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B Kunkel

Publications and source records attributed to B Kunkel.

At least 37 records · Page 2Linked to original sources
PubMed1990

The Bacillus subtilis gene for the development transcription factor sigma K is generated by excision of a dispensable DNA element containing a sporulation recombinase gene.

The structural gene (sigK) for the mother-cell RNA polymerase sigma-factor sigma K in Bacillus subtilis is a composite of two truncated genes, named spoIVCB and spoIIIC, which are brought together by site-specific recombination during sporulation. We now show that the recombination event is compartmentalized in that the mother cell, but not the forespore chromosome, undergoes rearrangement. We also show that spoIIIC (encoding the carboxy-terminal portion of sigma K) lies approximately 42 kb downstream of spoIVCB (encoding the amino-terminal portion) and that the joining of the truncated coding sequences is a reciprocal recombination event in which intervening DNA is deleted from the chromosome as a circle. The rearrangement is governed by the product of a gene named spoIVCA located in the excised DNA, as demonstrated by the observations (1) that the product of spoIVCA, but not the product of any other stage-IV sporulation gene tested, is required for the rearrangement, and (2) that the presence of a cloned copy of the rearranged sigK gene in the chromosome bypasses the requirement for the spoIVCA gene product in sporulation. Because cells engineered to contain an intact copy of sigK sporulate normally, we conclude that the sigK rearrangement is not essential for the control of gene expression during sporulation, and we infer the existence of an additional mechanism for restricting sigma K-directed transcription to the mother-cell chamber of the sporangium. Finally, the construction of a strain deleted for the entire sigK intervening sequence shows that the 42-kb element contains no genes essential for viability.

Bacillus subtilis↗
PubMed1989

Switch protein alters specificity of RNA polymerase containing a compartment-specific sigma factor.

During sporulation in Bacillus subtilis, expression of developmental genes spoIVCB and cotD is induced in the mother cell compartment of the sporangium at morphological stages IV and V, respectively. A 27-kilodalton RNA polymerase sigma factor called sigma K (or sigma 27) has been found that causes weak transcription of spoIVCB and strong transcription of cotD. A 14-kD protein was also discovered that changes the specificity of sigma K-containing RNA polymerase, greatly stimulating spoIVCB transcription and markedly repressing cotD transcription. Both sigma K and the 14-kD protein are products of genes known to be required for expression of specific genes in the mother cell. Thus, sigma K directs gene expression in the mother cell and it is proposed that inactivation or sequestering of the 14-kD protein switches the temporal pattern of gene expression during the transition from stages IV to V of development.

Amino Acid Sequence↗
PubMed1989

Chromosomal rearrangement generating a composite gene for a developmental transcription factor.

Differential gene expression in the mother cell chamber of sporulating cells of Bacillus subtilis is determined in part by an RNA polymerase sigma factor called sigma K (or sigma 27). The sigma K factor was assigned as the product of the sporulation gene spoIVCB on the basis of the partial aminoterminal amino acid sequence of the purified protein. The spoIVCB gene is now shown to be a truncated gene capable of specifying only the amino terminal half of sigma K. The carboxyl terminal half is specified by another sporulation gene, spoIIIC, to which spoIVCB becomes joined inframe at an intermediate stage of sporulation by site-specific recombination within a 5-base pair repeated sequence. Juxtaposition of spoIVCB and spoIIIC need not be reversible in that the mother cell and its chromosome are discarded at the end of the developmental cycle. The rearrangement of chromosomal DNA could account for the presence of sigma K selectively in the mother cell and may be a precedent for the generation of cell type-specific regulatory proteins in other developmental systems where cells undergo terminal differentiation.

Amino Acid Sequence↗
PubMed1989

Temporal and spatial control of the mother-cell regulatory gene spoIIID of Bacillus subtilis.

Gene expression during endospore formation in Bacillus subtilis is compartmentalized between the mother-cell and forespore chambers of the sporangium, which follow separate pathways of cellular differentiation. The earliest acting regulatory gene so far identified in the mother-cell line of gene expression is spoIIID, whose product is required for the transcription of the composite gene (sigK) encoding the mother-cell RNA polymerase sigma-factor sigma K and for the chromosomal rearrangement that gives rise to the composite gene. Here we report the nucleotide sequence of spoIIID and studies on the temporal, spatial, and genetic control of its expression during sporulation. We show that the deduced spoIIID gene product, a 93-residue-long polypeptide, is a previously identified transcription factor that is known to activate the promoter for the sigK gene in vitro. Expression of spoIIID is largely confined to the mother-cell chamber of the sporangium and is turned on at, or shortly before, the time (hour 3 of sporulation) that the mother-cell chromosome is rearranged and transcription of the sigK gene commences. This gene expression depends strongly on the sporulation sigma-factor sigma E and partially on the spoIIID gene product, itself. We conclude that the timing and compartmentalization of the rearrangement and transcription of the sigK gene and, hence, of subsequent gene activation in the mother cell, are, in part, direct consequences of the temporal and spatial control of spoIIID gene expression.

Amino Acid Sequence↗
PubMed1989

[Hemodynamic study of the development of tolerance in intravenous nitrate therapy].

UNLABELLED: To investigate possible tolerance development under an intravenous treatment with nitrates, 22 patients with coronary artery disease were randomly assigned to receive either 4 mg/h of ISDN (n = 12) or placebo (n = 10) and were given additional 10 mg of ISDN or placebo after 23 h. Pulmonary artery pressures (PAP), cardiac output, and heart rate were registered before, and 4 h, 22.5 h, and 24 h after the beginning of treatment. At baseline both groups were similar with regard to pulmonary artery diastolic pressure (PADP) at rest and at comparable work load. Each patient of the placebo group showed identical PAPs at work. ISDN led to a 42-59% decrease of PADP at rest and 29-37% decrease at comparable work load. After 22.5 h a statistically insignificant reduction of ISDN effect was observed which could be reversed by additional ISDN p.o. A detailed analysis of the ISDN group showed seven patients with a persistently lowered PADP, (table; see text) whereas five patients demonstrated a partial diminuation of the ISDN effect. No patient showed a complete tolerance. In the placebo group blood pressure did not show any change during the treatment period (143 +/- 21/84 +/- 10 mmHg vs 137 +/- 17/79 +/- 10 mmHg), whereas ISDN infusion resulted in a continuously lowered blood pressure (150 +/- 22/83 +/- 11 mmHg vs 125 +/- 15/72 +/- 9 mmHg (p less than 0.001). Cardiac output and heart rate were similar under ISDN and placebo treatment. CONCLUSION: Continuous infusion of 4 mg of ISDN/h over 24 h and an additional dose of 10 mg of ISDN after 23 h provided a significant reduction in PADP, blood pressure and rate pressure product over 24 h at rest and during exercise.

Administration, Oral↗
PubMed1988

The promoter for a sporulation gene in the spoIVC locus of Bacillus subtilis and its use in studies of temporal and spatial control of gene expression.

We have identified the transcription start site and regulatory region governing the expression of a sporulation gene in the spoIVC locus of Bacillus subtilis. Efficient expression and developmental regulation of this gene was controlled from a promoter region that extended no more than 110 base pairs upstream and no more than 4 base pairs downstream from the start site of transcription, on which basis we infer that spoIVC is regulated at the level of transcription initiation. Using a transcriptional fusion of the spoIVC gene to the lacZ gene of Escherichia coli, we found that spoIVC expression was turned on at the third to fourth hour of sporulation (at about the developmental stage [IV] that its products are required in spore formation) and that this transcription was largely restricted to the mother cell chamber of the sporangium. Mutations in many different spo genes (causing blocks at stages 0 to V) were found to influence (negatively and positively) the level of spoIVC expression. Our results distinguish the mode of spoIVC regulation from that of previously studied sporulation genes and indicate that it is representative of a new regulon of mother cell-specific gene expression.

Bacillus subtilis↗
PubMed1987

[Therapy of latent cardiomyopathy with verapamil].

In an open, randomized cross-over trial lasting two months, 21 patients with latent cardiomyopathy were either untreated or received verapamil 120 mg three times daily. Angina and dyspnea improved in 14 of the 21 patients. These symptoms worsened in one, remained unchanged in six (P less than 0.05). During exercise the pulmonary artery diastolic pressure fell from a mean of 25.3 +/- 7.6 to 20.1 +/- 6.6 mm Hg (P less than 0.05); (at rest, from mean of 10.7 +/- 5.2 to 9.0 +/- 4.5 mm Hg - not significant). In nine patients with a raised resting PA diastolic pressure verapamil produced a significant reduction (from 15.4 +/- 2.7 to 11.1 +/- 4.1 mm Hg) (P less than 0.05). All other hemodynamic parameters remained unchanged. These clinically and hemodynamically favorable effects are possibly due to improved diastolic ventricular function by verapamil. In latent cardiomyopathy any impairment of diastolic relaxation may be more important pathogenetically than reduction in systolic ventricular function.

Adult↗
PubMed1987

Development and regression of right heart ventricular hypertrophy: biochemical and morphological aspects.

Male Wistar rats were exposed, in a hypobaric chamber, to a simulated altitude of 6000 m for up to four weeks. The animals quickly developed pulmonary hypertension with an important media hypertrophy of the pulmonary arteries, followed by severe right heart hypertrophy (cor pulmonale). Right heart hypertrophy is evident in three morphologically and biochemically definable stages. In stage 1 (1st-2nd week) a manifest thickening of heart muscle cells develops due to increased protein synthesis. In stage 2 (2nd-3rd week) one can find, in the regular biochemical composition of heart muscle, an activation of mitochondrial ATPase, a multiplication of mitochondria, a proliferation of interstitial cells and an increase in interstitial volume. In stage 3 (3rd-4th week) the hypertrophied myocardium exhibits signs of biochemical and morphological decompensation. Besides a loss of myofibrils and a reduction in mitochondrial ATPase, DNA and protein concentrations sink to subnormal values. Only myocardium from stage 1 of hypertrophy shows complete reversibility after cessation of hypobaric conditions, but not so in stage 3. Parallel with the developing cor pulmonale, the animals also react with a small hypertrophy of the left heart ventricle. This concomitant growth persists under normobaric conditions, too. These investigations document that growth of myocardium under extreme conditions shows a phasic development. Severe forms of myocardial hypertrophy do not always seem to be reversible.

Adenosine Triphosphatases↗
PubMed1987

[Magnetic resonance tomography of the postoperative lumbar spine. A comparison of the MR versus CT images in recurrent intervertebral disk prolapse].

In the present study, 40 patients who had undergone disc surgery were examined by high resolution CT and MR for possible recurrence of the disc prolapse and the results are compared. It appears that high resolution spinal MR, using its various tissue parameters provides no new insights into possible recurrence of a disc prolapse. As is the case with CT, the investigator must also evaluate other morphological and clinical factors. In spite of this, MR can be useful in the investigation of abnormal spines.

Diagnostic Errors↗
PubMed1987

[Repeated recurrences after balloon dilatation--dilate or operate?].

In a total of 333 patients who had undergone a first successful transluminal coronary angioplasty (TCA) of a single stenosis in a native coronary vessel, restenosis occurred in 15% (follow-up angiography was performed in 94% of these patients). The restenosis rate was higher in bypass stenoses (45%) and in reopened vessels (54%). Repeat dilatation of restenoses showed a high primary success rate (93%) and only a few complications (2%). In this group, recurrent restenosis was observed in 33% of patients. Thirteen patients with recurrent restenoses (11 patients with two recidivations and two patients with three) underwent a total of 41 dilatation attempts. The degree of the recurrent stenosis (prior to the first TCA: 89%; prior to the second: 82%; prior to the third: 74%), the number of eccentric stenoses (8; 7; 5, respectively) and the length of the stenotic obstruction (5.2 mm; 4.7 mm; 4.3 mm, respectively) decreased. Accordingly, exercise tolerance was improved (99 W, 133 W, 146 W). To date, follow-up angiography and functional investigations have been performed in 11 out of 13 patients. Good long-term results have been observed in eight patients and another restenosis in three. It is concluded that repeat angioplasty is a reasonable therapeutic approach also in patients with recurrent restenosis.

Angioplasty, Balloon↗
PubMed1987

Myocardial biopsy in patients with hypertrophic cardiomyopathy: correlations between morphologic and clinical parameters and development of myocardial hypertrophy under medical therapy.

Left ventricular biopsies from 38 patients with hypertrophic cardiomyopathy (HOCM 28, HNCM 10) were investigated to evaluate possible correlations between morphological and clinical parameters. No correlation was found between the degree of myocardial hypertrophy (muscle cell diameter), nuclear size of the myocytes, fibrous tissue content and various clinical data such as pressure gradient, left ventricular end-diastolic pressure, Sokolow index and heart volume. In 11 patients with HOCM, a second biopsy was performed after medical therapy (verapamil, n = 9; propranolol, n = 2) over 33 +/- 12 months. Increasing myocardial hypertrophy (cell diameter 16.2 +/- 4.4 mu vs. 20.3 +/- 4.2 mu) was observed in all 11 patients. The interstitial fibrous tissue content increased from 5.7 +/- 6.3 to 12.7 +/- 6.8%. The volume fraction of myofibrils decreased (48.8 +/- 2.7 vs. 43.6 +/- 5.3%). The morphological changes were observed regardless of the clinical outcome which was improved in four, unchanged in five and worsened in two cases. The underlying hypertrophic process in HCM seems to be slowly progressive in most patients and cannot be influenced by medical treatment.

Adult↗
PubMed1987

[Imaging of aortocoronary bypasses with intravenous digital subtraction angiography].

We examined 24 patients with 52 coronary bypass grafts, an average of 18 months after their respective operations. During the course of 1 week, a coronary angiography and a digital subtraction angiography (DSA) incorporating an intravenous injection of contrast medium were performed. Conventional coronary angiograms showed 40 bypasses as being open, ten as being occluded, and two could not be displayed at all. With the aid of digital angiography, 50 out of 52 bypasses could be classified as either open or occluded. In 44 out of 52 bypasses, DSA and coronary angiogram results were identical. Using DSA, three out of ten angiographically occluded bypasses were falsely diagnosed as being open and three out of 40 open bypasses as occluded. Two bypasses could not be interpreted due to poor picture quality. In the diagnosis "open bypass" the degree of both sensitivity and specificity subsequently amounted to 92.5%, and 70% in the diagnosis "occluded bypass". The distal part of the bypasses, as well as the proximal and distal part of the anastomoses, could not be evaluated for the most part. Furthermore, on account of the comparatively inferior quality of the pictures, detection of bypass stenosis is not reliable using digital subtraction angiography. Intravenous digital subtraction angiography may therefore serve as a screening method in the evaluation of coronary bypass grafts.

Coronary Angiography↗
PubMed1987

Long-term observations in mild forms of cardiomyopathy.

24 patients suffering from a mild cardiomyopathy with normal or nearly normal ejection fraction and histologic evidence of cardiac fiber hypertrophy were followed-up over 5.5 +/- 1.9 years. Patients presented predominantly with dyspnea, angina and palpitations. During the observation period, the severity of symptoms increased only slightly. The ECG showed atrial arrhythmias in 34% and premature ventricular beats or conduction disturbances in the majority. During the 5.5 year follow-up period four patients had developed an intermittent III AV-block and two patients a bundle branch block. The heart volume determined by X-ray increased insignificantly (893 +/- 224 to 933 +/- 245 ml/1.73 m2; n.s.), while left ventricle end-diastolic (5.5 +/- 1.1 to 5.6 +/- 0.6 cm) and end-systolic (3.9 +/- 1.2 to 3.7 +/- 0.7 cm) diameter remained nearly constant. Pulmonary artery pressure at rest (18 +/- 5.9 to 17.8 +/- 4 mm Hg) and during exercise (40.5 +/- 9.5 to 37.4 +/- 7.8 mm Hg) showed no significant change. However, cardiac output decreased significantly at rest from 5.6 +/- 1.6 l/min/1.73 m2 to 4.5 +/- 0.7 l/min/1.73 m2 (p less than 0.01) and during exercise from 13 +/- 4.1 l/min/1.73 m2 to 10.4 +/- 2.3 l/min/1.73 m2 (p less than 0.05). It is concluded that patients with this mild cardiomyopathy show only minor changes over a period of 5.5 years. The prognosis seems to be promising in most cases.

Adult↗
PubMed1987

Calcium antagonist treatment in mild forms of cardiomyopathy.

Twenty-one patients with a mild form of cardiomyopathy (with normal ejection fraction but histologically-confirmed hypertrophy of myocardial cells and/or elevated diastolic pulmonary artery pressure during exercise) received 120 mg verapamil t.i.d. or no therapy at all for a period of 2 months in an open randomized cross-over study. Out of the 21 patients, 14 improved clinically, one patient's condition deteriorated and six remained unchanged (p less than 0.05). The mean diastolic pulmonary artery pressure during exercise decreased (25.3 +/- 7.6 to 20.1 +/- 6.6 mm Hg, n = 21, p less than 0.05). At rest, the decrease was only significant in the subgroup with pressures above 12 mm Hg (15.4 +/- 2.7 to 11.1 +/- 4.1 mm Hg, n = 9, p less than 0.05). All other hemodynamic data displayed no significant change. The benefits of verapamil therapy may be attributed to an improvement in diastolic ventricular function. The disturbance in diastolic relaxation might be of greater importance than the disturbance in systolic function in patients with mild forms of cardiomyopathy.

Adult↗
PubMed1987

Myocardial structure and left ventricular function in hypertrophic and dilative cardiomyopathy and aortic valve disease.

Left ventricular biopsies from 126 patients with advanced (EF less than 50%, n = 45) and mild (EF 50-60%, n = 21) and latent cardiomyopathy (EF greater than 60%, n = 60) and 18 additional patients with aortic valve disease and 22 cases with hypertrophic cardiomyopathy were analyzed to define possible correlations between myocardial structure and function. Deterioration of ventricular function was combined with increasing muscle cell diameters (r = 0.47) and increasing nuclear size of the myocytes (r = 0.74) in latent and dilative cardiomyopathies and in patients with aortic valve disease (cell diameter, r = 0.6; nuclear size, r = 0.9). Patients with HCM showed a wide range of cell diameter and nuclear size. 24% of the latter patients had no bioptic evidence of myocardial hypertrophy. The mitochondrial volume of the myocytes was 23% in the normal and hypertrophied myocardium independent of the kind of disease and ventricular function. The volume fraction of the myofibrils continuously decreased with worsening of the left ventricular function in patients with latent and dilative cardiomyopathy (from 45 +/- 6.9 to 37.6 +/- 6.3%) and aortic valve disease (from 46.2 +/- 3.4 to 27.9 +/- 9.3%). Patients with hypertrophic cardiomyopathy presented with normal or slightly decreased values of myofibrils consistent with normal ventricular function (42.5 +/- 5.0). The data demonstrate that the degree of myocardial hypertrophy and certain ultrastructural findings are inversely correlated with left ventricular function.

Aortic Valve↗
PubMed1987

Comparison of verapamil and bepridil in the therapy of familiar cardiomyopathy of the Syrian hamster.

The effect of bepridil compared to verapamil on the cardiomyopathic hamster (Strain Bio 8262) was evaluated. Bepridil (10 mg/kg) was injected twice daily for 15 and 30 days. Verapamil (10 mg/kg) was injected twice daily for 30 days. Control animals were treated with NaCl. After life-day 30, large infarct-like lesions predominantly located in the central portion of the left ventricular walls were observed, while single cell necrosis occurred only in a few cases. In peripheral muscles, the necrotizing process started even before life-day 30. In the skeletal muscles, small foci of cell necrosis were the predominant type of lesion. Myocardial calcium accumulation and cell necrosis could be completely prevented by verapamil and were not influenced by bepridil. Both drugs were ineffective in the skeletal muscles. The infarct-like lesions of the myocardium demonstrate that a vascular component is involved in the pathogenesis of necrosis, in addition to the inherited disturbance of calcium metabolism. The results demonstrate that not all drugs with calcium antagonistic potencies have identical cardioprotective effects in the cardiomyopathic hamster.

Animals↗