Search PubMed⌕ Search

Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 469 records · Page 26Linked to original sources
PubMed1990

Isolation and characterization of an expressed hypervariable gene coding for a breast-cancer-associated antigen.

A human gene and cDNA coding for a breast-cancer-associated antigen (H23Ag) were isolated and characterized. The gene contains two exons and one intron. Part of the second exon is a tandem repeat array (TRA) consisting of multiple 60-bp G + C-rich units. We report here the characterization of unique sequences that are found in the H23Ag gene and cDNA, in addition to the 60-bp repeats. Analysis of the cDNA sequences revealed a putative ATG start codon preceded by two overlapping initiation consensus sequences (CCACC). The open reading frame determines an amino acid (aa) sequence consisting of three regions. The first region contains an initiating methionine and a highly hydrophobic putative signal peptide. This is followed by a variable number of highly conserved 20-aa repeat units (TRA). The last region, C-terminal to TRA, contains four potential N-linked glycosylation sites. The genomic nucleotide sequences demonstrate a putative promoter region that includes a 'TATA' box. A putative estrogen regulatory element is located 5' to the promoter region. The characterization of the gene and cDNA coding for the H23Ag presented here, may help to elucidate its possible function in human breast cancer.

Amino Acid Sequence↗
PubMed1990

[Metabolic studies in reactive hypoglycemia].

Idiopathic reactive hypoglycemia is a rare and controversial entity. We present a 56-year-old woman with attacks of faintness after meals containing sugar. Postprandial hypoglycemia was found and was diagnosed as idiopathic reactive hypoglycemia. She did not suffer any attacks after sugar was eliminated from her diet.

Dietary Carbohydrates↗
PubMed1990

Intravenous isosorbide-5-mononitrate in the treatment of acute myocardial infarction.

The action of isorsorbide-5-mononitrate (IS-5-MN) infusion (range 6.0 to 10.0 mg/hour) was studied in 24 patients with and without acute heart failure (hemodynamic subsets I to IV) during acute myocardial infarction. Hemodynamic measurements were performed by right-sided cardiac catheterization. Intravenous IS-5-MN demonstrated significant hemodynamic effects compared with baseline values. In subsets I and II, a decrease in pulmonary wedge pressure (PWP) and in cardiac index (CI), without significant changes in heart rate, mean arterial pressure or systemic vascular resistance index were demonstrated. In subsets III and IV, a major increase in CI and a decrease in systemic vascular resistance index, as well as a decrease in PWP were found. Again no changes occurred in mean arterial pressure and heart rate. The dosage was similar in subsets I to IV (8.0, 7.9, 7.8 and 7.3 mg/hour); thus, the differences in the responses could not be attributed to dosage. It appears that several different patterns of hemodynamic IS-5-MN action exist, assuming that IS-5-MN operates on preload and afterload levels. The action of IS-5-MN mechanisms seems to be dependent on an initial hemodynamic subset. No patient had any deleterious hemodynamic effects. A decrease in CI in subsets I and II was not of clinical importance with these dosages. No nitrate tolerance during 9.0 hours of continuous therapy appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1990

Expression of genes coding for pS2, c-erbB2, estrogen receptor and the H23 breast tumor-associated antigen. A comparative analysis in breast cancer.

Expression of the gene coding for a new breast tumor-associated antigen, H23, was compared to expression of genes coding for pS2, c-erbB2 and estrogen receptor (ER). Comparison involved mRNA expression in normal and malignant breast tissues as well as in non-breast tumors. Results obtained by RNA dot blot and Northern hybridizations showed that expression of the H23 antigen coding gene is a discriminatory marker in human breast cancer. It is expressed in 92% of breast tumors whereas 69%, 62% and 56% of breast tumors demonstrate significant mRNA levels of c-erbB2, ER and pS2, respectively. Non-malignant or normal breast tissue expresses much lower levels of the H23 antigen mRNA. From the comparative analysis presented here it is concluded that the gene coding for H23 antigen furnishes a most useful marker for human breast cancer.

Adenocarcinoma↗
PubMed1990

Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms.

The isolation and characterization of complementary DNAs (cDNAs) which code for an epithelial antigen aberrantly expressed in human breast tumor tissue are described here. The only information regarding the primary structure of this potentially important antigen has been a 20-amino-acid repeat motif. We now report the complete amino acid sequences of different forms of the human epithelial tumor antigen as deduced from the nucleotide sequence of isolated non-repeat cDNAs. The diversity of protein forms is generated by a series of alternative splicing events that occur in the regions located upstream and downstream to a central tandem repeat array. Isolated cDNAs coding for the upstream region show that differential usage of alternative splice acceptor sites may generate two protein forms containing putative signal peptides of varying hydrophobicities. The complexity of possible antigen forms is further compounded by alternative splicing events occurring in the region 3' to the repeat array. The isolated cDNAs 3' to the tandem repeats indicate that whereas one mRNA transcript is colinear with the gene, and defines an open reading frame (ORF) containing 160 amino acids downstream to the repeat array, a second cDNA correlates with a mRNA that is generated by a series of splicing events. The deduced amino acid sequence of the spliced cDNA contains an ORF that is identical for 149 amino acids downstream to the repeat array with the amino acid sequence of the unspliced cDNA. At this point it diverges and continues for an additional 179 amino acids. The sequence contains a highly hydrophobic 28-amino-acid peptide, located towards the carboxyl terminus, that may correspond to a transmembrane region. The cDNAs and deduced amino acid sequences, presented here, define the complete amino acid sequences of the epithelial tumor antigen and demonstrate the existence of multiple protein forms that probably localize to different cellular and extracellular compartments.

Amino Acid Sequence↗
PubMed1990

A transcribed gene, containing a variable number of tandem repeats, codes for a human epithelial tumor antigen. cDNA cloning, expression of the transfected gene and over-expression in breast cancer tissue.

A monoclonal antibody, H23, that specifically recognizes a breast-tumor-associated antigen, was used to isolate a cDNA insert that codes for the antigenic epitope. Nucleotide sequencing of this cDNA, as well as a longer 850-bp cDNA insert, shows that they are composed of 60-bp (G + C)-rich tandem repeating units. The coding strand was determined and codes for a proline-rich 20-amino-acid repeat motif. A comparison of the highly conserved repeat unit with the deduced flanking amino acid sequences demonstrates conservation of specific subregions of the repeat consensus within the flanking amino acids. Hybridization of the 60-bp cDNA probe with RNAs extracted from a variety of primary and metastatic human tumors yields relatively high levels of hybrid with the breast carcinomas, as compared to lower hybrid levels with RNAs from other epithelial tumors. RNA extracted from breast tissue adjacent to the tumor or from benign breast tumors, demonstrates low or undetectable levels of hybridization. Probing Southern blots with the 60-bp repeat shows that the tumor antigen is highly polymorphic and contains a variable number of tandem repeats (VNTRs). The VNTR nature of the gene was confirmed by probing Southern blots with unique genomic sequences that are physically linked to an isolated gene fragment that also contains the tandem repeat array. Mouse cells transfected with this gene fragment produce tumor antigen that is readily detected by H23 monoclonal antibodies. The allelic forms seen in 10 different primary human tumors demonstrate 100% concordance with the various mRNA species expressed. These studies are extended to the protein forms detected by immunoblot analyses that show both a correlation of the expressed tumor antigen species with the allelic forms as well as significantly increased expression in breast cancer tissue. The above studies unequivocally establish the over-expression of a VNTR gene coding for an epithelial tumor antigen in human breast cancer tissue.

Amino Acid Sequence↗
PubMed1990

Tissue oxygen partial pressure distribution within the human skeletal muscle during hypercapnia.

In ten subjects CO2-inhalation elicited a significant increase in mean oxygen partial pressure within biceps muscle by more than 35%. Though mean oxygen partial pressure within biceps muscle increased, the distribution of oxygen partial pressure (pO2-histogram) did not change suggesting a physiological distribution of oxygen delivery within biceps muscle during hypercapnia. Buffering the blood pH did not abolish the effects of the CO2-inhalation. Therefore, a decrease of peripheral blood pH could not account for the hypercapnia induced increase of mean oxygen partial pressure within biceps muscle. Our data suggest that oxygen delivery to skeletal muscle was increased during hypercapnia, most probably due to a hypercapnia induced rise of mean capillary blood flow.

Adult↗
PubMed1990

Hemodynamic and coronary vasodilative action of two nitroglycerin oral spray formulations.

This study compared glycerol trinitrate (NTG) oral spray in a new hydrophilic formulation with a reference aerosol in a lipophilic base with respect to the time to onset of action on hemodynamics and on the coronary vasomotor tone. Differences in the profile of action between the two spray formulations were assessed in two groups of ten patients each. In each of the two groups the patients were randomly assigned to receive 0.8 mg of aerosolized NTG in either the hydrophilic or lipophilic base in double-blind fashion. The patients of group A had stable, exercise-induced angina pectoris, in whom responses to the sprays were evaluated under resting conditions. The patients of group B were suspicious of vasospastic or mixed form of angina pectoris, in whom the effects of the sprays were studied under diagnostic ergonovine provocation. The onset and extent of action of the sprays were assessed by serial measurements of hemodynamic parameters and repeat quantitative coronary angiography. The two formulations of NTG oral spray had a comparably potent coronary vasodilator effect in patients under resting conditions and under ergonovine provocation. As far as hemodynamic action is concerned, the new hydrophilic spray exerted its hemodynamic effect more rapidly than the lipophilic spray. Thus, the new NTG oral spray promises to afford therapeutic advantages for the relief of anginal attacks as well as hemodynamic unloading in congestive heart failure and acute pulmonary hypertension.

Administration, Oral↗
PubMed1990

Reversal of protamine-induced catastrophic pulmonary vasoconstriction by prostaglandin E1.

A case of catastrophic pulmonary vasoconstriction occurring after cardiopulmonary bypass after protamine reversal of heparin treated successfully with intravenous prostaglandin E1 is reported. Systemic hypotension was counteracted by epinephrine given through the left atrium. Protamine-heparin reactions are reviewed and a pathophysiological mechanism for the beneficial effect seen with prostaglandin E1 is proposed.

Alprostadil↗
PubMed1990

Primary structure and post-translational processing of the Berne virus peplomer protein.

The nucleotide sequence of the peplomer (P) protein gene of Berne virus (BEV), the torovirus prototype, was determined. The gene encodes an apoprotein of 1581 amino acids with an Mr of about 178K. The open reading frame was cloned behind the T7 RNA polymerase promoter and its translation product was identified as the BEV P protein precursor by in vivo expression and immunoprecipitation. The deduced amino acid sequence contains a number of domains which are typical for type I membrane glycoproteins: an N-terminal signal sequence, a putative C-terminal transmembrane anchor, and a cytoplasmic tail. Eighteen potential N-glycosylation sites, two heptad repeat domains, and a possible "trypsin-like" cleavage site were identified. The mature P protein consists of two subunits and their electrophoretic mobility upon endoglycosidase F treatment strongly suggests that the predicted cleavage site is functional in vivo. The heptad repeat domains are probably involved in the generation of an intra-chain coiled-coil secondary structure; similar inter-chain interactions can play a role in P protein oligomerization. Using a sucrose gradient assay the P protein was indeed shown to form dimers. The intra- and inter-chain coiled-coil interactions may stabilize the elongated BEV peplomers.

Amino Acid Sequence↗
PubMed1990

Impact of ozone, acid mist and soil characteristics on growth and development of fine roots and ectomycorrhiza of young clonal Norway spruce.

As part of the joint 14-month exposure experiment on Norway spruce (Picea abies (L.) Karst.) sensitivity to pollution (two levels of ozone plus acid mist) of growth and development of the fine-root system and of mycorrhizae, have been investigated in two forest soils from areas showing forest decline. This study shows that differences in fine-root biomass and the occurrence of species of ectomycorrhizae were mainly due to prevailing conditions within the acid or calcareous substrate. The pollution treatment resulted in higher numbers of short root tips in only one soil, whereas the percentage of ectomycorrhizal roots with a well-developed mantle was low (10-23%) in both soils, irrespective of exposure of trees to ozone and acid mist. There was no consistent response, with the two clones examined, in terms of mycorrhizal frequency, beaded short roots and renewed growth. Regarding the effects on root growth, data cannot be used unrestrictedly for extrapolation to a more complex field situation.

Journal Article↗
PubMed1990

Estrogen receptors in the adrenal cortex of the possum (Trichosurus vulpecula).

1. Specific [3H]estradiol binding activity with characteristics of estrogen receptors was found in the cytosols and nuclear extracts of the adrenal cortex proper and special zone of the brushtail possum (Trichosurus vulpecula). 2. The specific estradiol receptor had a sedimentation coefficient on sucrose gradients of approximately 9S and a molecular weight on gel filtration of more than 200,000. The adrenal cortex cytosol binds [3H]estradiol with high affinity (Ka 5.5 X 10(9) M-1), and limited capacity (Bmax 62.7 fmol/mg cytosol prot). In competition experiments with different steroids the receptor showed a high affinity for four estrogens and a very low affinity to androgens, progesterone and cortisol. 3. There was no difference in the affinity and maximum binding capacity of the cytosols from cortex proper in male and female animals, but the binding capacity of the special zone of females was half that of cortex proper. Estradiol receptors were found in the kidney, liver, lung, testis and muscle but only in the adrenal and prostate was the binding capacity relatively high compared with the uterus. 4. The specific binding capacity of [3H]estradiol to cytosols of adrenal cortex at different stages of the estrus cycle and pregnancy was unrelated to that of the uterus. In the adrenal the receptor concentration was lowest at estrus, when uterine concentration was high, while in late pregnancy the binding of adrenal cortex and uterus cytosols was almost the same. 5. The possible physiological significance of the presence of a specific estrogen receptor in male and female possums is discussed.

Adrenal Cortex↗
PubMed1990

Inhibition of platelet function during in vivo infusion of isosorbide mononitrates: relationship between plasma drug concentration and hemodynamic effects.

Isosorbide monitrates (IS-2-MN and IS-5-MN), hepatic metabolites of isosorbide dinitrate, inhibit platelet function in vitro very differently, with IS-2-MN being much more potent than IS-5-MN. To assess their antiplatelet properties in vivo and to compare time and dosage requirements, we infused both IS-2-MN and IS-5-MN for 30 minutes, on 2 separate days, into nine patients with stable coronary artery disease, at rates of 4 mg/hr (n = 4) and 8 mg/hr (n = 5). Two additional patients received IS-5-MN at 16 mg/hr. Platelet aggregation and thromboxane (TX) B2 generation in response to various agonists, drug plasma concentrations, and blood pressure were monitored throughout the study. A significant decrease in platelet aggregation and TXB2 production by adenosine diphosphate and adrenaline occurred in seven of nine patients receiving IS-2-MN and in 7 of 11 patients receiving IS-5-MN. Response was dose related, with more patients responding at 8 mg/hr to IS-2-MN (five of five) than to IS-5-MN (three of five), and was maximum at the end of the infusion time, corresponding to peak plasma levels. Patients responding to drug infusions with an inhibition of platelet function were characterized by a greater vascular responsiveness compared to nonresponders, since the decrease in systolic blood pressure (mean +/- SEM) was significantly greater in the former (15.4 +/- 3.2) than in the latter (2.5 +/- 2.1, p less than 0.05). Therefore both mononitrates, when administered at infusion rates between 8 and 16 mg/hr, are accompanied by a consistent inhibition of adenosine diphosphate- and adrenaline-induced aggregation and TX generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1990

The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats.

It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis.

Animals↗
PubMed1990

High linoleic acid diets ameliorate diabetic nephropathy in rats.

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11% fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gamma linolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (FO; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF1 alpha to thromboxane B2 (TXB2), the stable metabolites of PGI2 and TXA2, respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF1 alpha/TXB2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.

Animals↗
PubMed1990

Postural hypotension: pressor effect of octreotide not mediated by norepinephrine.

Orthostatic hypotension of the Shy-Drager syndrome is a chronic incapacitating condition characterized by lack of an appropriate increase in the plasma norepinephrine level in response to standing. Recently, the somatostatin analogue octreotide has been reported to induce a pressor response in patients having this syndrome. We have reported a case of Shy-Drager syndrome in which octreotide was effective, but the rise in blood pressure was not accompanied by an increase in the plasma norepinephrine level. Hence, the pressor effect of octreotide is not mediated by stimulation of the sympathetic nervous system, but probably through splanchnic vasoconstriction.

Dihydroergotoxine↗