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Biomedical subjects

B Kunkel

Publications and source records attributed to B Kunkel.

At least 19 recordsLinked to original sources

Assessment of spatial and temporal velocity profiles distal of normally functioning Björk-Shiley prosthesis by the Doppler method.

By Doppler echocardiography, the performance of heart valve prostheses is assessed with the aid of maximal transprosthetic velocities, which, however, may not be representative for the full spatial velocity profile in the vicinity of mechanical valve substitutes due to flow separation by the open occluder. The purpose of this study was to determine characteristics of velocity profiles downstream of a normally functioning Björk-Shiley prosthesis. In a pulsatile flow apparatus, different flow rates of 6.3 and 8.4 l/min were delivered. Using a spatially and temporally resolving ultrasonic Doppler method, velocity profiles 20 and 30 mm distal from the prosthesis were registered and displayed in a three-dimensional grid. The spatial velocity profile was found to deviate substantially from a flat profile at these transducer positions at the two flow conditions. Distal to the minor orifice, velocities measured only 70 and 80% of those downstream of the major orifice. In between, a region of relatively slow moving flow was present. The shape of the profiles remained essentially unchanged during acceleration and deceleration of flow. Thus, spatially resolved velocity profiles downstream of mechanical prostheses can be registered by an ultrasonic Doppler device. These findings may be useful for the detection of beginning malfunction both in the experimental and the clinical setting.

Blood Flow Velocity

Assessment of cardiac adrenergic supply in mitral valve prolapse using m-[123I]iodobenzylguanidine scintigraphy.

Presynaptic as well as postsynaptic adrenergic regulation abnormalities are reported in symptomatic patients with mitral valve prolapse. This study was undertaken to evaluate presynaptic sympathetic supply by m-[123I]iodobenzylguanidine scintigraphy in 17 preselected patients with mitral valve prolapse and symptoms suggestive of hyperadrenergic dysautonomia as compared to normal scintigraphic findings. Mitral valve prolapse was echocardiographically proven within the left parasternal long axis view. Percentual activity of m-[123I]iodobenzylguanidine in 33 sectors of all oblique slices along the short axis was calculated relative to the maximal uptake, set at 100%. In general, no significant differences of mean values of sectoral quantitative uptake of m-[123I]iodobenzylguanidine were detectable between patients and the control group. Only in two sectors of the basal anterolateral region P values < 0.01 were present. Thus, using m-[123I]iodobenzylguanidine scintigraphy as marker of cardiac adrenergic supply, no evidence of altered presynaptic hyperadrenergic supply was present in patients with mitral valve prolapse. These findings suggest postsynaptic regulation abnormalities to be preponderant in this condition.

3-Iodobenzylguanidine

[Rate of success and restenosis of PTCA in patients over 75 years of age].

In 82 patients (pts), ages 75-90 years (52 m, 30 f; mean age 77 +/- 3 years) with mainly unstable angina (59 pts) or acute myocardial infarction (7 pts) a PTCA or recanalization was attempted. Successful PTCA was achieved in 57 of 69 pts (83%); occlusions could be reopened in all six pts with myocardial infarction and totally occluded infarct related artery, and in three of seven pts with stable or unstable angina pectoris. The primary success rate of PTCA alone in pts with unstable angina was 81%, and improved to 92% in pts with stable angina. Sixteen procedures were multiple vessel and six were multiple lesion PTCA, so that the lesion-related success rate of PTCA was higher (87%). One patient died in connection with the procedure (procedure related-mortality 1.2%), two pts underwent myocardial infarction (2.4%), one patient emergency bypass grafting (1.2%). The in-hospital mortality was 4.9% and concerned exclusively patients with unstable angina and unsuccessful procedure. Local complications at the puncture site occurred in two patients. The angiographic restenosis rate of PTCA was 58% (44% in patients with stable and 63% in patients with unstable angina pectoris). Seventeen patients with 19 restenoses had successful repeat PTCA; reintervention failed in two patients. We conclude that PTCA can be performed in patients of old age with a resulting comparable primary success rate as in younger patients. Complications seem to be more frequent. The restenosis rate is higher, but with regard to stable and unstable angina, not significantly so. The prognosis in patients with unstable angina and unsuccessful procedure is apparently unfavorable.

Aged

Hypertrophic obstructive cardiomyopathy as a manifestation of a cardiocutaneous syndrome (Noonan syndrome).

The case of a 50-year-old patient with hypertrophic obstructive cardiomyopathy is reported. The patient demonstrated somatic signs of the Turner phenotype, but a cytogenetically normal karyotype was shown. These findings were compatible with the diagnosis of Noonan syndrome. The most commonly diagnosed cardiac disease in this syndrome is pulmonary stenosis, followed by hypertrophic cardiomyopathy. The patient's prognosis is limited by the natural history or the typical complications of the underlying cardiac lesion.

Cardiomyopathy, Hypertrophic

Compartmentalized gene expression during sporulation in Bacillus subtilis.

Two important features of endospore development in Bacillus subtilis--the compartmentalization of mother cell gene expression and the coordination of mother cell gene expression with forespore development--are governed by the highly regulated expression of the sigK gene, which encodes the mother cell-specific RNA polymerase sigma factor sigma K. Compartmentalized expression of sigK is associated both with a chromosomal DNA rearrangement and with the restriction of sigK transcription to the mother cell. A third mode of sigK regulation, which occurs at the level of activation of the sigK gene product by proteolytic processing, serves to couple gene expression between the mother cell and forespore compartments of the developing sporangium.

Bacillus subtilis

Forespore-specific transcription of a gene in the signal transduction pathway that governs Pro-sigma K processing in Bacillus subtilis.

We present studies on the regulation of a developmental gene (spoIVB) whose product is required at a late stage of morphogenesis during the process of sporulation in Bacillus subtilis. Earlier work implicated the spoIVB gene product in a signal-transduction pathway that governs the conversion of pro-sigma K to the mature and active form of the mother cell sigma factor, sigma K, in response to a signal generated within the forespore chamber of the sporangium. We now show that (1) spoIVB is induced at the engulfment stage of sporulation, (2) this transcription is restricted to the forespore, and (3) spoIVB is under the direct control of the forespore sigma factor sigma G. The discovery that spoIVB is a forespore-expressed gene suggests that the spoIVB gene product, or a developmental event under its control, triggers the processing of pro-sigma K and thereby mediates the coupling of sigma K-directed gene expression in the mother cell to sigma G-directed gene expression in the forespore. We also show that spoIVB transcription is partially dependent on the action of the mother cell regulatory gene spoIIID, a finding that suggests that the transcription of certain forespore-expressed genes is influenced by events in the mother cell.

Bacillus subtilis

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

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

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

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

[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

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

[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

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

[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

[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

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