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Biomedical subjects

D Ahmad

Publications and source records attributed to D Ahmad.

At least 37 records · Page 2Linked to original sources

Evolution of resting lung function in the first year after cardiac transplantation.

The aim of our study was to characterize the time course and magnitude of the changes in lung function in the first year after cardiac transplantation. Resting pulmonary function tests (spirometry, lung volumes and transfer factor) were performed in 14 patients prior to and at 1, 3 and 12 months after surgery. Resting central haemodynamics were also measured serially in the first year post-transplantation. Before transplantation, patients had impaired resting lung function with marked decrease in transfer factor (TL,CO). Although resting central haemodynamics improved markedly within the first week after cardiac transplantation, lung function (forced expiratory volume in one second (FEV1)) was significantly improved only at three months post-transplantation. TL,CO, however, decreased further early after cardiac transplantation. By 12 months, FEV1 and forced vital capacity had increased significantly by 31 and 33%, respectively, while total lung capacity increased by 22%. On the other hand, TL,CO did not increase significantly and remained well below normal at 12 months after cardiac transplantation, at a value equal to 68% of predicted. We conclude that the resting abnormalities in lung function of most patients with heart failure are reversible after cardiac transplantation, except for TL,CO which remains below normal values. Recovery of lung function, however, lags behind the improvement in cardiac function.

Adult↗

Lack of stereoselectivity of the peroxisome proliferation induced by 2-phenylpropionic acid: evidence against a role for lipid disturbance in peroxisome proliferation.

The significance of disturbances of lipid metabolism caused by xenobiotic acyl-CoAs as possible causes of peroxisomal proliferation has been studied with the enantiomers of 2-phenylpropionic acid (2-PPA), the (R)-enantiomer of which is converted to the acyl-CoA in rats while its (S)-antipode is not. rac-2-PPA (250 mg/kg/day ip x 3) was shown to be an hepatic peroxisomal proliferator in male Sprague-Dawley rats on the basis of increases in microsomal cytochrome P-450 content and lauric acid hydroxylation and hepatic CN(-)-insensitive palmitoyl-CoA oxidation, a peroxisomal marker activity, while electron microscopy revealed a rise in the peroxisome/mitochondria ratio in hepatocytes. Further studies established the dose-response relationships for these biochemical changes. The (R)- and (S)-enantiomers were administered at a dose of 50 mg/kg/day ip x 3 and both were peroxisome proliferators of very similar potency. The effects of 100 mg/kg/day ip x 3 of the racemate, a dose giving ca. 75% of maximal response, were essentially additive of those of 50 mg/kg/day ip x 3 of its two component isomers. The stereoselectivity of acyl-CoA formation from the enantiomers of 2-PPA was confirmed by their differential inhibition of microsomal palmitoyl-CoA synthesis. Taken together, these data indicate that it is very unlikely that the acyl-CoA of 2-PPA plays any role in the peroxisomal proliferation which this compound causes in the rat.

Acyl Coenzyme A↗

Technique for assessing nasal airway resistance in patients treated prosthetically.

This investigation was designed to compare nasal airway resistance (Rnaw) values by use of "head-out" plethysmography and standard posterior pressure-flow rhinometry. Fourteen adults who had prostheses because of velopharyngeal inadequacy caused by a variety of etiologic conditions were examined. Each patient performed rest breathing and sustained /m/ productions to develop Rnaw values for comparison. The results revealed increased Rnaw and decreased cross-sectional nasal airway area and derived velopharyngeal orifice area when the appliances were in place. The two techniques for assessing Rnaw produced comparable results when certain conditions were met. Clinical implications for team assessment of patients involved with prosthetic management are discussed.

Adult↗

Identification and mapping of the gene translation products involved in the first steps of the Comamonas testosteroni B-356 biphenyl/chlorobiphenyl biodegradation pathway.

In this study, we have mapped Comamonas testosteroni B-356 genes encoding enzymes for the conversion of biphenyl and 4-chlorobiphenyl into the corresponding meta-cleavage compounds onto a 6.3-kb DNA fragment, and we have determined the subunit composition of the enzymes involved in this pathway. The various proteins encoded by this 6.3-kb DNA fragment and by subclones derived from it were overexpressed and selectively labelled using the T7 polymerase promoter system in Escherichia coli. They were then analyzed using SDS-PAGE, which allowed the encoding locus of each polypeptide to be mapped. Despite apparent dissimilarity in the congener selectivity patterns of the initial oxygenase of strain B-356 with those of Pseudomonas sp. strain LB400, the number and sizes of the polypeptides involved in the enzymatic conversion of biphenyl or 4-chlorobiphenyl into the meta-cleavage product appear to be similar in the two strains. In both strains, the bph operon encodes the following: the large (51-kDa polypeptide encoded by bphA) and the small (22-kDa polypeptide encoded by bphE) subunits of the iron sulphur protein, which is thought to interact directly with the substrate to introduce the oxygen molecule; the ferredoxin (12-kDa polypeptide encoded by bphF) involved in electron transfer from the reduced ferredoxin reductase to the oxidized iron sulphur protein; the 29-kDa polypeptide of the 2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase encoded by bphB; and the 32-kDa polypeptide of the 2,3-dihydroxybiphenyl-1,2-dioxygenase encoded by bphC, which catalyzes meta-1,2 fission of the aromatic ring. A major difference between strain B-356 and strain LB400 is that the bphG gene encoding biphenyl dioxygenase ferredoxin reductase is located outside the bph gene cluster in strain B-356. Several lines of evidence indicate that bphG is absent in clones carrying the bph operon from strain B-356.

Base Sequence↗

Intracavitary aspergilloma: transthoracic percutaneous injection of amphotericin gelatin solution.

For aspergillomas in patients with fibrocavitary lung disease, surgery is often not recommended. Injection or lavage of the cavities with solutions of potassium iodide or antifungal agents has had varying success and requires repeated sessions because of nonretention of the therapeutic agent within the cavity. In three patients with four aspergillomas, the authors used fluoroscopic or computed tomographic (CT) guidance to inject amphotericin in gelatin as a liquid that solidifies within the cavity at body temperature. The patients were followed up with serial chest radiography or CT. The mixture was successfully instilled in every case. Three of the four aspergillomas completely resolved within 3 months or less, with no evidence of recurrence at follow-up of 6-18 months. The remaining aspergilloma decreased in size, but the patient needed pneumonectomy because of recurrent hemoptysis within 6 months of amphotericin injection. Transthoracic instillation of a liquid mixture of amphotericin and gelatin that solidifies rapidly at body temperature may be useful as a one-step treatment for aspergillomas.

Adult↗

Effects of chlorobenzoate transformation on the Pseudomonas testosteroni biphenyl and chlorobiphenyl degradation pathway.

Bacterial conversion of biphenyl (BP) and chlorobiphenyls (CBPs) to benzoates and chlorobenzoates (CBAs) proceeds by introduction of molecular oxygen at the 2,3 position, followed by a 1,2-meta cleavage of the molecule. Complete mineralization of CBPs requires the presence of two sets of genes, one for the transformation fo CBPs into CBAs and a second for the degradation of CBAs. It has been shown previously that removal of the CBAs produced from the degradation of CBPs is essential for efficient degradation of CBPs. In this study we confirmed that CBAs inhibit BP and CBP transformation in Pseudomonas testosteroni B-356. Among the three monochlorobenzoates tested, 3-chlorobenzoate was the most effective inhibitor. Furthermore, we found that in strain B-356, CBA transformation is controlled by BP-induced oxygenases that are not present in benzoate-grown cells. We found that this BP-linked CBA transformation pathway transformed CBAs produced from CBPs into several metabolites, including chlorocatechols and corresponding muconic semialdehydes. These metabolites inhibited the 2,3-dihydroxybiphenyl 1,2-dioxygenase, while CBAs by themselves had no effect on this enzyme. Therefore, on the basis of this and other observations, it appears that when CBAs produced from CBPs accumulate in the growth medium, they are converted into unproductive metabolites that reduce the flux of the BP and CBP degradation pathway. The practical implications of these interactions on the microbial degradation of polychlorinated BPs are also discussed.

Benzoates↗

Contralateral pneumonectomy after single-lung transplantation for emphysema.

An intractable contralateral air leak developed in a 46-year-old woman after right single-lung transplantation for emphysema. A left pneumonectomy was performed on postoperative day 17, leaving the patient with only one transplanted lung. Fifteen months postoperatively the patient is well and has satisfactory pulmonary function. Survival with a good quality of life is possible after single-lung transplantation and bilateral sequential pneumonectomies.

Female↗

The safety of low-dose prednisone before and immediately after heart-lung transplantation.

Preoperative steroid use has been considered a contraindication to heart-lung as well as lung transplantation. Moreover, most centers delay prednisone administration until 2 to 3 weeks postoperatively until airway healing is secure. We have performed 19 heart-lung transplantations and four single-lung transplantations since 1983. Five recipients (4 heart-lung, 1 single lung) had received prednisone, 5 to 40 mg daily, for 2 to 10 years preoperatively. All recipients were administered prednisone, 0.5 mg/kg daily, starting on postoperative day 1, with a taper to 0.2 mg/kg daily by 4 weeks. Minnesota antilymphocyte globulin (for 10 days), cyclosporine, and azathioprine were also employed. Bronchoscopy, lavage, and transbronchial biopsies were performed every 2 weeks for 3 months postoperatively. No patient had a serious airway complication; 2 heart-lung recipients, not on prednisone preoperatively, had a minor tracheal slough detected on bronchoscopy that resolved spontaneously. Actuarial survival after heart-lung transplantation is 84% +/- 8% and 69% +/- 16% at 1 year and 2 years, respectively. We conclude that prednisone commencing at a dose of 0.5 mg/kg daily from the first postoperative day is a safe practice after heart-lung transplantation. The long-term use of low-dose prednisone before heart-lung transplantation does not preclude normal tracheal healing. The safety of prednisone before and immediately after single-lung transplantation awaits confirmation by further experience.

Adolescent↗

Bioconversion of 2-hydroxy-6-oxo-6-(4'-chlorophenyl)hexa-2,4-dienoic acid, the meta-cleavage product of 4-chlorobiphenyl.

Bacterial conversion of 4-chlorobiphenyl (4-CB) usually proceeds through a pathway involving an initial oxidation of the unsubstituted ring in the 2,3 position followed by a 1,2 meta-cleavage. The meta-cleavage product (MCP) is converted through a single hydrolysis step into chlorobenzoic acid. However, several other acidic metabolites that were not expected as part of this pathway have already been described. In this paper, we used strains of Pseudomonas putida carrying cloned genes from Pseudomonas testosteroni B-356 that are involved in polychlorinated biphenyl (PCB) degradation to demonstrate that several acidic metabolites found in the culture media of various bacteria grown in the presence of 4-CB result from alternative novel bioconversion pathways of MCP. The degradation products of MCP through these pathways were identified as analogues with saturated or shorter side chains or as 4'-chlorophenyl-2-picolinic acid; pathways leading to their formation are proposed.

Biodegradation, Environmental↗

Subcloning of bph genes from Pseudomonas testosteroni B-356 in Pseudomonas putida and Escherichia coli: evidence for dehalogenation during initial attack on chlorobiphenyls.

The bphA, -B, -C, and -D genes from Pseudomonas testosteroni B-356 were mapped to a 5.5-kb DNA fragment of cloned plasmids pDA1 and pDA2 by use of deletion and insertion mutants of these plasmids. The expression of each of these genes was evaluated in Escherichia coli and in Pseudomonas putida, and it was found that the bphC and bphD genes are well expressed in both E. coli and P. putida cells while the bphA and bphB genes are very poorly expressed in E. coli, even when placed downstream of a tac promotor. P. putida clones carrying the bphA gene were used to study the metabolites produced from 4,4'-dichlorobiphenyl, 2,2'-dichlorobiphenyl, and 2,4'-dichlorobiphenyl. It was shown that dehalogenation of 4-Cl and 2-Cl occurs in the course of the initial oxygenase attack on these molecules, which always occurs on carbons 2 and 3, independently of the positions of the chlorine atoms. Our data also suggest that in the case of polychlorobiphenyl congeners carrying chlorine atoms on both rings, it appears that, depending on the chlorine positions, dioxygenation will occur predominantly on one ring over the other. However, attack of the more resistant ring is not excluded, resulting in multiple conversion pathways.

Biodegradation, Environmental↗

The importance of acquired diffuse bronchomalacia in heart-lung transplant recipients with obliterative bronchiolitis.

The results of heart-lung transplantation are improving with increasing experience in postoperative management, but obliterative bronchiolitis may still develop late postoperatively. We have performed 19 heart-lung transplants, with 1-month, 1-year, and 2-year actuarial survival rates of 95% +/- 5%, 84% +/- 8%, and 69% +/- 16%, respectively. Three early recipients died of bronchiolitis, and four patients who were operated on more than 2 years ago are currently being followed up with bronchiolitis. Since August 1988, 13 surviving recipients have undergone serial postoperative bronchoscopies and transbronchial biopsies with topical analgesia. Diffuse bronchomalacia, involving the main bronchi down to the fifth-order bronchi bilaterally, has developed in four patients with bronchiolitis 9 +/- 2 months after the diagnosis of bronchiolitis was confirmed. Pulmonary function tests have revealed a lower ratio of forced expiratory volume in 1 second to forced vital capacity, lower specific airway conductance, and higher airway resistance in heart-lung recipients with bronchomalacia than in patients with bronchiolitis alone. We conclude that diffuse bronchomalacia occurs frequently in heart-lung transplant recipients who have obliterative bronchiolitis. Bronchomalacia worsens the functional airflow obstruction caused by bronchiolitis and may play an important role clinically in the declining respiratory status of heart-lung transplant recipients.

Adolescent↗

Importance of chronic aspiration in recipients of heart-lung transplants.

In a series of eleven recipients of heart-lung transplants (HLT), five have obliterative bronchiolitis. Five of the eleven patients have chronic cough as well as slower than normal gastric emptying and/or oesophageal dysmotility; all five have evidence of bronchiectasis and three have obliterative bronchiolitis. Three of the patients improved after the introduction of treatment to prevent reflux, and another, who had a large phytobezoar, improved after pyloroplasty. In patients with chronic cough after HLT, with or without dyspeptic symptoms or recurring pulmonary sepsis, investigation of oesophageal motility and gastric emptying should be undertaken.

Adult↗

Cloning and expression of genes involved in 4-chlorobiphenyl transformation by Pseudomonas testosteroni: homology to polychlorobiphenyl-degrading genes in other bacteria.

The genes of Pseudomonas testosteroni strain B-356, specifying the transformation of 4-chlorobiphenyl (4-CB) into 4-chlorobenzoic acid (4-CBA) were cloned into Pseudomonas putida KT2440 using a broad-host-range cosmid, pPSA842. Of 10,000 clones tested, four were able to transform 4-CB. Gas chromatographic and mass spectrometric analysis of the catabolic products from two of the 4-CB-transforming clones carrying the hybrid plasmids, pDA1 and pDA2, demonstrated that pDA1 carried a complete set of structural genes involved in the transformation of 4-CB into 4-CBA, while pDA2 contained part of the pathway genes leading up to the meta-cleavage compound. Restriction endonuclease mapping and subcloning of pDA1 and pDA2 showed that the clones contained a common stretch of DNA of about 9.1 kb and that pDA2 carried gene(s) involved in regulation. Probing blots of genomic DNA from 13 different polychlorinated biphenyl(PCB)-degrading bacteria with radio-labelled pDA1 and pDA2, suggested that many PCB-degrading pathways have a common phylogenetic origin.

Biphenyl Compounds↗

Reduction in bleeding after heart-lung transplantation. The importance of posterior mediastinal hemostasis.

To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results.

Adolescent↗

Isolation and preliminary characterization of a 2-chlorobenzoate degrading Pseudomonas.

Pseudomonas sp. strain B-300, which is able to utilize 2-chlorobenzoic acid, was isolated from a soil sample by enrichment culture. This strain was shown to grow on 2-chlorobenzoic acid and to completely degrade the substrate with concomitant chlorine ion release. Concentrations of 2-chlorobenzoic acid higher than 0.5% (w/v) were toxic to the cells. Our study also suggested that in the presence of glucose, 2-chlorobenzoic acid is converted to catechol or chlorocatechol; these are in turn transformed to muconic and chloromuconic acid, respectively, suggesting a repression by glucose of some of the degradation pathway enzymes. A similar scheme was already described for 3-chlorobenzoate degradation by pAC25 plasmid.

Biodegradation, Environmental↗

A deficiency in cyclic AMP results in pH-sensitive growth of Escherichia coli K-12.

Mutants of Escherichia coli K-12 deficient in adenyl cyclase (cya) and catabolite activator protein (crp) have been shown to grow more slowly than their parent strains in glucose-minimal medium. Their growth rate decreased markedly with increasing pH between 6 and 7.8. We have shown that this pH sensitivity is a direct consequence of the cya mutation, because a mutation to pH resistance also restored ability to ferment a variety of sugars. The proton motive force-dependent uptake of proline and glutamate was also reduced and sensitive to pH in the cya mutant. The membrane-bound ATPase activity was normal. The rate of oxygen uptake by cells, although reduced, was pH insensitive. We suggest several explanations for this phenotype, including a possible defect in energy transduction.

Adenylyl Cyclases↗