuclear factor (NF)-1. The effects of another methylxanthine, pentifylline (PTF), shown herein to be a tenfold more potent inhibitor of collagen synthesis than PTX, and interferon-alpha, -beta, and -gamma were studied in parallel. Analysis of extracellular protein and RNA from 48-h-treated fibroblasts showed that PTX, PTF, and interferons decreased alpha 1(I), alpha 2(I), and alpha 1(III) procollagens by reducing the steady-state levels of the corresponding procollagen mRNA transcripts. Reduction of procollagen mRNA levels appeared to be dependent on new protein synthesis, as it was prevented by treatment with cycloheximide. Assay for the presence of nuclear NF-1 by gel mobility shift analysis showed that extracts from interferon, PTX, and PTF-treated fibroblasts lacked proteins recognizing the consensus DNA binding sequence for NF-1. Taken together, these observations suggest interferons and methylxanthines may inhibit fibroblast collagen synthesis by a common mechanism requiring new protein synthesis that suppresses procollagen gene transcription through down-regulation of NF-1.

Adult↗
PubMed1995

Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts.

It is thought that normal fibrotic repair progresses to dermal fibrosis when fibroblasts are activated persistently by chronic exposure to cytokines such as transforming growth factor-beta. However, additional cytokines and mechanisms may play a role in the development of fibrosis. Thus, we examined a recently described T-lymphocyte/macrophage-derived cytokine, oncostatin M, for its effect on the production of collagen and glycosaminoglycan by microcultures of normal dermal, sclerodermal, and keloidal fibroblasts. Treatment with oncostatin M for 48 h induced dose-dependent (1-100 ng/ml) increases in the collagen and glycosaminoglycan production of nine normal fibroblast strains, which in the absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, respectively. Oncostatin M treatment increased both types I and III procollagens and their mRNA transcripts, as well as levels of hyaluronic acid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronectin or general noncollagenous protein synthesis. In contrast, the collagen production of six of eight sclerodermal and keloidal fibroblast strains was essentially unresponsive to oncostatin M treatment, with 100 ng/ml inducing an average increase of only 34% for the eight fibrotic strains. Oncostatin M stimulation of fibrotic fibroblast glycosaminoglycan production was also hyporesponsive, as 100 ng/ml of oncostatin M induced an average increase of only 101%. These results indicate that oncostatin M could function as a stimulator of normal fibrotic repair via activation of fibroblast collagen and glycosaminoglycan synthesis and that the persistent activation of sclerodermal and keloidal fibroblasts is accompanied by a loss of sensitivity to oncostatin M stimulation.

Adult↗
PubMed1995

Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65-60 antigen by T cells of patients with recurrent oral ulcers.

T cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91-105 in ROU, compared with healthy or disease controls (P < 0.01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91-105 in ROU was significantly greater than in healthy (P < 0.0001) or disease controls (P < 0.01). A comparative investigation with the homologous human 60-kD hsp peptide 116-130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P < 0.01) or disease controls (P < 0.001). The potential involvement of the T cell epitope 91-105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91-105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116-130.

Adult↗
PubMed1995

Bilateral sequential lung transplantation for end stage septic lung disease.

BACKGROUND: Bilateral sequential lung transplantation (BSLT) has been widely adopted as an alternative to combined heart and lung transplantation for the management of end stage septic lung disease in many transplant centres. METHODS: A retrospective review was undertaken of the first 32 consecutive patients with septic lung disease to undergo BSLT at the Freeman Hospital. RESULTS: Between April 1988 and October 1994 32 patients underwent BSLT. Survival at 30 days was 85% and actuarial survival at one year was 70%. Improved pulmonary function was seen in all surviving patients. CONCLUSION: BSLT for septic lung disease offers comparable survival to heart-lung transplantation, with excellent functional results. Long term results may be superior because the disadvantages of transplanting the heart are avoided.

Adolescent↗
PubMed1995

Visual fixation and smooth pursuit eye movement abnormalities in patients with schizophrenia and their relatives.

Increasing evidence suggests that smooth pursuit eye movement (SPEM) dysfunction may serve as an endophenotype or genetic marker of schizophrenia. The authors tested SPEM and visual fixation (VF) in 31 patients with schizophrenia, 33 of their first-degree relatives, and 24 patients with major depressive disorder. A high rate of abnormal VF was found in schizophrenic patients and their first-degree relatives, but not in affective disorder patients with or without psychotic features. Rate of VF abnormality distinguished schizophrenic patients from acutely depressed mood disorder patients; SPEM did not. VF and SPEM performance correlated only moderately, suggesting that the pathophysiologies of these two eye movement abnormalities may be partially independent. Implications for identifying a schizophrenia endophenotype are discussed.

Adult↗
PubMed1994

Red cell aplasia resembling Diamond-Blackfan anemia in seven children in a family.

PATIENTS AND METHODS: Seven children of the same family with a possible variant of Diamond-Blackfan anemia (DBA) are reported. Five were male siblings, and the other two were their cousins, one male and one female. All were products of consanguineous marriages of healthy parents. All cases occurred within one generation. Anemia was present at birth or shortly after birth. Hepatosplenomegaly was present in all. Four had short stature. Hematological findings included normochromic, normocytic, or macrocytic anemia, marked reticulocytopenia, with initial normal white blood cell and platelet count, and absent or markedly decreased erythroid precursors on bone marrow examination. All were treated initially with prednisolone; in one patient oxymetholone was added. RESULTS: Three children failed to respond to the initial treatment, and also failed to respond to cyclosporin A and pulse doses of methylprednisolone. Myelofibrosis occurred in two siblings, 9 and 11 years from diagnosis. In two children the disease recurred 9 and 12 years after initial diagnosis. CONCLUSIONS: Our cases point to a possible variant of DBA characterized by the presence of normochromic normocytic anemia, hepatosplenomegaly, absent skeletal malformations, and unusual long- term complications.

Child↗
PubMed1994

Heat shock protein peptides reactive in patients with Behçet's disease are uveitogenic in Lewis rats.

Mycobacterial and homologous human heat shock protein T cell peptide epitopes specific for T lymphocytes in Behçet's disease were investigated for their pathogenicity in Lewis rats. The potential pathogenicity of eight peptides and two controls was assessed by administering the peptides in enriched Freund's adjuvant into the footpads of male Lewis rats. Anterior uveitis which is a major manifestation of Behçet's disease was induced with two out of the four mycobacterial and all four homologous human peptides. The most effective peptides inducing iridocyclitis in 64-75% of rats were peptides with amino acids 336-351 and 136-150, derived from the sequence of the human 60-kD heat shock protein. A few of the rats also showed evidence of focal loss of photoreceptors. These results suggest that selected peptides within heat shock protein 60 kD which function as T cell epitopes in Behçet's disease are capable of inducing uveitis in rats. This supports the view that the peptide T cell determinants may be involved in the pathogenesis of Behçet's disease.

Amino Acid Sequence↗
PubMed1994

Odor discrimination deficits in schizophrenia: association with eye movement dysfunction.

Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory.

Adult↗
PubMed1994

Videothoracoscopy in the diagnosis of intrathoracic pathology: early experience.

We report our experience using the new technique of videothoracoscopy in the diagnosis of intrathoracic pathology. In the last 12 months, 40 patients (24 male; 16 female) have undergone investigation by this method. Lung biopsy has been performed in 17 patients, pleural biopsy in 20 patients and mediastinal biopsy in three patients. The majority had been referred after other investigations had been inconclusive. All biopsies were diagnostic except one mediastinal biopsy. This early experience suggests that videothoracoscopic biopsy is a well-tolerated technique with high diagnostic yield.

Adolescent↗
PubMed1993

T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behçet's disease.

T cell epitopes of the 65-kDa heat shock protein (HSP) were mapped in patients with Behçet's disease (BD), by stimulating T cells with the overlapping synthetic peptides derived from the sequences of the Mycobacterium tuberculosis 65-kDa HSP. Significant lymphoproliferative responses were stimulated with four HSP peptides in BD, as compared with the related disease (recurrent oral ulcers), unrelated disease, and healthy controls (p < 0.05 to 0.005). In order to assess the relative frequency of sensitized lymphocytes by these peptides, 7353 short term cell lines were generated from the lymphocytes of patients and controls. Peptides 111-125, 154-172, and 311-325 (p < 0.001) and peptide 219-233 (p < 0.02) yielded significantly greater frequency of STCL in BD than in healthy and disease controls. All but peptide 154-172 stimulated only the CD4+ subset of T cells, although there was no evidence that reactivity to the selected peptides is restricted by DR2 to DR7 Ag. HLA-B51 is significantly associated with BD, but there was no evidence that B51 was a restricting element, when B51+ patients were compared with B51- patients with BD, and with B51+ healthy control subjects. A comparative investigation was then carried out between the corresponding mycobacterial and human HSP peptides. Similar or higher lympho-proliferative responses were stimulated by the human peptides compared with the mycobacterial peptides. These results suggest that the four peptide determinants within the 65-kDa HSP might be involved in the pathogenesis of BD. Whereas the high microbial load and associated stress proteins found in oral ulceration of BD may initiate an immune response to these conserved epitopes, expression of autoreactive T cell clones might be stimulated by immunodominant T cell epitopes of endogenous HSP which may induce immunopathologic changes.

Adult↗
PubMed1993

Heart-lung transplantation combined with correction of interrupted aortic arch.

We describe a new technique for heart-lung transplantation in a patient with interrupted aortic arch. The operation was performed in a 21-year-old patient with situs solitus, double-inlet left ventricle, transposition of great arteries, type A interrupted aortic arch, and pulmonary hypertension. One-stage correction of interrupted aortic arch was undertaken using recipient ductal and pulmonary arterial tissues. The early postoperative course was uneventful, with clinical and radiological evidence of satisfactory result. We conclude that it is entirely feasible to undertake heart-lung transplantation in the presence of interrupted aortic arch using this technique, which requires no period of circulatory arrest and results in a tension-free anastomosis.

Adult↗
PubMed1993

[Outcome of conservative treatment of high-degree vesicoureteral reflux].

We performed a retrospective study to evaluate the results of a nonsurgical approach of primary high grade vesicoureteral reflux (VUR). 241 patients (209 III and 32 IV) were reviewed during and average time of 9.4 years. 55% of them were under 6 months and 52% had bilateral reflux (50% III and 63% IV). During the observation period spontaneous resolution of reflux was observed in 126 (60%) with grade III at 5 years and 26% in patient with grade IV at 4 years. In both grades the duration of persistent reflux was analyzed using life-table method. When age at presentation was compared with duration of reflux there was a shorter time of reflux in those patients presenting from age 0 to 6 months. New renal scars developed in 5 patients during the period of observational therapy. We conclude that high grade VUR can resolve over a protracted interval. On basis of this analysis, we advocate the surgical correction in these patients after 5-year period to grade III and 2-year to grade IV.

Child↗
PubMed1992

Synthesis and biological studies of unsaturated acyclonucleoside analogues of S-adenosyl-L-homocysteine hydrolase inhibitors.

The design, synthesis, and biological evaluation of several unsaturated acyclonucleosides related to augustmycin A are described. The (propargyloxy)methyl acyclonucleoside analogues of 6-chloropurine, adenine, 6-methoxypurine, hypoxanthine, 6-mercaptopurine, and azathioprine have been prepared. The 9-[(propargyloxy)methyl]adenine (5) and 9-[(propargyloxy)methyl]hypoxanthine (12) analogues were converted to the corresponding 5'-tributylstannyl intermediates (9 and 13), respectively, which gave 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]adenine (10) and 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]hypoxanthine (14), respectively, after iododestannylation. The [125I]-radiolabeled congeners of 10 and 14 were prepared as potential metabolic markers. Among the unsaturated acyclonucleosides tested, 9-[(propargyloxy)methyl]-6-chloropurine (3), 9-[(propargyloxy)methyl]-6-mercaptopurine (15), 9-[(propargyloxy)methyl]azathioprine (17), and angustmycin A analogue 10 showed inhibition of cancer cell growth, but only at a minimal level, and 17 also showed 14% cancer cell death in vitro. Compound 10 provided approximately 50% protection against HIV at 10(-4) M concentrations. Biodistribution results of [125I]-10 in mice indicate that compound 10 is readily metabolized via deiodination in vivo, possibly by serving as a substrate for the enzyme S-adenosyl-L-homocysteine hydrolase.

Adenine↗