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Biomedical subjects

J B Weiss

Publications and source records attributed to J B Weiss.

At least 19 recordsLinked to original sources

Characterization of a series of novel fucose-containing glycosphingolipid immunogens from eggs of Schistosoma mansoni.

Lipid extracts of eggs, worms, and cercariae of the parasitic trematode Schistosoma mansoni have been shown to contain a large number of highly immunogenic glycolipids (Weiss, J. B., Magnani, J. L., and Strand, M. (1986) J. Immunol. 136, 4275-4282). Three fractions of schistosome egg glycolipids were selected on the basis of their reactivity with an anti-schistosome monoclonal antibody (128C3/3), which recognizes a developmentally regulated carbohydrate epitope present on both glycolipid and glycoprotein antigens from S. mansoni. These fractions were purified by silica gel chromatography and preparative high performance thin layer chromatography and characterized by monosaccharide, fatty acid, and linkage analysis with gas chromatography-mass spectrometry, as well as by positive and negative ion fast atom bombardment-mass spectrometry. The immunogens were shown to be glycosphingolipids having homologous structures based on a highly novel extension of glucosylceramide. Monosaccharide inhibition studies indicated that the epitope recognized by 128C3/3 residues in an outer region of the immunogens consisting of Fuc2GlcNAc (where Fuc is fucose) repeating units. The largest antigen characterized may have the following structure, based on the evidence presented in this paper. [sequence: see text] The evidence indicated the existence of a series of glycan structures created by deletions of one or more Fuc1----3 side chains from the above structure.

Animals

Classification of subgroups of Giardia lamblia based upon ribosomal RNA gene sequence using the polymerase chain reaction.

A sensitive and specific polymerase chain reaction-based assay has been developed to detect and analyze polymorphism in the Giardia lamblia 18S ribosomal RNA gene. Efficient amplification required the inclusion of cosolvents (glycerol and dimethyl sulfoxide) in the reaction. Following the optimization of conditions for amplification and subsequent hybridization of amplified product with radiolabeled oligonucleotide probe, a detection limit of less than one organism's worth of DNA was achieved. Thirty-five different G. lamblia strains obtained from various human and animal host types and geographic locations were analyzed by this method. The strains could be divided into 3 groups on the basis of defined nucleotide substitutions within the 183-bp amplified DNA fragment of the 18S ribosomal RNA gene. The groupings based upon the 18S ribosomal RNA gene sequence correlated with groupings previously assigned based upon patterns of surface antigens and restriction enzyme analysis. Analysis of the G. lamblia 18S ribosomal RNA gene sequences present in fecal specimens obtained from giardiasis patients revealed the presence of the different sequence types in these specimens. Some specimens contained more than one sequence type. The identification of subgroups of G. lamblia may facilitate studies of virulence, infectivity, and the epidemiology of giardia infection.

Amino Acid Sequence

Concentrations of endothelial-cell-stimulating angiogenesis factor, a major component of human uterine angiogenesis factor, in human and bovine embryonic tissues and decidua.

Embryonic development involves the establishment of new patterns of vascular growth in the fetus and within the lining of the womb. A factor, human uterine angiogenesis factor, has been purified from the decidua and stimulates the growth of blood vessels in collagen sponge implants and in the chick chorioallantoic membrane. Evidence is presented that suggests that a major active component of human uterine angiogenesis factor is an activator of latent matrix metalloproteinases, of low M(r), called endothelial-cell-stimulating angiogenesis factor and that this factor is present in substantial quantities in a number of embryonic tissues.

Angiogenesis Inducing Agents

Activation of the matrix metalloproteinase inhibitor complex by a low molecular weight angiogenic factor.

Tissue inhibitor of matrix metalloproteinases is the major inhibitor of the collagenolytic enzymes and the inhibitory complex has been thought to be irreversible. In this paper we show that a low molecular weight non-protein endothelial cell stimulating angiogenic factor is able to reactivate the enzyme from the inhibitor complex and liberate free inhibitor. The importance of an angiogenic factor able to initiate limited degradation of extra-cellular matrix such that space is created for new capillary growth is discussed.

Angiogenesis Inducing Agents

Increased endothelial cell stimulating angiogenesis factor in patients with tibial fractures.

Angiogenesis is an important step in the normal process of fracture healing, irrespective of the method of fixation. Using a quantitative assay, the amount of endothelial cell stimulating factor (ESAF) has been determined in a small group of patients with tibial fractures. ESAF levels were found to be increased when compared with normal volunteers, although this increase was relatively less in fractures held with intramedullary nails than with external fixation.

Adult

Low molecular weight angiogenesis factors.

A number of substances have been proposed for the role of angiogenesis factors. Many of these are of protein origin and are therefore amenable to the tools of the molecular biologist. However a number of low molecular weight angiogenesis factors are emerging as important initiators and/or cofactors of neovascularization. Of these a number are known to stimulate angiogenesis indirectly, possibly through an inflammatory response. Some putative angiogenic factors stimulate microvessel endothelial cells nonspecifically, also causing migration and proliferation of large vessel cells. Others are specific for microvessel cells either for stimulating migration, proliferation or both. The nature and action of the low molecular weight factors in vivo and in vitro are reviewed.

Angiogenesis Inducing Agents

Raised levels of latent collagenase activating angiogenesis factor (ESAF) are present in actively growing human intracranial tumours.

Endothelial cell stimulating angiogenesis factor (ESAF) is a potent, low molecular mass mitogen, specific for endothelial cells. In common with various protein growth factors, it displays angiogenic activity in a variety of biological test systems. However, it differs from these other factors by virtue of its low molecular mass and its ability to activate latent matrix metalloproteinases in a dose dependent manner. This activity has been used to quantify the factor in both normal and diseased brain tissue. The concentration of ESAF determined in biopsies from different types of intracranial tumours varied: in some tumour types the level was close to that of control samples whereas in others it rose to levels comparable to those encountered in the pineal gland, the richest source of ESAF in mature mammals. Tumours considered to be benign contained significantly less ESAF than those neoplasms classified as being malignant (P = 0.025). There was also a correlation between the mitotic activity of tumour samples, as determined by conventional H & E histochemical staining and the ESAF concentration present. These findings agree with previous studies in which elevated ESAF levels have been found in tissue where proliferation of vascular elements has been observed.

Adult

Elevated endothelial-cell-stimulating angiogenic factor activity in rodent glycolytic skeletal muscles.

1. Capillary density is greater in skeletal muscles comprised of predominantly oxidative (type I) fibres than in those comprised of mainly glycolytic (type II) fibres. In order to investigate further the angiogenic mechanisms involved in muscle capillarization, endothelial-cell-stimulating angiogenic factor activities in various rodent skeletal muscles were compared. 2. Eleven untrained adult male Wistar rats were killed and the predominantly oxidative (type I) muscle,s soleus and heart, the predominantly glycolytic (type II) muscle, extensor digitorum longus, and the mixed-fibre muscle, gastrocnemius, were removed. Each sample was separately homogenized and centrifuged and the supernatants were diafiltered to isolate the low-molecular-mass fraction containing endothelial-cell-stimulating angiogenic activity. This was assayed for its ability to activate latent collagenase and was expressed as units, where 1 unit represents the percentage activation of the enzyme h-1 (mg of protein in the supernatant)-1. 3. The results (medians and ranges) demonstrated significantly greater endothelial-cell-stimulating angiogenic factor activity in extensor digitorum longus muscle (2.14 units, 0.62-2.87 units, n = 13) than in soleus (0.82 units, 0.59-1.79 units, n = 15), gastrocnemius (0.34 units, 0.28-0.40 units, n = 4) or heart (0.43 units, 0.16-0.52 units, n = 11) (P less than 0.01 for each) muscle. 4. These findings suggest that endothelial-cell-stimulating angiogenic activity in muscle is either inversely or not related to the local capillary density, which may be at or near a maximum in physiologically contracting, predominantly oxidative muscles.

Angiogenesis Inducing Agents

Peptides from live yeast cell derivative stimulate wound healing.

Live yeast cell derivative is an alcoholic extract from yeast (Saccharomyces cerevisiae) that has previously been shown by three groups of workers to stimulate wound healing. Live yeast cell derivative is a complex mixture, and it was not known which of its many components was responsible for the biological activity. This study describes the separation and analysis of the major components, one of which is a peptide fraction that stimulates wound healing. The fraction consists of a mixture of peptides from 6000 to 17,000 d. It causes angiogenesis in a chick embryo yolk sac membrane assay and in a rabbit cornea assay, and it dramatically stimulates wound healing in the "Schilling/Hunt" wire mesh cylinder model at concentrations 25-fold lower than those required for the intact live yeast cell derivative.

Animals

Production of endothelial cell stimulating angiogenesis factor (ESAF) by chondrocytes during in vitro cartilage calcification.

The aim of this study was to identify the stimulus for production of the latent collagenase and angiogenic activator ESAF by growth plate chondrocytes. Stimulation correlated most closely with matrix calcification. Alkaline phosphatase was necessary for calcification (and so stimulation of ESAF production) but we could find no evidence for a direct link with ESAF production. ESAF production was also stimulated by addition of preformed mineral to non-calcified cultures but was inhibited by dexamethasone. Protein synthesis was necessary for the stimulation of ESAF production by calcification, though ESAF is not itself a protein. Based on these findings we suggest that chondrocytes, at a suitable stage of maturation in the growth plate, are stimulated to produce ESAF by the proximity of crystals in the matrix. Stimulation, which may consist of the induction of an enzyme or transport protein, leads to the release of this potent activator of collagenolysis as part of the angiogenic cascade.

Alkaline Phosphatase

Influence of local anesthetic solution on postdural puncture headache.

A total of 2,511 patients who received spinal anesthesia for cesarean delivery were observed for the development of postdural puncture headache (PDPH); 804 patients received a mixture of tetracaine and procaine, 942 received bupivacaine-glucose, and 765 received lidocaine-glucose. They were observed for the development of PDPH for a minimum of 72 h. PDPH occurred in 9.54% of patients who received lidocaine-glucose during the first 36 h compared with 7.64% of patients who received bupivacaine-glucose and 5.85% of patients who received tetracaine-procaine. The differences between all groups was statistically significant. No differences were found in the percentage of patients who ultimately required epidural blood patch for relief of symptoms after 36 h.

Adult

The folding properties of the Escherichia coli maltose-binding protein influence its interaction with SecB in vitro.

It has been proposed that the cytoplasmic SecB protein functions as a component of the Escherichia coli protein export machinery by serving as an antifolding factor that retards folding of the precursor maltose-binding protein (preMBP) into a translocation-incompetent form. In this study, it was found that SecB directly interacts with wild-type preMBP and various mutationally altered MBP species synthesized in vitro to form a SecB-MBP complex that can be precipitated with anti-SecB serum. The association of SecB with wild-type preMBP was relatively unstable; such a complex was formed only when SecB was present cotranslationally or after denaturation of previously synthesized preMBP and was detected with only low efficiency. In marked contrast, MBP species that were defective in the ability to assume the stable conformation of wild-type preMBP or that exhibited significantly slower folding kinetics formed much more stable complexes with SecB. In one case, we demonstrated that SecB did not need to be present cotranslationally for complex formation to occur. Formation of a complex between SecB and MBP was clearly not dependent on the MBP signal peptide. However, we were unable to detect complex formation between SecB and MBP lacking virtually the entire signal peptide but having a completely intact mature moiety. This MBP species folded at a rate considerably faster than that of wild-type preMBP. The propensity of this mutant protein to assume the native conformation of mature MBP apparently precludes a stable association with SecB, whereas an MBP species lacking a signal peptide but exhibiting altered folding properties did form a complex with SecB that could be precipitated with anti-SecB serum.

ATP-Binding Cassette Transporters

Factors influencing the in vitro translocation of the Escherichia coli maltose-binding protein.

An in vitro system has been utilized to study the translocation of newly synthesized Escherichia coli maltose-binding protein (MBP) into inverted membrane vesicles. Approximately 40% of precursor MBP (pMBP) synthesized with a wild-type signal peptide was imported into vesicles. However, MBP species with even minor alterations in the signal peptide hydrophobic core were imported into vesicles with an efficiency much lower than predicted from in vivo studies. Posttranslational import of wild-type pMBP into vesicles could be demonstrated if membranes were added after the termination of protein synthesis. However, if vesicles were present throughout the synthesis reaction, most pMBP import occurred either cotranslationally or very soon after completion of synthesis. The wild-type pMBP rapidly became incompetent for posttranslational translocation upon continued incubation in the absence of membranes, whereas pMBP species with altered folding properties remained competent for significantly longer periods. The rate of in vitro pMBP folding was affected by the nature of the signal peptide. The evidence suggests that one or more soluble factors may interact with the newly synthesized pMBP to help maintain it in a translocation-competent state and to promote its entrance into the export pathway.

ATP-Binding Cassette Transporters

Anesthetic-related maternal mortality, 1954 to 1985.

This is a population-based study of the safety of obstetrical anesthesia in the Commonwealth of Massachusetts between 1954 and 1985. We used data collected by the state Committee on Maternal Mortality, which was founded in 1941. There were a total of 37 maternal deaths during the study period due to anesthetic-related complications. During the same time period, there were 886 maternal deaths. Thus, anesthetic-related mortality comprised 4.2% of all deaths, and the mortality rate was 1.5 per 100,000 live births between 1955 and 1964, 1.5 per 100,000 live births between 1965 and 1974, and 0.4 per 100,000 live births between 1975 and 1984. In the first decade of this study, aspiration during administration of a mask anesthetic was the primary cause of death. During the second decade, cardiovascular collapse associated with regional anesthesia was the primary cause of death. During the last decade of this study, all deaths were associated with general endotracheal anesthesia. As a result of this study and having identified the changes in the standard of care in Massachusetts that led to the reduction in maternal mortality, we offer recommendations to further improve the safety of anesthesia for childbirth in this country.

Adolescent

Endothelial cell-stimulating angiogenesis factor in vitreous from extraretinal neovascularizations.

The presence of endothelial cell-stimulating angiogenic factor (ESAF) in diseased human vitreous humour has been established. The molecular mass and chromatographic behavior of this material and its property of activating procollagenase indicate it to be identical to the ESAF isolated from other sources. The biological activity of ESAF from human vitreous was demonstrated by its ability to induce positive responses in the rabbit corneal pocket, and in the chick chorioallantoic membrane and yolk sac membrane tests.

Angiogenesis Inducing Agents