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Biomedical subjects

S Goodman

Publications and source records attributed to S Goodman.

At least 127 records · Page 7Linked to original sources
PubMed1993

Outer membrane protein YadA of enteropathogenic yersiniae mediates specific binding to cellular but not plasma fibronectin.

The binding of bacteria or bacterial products to host proteins of tissue extracellular matrix may be a mechanism of tissue adherence. We investigated interactions of the plasmid-encoded outer membrane protein YadA, which confers pathogenic functions on enteropathogenic yersiniae, with fibronectin. Attachment of YadA-positive and YadA-negative recombinant Yersinia enterocolitica strains to cartilage-derived human cellular fibronectin and human plasma fibronectin in the solid phase revealed that YadA mediates binding of yersiniae to cellular fibronectin in a saturable, concentration-dependent manner. The interaction could be inhibited by an anti-YadA-specific anti-serum. An anti-beta 1-integrin antibody and the synthetic peptide G-R-G-D-S-P, representing the binding site for alpha 5 beta 1-integrin on fibronectin, did not block attachment of YadA-positive yersiniae to cellular fibronectin, indicating a binding site for YadA on cellular fibronectin independent of the R-G-D-S-containing site. By contrast, YadA failed to mediate binding to plasma fibronectin immobilized on nitrocellulose or plastic surfaces. These observations provide evidence for the hypothesis that the binding region for YadA in cellular fibronectin is not present in plasma fibronectin. This study is the first report on differential binding of bacteria to splicing variants of fibronectin. Further experiments might answer the question whether binding of YadA to cellular fibronectin contributes to the pathogenesis of yersiniae, both to the initial adhesion of the bacteria to the matrices of the host and to the arthritogenic potential of enteropathogenic yersiniae.

Adhesins, Bacterial↗
PubMed1993

Cement particles inhibit bone growth into titanium chambers implanted in the rabbit.

Particles of bone cement have been shown previously to stimulate the resorption of bone. The purpose of this study was to determine whether particles of bone cement (BC) have an adverse effect on bone ingrowth. The bone harvest chamber was implanted bilaterally in the proximal tibial metaphysis of 6 mature rabbits. Both the fixed outer cylinder and the inner removable core of the chamber have a transverse 1 mm wide pore providing a continuous canal for tissue ingrowth. After an initial 6-week period for osseointegration of the outer cylinder, the contents of the inner core were harvested repeatedly at 3 weekly intervals. In the first series of rabbits, the carrier solution, 1% sodium hyaluronate (Healon) was implanted first. In subsequent implantations, Healon was mixed with small fabricated particles of BC (averaging 3.54 mm in diameter) to fill the channel of the core. The contralateral chamber was left empty and served as a control. In the second series of rabbits, implantation was carried out sequentially using the same material bilaterally. The sections from the control harvests, and those with Healon alone contained extensive trabecular bone arranged longitudinally in the canal, in a fibrovascular stroma. The sections containing BC particles were infiltrated by foamy, mononuclear and multinuclear histiocytic cells. Less trabecular bone was seen in the sections containing BC particles compared to the control sections or those containing Healon alone. Previous studies have shown that particles of bone cement stimulate bone resorption. In this study, BC particles have also been shown to diminish the formation of new bone.

Animals↗
PubMed1993

Factors influencing third party payer costs for allogeneic BMT.

To assess how payer costs for allogeneic BMT relate to patient characteristics and clinical complications, a retrospective cohort study of 402 persons undergoing allogeneic BMT between 1980 and 1987 at a university-based BMT center was designed to determine total inpatient payer costs, including hospital and physician costs, and number of days hospitalized during the first 180 days following BMT. The average total inpatient payer cost (in 1990 dollars) during the first 180 days following BMT was $208,410. Inflation-adjusted inpatient payer costs increased from $227,806 in 1980 to $308,545 in 1983, and then decreased to $156,163 by 1987. In multivariate analysis, inpatient payer costs were strongly associated with occurrence of CMV infection (increase of $53,517; p = 0.0001) or acute GVHD (increase of $46,500; p = 0.001), and significantly associated with malignant (versus non-malignant) disease (decrease of $36,633; p = 0.05), even after adjusting for length of survival and year of BMT. Inpatient payer costs were not related to patient age, sex or race. Despite recent reductions in inpatient payer costs for BMT, CMV infection and acute GVHD continue to be associated with tremendous costs to third party payers. Further reductions in the costs of BMT may require improved prevention of CMV infection and GVHD.

Adolescent↗
PubMed1993

Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction.

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.

Bone Marrow Transplantation↗
PubMed1992

Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.

Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.

Animals↗
PubMed1992

Effect of amplitude of micromotion on bone ingrowth into titanium chambers implanted in the rabbit tibia.

The micromotion chamber for implantation in the rabbit tibia consists of two titanium components that have a 1 mm contiguous pore for bone ingrowth. The fixed, outer cylinder of the chamber contains a movable inner core that can be manually rotated. The model is unique because specific, discrete, daily periods of motion of a predetermined amplitude and frequency can be delivered to the ingrowing tissue. In the present study, we compared the histological and scintigraphic results of bone ingrowth into chambers having a congruently shaped interface that was moved 20 cycles/d with an amplitude of either 0.5 or 0.75 mm. Histological sections from both amplitude groups contained extensive new woven and trabecular bone, embedded in a fibrovascular network. However, the chambers with a larger amplitude of motion yielded less bone ingrowth than those with a smaller amplitude. These studies suggest that short, discrete periods of motion can stimulate the formation of fibrous tissue rather than bone using the parameters chosen in this model.

Animals↗
PubMed1992

Purtscher's-like retinopathy in chronic renal failure.

PURPOSE: The authors describe the clinical findings of three young women with the previously unreported association of Purtscher's-like retinopathy and chronic renal failure. METHODS: The authors reviewed the clinical records of three women with chronic renal failure who had been seen at the Oregon Health Sciences University with acute, profound visual loss associated with a severe vaso-occlusive Purtscher's-like retinopathy. RESULTS: Two of the three patients previously had renal transplants, and both were experiencing allograft rejection. One of these two patients was undergoing hemodialysis. The retinopathy was bilateral in two patients, and unilateral in the third. Each of the 5 affected eyes had severe initial loss of vision to less than 20/400, and only one of these eyes had significant visual recovery. None of the patients had recent trauma, pancreatitis, autoimmune disease, or other condition known to be associated with Purtscher's-like retinopathy. CONCLUSION: A retinal vaso-occlusive disorder resembling Purtscher's retinopathy can occur in patients with chronic renal failure, even in the absence of trauma, pancreatitis, or known autoimmune disease. While the precipitating factor(s) remains unclear, it appears that the retinopathy in this setting may be more severe and associated with a poorer visual prognosis.

Adult↗
PubMed1992

Intermittent micromotion inhibits bone ingrowth. Titanium implants in rabbits.

We studied the effects of micromotion on bone ingrowth into a 1-mm canal through a titanium chamber implanted in the proximal tibia of rabbits. The implant surface became "osseointegrated," but an interior core was movable, allowing the central portion of the canal to be moved in relation to the ends. Thus, the ingrowing bone in the canal had to pass an area of ad latus motion. When implanted in rabbit tibiae, the canal became filled with ingrown cancellous bone. Bone ingrowth was inhibited by 20 cycles of 0.5-mm movement applied during a 30-second period once daily. With this regimen, the canal was usually filled with vascularized fibrous tissue and significantly less bone. The micromotion chamber may enable detailed studies of the effects of different motion variables on ingrowth of bone.

Alloys↗
PubMed1991

Identification of a major antigenic epitope on CNBr-fragment 11 of type II collagen recognized by murine autoreactive B cells.

Immunization of certain strains of mice with native type II collagen (CII) induces both development of arthritis and an antibody response to autologous CII. The autoantibody response in a high-responder strain, the DBA/1 mouse, has been described earlier, and a number of monoclonal antibodies have been characterized for arthritogenicity and autoreactive binding to cartilage in vivo and in vitro. Here we map the antigenic epitope of one of these arthritogenic monoclonal antibodies (CII-C1). It belongs to a group of antibodies recognizing the CNBr fragment alpha 1(II)-CB11 of CII. Using the enzyme-linked immunosorbent assay technique, we show that the antibody reacts only with native, triplehelical CII, but not with other collagens. The antibody is able to stain specifically the CB11 fragment by immunoblotting, suggesting some partial renaturation of the CNBr fragment into triple-helical structures after blotting. The binding site of CII-C1 on CB11 was further focused by rotary shadowing of antibody-labeled CII to a site 89 +/- 8 nm from the amino end of CII, corresponding to the middle of CB11. This location was confirmed by cleavage of CB11 with trypsin, separation of the tryptic peptides by high-performance liquid chromatography and dot-blot analysis of the antigenic peptides with the CII-C1 antibody. Sequencing of the single positive peptide located the antigenic epitope within the sequence GFAGQAGPAGATGAPGRP (residues 316-333). Assuming 0.29 nm per residue, this corresponds to a position within 92-96.5 nm from NH2 terminal end of CII. Apart from glycine residues, which are not exposed on the triple-helical structure, only two amino acid residues (F-x-y-Q) are conserved in CII from different species but are not found in the triple-helix of other collagens except type IV collagen. Therefore, this structure is likely to be of critical importance for the binding of the CII-C1 antibody. Of potential importance is that this structure is also found in certain other arthritogenic proteins such as 65-kDa mycobacterial protein, in CMV and EBV.

Amino Acid Sequence↗
PubMed1991

Expression of the cystic fibrosis gene in human development.

The specialised epithelia lining the respiratory tract, pancreatic ducts, male genital ducts and sweat gland ducts are defective in the severe inherited disease, cystic fibrosis (CF). We have looked at the expression of the CF gene in human fetal tissues to throw light on the development of function in specialised ductal epithelia and to determine the age of onset of the CF disease process. The CF gene is already seen to be transcribed in mid-trimester fetal lung, pancreas and male genital ducts. Hence, by this developmental stage, and before they are fully differentiated, these epithelia have the capability to perform important transport functions. Epithelial cell cultures derived from fetal pancreas and male genital ducts maintain expression of the CF gene in vitro and so form good models for analysing CF gene function and differentiation of these specialised epithelia.

Blotting, Northern↗
PubMed1991

Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx.

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

Adult↗
PubMed1990

Use of synthetic oligoribonucleotides to probe RNA-protein interactions in the MS2 translational operator complex.

Synthetic oligoribonucleotides have been used to probe the interaction of MS2 coat protein with the translational operator of the MS2 replicase gene. We have investigated the possible formation of a transient covalent bond between the single-stranded uridine residue, at position -5, and a cysteine side-chain on the coat protein, by the incorporation of a chemically modified residue (5-BrU) at this position. This chemically synthesised operator variant has a binding constant of between 10 and 50 times greater than that of the wild type and is therefore comparable with the tight binding variant having a cytidine substituted at the -5 position. Dissociation kinetics show that the complex with the 5-BrU operator is more stable than the -5C variant; a result which is consistent with the formation of a Michael adduct at the -5 position. In addition, a number of other chemical variants of the operator have been analysed. These include operators incorporating deoxyadenine residues at each of the important single-stranded adenine sites. Recently the Michael adduct proposal has been challenged on the basis of mutagenesis of the coat protein cysteine residues. These results are discussed in the light of our data in support of Michael adduct formation.

Base Composition↗
PubMed1990

CT appearances of relapse of lymphoma in the lung.

The patterns of pulmonary relapse were studied in 15 patients with Hodgkin's disease and one patient with Non-Hodgkin's lymphoma. All the patients with Hodgkin's disease had mediastinal lymphadenopathy at initial diagnosis. For those patients with no prior episodes of relapse the mean time to pulmonary involvement was 2 years 11 months compared to over 8 years for those who first relapsed elsewhere. Thirteen patients are still alive; five have been followed up for more than 2 years. Pulmonary involvement consisted of: 1. nodules, either central (12 patients) or peripheral (10 patients), often with connection to the pleura or mediastinum, and sometimes with cavitation; 2. consolidation with or without cavitation (four patients); 3. mediastinal extension into the lung parenchyma (three patients). In seven patients there was evidence of newly enlarged mediastinal nodes. Pleural effusions or masses were seen in six patients and pericardial involvement in one. The chest wall was involved in five. A combination of three or more of these signs were present in 11 patients. The pattern of involvement seen in the patient with Non-Hodgkin's lymphoma was indistinguishable from that seen in Hodgkin's disease. This study has demonstrated a variety of CT appearances useful in establishing or suggesting the diagnosis of pulmonary relapse. Enlarged mediastinal nodes were not a prerequisite but had been present in all patients at some stage in the course of the disease.

Adolescent↗
PubMed1990

Membrane protein band 3 alteration associated with neurologic disease and tissue-reactive antibodies.

Immunological analogues of band 3, the anion transporter, have been identified in all cells that have been studied, including both isolated neurons and neurons of the central nervous system. We studied band 3 structural/functional relationships in a family in which the proposita has a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis). Biochemical studies of erythrocytes from the proposita, her mother and brother revealed that maximal sulfate transport velocity (Vmax) and sodium transport were increased, glucose efflux was decreased. Ankyrin binding was normal. Immunologic studies revealed increased IgG binding to middle-aged cells of the proposita and her brother, binding of antibodies to aged band 3 to a distinct region of band 3 in erythrocyte membranes in immunoblots, and binding of choreoacanthocytosis sera IgG to erythroid and brain band 3 and synthetic peptides of band 3 in immunoblots. Antibodies to neural and, to a lesser extent, renal tissue were observed in choreoacanthocytosis sera. These antibodies appear to have a band 3 specificity. Monoclonal antibodies to 150 residues of the carboxyl terminus of band 3 stained two band 3 fragments in immunoblots of chymotrypsin-digested membranes that are not present in control cells. This suggests that band 3 is altered in this autosomal recessive neurologic disorder. In addition, these monoclonal antibodies stained five band 3 breakdown products in membranes of untreated red cells in both control and choreoacanthocytosis cells. The possibility that a disturbance of some function of band 3 may contribute to the neurologic abnormalities in affected individuals is intriguing. This is the first evidence for abnormalities of membrane transport in the neurologic disorder known as choreoacanthocytosis.

Acanthocytes↗