Biomedical subjects
Publications and source records attributed to M Jacobs.
Aortoesophageal fistula is a rare disorder that may result from many causes. In this report, we describe the unique case of a 71-year-old woman who developed an aortoesophageal fistula following prolonged placement of a nasogastric tube. The presence of dense fibrous adhesions between the aorta and esophagus may have facilitated the development of aortoesophageal fistula in this patient.
PURPOSE: Serologic tests to detect invasive candidiasis generally have been unreliable. We prospectively evaluated the clinical utility of a new, promising commercial latex particle agglutination test (i.e., Cand-Tec, Ramco Laboratories, Inc., Houston, Texas). This assay detects Candida antigens in serum. PATIENTS AND METHODS: We examined the reliability of Cand-Tec to diagnose invasive candidiasis in 142 consecutive in-patients intensively treated with chemo-radiation therapy. Serum samples were collected at admission and then weekly, until the patients' death or hospital discharge. Evaluation for clinical utility was done using various reference titers. Twenty-nine patients had invasive candidiasis whereas 113 patients did not have documented invasive candidal infections. RESULTS: At a titer of 1:8, the Cand-Tec test had sensitivity of 38%, specificity of 90%, positive predictive value of 50%, and negative predictive value of 85%. Weekly use of the Cand-Tec test did not improve early detection of invasive candidiasis, providing only a mean interval of 0.4 day from the first positive Cand-Tec result to a definitive diagnosis of invasive candidiasis by blood culture, tissue biopsy, or autopsy. In addition, surveillance cultures from the oropharynx or stool were not helpful in identifying those patients who would develop an invasive fungal infection. CONCLUSION: In the context of current clinical management strategies for suspected fungal infection, the Candida antigen detection assay (Cand-Tec) is not a reliable method for diagnosis of deep candidiasis in neutropenic patients. Until better methods of early detection are available, patients at high risk for the development of invasive candidiasis should continue to receive empiric antifungal agent therapy.
The vitamin K-dependent carboxylase catalyzes the posttranslational modification of specific glutamic acid residues to form gamma-carboxyglutamic acid residues within the vitamin K-dependent proteins. This enzyme recognizes the gamma-carboxylation recognition site on the propeptide of the precursor forms of the vitamin K-dependent blood coagulation proteins. To purify this enzyme to homogeneity, the carboxylase from bovine liver microsomes was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), the protein was fractionated with ammonium sulfate, and then the enzyme was isolated by affinity chromatography using a synthetic peptide based upon the structure of the prothrombin propeptide. Elution with 10 mM propeptide yielded a single major band on SDS gel electrophoresis with a molecular weight of 77,000. In the presence of high concentrations of propeptide, only minimal carboxylase activity was measurable. Antibodies to the protein inhibited the carboxylase activity in crude preparations. In an alternative affinity purification strategy the propeptide was coupled through an NH2-terminal cysteine to an activated thiol-Sepharose column. The carboxylase-propeptide complex was eluted at 25 degrees C by reductive cleavage of the enzyme-propeptide complex in the presence of detergent and phospholipids. The eluted protein (Mr, 77,000) contained both stable vitamin K-dependent carboxylase and vitamin K epoxidase activity. The protein, purified by either method, was detected as a single band (Mr, 77,000) in a Western blot using anti-carboxylase antibodies. A 10,000-fold purification of carboxylase activity from crude microsomes was estimated. Purified bovine liver vitamin K-dependent carboxylase should facilitate the study of its structure and of the mechanism of action of vitamin K as a cofactor in the reaction catalyzed by this enzyme.
Two Caucasian females in whom an orbital mass was the first sign of metastasis from a breast carcinoma are described. Each subject had undergone a radical mastectomy to treat a primary breast carcinoma, one six years and the other eight years previously. Each presented with ipsilateral proptosis, and restricted upper eyelid action; one had altered ocular motility. In each subject an open biopsy of the orbital mass via an eyelid crease incision revealed metastatic scirrhous adenocarcinoma of the breast. The clinical features, investigations, and treatment of orbital metastases from breast carcinoma are discussed.
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While it is recognized that need for care is the dominant factor influencing utilization of health services, little is known regarding the determinants of ambulatory care use by the noninstitutionalized elderly. It is important to examine the relationships among need factors and how physical and mental dysfunctions influence use of services. This study uses a LISREL model to identify the extent to which ambulatory care use was affected by physical or mental functioning and whether strong linkages would be exhibited by both factors.
Endothelin-1 (ET-1) elicits a contractile response from intact and endothelium-denuded rings of rabbit aorta and carotid artery. At low doses of ET-1, the response is attenuated in the presence of endothelium. The specific receptors that mediate the contractile response are located by autoradiography on the vascular smooth muscle although the decrease in response in intact rings may imply that they are also present on the endothelium.
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The nutritional status of the children attending the crèche and the primary school in Mamre was assessed using standards derived by the National Center for Health Statistics in the USA. The results for children aged under 11 years are presented. Of the 75 children at the crèche 9% were below the 3rd percentile of weight for age, 11% below the 3rd percentile of height for age and 1% below the 3rd percentile of weight for height. A significantly larger proportion of boys than of girls were under the 3rd percentile of height for age. Of the 430 primary school children aged under 11 years 10.2% were below the 3rd percentile of weight for age, 10.9% below the 3rd percentile of height for age and 4.4% below the 3rd percentile of weight for height. A significantly larger proportion of primary school boys aged 8-10 years than of girls were below the 3rd percentile of weight for height. Significantly more girls aged 5-7 years than girls aged 8-10 years were underweight for age.
A microsomal membrane preparation from hypocotyls of dark-grown Cucurbita pepo L. (zucchini) seedlings contains specific high-affinity binding sites for the non-hydrolyzable GTP analog guanosine 5'-[gamma-thio]triphosphate (GTP-gamma-S). Both the binding affinity and the pattern of binding specificity for GTP and guanine nucleoside triphosphate analogs are shared with the more thoroughly characterized animal G-proteins that are known to be involved in signal transduction. The sensitivity of GTP-gamma-S binding to Mg+2 ions and temperature was similar to that reported for rabbit liver G-protein, although the plant complex dissociated more readily. GTP-gamma-S could be recovered unchanged from the binding complex. Proteins (Mr 33 and 50 kDa) present in zucchini membrane preparations were revealed by immunoblotting with antiserum specific for the alpha subunit of platelet GS. These may be homologous to animal G-proteins.
Several mutants have been isolated at the Arabidopsis thaliana (L.) Heynh. alcohol dehydrogenase (ADH) gene locus using allyl alcohol selection on ethyl methanesulfonate (EMS)-mutagenized seeds. Eleven mutants were isolated in the ADH1-A electrophoretic allele, and 21 in the ADH1-S allele. These null mutants are characterized by the absence of measurable ADH activity and genetic data showed that the mutations were confined to the ADH1 gene locus of Arabidopsis. Eleven mutants in the ADH1-A background were further characterized at the protein and mRNA level. These experiments revealed striking differences in the ADH protein and mRNA content. Some of the mutants did not synthesize any mRNA or ADH-like protein, whereas some of them had a nearly normal level of ADH protein and mRNA. Others had a very low level of both protein and mRNA. ADH null mutants differed physiologically from the wild type by their higher sensitivity to anaerobic treatment in plants and significantly reduced resistance to acetaldehyde in suspension cultures.
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The ligand-binding domain of the low density lipoprotein (LDL) receptor is composed of seven cysteine-rich repeats, each approximately 40 amino acids long. Previous studies by van Driel et al. [van Driel, I. R., Goldstein, J. L., Sudhof, T. C. & Brown, M. S. (1987) J. Biol. Chem. 262, 17443-17449] showed that if the first repeat of the ligand-binding domain (encoded by exon 2) is deleted, the receptor fails to bind an anti-LDL receptor monoclonal antibody (IgG-C7) but continues to bind LDL with high affinity. Cultured fibroblasts from a Black South African Xhosa patient (TT) with the clinical syndrome of homozygous familial hypercholesterolemia demonstrated high-affinity cell-surface binding of 125I-labeled LDL but not 125I-labeled IgG-C7. Previous haplotype analysis, using 10 restriction fragment length polymorphic sites, suggested that the patient inherited two identical LDL receptor alleles. The polymerase chain reaction technique was used to selectively amplify exon 2 of the LDL receptor gene from this patient. Sequence analysis of the amplified fragment disclosed a deletion of six base pairs that removes two amino acids, aspartic acid and glycine, from the first cysteine-rich ligand binding repeat. The mutation creates a new PstI restriction site that can be used to detect the deletion. The existence of this mutant allele confirms that the epitope of IgG-C7 is located in the first cysteine-rich repeat and that this repeat is not necessary for LDL binding. The mutant gene produced a normally sized 120-kilodalton LDL receptor precursor protein that matured to the 160-kilodalton form at less than one-fourth the normal rate. Thus, deletion of two amino acids within the first cysteine-rich repeat retards receptor transport from the endoplasmic reticulum to the cell surface, in contrast to deletion of the entire first repeat, which has no effect on receptor maturation.
A non-occluded multiple application skin blanching assay has been used to determine the effect of applied phosphatidylcholine (PC) on the bioavailability of corticosteroids. One forearm of each of ten volunteers was treated twice daily for one week with PC presented as a liposomal suspension in Sørensen's (pH 5.0) phosphate buffer (2.5 mg PC/0.5 mL) while the other arm was treated with 0.5 mL of phosphate buffer. For the following two weeks this treatment regimen was continued but in addition, each of four corticosteroid formulations (containing (i) hydrocortisone 0.1%, (ii) clobetasone butyrate 0.05%, (iii) betamethasone 0.1% and (iv) clobetasol propionate, 0.05%) was applied to sites on both arms. 5 +/- 1 mg of each cream was applied twice daily to the sites on day 1, then once daily for a further four days; after two days of no application, the protocol was repeated. Estimation of pallor was usually made four times daily. At the end of the second week of corticosteroid application the blanching response to all four formulations on the PC treated arms was significantly higher than on the buffer treated arm. Tachyphylaxis to the applied corticosteroids was markedly less apparent on the lipid-treated arms. It is proposed that the applied phospholipid either supplements the lipid content of the skin or provides a thin film in intimate epidermal contact. Such a film may promote hydration of the stratum corneum and also provide an environment into which corticosteroids initially partition before a subsequent, more controlled, release to the underlying tissue.