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J W Mack

Publications and source records attributed to J W Mack.

At least 19 recordsLinked to original sources
PubMed2001

A study of the influence of the hydrophobic core residues of yeast iso-2-cytochrome c on phosphate binding: a probe of the hydrophobic core-surface charge interactions.

To gain insight into the role of hydrophobic core-surface charge interactions in stabilizing cytochrome c, we investigated the influence of hydrophobic core residues on phosphate binding by mutating residues in yeast iso-2-cytochrome c to those corresponding to iso-l-cytochrome c in various combinations. Heat transition of ultraviolet CD was followed as a function of pH in the presence and absence of phosphate. Thermodynamic parameters were deduced. It was found that the I20V/V43A/M98L mutation in the hydrophobic core, whose locations are remote from the putative phosphate sites, modulates phosphate interactions. The modulation is pH dependent. The I20V/ M98L and V43A mutation effects are nonadditive. The results lead to a model analogous to that of Tsao, Evans, and Wennerstrom, where a domain associated with the ordered hydrophobic core is sensitive to the fields generated by the surface charges. Such an explanation would be in accord with the observed difference in thermal stability between iso-2 and horse cytochromes c.

Amino Acid Sequence↗
PubMed2000

Backbone motions in a crystalline protein from field-dependent 2H-NMR relaxation and line-shape analysis.

We have used 2H-nmr to study backbone dynamics of the 2H-labeled, slowly exchanging amide sites of fully hydrated, crystalline hen egg white lysozyme. Order parameters are determined from the residual quadrupole coupling and values increase from S2 = 0.85 at 290 K to S2 = 0.94 at 200 K. Dynamical rates are determined from spin-lattice relaxation at three nmr frequencies (38.8, 61.5, and 76.7 MHz). The approach used here is thus distinct from solution nmr studies where dynamical amplitudes and rates are both determined from relaxation measurements. At temperatures below 250 K, relaxation is independent of the nmr frequency indicating that backbone motions are fast compared to the nmr frequencies. However, as the temperature is increased above 250 K, relaxation is significantly more efficient at the lowest frequency, which shows, in addition, the presence of motions that are slow compared to the nmr frequencies. Using the values of S2 determined from the residual quadrupole coupling and a model-free relaxation formalism that allows for fast and slow internal motions, we conclude that these slow motions have correlation times in the range of 0.1 to 1.0 microsecond and are effectively frozen out at 250 K where fast motions of the amide planes with approximately 15 ps effective correlation times and 9 degrees rms amplitudes dominate relaxation. The fast internal motions increase slightly in amplitude as the temperature rises toward 290 K, but the correlation time, as is also observed in solution nmr studies of RNase H, is approximately constant. These findings are consistent with hypotheses of dynamic glass transitions in hydrated proteins arising from temperature-dependent damping of harmonic modes of motion above the transition point.

Animals↗
PubMed1993

The mechanism of interaction of filaggrin with intermediate filaments. The ionic zipper hypothesis.

Filaggrins of mammalian epidermis represent archetypical examples of intermediate filament-associated proteins that can bind large numbers of intermediate filaments in vitro (and keratin filaments in vivo) into macrofibrils. To explore the mechanism of this interaction, the secondary structures of filaggrins were analyzed. As much as 80% of mouse and human filaggrins consist of multiple repeating elements. The first level consists of a tetrapeptide beta-turn motif in which about 35% of the turns are positively charged and about 10% are negatively charged. At the next level, triplets of this motif form segments 13 to 14 residues in length, which in turn are repeated two to six times into blocks separated by short hydrophobic sequences to constitute a complete filaggrin molecule. Thus, filaggrins evolved by frequent duplications of a primordial repeat unit of about 13 to 14 residues with subsequent retention of the conserved beta-turn and charge characteristics. To test how these features bind filaments, two approaches were used. Of a series of synthetic peptides, those of 20 to 26 residues (about 2 segments) containing at least five beta-turns with a net charge of +2 (that is, about 40% of the turns are positively charged) were as effective as full length filaggrin in binding large numbers of both type I/II keratin and type III vimentin/desmin filaments, as judged by electron microscopy. Secondly, macrofibrils formed from unlabeled filaggrin and keratin filaments labeled in vivo with [1-13C]glycine or L-[4,4,5,5-2H4]lysine were probed by nuclear magnetic resonance. The effective isotropy and time scale of mobilities of the glycine-labeled end domains were essentially identical in keratin filaments alone and those bound in macrofibrils, suggesting that filaggrins do not bind filaments by way of their end domains. However, the lysine-labeled rod domains of the filaments in macrofibrils were considerably more constrained than in filaments alone. These data support the hypothesis that filaggrins bind filaments by way of simple ionic and/or H-bonding interactions between the conserved positive and negative charges on the beta-turns of filaggrins and the conserved distributions of negative and positive charges along the packed rod domains of intermediate filaments, as in an ionic zipper.

Amino Acid Sequence↗
PubMed1991

Glycine loops in proteins: their occurrence in certain intermediate filament chains, loricrins and single-stranded RNA binding proteins.

Quasi-repetitive, glycine-rich peptide sequences are widespread in at least three distinct families of proteins: the keratins and other intermediate filament proteins, including nuclear lamins; loricrins, which are major envelope components of terminally differentiated epithelial cells; and single-stranded RNA binding proteins. We propose that such sequences comprise a new structural motif termed the 'glycine loop'. The defining characteristics of glycine loop sequences are: (1) they have the form x(y)n, where x is usually an aromatic or occasionally a long-chain aliphatic residue; y is usually glycine but may include polar residues such as serine, asparagine, arginine, cysteine, and rarely other residues; and the value of n is highly variable, ranging from 1 to 35 in examples identified to date. (2) Glycine-loop-containing domains are thought to form when at least two and to date, as many as 18, such quasi-repeats are configured in tandem, so that the entire domain in a protein may be 50-150 residues long. (3) The average value of n, the pattern of residues found in the x position and the non-glycine substitutions in the y position appear to be characteristic of a given glycine loop containing domain, whereas the actual number of repeats is less constrained. (4) Glycine loop sequences display a high degree of evolutionary sequence variability and even allelic variations among different individuals of the same vertebrate species. (5) Glycine loop sequences are expected to be highly flexible, but possess little other regular secondary structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Solid-state NMR studies of the dynamics and structure of mouse keratin intermediate filaments.

The molecular dynamics and structural organization of mouse epidermal keratin intermediate filaments (IF) have been studied via solid-state nuclear magnetic resonance (NMR) experiments performed on IF labeled both in vivo and in vitro with isotopically enriched amino acids. As a probe of the organization of the peripheral glycine-rich end domains of the IF, carbon-13 NMR experiments have been performed on subfilamentous forms (prekeratin) and on IF reassembled in vitro that had been labeled with either [1-13C]glycine or [2-13C]glycine, as more than 90% of the glycines of the keratins are located in the end domains. Although cross-labeling to seryl residues was observed, the proportion of serine located in the end domains is nearly the same as that for glycine. Measurements of carbon relaxation times, nuclear Overhauser enhancements, and signal intensities show that the motions of the peptide backbone in the end domains are effectively isotropic, with average correlation times distributed over the range of 0.2-20 ns. These results indicate that the end domains of IF are remarkably flexible and have little or no structural order. To probe the structural organization of the coiled-coil rod domains of the IF, separate samples of native keratin IF, raised in primary tissue culture, were labeled with L-[1-13C]leucine, L-[2H10]leucine, or L-[2,3,3-2H3]leucine, as greater than 90% of the leucyl residues of the keratin IF types studied are located in the coiled coils which form the central core of IF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of varied cardioplegic perfusion pressure on myocardial preservation with critical coronary stenosis.

Inadequate delivery of cardioplegic solution distal to coronary artery stenosis may result in increased injury during ischemic arrest. This study was performed to determine the effects of cardioplegic perfusion pressure on cardioplegia delivery and myocardial preservation in hearts with critical coronary artery stenosis. Twenty dogs underwent 90 minutes of cold potassium cardioplegic arrest with partial occlusion of the circumflex coronary artery. Group 1 received cardioplegia at 50 mm Hg pressure, Group 2 at 90 mm Hg pressure, and Group 3 at 130 mm Hg pressure. It was found that cooling rates were 5.4 degrees, 9.1 degrees, and 18.2 degrees C per minute in the nonischemic area (p = 0.004) and 2.0 degrees, 4.5 degrees, and 7.9 degrees C in the ischemic area (p = 0.008) in Groups 1, 2, and 3, respectively. Total of cardioplegic solution flows were 86, 188, and 262 ml per minute per 100 gm in Groups 1, 2, and 3, respectively (p = 0.001). However, flow did not differ significantly between groups in the ischemic area. Rate of rise of left ventricular (LV) pressure decreased significantly in Groups 1 and 2 but not in Group 3 (p = 0.002). Other measured variables did not differ significantly between groups, although LV function curves showed less deterioration in the high-pressure groups. It is concluded that higher cardioplegic perfusion pressure resulted in more rapid cooling in normal and ischemic areas and slightly better preservation of ventricular function as measured by some indexes. However, preservation was generally good for each of the pressures for up to 90 minutes of ischemia when the septum was consistently cooled to 10 degrees C.

Adenosine Triphosphate↗
PubMed1985

Current status of coronary artery bypass grafting for coronary artery atherosclerosis.

Coronary artery bypass grafting has now undergone 18 years of proven benefit in the treatment of myocardial ischemic disease. The technique of CABG has been further extended to other situations in which myocardial blood supply is threatened, such as cardiac trauma, aneurysms of coronary arteries, and congenital lesions. The emphasis in choosing CABG over medical therapy in 1985 should be preservation of myocardium at jeopardy of infarction as well as relief of angina. Proximal stenoses in vessels subserving viable muscle that is ischemic at rest or with minimal exercise should be treated with reperfusion by angioplasty or CABG to prevent further injury. After infarction occurs and ventricular function is impaired, CABG is also necessary to preserve remaining myocardium at jeopardy. Such an aggressive approach seems warranted with today's excellent surgical results. Long-term results have also improved, as more attention has been paid to saphenous vein graft preparation, use of mammary artery grafts, complete revascularization, use of antiplatelet agents, control of spasm, and identification of hypercoagulable states that may require sodium warfarin (Coumadin). Angioplasty of vein grafts and distal anastomoses also appears promising to help extend the results of initial CABG. Figure 1 is our recommended approach for the treatment of coronary atherosclerosis.

Angina Pectoris↗
PubMed1985

Management of blunt and penetrating external esophageal trauma.

The records of 26 patients with external blunt or penetrating esophageal trauma were reviewed to determine clinical features and results of therapy. Twenty-one injuries (four blunt, 17 penetrating) were to the cervical esophagus, and five to the thoracic esophagus. Major physical signs included subcutaneous air, neck hematoma, and blood in the nasogastric tube. Helpful roentgenographic findings were cervical and/or mediastinal air, mediastinal widening, pleural effusion, and pneumothorax (15%). Nine of 12 (75%) contrast studies and five of six (83%) esophagoscopies were positive. Twenty-four patients had associated injuries, the most common of which was tracheal (14 patients) (64%). All patients were managed by prompt surgical exploration, primary closure, and drainage. There were three early deaths. Thirteen patients had postoperative complications, four of which were esophageal leaks. Two of the leaks caused mediastinitis, pleural sepsis, and led to death. They were not treated by early esophageal exclusion or excision. There were no significant strictures or esophageal sequelae in the other patients. It is concluded that early primary closure and drainage results in a relatively high incidence of survival. If a thoracic esophageal leak occurs, aggressive management of prompt esophageal exclusion or excision is necessary to control sepsis and improve survival.

Adolescent↗
PubMed1985

Avoidance of malignant hyperthermia in a porcine model for experimental open heart surgery.

The porcine heart is an excellent physiological and anatomical experimental model because of its close similarity to the human heart. However, the pig is difficult to use in chronic experiments because of its propensity to develop malignant hyperthermia (MH). We have employed a technique which greatly reduces the incidence of MH in the chronic pig model, making its use feasible for a variety of experimental protocols.

Anesthesia↗
PubMed1985

Quantitative evaluation of the myocardial preservative characteristics of nifedipine during hypothermic myocardial ischemia.

Nifedipine, a slow calcium-channel blocker, has been used to preserve myocardial function in the ischemic heart. To quantitatively evaluate the effectiveness of nifedipine as a cardioplegic agent during moderate hypothermia (28 degrees C), 15 pigs were evaluated on total and right heart bypass with measurement at normothermia and after 1 hour of hypothermic ischemia of stroke volume, coronary blood flow, myocardial oxygen consumption, and lactate extraction. Myocardial tissue gases (oxygen and carbon dioxide) were continuously monitored. Animals were divided into three groups: hypothermic ischemia, hypothermic ischemia with infusion of nifedipine carrier without nifedipine, and hypothermic ischemia with nifedipine and its carrier. A significant decrease in stroke volume was seen in all three groups; however, the depression was significantly greater following hypothermic ischemia than following cardioplegia with either nifedipine or its carrier. The mean recovery value of stroke volume was highest in the nifedipine group, but this difference between nifedipine and its carrier alone did not reach statistical significance. Coronary blood flow, myocardial oxygen consumption, lactate extraction, and tissue gases failed to substantiate a significant benefit when nifedipine was compared with its carrier alone. We conclude that under these hypothermic conditions, no proven statistically significant advantage was noted in the nifedipine group when compared with the nifedipine carrier group in swine. However, both nifedipine and the carrier were superior as a myocardial preservative when compared with hypothermic ischemic arrest alone.

Animals↗
PubMed1983

Emergency lobectomy for massive hemoptysis in cystic fibrosis.

Massive hemoptysis occurs in 50% to 70% of patients with cystic fibrosis and carries an immediate mortality of up to 32%. Cystic fibrosis is regarded by many as a disease in which thoracic operations are ill-advised. A 21-year-old woman with mild cystic fibrosis presented with unrelenting massive hemoptysis, was not helped by medical management, and underwent a successful left upper lobectomy. We suggest that thoracotomy does have a role in the management of massive hemoptysis in selected patients with cystic fibrosis. On the basis of our case and all other cases reported in the English literature, we suggest criteria for determining which patients are suitable candidates for emergency thoracotomy.

Adult↗
PubMed1983

Massive hemoptysis in cystic fibrosis.

Massive hemoptysis occurs in 5% to 7% of patients with cystic fibrosis. Approximately 11% of these patients will die within 48 hours of manifestation because of uncontrolled hemoptysis and asphyxiation. If conservative medical treatment fails to control hemoptysis, fiberoptic or rigid bronchoscopy is the least risky and most accurate method of localizing the source of hemoptysis. Acute control of hemoptysis can be obtained in up to 100% of patients with endobronchial Fogarty balloon tamponade and in up to 88% of patients with bronchial artery embolization. Emergency thoracotomy can be performed if the above fail, but only in patients with mild cystic fibrosis and adequate pulmonary reserve.

Bronchoscopy↗
PubMed1981

Persistent stenosis and deformity of the right pulmonary artery after correction of the Waterston anastomosis.

Between July, 1975, and July, 1979, 16 patients with cyanotic heart disease and previously constructed ascending aorta-right pulmonary artery (AA-RPA) shunts underwent subsequent operations. Fourteen of the 16 had significant physiological and anatomic problems associated with the shunts. Eight had kinking and preferential flow to the right pulmonary artery (RPA), four had preferential flow without kinking, and two had small pulmonary arteries bilaterally. Various techniques were used to close the RPA after Waterston takedown: direct suture in four, pericardial patch in five, prosthetic patch in four, and conduit in three. Five patients required reoperation 3 months to 3 years after Waterston dismantling because of persistent deformity of the RPA. Four patients had pericardial patch reconstruction of the RPA and one had direct closure of the opening in the RPA when the Waterston shunt was dismantled. All five patients received prosthetic patch enlargment of the RPA either alone or with a conduit. The four surviving patients are doing well 7 to 15 months following repair. Three have been studied angiographically and have been found to have no pulmonary artery deformity.

Angiography↗
PubMed1980

Bilateral pulmonary sequestrations.

The case history of a young man with bilateral intralobar sequestrations is presented. The patient underwent bilateral resection of the sequestrations, although only the left side was symptomatic. We have found no previous reports in the literature in which bilateral pulmonary resections were performed for this condition. We present the clinical features and management of this unique case.

Adolescent↗
PubMed1979

Postoperative chylous pseudocyst.

A 59-year-old man underwent resection of aneurysm of the descending thoracic aorta with graft replacement. A postoperative chylothorax was managed by nonsurgical means and subsided. Subsequently, an expansile mass appeared in the left side of the chest and was surgically removed. This was found to be a chylous pseudocyst. Management of chylothorax and the details of this unique case are described.

Aortic Aneurysm↗
PubMed1977

The effect of maternal narcotic addiction on the newborn infant.

This paper presents a review of the literature on the effects of maternal narcotic addictions upon the foetus and newborn infant. Six children born to 'registered' narcotic addicts were studied, and particular attention was paid to any signs of narcotic withdrawal that might occur after birth. Although all the mothers took heroin or methadone regularly up to the time of delivery, minor physical signs which might have been considered part of the withdrawal syndrome occurred in only one baby. The absence of major withdrawal signs found in this study contrasts with previous findings. The reasons for these differences are discussed, and the implications of these observations for the management of the pregnant narcotic addict and her newborn infant are considered.

Abnormalities, Drug-Induced↗