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R Gasser

Publications and source records attributed to R Gasser.

At least 109 records · Page 6Linked to original sources
PubMed1990

The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes.

Preparations of mRNA isolated from rabbit lung and liver were used in the construction of libraries that were screened for cDNAs encoding the pulmonary or hepatic isozyme of the flavin-containing monooxygenase. The hepatic library was screened with cDNA encoding the flavin-containing monooxygenase expressed in pig liver, and a clone containing a 2.0-kilobase insert was detected and isolated. This cDNA insert encoded a protein of 535 amino acids with a primary structure 87% identical to that of the pig flavin-containing monooxygenase. The pulmonary library was screened with polyclonal antibodies to the flavin-containing monooxygenase expressed in rabbit lung, and a clone containing a 2.6-kilobase insert was detected and isolated. Although the protein encoded by this insert also contained 535 amino acids, its primary sequence was only 56% identical to that of the liver enzyme. The sequences of several peptides obtained by digestion of the purified rabbit pulmonary flavin-containing monooxygenase with trypsin matched exactly with sequences derived from the cDNA structure. Tissue-specific distribution of mRNA for the hepatic and pulmonary isozymes of the flavin-containing monooxygenase was consistent with the distribution of protein, an indication that expression of flavin-containing monooxygenase is controlled at the level of transcription. Analysis of genomic DNA indicates that both the hepatic and pulmonary enzymes may be products of single genes.

Amino Acid Sequence↗
PubMed1990

The flavin-containing monooxygenase expressed in pig liver: primary sequence, distribution, and evidence for a single gene.

The primary sequence of the flavin-containing monooxygenase expressed in pig liver has been derived from the nucleotide sequence of cloned cDNA. The derived sequence is composed of 532 amino acids and represents a protein having a molecular weight of 58,952. The complete sequence was obtained from a single clone containing 2070 bases. A second clone, obtained from an independent library, yielded an identical sequence for the 1374 bases present. The amino acid composition compiled from the derived sequence is very similar to that obtained previously from the purified protein. In addition, a 10 amino acid sequence in a peptide formed from the purified protein by digestion with V8 protease exactly matches the derived sequence for residues 309-318. The flavin-containing monooxygenase expressed in pig liver is also expressed in pig lung and kidney as determined by analysis of both microsomal proteins and mRNA. The ratio of mRNA to protein for the enzyme in kidney is about 5 times greater than the same ratio for liver and about twice the ratio for lung. The reasons for these differences are not understood. Southern analysis of genomic DNA indicates that there is a single gene encoding the flavin-containing monooxygenase expressed in pig liver. Therefore, the broad activity of this enzyme in liver appears to be the result of the catalytic diversity of a single protein.

Amino Acid Sequence↗
PubMed1990

Operation for N2 small cell lung carcinoma.

Of 48 patients with limited small cell lung carcinoma treated by different modes, but always including radical operation, a series of 25 patients with N2 lymph node metastases is reported. In a first period (1970 to 1977) treatment consisted solely of radical resection in 3 patients; chemotherapy was added to operation in 6, and local radiotherapy was added in 2. Since 1977, 14 patients were treated according to a comprehensive therapy protocol including radical resection (six pneumonectomies, one bilobectomy, seven lobectomies), chemotherapy, local radiotherapy, and prophylactic cranial irradiation. Eleven patients, in whom N2 disease was confirmed preoperatively, received chemotherapy as the first step, followed by "adjuvant" resection. Projected 5-year survival rate is 25% for the entire N2 group and 47% for the comprehensively treated group. Seven patients of this latter group are alive 12, 19, 30, 48, 66, 73, and 74 months after comprehensive therapy, equivalent to an observed 2-year survival rate of 38%. This is the largest reported series of patients with resected small cell lung carcinoma in the N2 stage treated at a single institution; the results are so encouraging that we can no longer advocate general refusal of radical lung resection for small cell lung carcinoma in the N2 stage if it is part of a multimodal therapeutic protocol.

Adult↗
PubMed1990

Calcium antagonists: pharmacologic agents in search of new clinical indications.

The broad availability of new pharmacologic agents is usually followed by both the search for similar compounds with more specific and refined actions and the expansion of clinical applicability for these agents. During the last twenty years extensive investigations have revealed that calcium (Ca) antagonists hold a multifaceted pharmacodynamic potential that includes not only the antiarrhythmic and antihypertensive effects of the drug but also the protection against excessive Ca entry into the cells of the cardiovascular system and subsequent cell damage. The physiologic age-dependent Ca accumulation in the arterial wall, which inevitably appears after the second decade, reaches maximal values in the age group of eighty-one to ninety years when the aortic wall exhibits a total Ca content that is 100 times higher than in arteries of infants. In animals we also find age-dependent accumulation of Ca in the arterial wall that is severely aggravated by uncontrolled diabetes or hypertension. Fleckenstein has shown that this arterial calcinosis can be prevented by chronic administration of Ca antagonists. Furthermore, Fleckenstein has demonstrated that excessive Ca overload of myocardial tissue constitutes a basic pathologic process in the development of cardiac necroses--brought about by extreme beta-adrenergic drive (overdoses of catecholamines), high doses of vitamin D3, dihydrotachysterol, alimentary factors such as K or Mg deficiency, or genetic defects (hereditary cardiomyopathy). Even cardiac hypertrophy, either idiopathic or as a consequence of hypertension, can be prevented by the action of Ca antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Noninvasive and invasive diagnosis of a huge congenital aneurysm of the left atrium: a case report.

An intrapericardial aneurysm of the left atrium in a twenty-eight-year old asymptomatic woman is reported. The aneurysm was diagnosed by two-dimensional echocardiography and the specific intraaneurysmatic flow pattern was described by color blood flow imaging. To the authors' knowledge such a noninvasive diagnosis of a left atrial aneurysm has never been reported in the literature before. The diagnosis was confirmed by angiocardiography. The aneurysm was successfully resected. The patient was discharged without medication and continues to do well.

Adult↗
PubMed1989

[Redilatation with the trefoil balloon catheter in 2 patients with a high degree of aortic stenosis].

Percutaneous transluminal balloon valvuloplasty (PTBV) is successfully applied in the treatment of calcified aortic stenosis. However, results following redilatation have not yet been dealt with in the literature. This method was successfully used in two patients (62a m/70a f) suffering from severe sclerotic aortic stenoses. Redilatation was undertaken in the first case after one month and after four in the second. A second redilatation by balloon catheter was done upon request of the patients after a further nine months. Following this third dilatation both patients suffered from femoral thrombosis which was treated surgically in the second case, while in the first local thrombolysis was done. In the management of the first patient valve replacement had to be performed four months after the last dilatation due to renewed complaints, while the second patient showed no evidence of recurrence within three months after the last dilatation.

Aged↗
PubMed1989

Mutational analysis of the Bradyrhizobium japonicum common nod genes and further nod box-linked genomic DNA regions.

By insertional and deletional marker replacement mutagenesis the common nod region of Bradyrhizobium japonicum was examined for the presence of additional, essential nodulation genes. An open reading frame located in the 800 bp large intergenic region between nodD1 and nodA did not appear to be essential for nodulation of soybean. Furthermore, a strain with a deletion of the nodI- and nodJ-like genes downstream of nodC had a Nod+ phenotype. A mutant with a 1.7 kb deletion immediately downstream of nodD1 considerably delayed the onset of nodulation. This region carried a second copy of nodD (nodD2). A nodD1-nodD2 double mutant had a similar phenotype to the nodD2 mutant. Using a 22-mer oligonucleotide probe partially identical to the nod box sequence, a total of six hybridizing regions were identified in B. japonicum genomic DNA and isolated from a cosmid library. Sequencing of the hybridizing regions revealed that at least three of them represented true nod box sequences whereas the others showed considerable deviations from the consensus sequence. One of the three nod box sequences was the one known to be associated with nodA, whereas the other two were located 60 to 70 kb away from nif cluster I. A deletion of one of these two sequences plus adjacent DNA material (mutant delta 308) led to a reduced nodulation on Vigna radiata but not on soybean. Thus, this region is probably involved in the determination of host specificity.

Base Sequence↗
PubMed1989

Free calcium in rat papillary muscle at contraction assessed with Ca-selective microelectrodes.

Direct measurements of free intracellular calcium (Ca)i are needed for an understanding of the regulation of contractility. An on-line measurement of (Ca)i with Ca-selective microelectrodes in intact muscle strips provides a suitable means of investigating this problem, although considerable methodologic difficulties exist. Measurements of (Ca)i concentrations during muscle contraction have been carried out by different methods such as Ca-binding techniques and aequorin luminescence, but remain unsatisfying, since they were not performed on intact muscle strips. The authors' measurements were carried out with Ca-selective microelectrodes on rat papillary muscles (stretched to optimal length in a perfusion bath of 1.54 mL at 30 degrees C). The impalement of electrodes was considered adequate when the heights of Ca-electrode potential and membrane potential remained constant for more than twenty minutes. For provoking contractile responses, the authors replaced the normal Tyrode solution by a caffeine-containing contracture solution (content in mM: 0 NaCl [choline], 4 CaCl2, 30 KCl, 25 caffeine, 1.05 MgCl2). Ca-selective microelectrodes were calibrated before and after each measurement and only those impalements were taken as adequate that showed identical calibration curves before and after the experiment. They measured the (Ca)i at 20%, 50%, and 80% of maximal contractile force and obtained (Ca)i concentrations of 1.1 +/- 0.3 microM (at 20%), 3.6 +/- 1.2 microM (at 50%), and 11.8 +/- 0.27 microM (at 80%) (n = 6, +/- SEM). These results represent the fist on-line measurements of the myocardial (Ca)i concentrations with Ca++-selective microelectrodes in intact muscle strips during various degrees of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Do thrombocyte aggregation inhibitors modify silent episodes of unstable angina pectoris in combined anti-angina therapy?].

Pathological and clinical studies suggest that platelets play role in the pathogenesis of unstable angina. This study investigated the effect of aspirin on silent episodes of unstable angina. Patient exclusion criteria were acute infarction, left bundle branch block, and ST-depression greater than 0.1 mV in the ECG. 27 patients (pts; 20 m, 7 f; 42-72 yrs) in the CCU with unstable angina were randomized in two groups. Group A received a combination on nitrates, beta-blockers, and calcium entry blockers; in group B aspirin (500 mg/day) was added. 6 h after initiating therapy, Holter-ECG was implemented for 48 h. One pt of group A was excluded owing to infarction within these 48 h. 4 of 13 pts in group A and 5 of 13 in group B showed no ST-Segment abnormalities. 6 pts from each group displayed 2 to 5 ST-depressions greater than 0.1 mV from up to 10 min in 24 h; 3 in group A and 2 in group B had 1-5 lasting 11 to 25 min. In the second 24 h period, the number of ST-depressions decreased distinctly. Statistically, the results obtained did not differ significantly in the two groups. Furthermore, the duration of the silent ischemia did not correlate with the severity of coronary stenosis (angiography 3-8 days after admission). Thus, when combined with the aforementioned triple therapeutic regimen, aspirin does not appear to influence the silent episodes of unstable angina pectoris.

Aged↗
PubMed1989

Primary structures of cytochrome P-450 isozyme 5 from rabbit and rat and regulation of species-dependent expression and induction in lung and liver: identification of cytochrome P-450 gene subfamily IVB.

The primary structure of rabbit cytochrome P-450 isozyme 5 has been derived from the nucleotide sequence of cloned cDNA. Identical sequences were obtained for cDNAs constructed with mRNA from four different sources, lung and liver of untreated rabbits and liver from rabbits treated once or four times with phenobarbital. Isozyme 5 shows significant sequence identity only with rabbit P-450p2 (54%) and rat P-450LA omega (53%), which places it in a previously unrecognized cytochrome P-450 gene subfamily (IVB). A cDNA library was also constructed from rat pulmonary mRNA and screened with cDNA encoding rabbit isozyme 5. The amino acid sequence derived from a positive clone was compared with that of rabbit isozyme 5 and found to be 87% identical, significantly greater than observed between other similar forms of cytochrome P-450 from rabbit and rat. Alignment of the primary structures of rabbit isozyme 5 (506 residues), rat isozyme 5 (511 residues), rabbit P-450p2, and rat P-450LA omega shows 43% structural identity and a common 16-residue peptide near position 300 that is unique to these forms of cytochrome P-450. Analysis of mRNA from lung and liver of rabbit, rat, guinea pig, and hamster indicates that species and tissue differences in the expression and induction of isozyme 5 are likely regulated at the level of transcription. These differences fall into one of the following three groups: first, expression in lung and liver and induction in liver by phenobarbital (rabbit); second, expression in lung and liver but no hepatic induction (hamster); and third, expression in lung and little or no expression in liver regardless of treatment (rat and guinea pig).

Amino Acid Sequence↗
PubMed1989

[Myocardial damage following lightning injury].

In a 27-year-old woman, struck by lightning behind the left ear, the ECG showed signs of an acute posterior-lateral myocardial infarction after 1 h of unconsciousness and loss of memory. Her serum enzymes were increased as is typical of myocardial infarction, but the patient did not complain of cardiac symptoms. Besides clear signs of lightning injury, the patient showed a hemorrhage throughout the left breast and transient pericardial effusion was observed by echocardiography. In the course of two months, the ECG revealed a regression to unspecific ST-T-deviations and serum enzymes became normal. TI-201-myocardial-scintigraphy (SPECT), done six days and two months after lightning injury, excluded reversible and irreversible perfusion defects.

Adult↗
PubMed1988

Restriction by nitrendipine of excessive concentration of free intracellular calcium ions in ventricular myocardium of hypertensive rats.

In earlier investigations it has been found that high arterial blood pressure of salt-sensitive DAHL rats (DAHL-S) that received a diet containing 8% NaCl could be normalized by chronic treatment with specific calcium antagonists, as for instance, nitrendipine or anipamil. Parallel measurements on heart and arterial vasculature with atomic absorption spectrometry revealed that there was a rise in absolute calcium content upon development of hypertension, whereas under the influence of nitrendipine, not only the blood pressure and heart weight but also myocardial (and arterial) tissue calcium content remained in the physiologic range. In the present study, an additional determination of the free intracellular calcium ion concentration with Ca-sensitive microelectrodes was carried out. For technical reasons, the measurements were restricted to isolated resting rat papillary muscles (stretched to optimal length in a perfusion bath of 1.5 ml at 30 degrees C in normal Tyrode solution). The impalement of the electrodes was considered adequate when the heights of Ca potential and membrane potential were constant for more than twenty minutes. In order to produce severe systemic hypertension, a group of six-week-old DAHL-S rats was fed with an 8% NaCl diet over five weeks. Another group of DAHL-S rats received additionally 150 mg/kg nitrendipine twice a day orally. Salt-resistant DAHL-R rats, also fed with an 8% NaCl diet, served as controls. The findings of this preliminary study are as follows (n = 5 in each group): (table; see text).

Animals↗
PubMed1988

Primary structures of multiple forms of cytochrome P-450 isozyme 2 derived from rabbit pulmonary and hepatic cDNAs.

Rabbit pulmonary and hepatic mRNA was used to construct cDNA libraries that were screened with a cDNA probe (pf 3/46) to murine cytochrome P-450 homologous with rat cytochrome P-450b. Three types of cDNA clones were identified on the basis of restriction analysis with Bst EII. Two types of clones (B0 and B1) were present in a library constructed from pulmonary mRNA. The nucleotide sequence of B0 cDNA encodes a protein of 491 amino acids having a sequence identical to one reported for isozyme 2. The sequence derived from the b1 cDNA also contains 491 amino acids but differs from the B0 sequence at six positions. B1 clones were also obtained from a library constructed from hepatic mRNA isolated 12 hr after a single treatment with phenobarbital. A third type of clone (B2) was also obtained from this library, but no B0 clones were found. The sequence derived from the B2 cDNA contains 491 amino acids and differs from the B0 and B1 sequences at 11 and 15 positions, respectively. A second hepatic cDNA library, constructed from mRNA from the liver of a rabbit treated with phenobarbital daily for 4 days, contained B0 clones. The sequence of one of these was found to be identical to that of the pulmonary B0 clones.

Amino Acid Sequence↗
PubMed1987

New aspects of the kinetics of isoenzyme CK-MB during myocardial infarction: discontinuous release?

Intermittent liberation of the serum marker myoglobin is found in acute myocardial infarction, and the ST segment of the electrocardiogram also shows a phasic rise and fall. We therefore measured the serum marker CK-MB at close intervals of time and recorded an oscillation in the serum level. The peaks are not as high as in the serum myoglobin time curve, and it is not easy to decide if they represent the intermittent liberation of the serum marker. It was possible to distinguish between a "high release" and a "low release" group of patients: the former having a maximum CK-MB value of greater than 100 U/l and the latter of less than 100 U/l. Most patients showed 2-3 "initial peaks" within the first 8 h. The highest of these immediately preceded the climb to the definitive maximum value. We conclude that the small size of the peaks in the CK-MB time curve is due to a different mechanism of enzyme release.

Adult↗