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Biomedical subjects

J Kaufman

Publications and source records attributed to J Kaufman.

At least 19 recordsLinked to original sources

Three-dimensional reconstruction of human carotid arteries from images obtained during noninvasive B-mode ultrasound examination.

Previous investigators have demonstrated that B-mode ultrasonography can provide high resolution images of the carotid arteries. When combined with Doppler flow measurements, quantitative estimates of luminal narrowing may also be obtained. B-mode imaging is limited, however, in its ability to provide a composite view of the vessel wall, lumen and plaque. Spatial relations between structures visualized in individual frames must be inferred from repeated transducer passes over the designated site, or repeated review of recorded images, followed by a "mind's eye" reconstruction. Three-dimensional (3-D) reconstruction of serially recorded cross-sectional images from current B-mode systems represents a possible solution to this limited spatial display that preserves detail regarding vessel wall pathology. Accordingly, computer-based automated 3-D reconstruction was used to generate a tangible format with which to assess and compare serially and transcutaneously recorded 2-dimensional (2-D) B-mode images of the carotid arteries. One or more timed sweep recordings of the 2-D B-mode examination were obtained from 5 patients for 3-D reconstruction. In all cases, satisfactory 3-D reconstruction was accomplished in three 3-D formats: cylindrical, sagittal and lumen cast. Sagittal 3-D reconstruction provided information regarding pathologic alterations within the arterial wall. Experience with the cylindrical mode suggests that this 3-D format, particularly when the reconstructed vascular segment is hemisected, is optimally suited for those cases in which direct inspection of luminal topography is of special interest. The lumen cast display, used with a recently validated edge-detection algorithm, may enhance the use of B-mode ultrasound for assessment of luminal cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The dexamethasone suppression test in children and adolescents: a review and a controlled study.

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.

Adolescent

Different features of the MHC class I heterodimer have evolved at different rates. Chicken B-F and beta 2-microglobulin sequences reveal invariant surface residues.

Chicken beta 2-microglobulin (beta 2m) and class I (B-F19 alpha chain) cDNA clones were isolated and the sequences compared to those of B-F Ag isolated from chicken E. These clones represent the major expressed class I molecules on E, with B-F alpha size variants evidently due to alternative use of small exons in the cytoplasmic region. The cDNA sequences were compared to turkey beta 2m, the apparent allele B-F12 alpha and other vertebrate homologs, using the 2.6 A structure of the human HLA-A2 molecule as a model. Both chicken alpha 1 and alpha 2 domains resemble mammalian classical class I molecules and the MHC-encoded nonclassical molecules more than CD1 or the class I-like FcR. In contrast, the chicken alpha 3 domain is equally homologous to all alpha 3 domains, to beta 2m and to class II beta 2 domains. For each pair of extracellular domains (alpha 1 vs alpha 2, alpha 3 vs beta 2m), the level of sequence homology between mammalian and avian molecules is quite different. This suggests that the structurally homologous domains have been under different selective pressures during evolution. There is a very strong G + C bias in alpha 3 and beta 2m, leading to an overall change in amino acid composition in B-F compared to class I molecules from other taxa. Many of the surface residues are quite diverged, particularly in alpha 3 and beta 2m. There are fewer changes in intra- and interdomain contact sites. Some residues with important functions are invariant, including seven residues that bind the ends of the peptide, two residues that bind CD8, and three residues that are phosphorylated. The positions of the allelic residues are conserved. There are other patches of invariant residues on alpha 1, alpha 2, and beta 2m; these might bind TCR or other molecules involved in class I function.

Amino Acid Sequence

B-G: we know what it is, but what does it do?

B-G molecules are polymorphic cell surface proteins that are encoded by the chicken MHC. Here, Jim Kaufman and Jan Salomonsen briefly summarize developments in the molecular genetics, the structure and the tissue distribution of B-G molecules, and discuss possible functions of this intriguing multigene family.

Animals

Human coronary and peripheral arteries: on-line three-dimensional reconstruction from two-dimensional intravascular US scans. Work in progress.

To explore the feasibility of computer-based, on-line three-dimensional reconstruction, timed manual withdrawal (pullback) recordings were obtained with two-dimensional intravascular ultrasound (US) in 42 patients who underwent percutaneous revascularization. Three-dimensional processing was performed with commercial software that stacked serially obtained intravascular US scans and created a new set of data points in four steps: interpolation, segmentation, boundary encoding, and surface rendering. In all 42 patients, satisfactory on-line three-dimensional reconstruction was accomplished. In the first three patients, 70-90 seconds was required for three-dimensional processing, and display was limited to the sagittal format. In the next six patients, a sagittal display was rendered in 45-60 seconds, and on-line reconstruction in the cylindrical format was achieved within 30 additional seconds. In the last 33 patients, an unlimited number of sagittal views could be produced in 30-40 seconds, the extra time required for cylindrical display was shortened to 15-20 seconds, and a luminal cast display was added to the on-line menu.

Adult

Angiotensin-converting enzyme inhibitors in patients with bronchial responsiveness and asthma.

Twenty-one subjects with known bronchial hyperreactivity were prospectively randomized in double-blind fashion to receive one of two angiotensin-converting enzyme inhibitors (ACE-I), enalapril or spirapril, for three weeks. Spirometry and methacholine provocation were performed prior to, during, and following ACE-I usage. Three of 21 subjects developed a nonproductive cough. However, only one subject wheezed slightly. Spirometry and bronchial reactivity (PD20) were unchanged throughout the study.

Adolescent

Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor.

The purpose of this study was to evaluate the effects of exogenous recombinant basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of 34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of saline (group A), 1 microgram bFGF (group B), or 3 micrograms bFGF (group C), daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis, and collateral growth were assessed by angiography, transcutaneous oximetry (TcPO2), quantitative spectrophotometric assay of triphenyltetrazolium chloride reduction in muscle, capillary density (capillaries per square millimeter), and capillary per muscle fiber ratio. There were no significant differences in baseline TcPO2 among the three groups for both thigh and calf measurements. Angiography revealed extensive perfusion of the left hindlimb in all the assessed bFGF treated animals. Both thigh and calf TcPO2 values showed a significant increase in all groups over the 14 days ischemia was induced (p less than 0.0001), but the two treatment groups exhibited a much more rapid rise in TcPO2 than the control group (p less than 0.0001). The capillaries per square millimeter and capillaries per muscle fiber ratios were significantly increased in all posttreatment measurements for all animals that received bFGF. The treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle viability compared with controls based on triphenyltetrazolium chloride reduction. Whereas there was evidence of muscle infarction in both the thighs of groups A and B, there was none in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Case management services for children with special health care needs. A family-centered approach.

The Coordinating Center for Home and Community Care (CCHCC) has developed a comprehensive, multidisciplinary case management model that facilitates the discharge of technology-assisted children from hospital to home. Coordination of the variety of services necessary for optimal medical, educational, and psychosocial development of the child and family is provided with an emphasis on cost containment. The hallmark of this program is its ability to locate, coordinate, and monitor the quality, continuity, provision, and cost of services at home. The CCHCC model was designed to enable children who would otherwise remain hospitalized at a substantial cost to third party payers to move home, providing a humane choice for families while requiring less costly care for funders.

Child

Mice lacking MHC class II molecules.

We have produced mice that lack major histocompatibility complex class II antigens, permitting us to evaluate the role of these molecules in diverse aspects of T and B cell differentiation. The mutant mice show near-complete elimination of CD4+ T lymphocytes from the spleen and lymph nodes; the few remaining CD4-positive cells are preferentially localized to B cell follicles. Surprisingly, substantial numbers of CD4 single-positive cells reside in the thymus; however, these are not mature thymocytes as we currently recognize them. B lymphocytes occur in normal numbers and are capable of terminal differentiation to plasma cells. Nevertheless, several aberrations in the B cell compartment are demonstrable: a lack of germinal centers, fewer IgM+IgD+ cells in certain individuals, reduced production of serum IgG1, and complete inability to respond to T-dependent antigens. In short, the class II-negative mice have confirmed some old ideas about lymphocyte differentiation, but have provided some surprises.

Animals

Chicken major histocompatibility complex-encoded B-G antigens are found on many cell types that are important for the immune system.

B-G antigens are a polymorphic multigene family of cell surface molecules encoded by the chicken major histocompatibility complex (MHC). They have previously been described only on cells of the erythroid lineage. By using flow cytometry, section staining, and immunoprecipitation with monoclonal antibodies and rabbit antisera to B-G molecules and by using Northern blots with B-G cDNA clones, we demonstrate here that B-G molecules and RNA are present in many other cell types: thrombocytes, peripheral B and T lymphocytes, bursal B cells and thymocytes, and stromal cells in the bursa, thymus, and caecal tonsil of the intestine. The reactions also identify at least one polymorphic B-G determinant encoded by the B-F/B-L region of the chicken MHC. The serology and tissue distribution of B-G molecules are as complex as those of mammalian MHC class I and class II molecules. These facts, taken with certain functional data, lead us to suggest that B-G molecules have an important role in the selection of B cells in the chicken bursa.

Animals

The "adjuvant effect" of the polymorphic B-G antigens of the chicken major histocompatibility complex analyzed using purified molecules incorporated in liposomes.

The polymorphic B-G region of the chicken major histocompatibility complex has previously been shown to mediate an "adjuvant effect" on the humoral response to other erythrocyte alloantigens. We demonstrate here that B-G molecules purified with monoclonal antibodies exert this adjuvant effect on the production of alloantibodies to chicken class I (B-F) molecules, when the two are in the same liposome. The adjuvant effect may in part be mediated by antibodies, since the antibody response to B-G molecules occurs much faster than the response to B-F molecules, and conditions in which antibodies to B-G are present increase the speed of the response to B-F molecules. We also found that the presence of B-G molecules in separate liposomes results in a lack of response to B-F molecules. In the light of this and other data, we consider the possible roles for the polymorphic B-G molecules, particularly for the generation of B cell diversity, in the immune systems of birds and other animals.

Adjuvants, Immunologic

Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells.

T cell receptor (TCR) beta genes are rearranged prior to TCR alpha genes. A productively rearranged TCR beta gene suppresses further V beta gene rearrangement. Here we show that in beta TCR transgenic mice the TCR beta-chain can be expressed on the surface of immature CD4-8- thymocytes, but not on mature T cells, in the absence of any other known TCR chain and proteins of the CD3 complex. Analysis by NEPHGE and SDS-PAGE showed that at least some beta TCR exists on the surface as a large disulfide-linked complex with unknown acidic molecules. The introduction of the beta TCR gene into scid mice resulted in the expression of the beta TCR on the cell surface of thymocytes and induced the expression of CD4 and CD8 co-receptors as well as transcription of the alpha TCR locus.

Animals

Outcome of home care for technology-dependent children: success of an independent, community-based case management model.

Case management is important for successful home care of technology-dependent, respiratory-disabled children. Traditionally, the medical model of hospital-based home care and case management has been used for these children. The outcome may be different from when using independent, community-based home care and case management. We evaluated the results of 28 technology-dependent children [23 receiving mechanical ventilation and 5 receiving continuous positive airway pressure (CPAP)] from 8 hospitals, who utilized an independent, community-based, case management group to coordinate home care. After 26.3 +/- 20.6 months of follow-up, 13 children (46%) remained technology-dependent, 10 (36%) were technology-independent, and 5 (18%), all with neurologic dysfunction, had died. Only one death was caused by a complication of technology. All children with congenital anomalies (n = 4), primary pulmonary disease (n = 8), and neuromuscular disease (n = 4) survived, and 9 (56%) were weaned from technological support. Children with chronic respiratory failure secondary to central neurologic dysfunction (n = 12) did poorly: 5 died, 6 remained technology-dependent, and only 1 became independent of technology. Children with neuromuscular diseases tended to use less home care nursing at a lower home care cost. Parent satisfaction was high among those who responded (82%), indicating that the child, siblings, and family were better off with the child at home. These outcomes suggest that community-based home care and case management is a reasonable alternative to the hospital-based model.

Abnormalities, Multiple

Use of high density cultures of Escherichia coli for high level production of recombinant Pseudomonas aeruginosa exotoxin A.

An efficient fermentation method for the production of two modified recombinant Pseudomonas aeruginosa exotoxin As cloned in Escherichia coli BL21(lambda DE3) was developed. Cell densities of 16-30 g dry weight/1 were found to be most suitable for the induction of protein synthesis, which was under the isopropyl beta-D-thiogalactopyranoside (IPTG)-inducible T7 expression system. A concentration of 0.6 mM IPTG and induction time of 90 min were found to give the best results for production of the modified toxins. Using this procedure, gram amounts of the proteins were obtained in a 3-1 bench-top fermentor. The high density growth of the bacteria did not impair the integrity of the proteins and did not interfere with the purification procedure.

ADP Ribose Transferases