Biomedical subjects
Publications and source records attributed to J Kaufman.
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.
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.
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.
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)
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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.
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.
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.
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.
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.
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.
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.
Molecular variation among major histocompatibility complex (MHC) class I (B-F) proteins from B-homozygous chickens is apparently caused by C-terminal variation. Analysis of the total B-F protein pool revealed substantial heterogeneity with two or three molecular mass constituents, each being comprised by several isoelectric focusing variants. This heterogeneity could not be reduced by enzymatic deglycosylation. By contrast, proteolytic removal of a small (Mr 1000-4000) fragment from the alpha chain resulted in the generation of a Mr 36,000 fragment, common to all the molecular mass variants. Unlike the parent proteins, the Mr 36,000 fragment derived from isolated variants yielded identical, simple patterns in two-dimensional gel electrophoresis and identical finger prints in peptide mapping. This, together with N-terminal amino acid sequencing, as well as comparison of hydrophobicity properties of fragments obtained by gradual proteolytic digestion, indicated that the small peptide responsible for the major B-F heterogeneity was situated in the intracellular, C-terminal part.
Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital. To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations. Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L (2 mg/dL). These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital. One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions. Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified. Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL]) and mortality (7%) was lowest in the group with prerenal azotemia. In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause. The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%). Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient. Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure. Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
This study examined the prevalence of depressive disorders in a sample of 56 7- to 12-year-old maltreated children. Overall, 18% of the sample met the diagnostic criteria for major depression, and 25% met the criteria for dysthymia, with the majority of the children who met the criteria for major depression also meeting the criteria for dysthymia. Ratings of the different types of maltreatment children experienced, together with measures of the children's social supports, attributional style, and cortisol secretion were examined to determine which maltreated children were most likely to evidence a depressive disorder. A discriminant analysis conducted using a subset of these measures correctly classified 91% of the sample in terms of their diagnostic status.
Adjusted admission rates for respiratory distress (COPD, asthma, bronchitis, and pneumonia) varied up to 3.09-fold between the highest and lowest hospital market areas in 1986 for the state of Ohio. Reasons for the variability can be determined through small area analysis techniques with the help of area physicians. Substantial improvements in the availability, delivery, and cost of respiratory care would reasonably be anticipated as a result of such analysis and feedback.
A 26-year-old woman with common variable immunodeficiency syndrome (CVID) associated with frequent episodes of pneumonia underwent an open lung biopsy showing bronchiolitis obliterans organizing pneumonia (BOOP). Following corticosteroid therapy, there were no further episodes of pneumonia. In addition, there was roentgenographic and gas exchange improvement. This is the first case of BOOP in association with CVID. An immunologic basis of BOOP is postulated.