Biomedical subjects

M Gawaz

Publications and source records attributed to M Gawaz.

59 records · Page 4Linked to original sources

PubMed1990

Structure-function studies of adenine nucleotide transport in mitochondria. II. Biochemical analysis of distinct AAC1 and AAC2 proteins in yeast.

AAC1 and AAC2 genes in yeast each encode functional ADP/ATP carrier (AAC) proteins of the mitochondrial inner membrane. In the present study, mitochondria harboring distinct AAC proteins and the pet9 Arg96 to HIS mutant (Lawson, J., Gawaz, M., Klingenberg, M., and Douglas, M. G. (1990) J. Biol. Chem. 265, 14195-14201) protein have been characterized. In addition, properties of the different AAC proteins have been defined following reconstitution into proteoliposomes. Deletion of AAC2 but not AAC1 causes a major reduction in the mitochondrial cytochrome content and respiration, and this level remains low even when the level of AAC1 protein is increased to 20% that of the AAC2 gene product. In reconstitution studies, the rate of nucleotide transport by isolated AAC1 protein is approximately 40% that of the AAC2 protein. Thus, the lack of mitochondrial-dependent growth supported by the AAC1 gene product alone may be due to the combination of low abundance and reduced activity. Surprisingly, analysis of the Arg96 to His mutant protein revealed binding and transport activities similar to the functional AAC1 and AAC2 gene products. These observations are discussed in relation to a molecular analysis of this highly conserved small transporter and its function in conjunction with other proteins in the mitochondrial membrane.

Adenosine Triphosphate↗

PubMedDate not supplied

Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation.

Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis of MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p < 0.05) that correlated with severity of disease (r = 0.597, p = 0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p < 0.05) which well with severity of MOF (GMP-140, r = 0.611, p = 0.013; TSP, r = 0.643, p = 0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

Adolescent↗

PubMedDate not supplied

Role of activation-dependent platelet membrane glycoproteins in development of subacute occlusive coronary stent thrombosis.

BACKGROUND: Platelets have an important role in coronary thrombosis. METHODS: We studied 151 consecutive patients undergoing implantation of Palmaz-Schatz stents because of suboptimal results after coronary balloon angioplasty treated by intense anticoagulation. Surface exposure of the constitutively expressed glycoprotein complex IIb-IIIa (CD41), P-selectin (CD62P) and of the GPIIb-IIIa complex activated exposure (of ligand-induced binding site-1) were determined, in addition to platelet count and plasma fibrinogen, before and daily for 12 days after stenting in peripheral venous blood samples. RESULTS: Six of 151 patients (3.9%) developed subacute stent thrombosis within the first week after stenting. The relative risk of stent thrombosis was 18.5-fold for patients with enhanced GPIIb-IIIa surface expression (P < 0.003; 95% confidence interval 2.1 to 163.1) before stent placement. In the period after stenting, platelet activation occurred, with an increase in fibrinogen receptor activity and P-selectin degranulation above pre-stent values (P < 0.01). In logistic regression analysis, GPIIb-IIIa before stenting emerged as a risk factor for stent thrombosis, independent of the activational status of platelets, platelet count or fibrinogen levels (P < 0.02). However, after stenting, P-selectin surface expression acquired prognostic importance for stent thrombosis (P < 0.05). CONCLUSION: We conclude that changes in platelet membrane glycoproteins are of prognostic value in predicting subacute stent thrombosis.

Acute Disease↗

PubMedDate not supplied

Management of concomitant occlusive disease of coronary and carotid arteries using cardiopulmonary bypass for both procedures.

The incidence of neurological complications following operative treatment of concomitant occlusive disease of coronary and carotid arteries has been reported to be between 0.7 and 18 per cent by different preoperative screening methods and surgical strategy. From the opening of our institution in November 1984 until March 1988 5443 open-heart procedures were performed. In 116 patients of 3540 consecutive coronary artery bypass grafting (CABG) candidates simultaneous carotid endarterectomy (TEA) was carried out because of hemodynamically relevant stenosis of one or both carotid arteries; 50 patients were neurologically symptomatic with TIA's and amaurosis fugax preoperatively. Sixty of 66 patients with asymptomatic carotid artery stenosis had either a morphologically severe stenosis of the carotid artery or multifocal occlusive disease of the extracranial supraaortic arteries. Prior to carotid-TEA cardiopulmonary bypass was inserted with mild hypothermia maintaining a beating heart for pulsatile body perfusion. An intraluminal shunt was only used in patients with bilateral carotid stenosis. Intraoperative EEG-monitoring was carried out to detect cerebrovascular insufficiency. In 108/116 patients no neurological complications were observed, but 6/116 patients had transient minor neurological symptoms. Two of 116 patients sustained a severe neurological deficit with hemiplegia and one of them died on the 21st postoperative day. Based on these data we conclude that patients requiring carotid TEA and CABG should be operated upon simultaneously using cardiopulmonary bypass for both procedures.

Aged↗

PubMedDate not supplied

Successful treatment of patients with hairy cell leukemia (HCL) using a single cycle of 2-chloro-2'-deoxyadenosine (CdA).

2-Chloro-deoxyadenosine (CdA) is a new adenosine-deaminase (ADA) resistant purine analogue with high specificity for lymphoid cells. It was shown that CdA is very effective in hairy cell leukemia (HCL), refractory chronic lymphocytic leukemia and cutaneous T-cell lymphoma leading to lasting remissions in the majority of patients with HCL. We report the successful treatment of five patients with HCL at different stages of their disease using CdA, who were either previously untreated or had received interferon, splenectomy and deoxycoformycin (dCF), an ADA-inhibitor with high therapeutic efficacy in HCL. After one 7-day course of treatment, all patients reached remission. CdA was well tolerated and, only mild side effects such as skin rash, headache, fever, nausea were observed. Aplasia was pronounced in all instances with a slow recovery. The type of histomorphological procedure in preparing and evaluating bone marrow biopsies is emphasized to detect minimal residual infiltration by hairy cells.

Adult↗