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Biomedical subjects

M Mack

Publications and source records attributed to M Mack.

At least 91 records · Page 5Linked to original sources
PubMed1989

Molecular cloning of SNM1, a yeast gene responsible for a specific step in the repair of cross-linked DNA.

We have isolated yeast gene SNM1 via complementation of sensitivity towards bi- and tri-functional alkylating agents in haploid and diploid yeast DNA repair-deficient snm1-1 mutants. Four independent clones of plasmid DNA containing the SNM1 locus were isolated after transformation with a YEp24-based yeast gene bank. Subcloned SNM1-containing DNA showed (i) complementation of the repair-deficiency phenotype caused by either one of the two different mutant alleles snm1-1 and snm1-2ts; (ii) complementation in haploid and diploid yeast snm1-1 mutants by either single or multiple copies of the SNM1 locus; and (iii) that the SNM1 gene is at most 2.4 kb in size. Expression of SNM1 on the smallest subclone, however, was under the control of the GAL1 promotor. Gene size and direction of transcription was further verified by mutagenesis of SNM1 by Tn10-LUK transposon insertion. Five plasmids containing Tn10-LUK insertions at different sites of the SNM1-containing DNA were able to disrupt the function of genomic SNM1 after gene transplacement. Correct integration of the disrupted SNM1::Tn10-LUK at the genomic site of SNM1 was verified via tetrad analysis of the sporulated diploid obtained after mating of the SNM1::Tn10-LUK transformant to a haploid strain containing the URA3 SNM1 wild-type alleles. The size of the poly(A)+ RNA transcript of the SNM1 gene is 1.1 kb as determined by Northern analysis.

Blotting, Northern↗
PubMed1989

Molecular characterization of the two genes SNQ and SFA that confer hyperresistance to 4-nitroquinoline-N-oxide and formaldehyde in Saccharomyces cerevisiae.

The genes SNQ and SFA confer hyperresistance to 4-NQO and FA when present on a multi-copy plasmid in yeast. Both are non-essential genes since transplacement of SNQ by a disrupted snq-0::LEU2 yielded stable and viable haploid integrants. Southern analysis revealed that SNQ and SFA are single-loci genes, and OFAGE analysis showed that they are located on chromosome XIII and IV, respectively. Northern blot analysis of SNQ and SFA revealed poly(A)+ RNA transcripts of 2 kb and 1.7 kb, respectively. Nuclease S1 mapping showed SNQ to have a coding region of 1.6 kb and SFA, one of 1.3 kb. The 5' coding regions were determined for both genes, while the 3' end could only be determined for gene SNQ. Both genes do not appear to contain introns. The SFA locus was also mapped by transposon mutagenesis. Tn10-LUK integrants disrupted the SFA gene function at sites that were determined by subcloning to lie within the SFA transcription unit.

4-Nitroquinoline-1-oxide↗
PubMed1989

Cluster headache: increased incorporation of (1-14C)arachidonic acid into phosphatidylserine in polymorphonuclear cells.

Vasoactive metabolites deriving from arachidonic acid (AA) have been considered as putative mediators in the pathogenesis of various types of headache. In the present study we therefore compare the ability to synthesize AA containing precursor phospholipids in polymorphonuclear cells (PMNs) from healthy controls and cluster headache patients. 3.7% +/- 1.4 (mean +/- SD) of the (1-14C)AA incorporated into total PMN glycerophospholipids (GPLs) was recovered in the phosphatidylserine (PS) in a group of cluster headache patients (n = 12). This was almost twice the value of 1.9% +/- 0.8% found in a corresponding group of 24 healthy controls (p less than 0.001). A significant decrease in the incorporation of (1-14C)AA into phosphatidylcholine (PC) (p less than 0.01) and an increase in the incorporation of (1-14C)AA into phosphatidyletanolamine (PE) (p less than 0.05) were also found in cluster headache patients when compared to the control group. The increased incorporation of (1-14C)AA into PS in PMNs from this group of patients is interesting because PS plays an important role in the activation of protein kinase C, an enzyme involved in transmembrane signalling. The clinical implications of the present findings in cluster headache, if any, cannot yet be defined.

Adult↗
PubMed1989

Distribution of bronchoconstrictor responses in isolated-perfused rat lung.

We studied the effects of bronchoconstrictor stimuli administered selectively through isolated-perfused preparations of the bronchial and pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction was elicited with infusion of acetylcholine (ACh), histamine, and serotonin (5-HT). Bolus infusion of 10(-5) mol ACh caused a 3.5-fold increase in pulmonary resistance (RL) after infusion into the pulmonary circulation (PC) and a 2.5-fold increase in the bronchial circulation (BC) (P less than 0.05 vs. control) that was blocked selectively in each circulation with atropine. Administration of 10(-5) mol 5-HT into the BC caused only a 45% increase in RL; the same dose of 5-HT caused a 5.1-fold increase in RL in the PC. A biphasic (increase at lower doses/decrease at higher doses) change in RL was elicited by histamine that was converted to dose-related constriction after H2-receptor blockade with cimetidine in both BC and PC. Response to exogenous ACh remained viable for greater than 5 h. Infusion of the mast cell degranulating agent, compound 48/80 (48/80), caused increase in RL that corresponded to quantitative recovery of histamine in the perfusates of both BC and PC. Histamine concentration in the perfusate increased from 47.2 +/- 31.8 (base line) to 624 +/- 60.1 ng/ml (2-fold increase in RL) in the BC and from 38.3 +/- 17.7 (base line) to 294.4 +/- 38.1 ng/ml (50% increase in RL) in the PC (P less than 0.001 vs. baseline concentration) after a 0.1-mg/ml dose of 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Consonant and vowel perception and production: early English-French bilinguals and English monolinguals.

This study is a comparative analysis of the English phonetic systems of 10 fluent adult English-French bilinguals who acquired their two languages prior to age 8 and who were English-dominant, and of 10 adult English monolinguals. The objective of the study was to determine whether or not early English-dominant bilinguals perceive and produce speech as English monolinguals do. Discrimination and identification tests of synthetic (d-t) and (i-I) continua and speech production tests revealed that the bilinguals' discrimination and production of (d) and (t) and their production of (I) did not differ significantly from the monolinguals'. However, the bilinguals' identification of (d-t) and (i-I) and one aspect of their production of (i) did differ significantly from that of the monolinguals. The present results indicate that early bilingualism can yield monolingual-like performance in at least one of the bilinguals' languages, but only with respect to certain aspects of the phonetic system. These findings are viewed in light of sound-class distinctions, the perception-production dichotomy, and bilingual phonetic transfer and restructuring.

Adult↗
PubMed1988

Genetic characterization of hyperresistance to formaldehyde and 4-nitroquinoline-N-oxide in the yeast Saccharomyces cerevisiae.

The hyperresistance to 4-nitroquinoline-N-oxide (4-NQO) and formaldehyde (FA) of yeast strains transformed with the multi-copy plasmids pAR172 and pAR184, respectively, is due to the two genes, SNQ and SFA, which are present on these plasmids. Restriction analysis revealed the maximal size of SFA as 2.7 kb and of SNQ as 2.2 kb, including transcription control elements. The presence of the smallest 2.7 kb subclone carrying SFA increased hyperresistance to formaldehyde fivefold over that of the original pAR184 isolate. No such increase in hyperresistance to 4-NQO was seen with the smaller subclones of the pAR172 isolate. Disruption of the SFA gene led to a threefold increase in sensitivity to FA as compared with the wild type. Expression of gene SNQ introduced on a multi-copy vector into haploid yeast mutants rad2, rad3, and snm1 did not complement these mutations that block excision repair.

4-Nitroquinoline-1-oxide↗
PubMed1988

Arachidonic acid metabolism in polymorphonuclear cells in headaches. A methodologic study.

Prostaglandins and leukotrienes have been implicated in the pathogenesis of various types of headache, mainly because some, but not all, cyclo-oxygenase inhibitors are effective in their treatment. We have therefore investigated whether a pathologically changed turnover of arachidonic acid (AA)-containing phospholipids can be seen in headache patients, using isolated polymorphonuclear cells (PMNs) from healthy controls and patients with chronic paroxysmal hemicrania (CPH) and cluster headache. PMNs from healthy controls incorporated 55% of the added (1-14C)AA into total lipids, and 0.5% +/- 0.14% of this radioactivity was found in the phosphatidylserine (PS) fraction. PMNs from a cluster headache and a CPH patient showed 300% and 900% increase in PS labeling from AA, respectively. No other phospholipids showed any difference between controls and patients. The results are discussed in connection with membrane signal transduction via the PS-dependent protein kinase C.

Adult↗
PubMed1988

Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro.

To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10(-11) to 10(-7) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, PAF was an extremely potent contractile agonist (threshold 10(-11) M). This response was inhibited by the PAF antagonist, CV-3988 (10(-6) M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 +/- 0.79 x 10(-9) M). Neither atropine nor chlorpheniramine (10(-9) to 10(-6) M) attenuated the response to PAF + platelets. In the presence of platelets, 10(-7) M PAF caused an increase in perfusate concentration of serotonin from 0.93 +/- 0.037 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.

Animals↗
PubMed1987

Homeostatic regulation of airway smooth muscle tone by catecholamine secretion in swine.

We studied the homeostatic secretory response of catecholamine secretion elicited by progressive bronchoconstriction in 18 swine in vivo. The potential reserve of the sympathetic nervous system (SNS) was first assessed by exogenous nicotinic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). A dose of 250 micrograms/kg iv DMPP caused an increase in plasma norepinephrine (NE) concentration from 207 +/- 86 (basal) to 2,625 +/- 448 pg/ml (P less than 0.02) and in plasma epinephrine (EPI) from 10 +/- 5.0 to 1,410 +/- 432 pg/ml (P less than 0.05) in four swine. In four other swine, bronchoconstriction induced by aerosolized prostaglandin F2 alpha caused approximately a fivefold increase in airway resistance without hemodynamic changes. No increase in plasma EPI was observed. However, plasma NE increased from 330 +/- 131 to 1,540 +/- 182 pg/ml (P less than 0.02). In five swine receiving aerosolized acetylcholine (ACh), similar changes in airways resistance were not associated with significant changes in catecholamine concentration when mean arterial blood pressure (MAP) was unchanged. However, inhalation of sufficient ACh to cause a greater than 10% decrease in MAP caused progressive increase in catecholamine secretion. Plasma EPI increased from 32 +/- 16 (MAP = 124 +/- 7 Torr) to 1,165 +/- 522 pg/ml (MAP = 94 +/- Torr). Hypoxemia that occurred with bronchoconstriction (greater than or equal to 50 Torr) did not cause catecholamine secretion. However, severe hypoxemia (PO2 less than 30 Torr) caused large increases in plasma EPI concentrations from 84 +/- 27 to 1,463 +/- 945 pg/ml (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Distribution of airway contractile responses within the major diameter bronchi during exogenous bronchoconstriction.

The distribution of bronchoconstrictor responses within airway generations zero to 6 was studied by tantalum bronchography during exogenous bronchoconstriction with methacholine (MCh), prostaglandin F2 alpha (PGF2 alpha), norepinephrine (NE), and the thromboxane mimetic U-46619 [(15S)-hydroxyl-11 alpha,9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acid] in 12 mongrel dogs undergoing vagotomy and beta-adrenergic blockade. Dose-response curves to each agonist were generated in random order, and tantalum bronchograms and simultaneous measurements of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were obtained at the plateau of the response of each dose of agonist after intravenous (iv) infusion. At 5 X 10(-7) mol/kg, NE (after beta-adrenergic blockade) caused an increase to 254 +/- 27.3%, PGF2 alpha to 368 +/- 50.0%, U-46619 to 522 +/- 98.5%, and MCh to 1,204 +/- 173% of baseline in RL. However, airway diameter changes within the major diameter airways varied substantially for each agonist. Methacholine caused substantial contraction in all airways. Neither NE nor U-46619 caused significant airway narrowing in generations zero or 1, although both agonists caused greater than 30% narrowing in sixth generation airways. Prostaglandin F2 alpha (5 X 10(-7) mol/kg) cause an increase in RL of greater than 350%; however, this was accompanied by an approximately 10% increase (dilation) in airway diameter in generation 1 through generation 4 airways and an approximate 25% narrowing in generation 6 airways. We demonstrate that both alpha-adrenergic agonists and thromboxane analog cause substantial bronchoconstriction in situ in the central air-ways of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Cost analysis of a mucoadhesive foam versus conventional treatment for postepisiotomy patients.

The cost of treating postepisiotomy pain and edema with foam containing 1% hydrocortisone acetate and 1% pramoxine hydrochloride and a spray with 20% benzocaine was compared in 200 postpartum patients. Treatment with foam was demonstrated to be more effective than benzocaine spray with greater pain relief and reduction of edema as shown by lower patient need of supplemental pain-relief measures. Treatment with foam was also determined to be less expensive than benzocaine spray when the cost of the supplemental pain-relief measures for benzocaine-treated patients were assessed. Methods used to determine actual hospital costs are presented, and supplemental pain relief treatments are discussed. Use of this type of cost analysis may be useful to the P & T Committee when determining actual cost-effectiveness of different treatment modalities.

Aerosols↗
PubMed1983

Further evidence of acoustic invariance in speech production: the stop-glide contrast.

We have conducted a detailed comparative acoustic analysis of the labial stop and glide, [b] and [w], and we have attempted to identify an invariant acoustic property which can accurately distinguish stops and glides. To this end, we conducted three experiments. In experiment I, we undertook computer analysis of the labial stop [b] and the labial glide [w] as produced in five vowel contexts by two speakers. Results indicated that transition durations and formant frequencies often differed considerably in these two classes of sounds--and to a much greater extent than suggested in previous perception experiments. In experiment II we examined a measure of amplitude--unit energy. We calculated the degree of relative amplitude change occurring in the vicinity of the stop and glide release and found reliably larger changes in energy associated with the stop release than the glide release across vowel contexts and speakers. These changes seemed to provide an invariant property characterizing the stop--glide contrast. In experiment III we tested the generality of our claims by examining a new set of data consisting of the stops [d] and [g] and the glide [y]. Results of this experiment further supported our hypothesis. We have related our findings to a general theory of acoustic invariance in speech.

Humans↗
PubMed1982

Aortic regurgitation and sinus of Valsalva-right atrial fistula after blunt thoracic trauma.

Non-penetrating chest trauma commonly causes a wide variety of cardiac injuries. Disruption of the aortic valve with resultant aortic regurgitation is not uncommon; conversely, a sinus of Valsalva-right atrial fistula, in the absence of a congenital sinus of Valsalva aneurysm, has been reported only once previously. This report describes the detection by preoperative cardiac catheterisation of both aortic regurgitation, and a sinus of Valsalva-right atrial fistula after blunt chest trauma, and its surgical management. The need for preoperative cardiac catheterisation in patients suffering from non-penetrating cardiac trauma is emphasised, even when the diagnosis appears cleas, because of the diverse nature and possible multiplicity of cardiac lesions.

Adult↗