PubMed Health⌕ Search

Biomedical subjects

B Wetzel

Publications and source records attributed to B Wetzel.

At least 19 recordsLinked to original sources
PubMed2000

Embryonic vasculogenesis by endothelial precursor cells derived from lung mesenchyme.

During development, the lung mesenchyme has a dynamic relationship with the branching airway. Embryonic lung mesenchyme is loosely packed and composed of indistinguishable cells, yet it is the source of vascular progenitors that will become endothelial cells, smooth muscle cells and fibroblasts. In the lung, vessel development in the periphery proceeds first through vasculogenesis, the migration and assembly of cells into a primitive network, and subsequently, through angiogenesis, the sprouting of vessels from this network. As a way to assess the cellular and molecular mechanisms of lung vascularization, we have isolated and cloned cell lines from mouse fetal lung mesenchyme (MFLM). Two of these MFLM cell lines, MFLM-4 and MFLM-91U, display characteristics of an endothelial lineage. RNA analysis demonstrates transcripts for the vascular endothelial growth factor receptors R1 and R2, the receptor tyrosine kinases, Tie-1 and Tie-2, as well as the Tie-2 ligands, Ang-1 and -2. The MFLM cell lines form extensive networks of capillary-like structures with lumens when cultured on a reconstituted basement membrane. In vivo, following blastocyst injection, the MFLM cells chimerize endothelium of the lung and areas of the heart vasculature. The results from these studies suggest that MFLM-4 and MFLM-91U, derived from embryonic lung mesenchyme, can function in vitro and in vivo as endothelial precursors and as models of cardiopulmonary vascularization. Dev Dyn 2000;217:11-23.

Animals↗
PubMed1989

The evolution of correlative techniques for electron microscopy--an overview.

The papers presented at this Pfefferkorn Conference demonstrate the dramatic recent progress in the science of biological specimen preparation for electron microscopy. This progress results largely from increased use of more diverse, critical, correlative scientific methods. This paper outlines several strategies that tend to promote this type of scientific approach, and that have proven generally useful in biological research. The strategy most commonly chosen to augment both the empirical and the cross-disciplinary components of structural studies is the correlative use of diverse experimental techniques on samples which are parallel to those prepared for microscopy. This type of approach tends to advance our understanding of biological structure and function and also of the scientific methodology. Such approaches redirect attention to the biological problem under study and tend to open new areas of investigation. A second strategy which promotes more rigorous scientific approaches is the application of correlative techniques to identical structures. In contrast with parallel studies, data from identical structures document directly the coincidence of different features within each individual structure, and these data establish the distributions of these features in the study population based on relatively few observations. A third strategy to promote more critical science is to utilize the effects of the specimen preparation as experimental parameters by varying the preparative methods with appropriate controls. This approach is especially valuable in studies of biological specimen preparation, where the potential impact of systematic errors warrants especially rigorous scientific practice.

Animals↗
PubMed1989

Structure-activity relationships and pharmacological profile of selective tricyclic antimuscarinics.

The discovery of the M1-selective receptor antagonist pirenzepine was the impetus for a research project directed towards the development of selective muscarinic antagonists. In the pursuit of this objective, compounds with different selectivity profiles have been found. AF-DX 116 was the first cardioselective antagonist synthesized. Subsequently novel M2 receptor antagonists have been discovered with higher potency and selectivity. Moreover, a pirenzepine-type compound UH-AH 37 has been identified that, in contrast to pirenzepine, shows a higher affinity for ileal than for atrial muscarinic receptors. Among tricyclic muscarinic receptor antagonists three different selectivity profiles have been identified, namely: M1 greater than M3 greater than M2, Msm for pirenzepine; M2 greater than M1 greater than M3, Msm for AF-DX 116, AF-DX 384, AQ-RA 741; and Msm congruent to M1 greater than M2, M3 for UH-AH 37 and its (+) enantiomer.

Antidepressive Agents, Tricyclic↗
PubMed1987

Characteristic shape and surface changes in epithelial transformation.

Previous work has suggested that adhesive or cytoskeletal structures alter during epithelial transformation. The purpose of the present studies was to see whether such reorganizations were accompanied by consistent changes in the biophysical characteristics of cells. We used in vitro cell lines from rat liver and respiratory tract epithelium that became tumorigenic over a period of 11-15 months. For populations sampled at several time points before and after this transition, the shape of individual cells was analysed by calculating the values of many geometrical descriptors. The data were collected from cells imaged by reflected light interference. Interference contours on the cells were digitized, and the descriptor values calculated by computer program. Cell lines derived from both liver (IAR 20PC1) and respiratory epithelium 1,000 W) lines showed progressive changes in the values of certain descriptors. The time-dependent differences among groups were statistically significant at a level of p less than 0.0001. By determining which descriptors underwent large changes, we found that some structural revisions occurred in common in the two types of cells. Cells from later passages of the lines rose from the substrate at a steeper angle, as determined by measuring the fraction of the area of the first interference contour that was occupied by successive contours. In addition, the projections on the perimeter became broader, and the perimeter became less complex. This kind of 'smoothing' of the cell perimeter took place in several contours, indicating that it was a surface change. Surface changes of this sort have not been noted previously in transformation. The results suggest that the structure of cells is altered in a consistent way during transformation, as detected by measuring of shape and surface configuration.

Animals↗
PubMed1986

Synthesis and antimicrobial activity of 7 alpha-methoxypyrimidinyl-ureidocephalosporins.

The synthesis of a series of 7 alpha-methoxy-7-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(4-hydroxyphenyl) acetamido]-3-cephem-4-carboxylates 2 is described. 7-[(R)-2-[3-[2-(p-Aminosulfonyl)-anilino-4-hydroxy-5-pyrimidinyl]ureido- 2-(4-hydroxyphenyl)acetamido]-7 alpha-methoxy-3-[(1-methyl-1H-tetrazol-5 -yl)thio]methyl-3-cephem-4-carboxylic acid, sodium salt (2k, UG-FA 132), has exhibited a broad range of antimicrobial activity. UG-FA 132 is highly active against Gram-positive and Gram-negative organisms, including Pseudomonas and lactamase producers, and shows potent activity against anaerobes. The high efficacy of UG-FA 132 was confirmed by in vivo experiments in mice.

Animals↗
PubMed1985

Synthesis and antibacterial activity of pyrimidinylureidopenicillins.

The 6R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(4-hydroxyphenyl) acetamido]-penicillanic acids (10), prepared by two synthetic routes, exhibit broad antimicrobial activity against Gram-positive and Gram-negative bacteria. Their structure activity relationships are discussed. 6R-[(R)-2-[3-[2-(p-Aminosulfonyl)anilino-4-hydroxy-5-pyrimidinyl] ureido]-2-(4-hydroxyphenyl)acetamido]-penicillanic acid, sodium salt (VX-VC 43, 10m), the most active compound, shows very low MIC (minimal inhibitory concentration) values against clinically important Gram-negative bacteria, primarily Pseudomonas aeruginosa.

Gram-Negative Bacteria↗
PubMed1985

Synthesis and antimicrobial activity of pyrimidinylureidocephalosporins.

The synthesis of a series of 7R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(aryl)acetamido]-3-cephem-4- carboxylates is described. Variation of the substituents at the 3-position in the cephem nucleus, at the 2-position of the pyrimidine ring, and of the phenyl residue in the acyl side chain is carried out. Qualitative structure-activity relationships in this series are discussed. VX-VD 2, the most interesting compound, exhibits broad antimicrobial activity against Gram-negative bacteria, including Pseudomonas aeruginosa.

Bacteria↗
PubMed1984

Interaction of forskolin with dually regulated adenylate cyclase.

Forskolin clearly has effects on all three known components of adenylate cyclase, Ni, Ns, and the catalytic subunit (C). Forskolin can activate the catalytic activity of adenylate cyclase directly in the absence of the Ni or Ns subunit, and, therefore, forskolin is acting at a site that is on the catalytic subunit or a closely associated protein. A lack of forskolin stimulation of cyclic AMP in intact cells does not necessarily imply that it requires or acts via the Ns protein, since, as shown for the cyc- S49 cells, the enzyme may be in an inhibited state because of the presence of Ni. The presence of a site on adenylate cyclase that can regulate not only the absolute activity of the enzyme but also its sensitivity to hormones raises the possibility that there may be substances endogenous to the cell that can functionally interact at this site. It is too early to speculate as to the nature of these substances. However, they could be extracellular, originating from other cells, or they could be intracellular. The final determination will rely on the identification and physical disposition of the forskolin-binding site and also the identification of endogenous compounds with forskolin-like activities.

Adenylyl Cyclase Inhibitors↗
PubMed1981

Modification of spectinomycin. 2. Derivatives of 4-dihydro-4-deoxy-4(R)-aminospectinomycin.

Acyl derivatives 5a approximately j and alkyl derivatives 7a approximately r of 4-dihydro-4-deoxy-4(R)-aminospectinomycin (1a) were prepared and tested for antibacterial activity. Only acyl compounds derived from long chain aliphatic acids showed activity in vitro, but were inactive when tested in vivo. All alkyl derivatives were active in vitro. In vivo however only the short chain derivatives 7a approximately c were active. Compound 7b showed higher activity than spectinomycin.

Bacteria↗
PubMed1977

Effects of retinoic acid on embryonic chick skin.

The influence of vitamin A on differentiating epithelia was examined in explants of skin from 14-day chick embryos exposed to retinoic acid (RA) in low, moderate, and high doses. The changes observed in RA-treated cultures are both dose- and time-dependent and are reversible when explants are transferred to control medium. The periderm sloughs prematurely and horizontal stratification is lost. Keratinization is inhibited and fewer desmosomes and tonofilaments are seen. Surface epidermal cells develop microvilli, bulge upwards, and detach. Golgi elements, rough endoplasmic reticulum, and polyribosomes are unusually prominent. Mucin granules form and gland-like structures develop with intercellular canaliculi characterized by tight junctions, brush borders, and dense secretory contents. On the basis of present evidence there are several possible mechanisms by which RA could alter epidermal differentiation. RA-induced gaps in the basal lamina allow direct contact between epidermal basal cells and fibroblasts and collagen fibers which could result in inappropriate dermal signals reaching the epidermis. In younger embryos the entire epidermis, including the mitotically inactive surface cells, appears to respond to RA, and this could imply an epigenetic modulation of cell phenotype. Finally, after the formation of a stratum corneum in older embryos only the relatively undifferentiated basal layer shows a metaplastic response, indicating that RA could be acting directly on the genome.

Aging↗
PubMed1977

Topography of nonneoplastic and neoplastic cells of common origin.

The possibility that neoplastic transformation may characteristically alter cell surface morphology prompted a comparison by scanning electron microscopy of nonneoplastic and tumorigenic cell lines from a single clone of mouse embryo cells. Among those studied by scanning electron microscopy, six lines of this clone proved nonneoplastic, and nine others underwent neoplastic transformation in culture, as evidenced by tumor production in vivo. Combined cinephotomicrography and scanning electron microscopy allowed the determination of postmitotic time and topography of individual cells without perturbing the cells or detectably altering their surface morphology; no pattern of morphological change as a function of postmitotic time was evident in either nonneoplastic or neoplastic cell populations. Accordingly, these cell populations could be compared under their usual conditions of attached asynchronous growth despite differences in proliferation rates. Cells of the neoplastic lines were characteristically less spread, and some lines displayed greater morphological variability than was evident among cells of nonneoplastic lines. However, most cells in all nine neoplastic lines and all six nonneoplastic lines were smooth surfaced. Thus, the exaggerated incidence of microvilli, ruffles, or blebs reported for established tumor-derived lines and most morphologically transformed lines did not prove a reliable criterion of neoplastic state for these cell lines of common origin grown under the same culture conditions.

Animals↗
PubMed1976

Cornifying Darier disease--a unique variant. I. Report of a case.

A unique variant of Darier disease is described in which a patient was disabled by large, painful, cutaneous horns present on all extremities. The cornified lesions were distinguished by the presence of numerous corps ronds in the basal portion of the greatly hyperkeratotic stratum corneum, hypertrophic dermal villi containing enlarged capillaries, vacuolar dilatation of rough endoplasmic reticulum in sublacunar basal cells, unusually numerous Odland bodies in spinous cells adjacent to lacunae, and persistent attachment of tonofilaments to disrupted desmosomes. Complete separation of tonofilaments from intact desmosomes was not observed. Scanning electron microscopy revealed varied surface morphological appearances of corps ronds and of the epidermal cells covering the elongated dermal villi. The surface cells of cutaneous horns showed little tendency to desquamate.

Adult↗
PubMed1975

Human lymphocytes: similarity of B and T cell surface morphology.

When viewed by scanning electron microscopy human lymphocytes fixed in suspension and processed with minimal cell loss appear uniformly covered with short microvilli. Contrary to previous reports, lymphocytes from subpopulations selectively enriched for T cells are villous and indistinguishable from B lymphocytes. Whereas lymphocyte surface architecture can change rapidly and substantially in response to environmental modifications, such as contact with an underlying surface, these alterations are similar for both B and T cells and do not serve to distinguish these subpopulations.

Animals↗