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Biomedical subjects

M Haas

Publications and source records attributed to M Haas.

At least 217 records · Page 12Linked to original sources
PubMed1990

Discrepancies in lipolytic activities induced by beta-adrenoceptor agonists in human and rat adipocytes.

A number of catecholamine and non-catecholamine beta-adrenoceptor agonists, including the lipolytically selective compound BRL 37344, were compared for lipolytic activity on human and rat adipocytes. On rat adipocytes, all compounds were full agonists, BRL 37344 being the most potent. On human adipocytes, only the catecholamines were full beta-adrenoceptor agonists. The other compounds were partial agonists, with intrinsic activities declining in the order fenoterol greater than salbutamol greater than clenbuterol greater than BRL 37344. This was the case with FFA- as well as with glycerol-production. Addition of 20 microM phentolamine did not enhance BRL 37344 activity. The isoprenaline- and BRL 37344-induced lipolysis on rat white adipocytes was stereoselectively antagonized by enantiomers of alprenolol, with atypical low potencies and stereoselectivity. It was concluded that (1) human and rat adipocyte beta-adrenoceptors mediating lipolysis are not essentially different, (2) partial agonism in human adipocytes is not explained by enhanced re-esterification and (3) BRL 37344 selectively stimulates rat adipocyte lipolysis.

Adipose Tissue↗
PubMed1990

Stereoisomers of calcium antagonists distinguish a myocardial and vascular mode of protection against cardiac ischemic injury.

Concentration-dependent effects of the enantiomers of the calcium antagonists, gallopamil, diltiazem, and bepridil have been studied in the Langendorff-perfused rat heart, subjected to 30 min of global ischemia. It is shown that the time course, as well as the height of the energy deprivation-induced left ventricular diastolic contracture that develops during ischemia, can be selectively inhibited by negative inotropic concentrations of the calcium antagonist enantiomers. The time needed for recovery from the diastolic contracture during the reperfusion phase can be shortened significantly by lower, vasodilating concentrations of the drugs. In normoxically perfused hearts, stereoselectivity factors (sf) of the enantiomers of the compounds amounted to 63, 10, and 2 for the negative inotropic and 12.6, 79, and 4 for the vasodilating activities of gallopamil, cis-diltiazem, and bepridil, respectively. The sf values of negative inotropism proved to be remarkably similar to sf values of 50 and 7.9 for gallopamil and cis-diltiazem in the protection of the ischemic contracture during ischemia, whereas the sf values of coronary flow increase closely paralleled the values of 7.9, 63, and 2.5 for gallopamil, cis-diltiazem, and bepridil, respectively, in protection during the reperfusion phase. The results strongly suggest that at reperfusion the vasoselective enantiomers of calcium antagonists provide protection related to improved tissue perfusion, and thereby possibly restoring the distorted ionic and energetic homeostasis, whereas the other enantiomers are more involved in a direct energy-saving activity, resulting in protection during the ischemic period.

Animals↗
PubMed1990

Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines.

Human T-cell leukemia and T-cell acute lymphoblastic leukemia cell lines were studied for alterations in the p53 tumor suppressor gene. Southern blot analysis of 10 leukemic T-cell lines revealed no gross genomic deletions or rearrangements. Reverse transcription-polymerase chain reaction analysis of p53 mRNA indicated that all 10 lines produced p53 mRNA of normal size. By direct sequencing of polymerase chain reaction-amplified cDNA, we detected 11 missense and nonsense point mutations in 5 of the 10 leukemic T-cell lines studied. The mutations are primarily located in the evolutionarily highly conserved regions of the p53 gene. One of the five cell lines in which a mutation was detected possesses a homozygous point mutation in both p53 alleles, while the other four cell lines harbor from two to four different point mutations. An allelic study of two of the lines (CEM, A3/Kawa) shows that the two missense mutations found in each line are located on separate alleles, thus both alleles of the p53 gene may have been functionally inactivated by two different point mutations. Since cultured leukemic T-cell lines represent a late, fully tumorigenic stage of leukemic T cells, mutation of both (or more) alleles of the p53 gene may reflect the selection of cells possessing an increasingly tumorigenic phenotype, whether the selection took place in vivo or in vitro. Previously, we have shown that the HSB-2 T-cell acute lymphoblastic leukemia cell line had lost both alleles of the retinoblastoma tumor suppressor gene. Taken together, our data show that at least 6 of 10 leukemic T-cell lines examined may have lost the normal function of a known tumor suppressor gene, suggesting that this class of genes serves a critical role in the generation of fully tumorigenic leukemic T cells.

Amino Acid Sequence↗
PubMed1990

Regulation of Na-K-Cl cotransport in cultured canine airway epithelia: a [3H]bumetanide binding study.

We examined [3H]bumetanide binding to membranes isolated from canine tracheal and bronchial epithelia and to confluent primary cultures of these cells. Crude plasma membranes from trachea and bronchus bind [3H]bumetanide in a saturable manner; tracheal membranes have a higher affinity but lower maximal binding (K1/2 approximately equal to 0.7 microM; Bmax approximately equal to 2.5 pmol/mg protein) than do bronchial membranes (K1/2 approximately equal to 3.5 microM; B(max) approximately equal to 7.5 pmol/mg). In both cases, saturable binding is reduced by greater than 65% when either Na, K, or Cl is removed from the medium. In primary cultures, saturable [3H]bumetanide binding (inhibited by a 30-fold excess of unlabeled bumetanide) occurs when [3H]bumetanide (1.0 microM) is added to the solution bathing the basolateral side of tracheal (1.20 +/- 0.10 pmol bound/mg total cell protein) and bronchial (1.79 +/- 0.52 pmol/mg) cultures; minimal binding is seen with apical [3H]bumetanide. Isoproterenol (10(-5) M; basolateral exposure) produces approximately 100% increase in saturable basolateral [3H]bumetanide binding to tracheal cultures and approximately 30% increase in bronchial cultures. Similar augmentation of binding is seen when apical Cl is reduced from 134 to 4 mM and when both apical and basolateral media are made hypertonic by addition of 100 mM sucrose. Under these latter two conditions, isoproterenol produces little or no additional increase in binding. Our results indicate that the increase in basolateral Cl influx via Na-K-Cl cotransport that must occur during beta-adrenergic stimulation of net salt secretion in canine airway epithelia is related to an actual increase in the number of functioning cotransporters in the basolateral membrane and is not simply due to a change in ion gradients. The increase in cotransport sites, however, may be secondary to initial stimulation of apical Cl channels, with resultant cell shrinkage.

Animals↗
PubMed1990

Interrater reliability of roentgenological evaluation of the lumbar spine in lateral bending.

Interrater reliability is described for the evaluation of lumbar motion and motion coupling patterns in lateral bending. Upright neutral and lateral bending lumbar films of 58 student volunteers were marked by three examiners. Segmental tilt, segmental rotation and motion categories were computed. The performance of the examiners was evaluated using the Kappa statistic and a comparison of rater discrepancy to the experimental measurement error. Although all three raters were proficient within the context of calculated measurement error, good reliability was not universally demonstrated. Concordance for rotation was moderate to good, while agreement for lateral bending was of questionable interpretation. Reliability for the segmental motion categories was good for L1-L4, but unacceptable at L5. The poor reliability at L5 resulted in unacceptable concordance for the lumbar global motion category for three raters. The use of lateral bending radiographs for categorization of the lumbar spine in clinical practice is questioned.

Adult↗
PubMed1990

The physics of spinal manipulation. Part IV. A theoretical consideration of the physician impact force and energy requirements needed to produce synovial joint cavitation.

The critical force and energy required to facilitate synovial joint cavitation are presented as functions of seven parameters: joint and patient stiffnesses, joint and patient elasticities, the proportion of impacting energy entering the joint and patient, and the critical joint distraction at which cavitation occurs. These parameters are governed by numerous properties of the patient, doctor, joint, and the adjustive process. Equations for the critical force and energy are derived and the seven parameters and their governing factors are discussed.

Biomechanical Phenomena↗
PubMed1990

Calcium antagonists show two modes of protection in ischemic heart failure.

Retrogradely perfused, isovolumically beating, paced rat hearts were subjected to 30 min of global ischemia in the absence and presence of nifedipine, verapamil, bepridil and quaternary bepridil at a concentration ranging from 3 to 10,000 nmol/l. Under constant pressure conditions, the arrest of coronary flow and the reduction of ventricular contraction during global ischemia were readily reversible and quickly returned at reperfusion. During ischemia, however, a diastolic contracture developed, which was slowly reversible upon reperfusion. The calcium antagonists studied appeared to delay and diminish in a concentration-dependent way the diastolic contracture during ischemia. Furthermore, they accelerated the reduction of this contracture at reperfusion. Nifedipine, bepridil and quaternary bepridil showed a 100 to 1000 times higher potency in accelerating the recovery of the diastolic contracture during the reperfusion phase than in reducing the development of diastolic tension during the ischemic period itself, whereas verapamil hardly discriminated these two phases. When the hearts were reperfused with nifedipine under constant flow conditions, reduction of the diastolic contracture during ischemia could still be observed, but the accelerated reduction of end-diastolic pressure during reperfusion was no longer present. The results are discussed in relation to the energy saving, negative inotropic activity of the drugs before the ischemic period and the strong coronary vasodilation, which seems to be involved in the protective activity of the drugs, especially during reperfusion.

Animals↗
PubMed1990

The physics of spinal manipulation. Part I. The myth of F = ma.

The product of the adjusting physician's mass and acceleration does not quantify the adjustive force as popularly believed, an error stemming from a misunderstanding of Newton's second law. In this paper, a gedanken experiment illustrates the misapplication of F = ma and suggests that the adjustive force depends on the impact velocity, mass of the doctor, and intrinsic physical properties of the doctor and patient.

Biophysical Phenomena↗
PubMed1989

The need for a search for a proximal pathogenic principle of human AIDS.

Some of the unexplained aspects of HIV/AIDS epidemiology, virology, and pathology (6, 13) may thus be due to a lack of knowledge of the basic virology of the virus complex and its pathological interaction with cells of the host. There may be no need to call upon anomalous immune responses, vicious transactivating activities, or new virological or biological principles if we can first do the basic virology of the disease-inducing viruses. While we do not want to propose that working out the virology will by necessity be easy on all counts, it may lead us all to more equitable immunological, pathological, and cell biological approaches to this formidable problem. A fine beginning has been made by Fisher et al. (10), Saag et al. (11), and others. To retrovirologists the problems appear not to be insurmountable.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Stereoisomers of BAY K 8644 show opposite activities in the normal and ischaemic rat heart. A comparison with nifedipine.

The effects of the stereoisomers and the racemate of the calcium agonist BAY K 8644 and the calcium antagonist nifedipine were studied on the Langendorff-perfused rat heart, subjected to 30 min of global ischaemia. The results show that (-)- and (+/-)-BAY K 8644 induced a strong positive inotropic effect at 100 and 1000 nmol/l and a vasoconstricting effect which was most prominent at 1 and 10 nmol/l, respectively. At higher concentrations the flow reduction was inverted to a flow increase, closely related to the positive inotropic activity. The inotropic status induced by the agonist before the onset of ischaemia was reflected in an accelerated development of the diastolic contracture during ischaemia. During the reperfusion, a complex triphasic effect on the recovery was found, in which probably positive inotropism, vasoconstriction, metabolic and mechanical factors are involved. The (+)-enantiomer of BAY K 8644 behaved as a weak calcium antagonist showing merely vasodilatation, which accelerated the recovery from the ischaemic contracture at reperfusion. The calcium antagonistic, vasodilating effects of the (+)-enantiomer were expressed in the racemate only during the reperfusion phase, where it took an intermediate position between the effects of the (-)- and (+)-enantiomer. In contrast, nifedipine, at negative inotropic - energy saving - concentrations, diminished the height and delayed the development of the energy deprivation-induced left ventricular diastolic contracture during ischaemia. The time needed for recovery from the contracture during reperfusion was significantly shortened already at a 100 times lower, vasodilating concentration of nifedipine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Cation-anion cotransport.

Two methods have been described for the study of cation-chloride cotransport systems. The zero-trans efflux method is designed to determine stoichiometric relationships between cotransported ions under conditions where ion exchanges cannot occur. These exchanges (e.g., Na+/Na+, K+/K+) may occur as partial or incomplete reactions of a cotransport process and can lead to erroneous determinations of the stoichiometry of the cotransport process. The zero-trans efflux method can also be used to study the effects of cell volume, pH, and intracellular ion concentrations on cotransport processes. The valinomycin method is used to determine the electrogenicity or electroneutrality of transport, and in this regard can be used in conjunction with other methods such as those employing potential-sensitive dyes or microelectrodes. Other, more recently developed ionophores with specificity for lithium rather than potassium have now been used to study the effect of Em on the ATP-dependent Na+/K+ pump. It may be possible to use such ionophores to confirm the suspected electroneutrality of (K+ + Cl-) cotransport systems, as well as for other studies of specific potassium transport processes in which valinomycin obviously cannot be used. Both methods discussed in detail in this chapter, and particularly the valinomycin method, were originally devised for use in red blood cells in order to take advantage of (or circumvent) properties of the red cell membrane, such as its low permeability to sodium and potassium and relatively high permeability to chloride. However, valinomycin has been used successfully to demonstrate the electroneutrality of (Na+ + K+ + 2Cl-) cotransport in MDCK cells, and the zero-trans efflux method should be applicable to the study of transport processes in other types of cells in suspension, so long as the transport system being studied can be accurately defined (e.g., as an inhibitor-sensitive or chloride-dependent cation flux) and comprises a significant fraction of the total salt efflux.

Animals↗
PubMed1989

The system of prosthetic treatment for CLAP patients.

The prosthetic treatment of CLAP patients is usually done in three phases: an interceptive treatment during two stages of orthodontics, the definitive prosthetic treatment and usually the secondary treatment. In the interceptive phase we use clasp-retained partials; the definitive treatment is achieved mostly by telescope-retained partials. There is seldom an indication for Maryland-bridges or for dental implants.

Cleft Lip↗
PubMed1989

Enterobacter sakazakii infections in neonates associated with intrinsic contamination of a powdered infant formula.

We report an outbreak of Enterobacter sakazakii infection and colonization in neonates related to an infant formula contaminated during the manufacturing process. The outbreak occurred in a 20-bed neonatal intensive care unit during a six-week period in 1988, and involved a total of four infants. Three infants had sepsis and three had bloody diarrhea; all patients responded to intravenous antibiotics and recovered without complications. The E sakazakii isolated from the formula had the same plasmid and multilocus enzyme profile as those isolated from patients. This outbreak demonstrates the significance of commercially contaminated formulas and emphasizes the need to limit contamination and multiplication of bacteria in enteral formulas.

Cross Infection↗
PubMed1989

Effects of verapamil on ischaemia-induced impairment of ATP-dependent calcium extrusion in rat heart sarcolemma.

1. The effects of ischaemia and reperfusion were studied on adenosine 5'-triphosphate (ATP)-dependent 45Ca2+-transport in rat heart sarcolemma vesicles. 2. The effect of verapamil, 1 mumol l-1, was studied by pretreatment of the hearts during Langendorff-perfusion and in vitro by adding the drug after isolation of the vesicles. 3. Without drug pretreatment the Ca2+-uptake appeared to be strongly reduced after 30 and after 60 min of global ischaemia, whereas after 30 min of reperfusion it was restored to slightly above the control level. 4. Verapamil pretreatment during the Langendorff perfusion significantly increased Ca2+-uptake in sarcolemma vesicles both before the onset of ischaemia and after 30 min of reperfusion, whereas no beneficial effect was found on the impaired uptake activity during the ischaemic period. 5. When tested in vitro after the isolation of the sarcolemma vesicles, verapamil only inhibited the Ca2+-uptake activity with an IC50 of 112 mumol l-1, which was increased to 250 mumol l-1 after ischaemia and reperfusion. 6. The present study indicates that pretreatment with verapamil, 1 mumol l-1, of the intact rat heart activates an ATP-dependent Ca2+ extrusion process that may contribute to decrease cellular calcium levels in control and, more importantly, in a reperfusion situation. In contrast, in vitro only a less potent inhibition of the extrusion process was found, indicating that physiological regulatory mechanisms may be altered in the vesicles.

Adenosine Triphosphate↗