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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1997

The soluble interleukin-2 receptor predicts mortality in older hospitalized men.

BACKGROUND: There is an inverse relationship between the soluble interleukin-2 receptor (sIL-2R) and serum albumin, cholesterol, transferrin, prealbumin, and hemoglobin. Inasmuch as low serum albumin and cholesterol have been associated with excess mortality, we hypothesized that elevated sIL-2R would predict mortality in older adults. OBJECTIVE: To determine if elevated sIL-2R predicts mortality in patients on a geriatric rehabilitation unit. DESIGN: Prospective cohort. SETTING: University-affiliated VA medical center. PARTICIPANTS: Seventy-two male patients aged greater than 60 years admitted to a geriatric rehabilitation unit. Patients with severe hepatic or renal disease were excluded. MEASUREMENTS: We measured serum albumin, prealbumin, cholesterol, transferrin, hemoglobin, body mass index (BMI), C-reactive protein (CRP), and sIL-2R upon admission. Subjects were followed for 1 year. RESULTS: Low serum albumin, prealbumin, and hemoglobin and high sIL-2R and CRP predicted 1-year mortality on univariate analysis. When these predictors were included as covariates in a Cox regression model, only sIL-2R was a significant independent predictor of mortality (P = .043). Multiple linear regression with the above covariates revealed that only sIL-2R predicted time to death at (P = .003). CONCLUSIONS: High sIL-2R and CRP and low albumin, prealbumin, and hemoglobin predicted mortality using univariate analysis on a rehabilitation unit. However, with multivariate analysis, sIL-2R was the sole predictor of mortality.

Aged↗
PubMed1997

Modulation of vascular tone by low density lipoproteins: effects on L-arginine transport and nitric oxide synthesis.

Low density lipoprotein (LDL) plays an important role in atherogenesis. Focal accumulation within the arterial intima of excess amounts of cholesterol-rich LDL leads to the migration and recruitment of monocytes, which then differentiate into macrophages after taking up large amounts of oxidatively modified LDL via their scavenger receptors and become lipid-laden 'foam cells' within the subendothelial space. It is generally accepted that oxidized LDL and hyperlipidaemia impair endothelial-dependent vascular relaxation, yet the existing literature on the effects of oxidatively modified LDL on endothelium-derived nitric oxide (NO) and prostacyclin (PGI2) release is inconclusive, since oxidized LDL has been reported to enhance or reduce NO and PGI2 production. Our studies using cultured human endothelial and smooth muscle cells have established that basal rates of L-arginine (NO precursor) transport, NO and PGI2 production and soluble guanylyl cyclase activity are unaffected by pretreatment (for 1 or 24 h) with native LDL, or with mildly or highly oxidized LDL. In contrast, highly oxidized LDL inhibited histamine-stimulated release of NO and PGI2 from human endothelial cells and induced an adaptive increase in the level of intracellular glutathione in human smooth muscle cells, a response which was prevented by the chain-breaking antioxidant alpha-tocopherol. Although initial rates of L-arginine transport and basal NO and PGI2 release from human endothelium are unaffected by oxidized LDL, agonist-stimulated release of these vasodilators is markedly attenuated. Elucidation of the mechanisms regulating these responses and their sensitivity to dietary antioxidants could lead to alternative strategies for reducing atherogenesis.

Animals↗
PubMed1997

A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck.

Combined chemoradiotherapy is superior to radiotherapy alone for stage III and IV squamous cell carcinoma of the head and neck, and concurrent use of both offers the advantage of synergistic interactions. Our prior trial demonstrated the ease and convenience of administering carboplatin during radiotherapy. Since paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has activity in squamous cell carcinoma of the head and neck and can act synergistically with both radiotherapy and platinum drugs, we initially added paclitaxel at 45 mg/m2/wk to carboplatin given at 100 mg/m2 during radiotherapy given at conventional fractions. The initial dose of paclitaxel was subsequently reduced to 40 mg/m2/wk. Thirteen of 18 patients entered so far have sufficient follow-up data; 12 are assessable for toxicity and 11 are assessable for response. One died early of progressive disease, two achieved a complete response, six achieved a partial response, and two had stable disease. Toxicities have so far been manageable for the 76 weekly doses administered. Chemotherapy dose reduction was needed in 10 patients. For the planned 100 doses of chemotherapy, 53 (53%) were administered as planned, 23 (23%) were reduced, and 24 (24%) were withheld due to neutropenia or mucositis. There were no toxic deaths, and no patient stopped therapy for toxicity. Paclitaxel/carboplatin can be administered during radiotherapy for squamous cell carcinoma of the head and neck with acceptable toxicities, and further accrual is needed to evaluate the effect of this combination.

Aged↗
PubMed1997

The influence of fashion magazines on the body image satisfaction of college women: an exploratory analysis.

This study examined the impact of exposure to fashion magazines on women's body image satisfaction. Participants were 39 undergraduate women, randomly assigned to two experimental conditions: half viewed fashion magazines prior to completing a body image satisfaction survey, and the remaining half, news magazines. Mean height and weight did not differ for the two groups. As hypothesized, women who viewed fashion magazines preferred to weigh less, were less satisfied with their bodies, were more frustrated about their weight, were more preoccupied with the desire to be thin, and were more afraid of getting fat than were their peers who viewed news magazines.

Adolescent↗
PubMed1997

Cerebral venous thrombosis in nephrotic syndrome.

This report describes cerebral venous sinus thrombosis, a rare and perhaps under-diagnosed complication of nephrotic syndrome. We review the pathophysiology of the coagulopathy associated with nephrotic syndrome including abrupt renal loss of antithrombin III. We propose a rationale approach to treating this condition with low-molecular-weight heparin and antithrombin III replacement.

Aged↗
PubMed1996

Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX.

The blood coagulation and regulatory proteins that contain gamma-carboxyglutamic acid are a part of a unique class of membrane binding proteins that require calcium for their interaction with cell membranes. Following protein biosynthesis, glutamic acids on these proteins are converted to gamma-carboxyglutamic acid (Gla) in a reaction that requires vitamin K as a cofactor. The vitamin K-dependent proteins undergo a conformational transition upon metal ion binding, but only calcium ions mediate protein-phospholipid interaction. To identify the site on Factor IX that is required for phospholipid binding, we have determined the three-dimensional structure of the Factor IX Gla domain bound to magnesium ions by NMR spectroscopy. By comparison of this structure to that of the Gla domain bound to calcium ions, we localize the membrane binding site to a highly ordered structure including residues 1-11 of the Gla domain. In the presence of Ca2+, Factor IX Gla domain peptides that contain the photoactivatable amino acid p-benzoyl-L-phenylalanine at positions 6 or 9 cross-link to phospholipid following irradiation, while peptides lacking this amino acid analog or with this analog at position 46 did not cross-link. These results indicate that the NH2 terminus of the Gla domain, specifically including leucine 6 and phenylalanine 9 in the hydrophobic patch, is the contact surface on Factor IX that interacts with the phospholipid bilayer.

Amino Acid Sequence↗
PubMed1996

The raz1 mutant of Arabidopsis thaliana lacks the activity of a high-affinity amino acid transporter.

The raz1 mutant of Arabidopsis thaliana (L.) Heynh. has been selected as resistant to the toxic proline analogue, azetidine-2-carboxylic acid (2AZ). Seedlings of the mutant tolerated fivefold higher concentrations of 2AZ (ED50 = 0.25 mM) than the wild-type seedlings (EC50 = 0.05 mM). The mutant gene was found to be semi-dominant and the corresponding RAZ1 locus was mapped on chromosome 5 at 69.6 +/- 1.8 cM. The resistance to 2AZ could be fully and exclusively accounted for by the lower uptake rate of the proline analogue in the mutant. The influx of L-proline in roots of wild-type seedlings could be dissected into two components: (i) a component with a high affinity and a low capacity for L-proline (Km) approximately 20 microM, Vmax approximately 60 nmol.(g FW)-1.h-1) and also a high affinity for L-2AZ (Ki approximately 40 microM) and (ii) a low-affinity, high-capacity component (Km) approximately 5 mM: Vmax = 1300 nmol.(g FW)-1.h-1). Clearly, the raz1 mutation affects the activity of a high-affinity transporter, because the high-affinity uptake of proline in the mutant was at least fivefold lower than in the wild-type, whereas the low-affinity uptake was unchanged.

Amino Acid Transport Systems↗
PubMed1996

MRI of spinal cord radiation necrosis simulating recurrent cervical cord astrocytoma and syringomyelia.

BACKGROUND: Although primary intramedullary tumors of the spinal cord with syrinx formation are well documented, there have been no reports of extensive syrinx formation or cystic degeneration associated with radiation necrosis. METHODS: We report a case of radiation necrosis and syrinx formation in a 49-year-old woman with a 5-year history of astrocytoma grade II of the cervical cord, who progressed to quadriparesis following surgery and radiation therapy. Magnetic resonance imaging (MRI) of the cervical and thoracic spine demonstrated enlargement of upper cervical cord (C1-C6) with diffuse increased signal enhancing mass by gadolinium, as well as appearance of syrinx from T4-T10. RESULTS: Autopsy findings indeed revealed a small, residual, infiltrating glioma in the upper cervical areas, but the diffuse parenchymal abnormality seen on MRI as prolonged T2 characteristics on double-echo spin-echo sequence was revealed to be radiation necrosis. CONCLUSION: What appeared to be a cystic cavity or syrinx at the thoracic level was also diagnosed as radiation necrosis with cyst formation on histologic examination.

Adult↗
PubMed1996

Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in isolated large and small rabbit coronary arteries.

1. Previous studies suggest that oxidatively modified low-density lipoproteins (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the large arteries of hypercholesterolaemic animals, whereas this may not be the case with regard to the impairment of coronary resistance vessels. For this reason, the effect of lipoproteins on coronary resistance arteries has been examined in this study. 2. The influence of lipoproteins on endothelium-dependent relaxation induced by acetylcholine (ACh) or sodium nitroprusside in PGF2 alpha-preconstricted rings from the large (1st order branch) and small coronary arteries (3rd order branch) and the aorta of New Zealand White rabbits, was investigated. 3. The sensitivity to ACh was greater in the large compared with the small diameter coronary arteries. 4. Endothelium-dependent relaxations were unaffected by native LDL. Oxidized LDL (0.5 and 1 mg protein mL-1) caused a reversible inhibition of relaxations in both preconstricted small and large coronary arteries which was overcome at high ACh concentrations. Similar inhibitions were found in the aorta. 5. Endothelium-independent relaxations elicited by sodium nitroprusside in the large and small coronary arteries were unaffected by the oxidized lipoproteins, indicating that soluble guanylate cyclase activity was unaltered. 6. It is concluded that inhibition of endothelium-dependent relaxation in the small diameter coronary arteries in hypercholesterolaemia may arise from products of oxidative modification of LDL present in the artery itself or released upstream from proximal lesions.

Acetylcholine↗
PubMed1996

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Developing a networking strategy for an integrated healthcare delivery system.

Dramatic changes in the healthcare industry are forcing organizations to find innovative ways to survive. The most critical component for organizational survival is the ability to communicate with and connect to internal and external information sources. It becomes imperative that organizations employ minimum standards and protocols in network design even as legacy systems remain in place as a part of their networks.

Computer Communication Networks↗
PubMed1996

Mseleni joint disease--a molecular genetic approach to defining the aetiology.

Mseleni joint disease (MJD) is an unusual form of progressive and widespread degenerative osteoarthropathy that has been identified in several hundred people in the remote Mseleni region of northern Zululand. Affected individuals experience articular discomfort in childhood and may be seriously handicapped as adults, often requiring prosthetic hip joint replacement. Although the condition clusters in families, there is no evidence of Mendelian inheritance and assessment of affected kindreds has not shown any evidence of genomic imprinting. To date our molecular work-up has entailed the study of 47 affected individuals from MJD kindreds to investigate familial predisposition based on the inheritance of a subset of markers and/or genes on the human genome, particularly those associated with the cartilage matrix. In addition, we have collected blood specimens form 111 unaffected but unrelated individuals from the same population group in order to determine whether any relationship exists between genetic components of the human leucocyte antigen (HLA) system and the MJD phenotype. Our investigations show the following: (i) there is no association between MJD and the HLA system which has previously been associated with non-Mendelian genetic conditions; (ii) COL2A1, which has been implicated in some forms of spondylo-epiphyseal dysplasia, may be involved in at least a subset of MJD patients; and (iii) type VI collagen is overabundant in degenerated hip joint cartilage.

Black People↗
PubMed1995

Flow sorting of the Y sex chromosome in the dioecious plant Melandrium album.

The preparation of stable chromosome suspensions and flow cytometric sorting of both the Y sex chromosome of the white campion, Melandrium album, and the deleted Y chromosome of an asexual mutant, 5K63, is described. The principle has been to maintain transformed roots in vitro, synchronise and block mitosis, reduce cells to protoplasts, and lyse these to release chromosomes. Such in vitro material, unlike many cell suspensions, showed a stable karyotype. Factors critical to producing high-quality chromosome suspensions from protoplasts include osmolality of isolation solutions and choice of spindle toxin and of lysis buffer. Agrobacterium rhizogenes transformed young growing root cultures were synchronised at G1/S with 50 microM aphidicolin for 24 h and released to a mitotic block with 30 microM oryzalin for 11 h. Protoplast preparations from such tissue routinely had metaphase indices reaching 15%. Suspensions of intact metaphase chromosomes, with few chromatids, were obtained by lysing swollen mitotic protoplasts in a citric acid/disodium phosphate buffer. Except for the presence of clumps of autosomal chromosomes near the X and Y chromosome zones, monoparametric histograms of fluorescence intensities of suspensions stained with 4',6-diamino-2-phenylindole showed profiles similar to theoretical flow karyotypes. Two types of Y chromosomes, one full-length and one partially deleted (from the asexual mutant), could be sorted at 90% purity (21-fold enrichment of Y). These results are discussed in the context of sex determination and differentiation in higher plants.

Cell Line, Transformed↗
PubMed1995

Loin pain hematuria syndrome: pain relief with intrathecal morphine.

Loin pain hematuria syndrome (LPHS) is characterized by hematuria and incapacitating loin pain. The pain experienced with LPHS is, in general, extremely difficult to treat. Many surgical and pharmacologic therapies have been directed at LPHS pain without success. This report documents successful pain control in a patient with LPHS using long-term intrathecal morphine delivered via an implantable pump. Intrathecal narcotic therapy may provide pain relief for the chronic pain of LPHS.

Adult↗
PubMed1995

RITA--registry of industrial toxicology animal-data--guides for organ sampling and trimming procedures in rats.

RITA (Registry of Industrial Toxicology Animal-data) is a pathology data base for the collection of validated histopathological data on tumours and potentially pre-neoplastic lesions observed in laboratory rodents. To enable a better comparison of information, standardized techniques for the preparation of histological slides have been established for all organs. The current paper describes the guidelines for organ sampling and trimming procedures applied in the RITA project, i.e. the number of sections to be taken, the direction in which an organ should be cut, the localization (anatomical site) from which a sample should be taken, and the size of an organ (or part of an organ) to be placed in cassettes for processing. Schematical illustrations and additional explanations are provided to support the proposed standardized procedures in histology laboratories.

Animals↗
PubMed1995

A dinucleotide mutation in dihydrodipicolinate synthase of Nicotiana sylvestris leads to lysine overproduction.

By applying a mutagenesis/selection procedure to obtain resistance to a lysine analog, S-(2-aminoethyl)L-cysteine (AEC), a lysine overproducing mutant in Nicotiana sylvestris was isolated. Amino acid analyses performed throughout plant development and of different organs of the N. sylvestris RAEC-1 mutant, revealed a developmental-dependent accumulation of free lysine. Lysine biosynthesis in the RAEC-1 mutant was enhanced due to a lysine feedback-desensitized dihydrodipicolinate synthase (DHDPS). Several molecular approaches were undertaken to identify the nucleotide change in the dhdps-r1 gene, the mutated gene coding for the lysine-desensitized enzyme. The enzyme was purified from wild-type plants for amino end microsequencing and 10 amino acids were identified. Using dicotyledon dhdps probes, a genomic fragment was cloned from an enriched library of DNA from the homozygote RAEC-1 mutant plant. A dhdps cDNA, putatively full-length, was isolated from a tobacco cDNA library. Nucleotide sequence analyses confirmed the presence of the previously identified amino end preceded by a chloroplast transit peptide sequence. Nucleotide sequence comparisons, enzymatic and immunological analyses revealed that the tobacco cDNA corresponds to a normal type of DHDPS, lysine feedback-regulated, and the genomic fragment to the mutated DHDPS, insensitive to lysine inhibition. Functional complementation of a DHDPS-deficient Escherichia coli strain was used as an expression system. Reconstruction between the cDNA and genomic fragment led to the production of a cDNA producing an insensitive form of DHDPS. Amino acid sequence comparisons pointed out, at position 104 from the first amino acid of the mature protein, the substitution of Asn to Ileu which corresponds to a dinucleotide mutation. This change is unique to the dhdps-r1 gene when compared with the wild-type sequence. The identification of the nucleotide and amino acid change of the lysine-desensitized DHDPS from RAEC-1 plant opens new perspectives for the improvement of the nutritional value of crops and possibly to develop a new plant selectable marker.

Amino Acid Sequence↗