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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 181 records · Page 10Linked to original sources
PubMed1990

Randomized prospective trial comparing the native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant therapy.

The dosage of the anticoagulant warfarin sodium is based upon the prolongation of the prothrombin time into an optimal therapeutic range. We have developed a new assay for the native prothrombin antigen that measures the fully gamma-carboxylated prothrombin using a radioimmunoassay. Based on preliminary data that indicated that the native prothrombin antigen predicted both bleeding and thrombotic complications more accurately than the prothrombin time in patients anticoagulated with warfarin sodium, we have performed a randomized prospective trial comparing the complication rate in warfarin-treated patients monitored with the native prothrombin antigen or the prothrombin time. Patients with indications for anticoagulation were randomized to be monitored by the native prothrombin antigen (therapeutic range, 12 to 24 micrograms/mL) or the prothrombin time index (therapeutic range, 1.5 to 2.0). Of the prothrombin time group (N = 80), seven (8.8%) had bleeding or thrombotic complications, with a complication rate of 9.5%/patient-year. In the native prothrombin antigen group (N = 76), one subject (1.3%) had a bleeding complication. The complication rate per patient-year was 1.5%. These results indicate an 85% reduction in the complication rate of the native prothrombin antigen group compared with the complication rate of the prothrombin time group. This difference is statistically significant by the Fisher exact test (P = .037) and by Kaplan Meier survival analysis (P = .040). This study suggests that the use of the native prothrombin antigen assay has the potential to decrease the complications associated with anticoagulation therapy with warfarin sodium.

Humans↗
PubMed1990

Yeast RAS2 affects cell viability, mitotic division and transient gene expression in Nicotiana species.

Overexpression of the budding yeast RAS2 gene in Nicotiana plumbaginifolia cells revealed that RAS2 acted as 'suicide' gene in freshly isolated protoplasts from leaves and blocked cell proliferation in cell suspension-derived protoplasts. Among a series of genes tested (such as npt II, CDC35, PDE2), RAS2 was the only one to block the expression of the cat gene, as measured in a transient gene expression assay. Another ras gene, v-Ha-ras, had similar effects. Furthermore, the RAS2 effect was species-specific and depended on the modulation of hormonal metabolism in the transfected cells, while no differences were noticed between the normal and the activated val19 gene. Transfected plant cells are shown to synthesize a RAS2 protein of the same electrophoretic mobility as the yeast RAS2 product. The results are discussed in the broader context of the evolutionarily conserved ras genes involved in vital cellular functions.

Cell Differentiation↗
PubMed1990

Hybrid genes in the analysis of transformation conditions. 3. Temporal/spatial fate of NPTII gene integration, its inheritance and factors affecting these processes in Nicotiana plumbaginifolia.

Freshly isolated haploid mesophyll protoplasts of Nicotiana plumbaginifolia were transformed for kanamycin resistance. In 38% of the 224 transformants analysed, transmission of the NPTII gene occurred as a homozygous trait, while 62% of the transformants were heterozygous for the trait. In the first case, the foreign DNA integration predominantly (95%) resulted in monogenic inheritance. The second group was characterized by a significant (46%) proportion of multiple insertions. However, there was no clear-cut difference in the integration pattern between the two groups. Furthermore, transformation rates were increased by 4- to 10-fold when transformed diploid protoplasts were treated with UV light or with 3-aminobenzamide. The number of insertion sites was also increased by these treatments. These results shed further light on the fate of the foreign DNA in transformed plants and on means to control or manipulate the integration event(s).

Benzamides↗
PubMed1990

Sequence analysis of two null-mutant alleles of the single Arabidopsis Adh locus.

Data presented in this paper deal with a further molecular characterization of 2 out of 32 EMS-induced Arabidopsis ADH null mutants that we isolated previously. In order to localize and characterize each mutation at the molecular level, we have cloned and completely sequenced the R002 and R006 null mutant alleles. For mutant R002, which does not contain any detectable levels of ADH protein and mRNA, we have found that the mutation is due to a single C to T base pair substitution in the reading frame; this leads to the incorporation of a TAG stop codon (amber nonsense mutation). For mutant R006, which contains normal levels of inactive protein and mRNA levels, we found a G to A base pair transition. This gives rise to a Cys to Tyr amino acid substitution in the active site of the ADH enzyme.

Alcohol Dehydrogenase↗
PubMed1990

Transformation of Aspergillus giganteus to hygromycin B resistance.

A wild strain of A. giganteus was transformed to hygromycin B resistance using a bacterial resistance gene under the control of A. nidulans sequences. Stable transformants arose by heterogenous integration, mainly of tandem repeats of vector DNA at various sites in the host genome. Between 6 and 30 resistant colonies were obtained per microgram DNA per 3 x 10(3) viable protoplasts. Vector DNA could be recovered by transformation of Escherichia coli with undigested genomic DNA from Aspergillus giganteus transformants.

Anti-Bacterial Agents↗
PubMed1990

In vivo 5-HIAA release from the anterior hypothalamus in the ovariectomized and estradiol treated rat following perfusion with progesterone.

In the present study the frequency and magnitude of the release of 5-Hydroxyindoleacetic Acid (5-HIAA) was measured from the anterior hypothalamus of ovariectomized (OVX) and OVX rats treated with estradiol (E2). Female, Holtzman strain rats were maintained on a photoperiod of 14 H light from 0100 to 1500 H and experiments performed from 0900 to 1700 H. Animals exhibiting four-day estrous cycles (250-300 gms) were OVX (20 days recovery) and a push-pull-cannula (PPC) implanted and stereotaxically aimed at the SCN region in the anterior hypothalamus. Following a 7-10 day recovery push-pull-perfusion (PPP) experiments were performed on either OVX females or on OVX females in which a silastic E2 implant (150 micrograms E2/ml. sesame oil), was placed sc 48 H prior to PPP. In other experiments progesterone (P4) was perfused in a pulsatile manner over the SCN region of the anterior hypothalamus. The overall average 5-HIAA release in the OVX treated rats (548 +/- 358 pg/10 min.) was similar to that in the OVX E2 group (694 +/- 148 pg/10 min). The average period of 5-HIAA release was (48.2 +/- 5.5 min) in the OVX group and (56.0 +/- 9.8 min) in the OVX E2 group. These results indicate that exposure of long term OVX rats (20 days) to E2 has no effect on the release or period of 5-HIAA release from serotonergic terminals concentrated in the SCN of the anterior hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cyclic changes in conjunctival smears from menstruating females.

Cytohormonal evaluation has become an accurate procedure for the assessment of estrogenic effect on the vaginal and buccal mucosa. Both show a cyclical variation in the maturation index (an "estrogenic value" based on epithelial maturation). Conjunctival smears were taken from the temporal conjunctiva of 11 premenopausal and 7 postmenopausal females on a near-daily basis. No females had evidence of ocular surface disease, including keratoconjunctivitis sicca. After fixation and Papanicolaou staining, maturation indices for each specimen based on the differential morphology were red in a single blind fashion by a Papanicolaou cytologist. Cyclical variations paralleling the menstrual cycle in eight of nine premenopausal women were noted with maturation index values ranging from 30 (low estrogen effect) to 82 (high estrogen effect), peaking on day 11 or 21 of the menstrual cycle. No cyclical change was found in postmenopausal smears and smears of subjects with endocrine abnormalities. Maturation index values ranged from 30 to 38. Conjunctiva appears to be an estrogen-sensitive epithelium.

Cell Division↗
PubMed1990

Muscle fatigue in McArdle's disease. Muscle fibre conduction velocity and surface EMG frequency spectrum during ischaemic exercise.

The origin of fatigue in McArdle's disease is still a matter of debate. Both a reduction of muscle membrane excitability and failure of excitation-contraction (E-C) coupling have been suggested as causes. We performed intermittent isometric biceps brachii contractions (80% maximal voluntary contraction, rate 30/min) under local ischaemia in 5 McArdle's disease patients and 26 healthy controls. Our results show that in McArdle's disease the exerted force is less, the surface EMG (SEMG) amplitude steadily increases, and that the power density spectrum (PDS) shifts to lower frequencies, the latter without significant differences when compared with normals. The most important finding is that muscle membrane excitability remains unimpaired during ischaemic exercise, establishing a dominant role for intramuscular lactic acid formation in the reduction of muscle fibre conduction velocity seen in normal subjects. As is indicated by the shift of the PDS towards lower frequencies, as well as by the increase in SEMG amplitude, it can be concluded that during ischaemic exercise in patients with myophosphorylase deficiency, fatigue occurs without alterations in muscle membrane excitability and is due to a failure of E-C coupling.

Adolescent↗
PubMed1990

Native and oxidized low-density lipoproteins have different inhibitory effects on endothelium-derived relaxing factor in the rabbit aorta.

1. The effect of native low-density lipoproteins (LDL) and oxidized LDL (OXLDL) on the relaxations to endothelium-derived relaxing factor (EDRF) in isolated, intact aortic rings of the rabbit were investigated. 2. Native LDL induced a concentration-dependent reversible inhibition of the relaxations elicited by acetylcholine (ACh) or A23187, in rings pre-contracted by noradrenaline (NA), adrenaline (Ad) and 5-hydroxytryptamine (5-HT), but not phenylephrine (PE), which was not influenced by indomethacin. 3. The inhibition was surmountable in the rings pre-contracted with NA and Ad and only partially in those pre-contracted with 5-HT. 4. OXLDL induced an inhibition of the relaxations elicited by ACh and A23187 which was independent of the contractile agonist. The extent of inhibition and its reversibility varied with the LDL from individual donors, but was unaffected by indomethacin. 5. Native and oxidized LDL inhibited relaxations evoked by exogenous nitric oxide (NO) to the same extent. Higher concentrations of NO overcame the inhibition. The inhibition was independent of the contractile agonist and the preparation of LDL from individual donors. 6. Only OXLDL inhibited reversibly relaxations evoked by glyceryl trinitrate (GTN) and the inhibition was independent of the LDL preparation from individual donors. 7. This study demonstrates that native and OXLDL influence the response to EDRF in isolated aorta. We suggest that these lipoproteins may contribute to the attenuation of responses to EDRF found in isolated arteries from hypercholesterolaemic and atherosclerotic animals.

Acetylcholine↗
PubMed1990

Multifocal serous chorioretinitis in beagle dogs.

In the years 1988 and 1989, routine ophthalmological examinations of dogs from the company-owned beagle colony revealed a clinically inapparent chorioretinitis in 7.4 and 10% of the animals, respectively, as it has previously been described by Weisse et al. (1981). The alterations were seen mainly in the non-tapetal fundus, and they appeared more frequently in both eyes than in just one eye. Infection tests as well as virologic, bacteriologic and histopathologic investigations were performed in order to clarify the origin. A direct evidence of virus particles from processed ocular material by electron microscopy was not possible. Tests for growth on MDCK cells were negative. In bacteriologic tests, a gram positive, filiform, branched microorganism was isolated. The histopathologic findings in the subacute stage were a focal atrophy of the first retinal neuron and a focal proliferation of glia cells.

Animals↗
PubMed1989

Vitamin K-dependent carboxylation. In vitro modification of synthetic peptides containing the gamma-carboxylation recognition site.

Synthetic peptides including the gamma-carboxylation recognition site and acidic amino acids were compared as substrates for vitamin K-dependent gamma-carboxylation by bovine liver carboxylase. The 28-residue proPT28 (proprothrombin -18 to +10) and proFIX28 (pro-Factor IX -18 to +10) were carboxylated with a Km of 3 microM. The Vmax of proPT28 was 2-3 times greater than that of proFIX28. An analog of proFIX28 that contained the prothrombin propeptide had a Vmax 2-3-fold greater than an analog of proPT28 that contained the Factor IX propeptide. proFIX28/RS-1, based upon Factor IX Cambridge, proFIX28/RQ-4, based upon Factor IX Oxford 3, and proFIX28 had equivalent Km and Vmax values. Analogs of proPT28 containing Ala6-Glu7 or Glu6-Ala7 were carboxylated at equivalent rates. A peptide containing Asp6-Asp7 was carboxylated at a rate of about 1% of that of Glu carboxylation. Carboxylation of peptides containing Asp6-Glu7 and Glu6-Asp7 yielded results identical with peptides containing Ala6-Glu7 and Glu6-Ala7. Carboxymethylcysteine was not carboxylated when substituted for Glu6 in a peptide containing Asp7. These results indicate that the prothrombin propeptide is more efficient in the carboxylation process than is the Factor IX propeptide, but that both propeptides direct carboxylation; the gamma-carboxylation recognition site does not include residues -4 and -1; aspartic acid and carboxymethylcysteine are poor substrates for the carboxylase, but aspartic acid does not inhibit the carboxylation of adjacent glutamic acids.

Amino Acid Sequence↗
PubMed1989

[Heart failure in a pig chronically infected with Sarcocystis miescheriana--a case report].

A pig infected with 2 x 10(5) sporocysts of Sarcocystis miescheriana which had survived the acute phase of the disease from 12 dpi until 17 dpi retarded in growth and finally died at 60 dpi. From gross pathological examination heart failure was assumed as the cause of death. Histopathologically severe Myocarditis eosinophilica fibrosa was diagnosed. The sections through the heart muscle contained numerous degenerating and some intact sarcocysts.

Animals↗
PubMed1989

The large vestibular aqueduct syndrome in children. A review of 12 cases and the description of a new clinical entity.

The large vestibular aqueduct as an isolated anomaly of the temporal bone has been previously identified radiologically, and its association with sensory neural hearing loss has been recognized. It has not, however, been defined as a distinct clinical entity in children. We studied 12 children, ages 3 to 9 years, with downward-fluctuating progressive high-frequency neurosensory hearing losses whose symptoms were thought to be related to the isolated enlargement of the vestibular aqueduct identified by high-resolution computed tomographic scanning. Previously it had been assumed that a large vestibular aqueduct is a temporal bone dysplasia that is a variant of the Mondini type of deformity and that the associated hearing loss is congenital in nature. Our clinical observations, however, indicate that the hearing loss in children with an isolated enlargement of the vestibular aqueduct is acquired during childhood. The natural history of this progressive deafness is reviewed, and a pathophysiologic hypothesis is presented.

Audiometry↗