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Biomedical subjects

M J Goldman

Publications and source records attributed to M J Goldman.

At least 19 recordsLinked to original sources
PubMed1997

Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis.

A human bronchial xenograft model was used to characterize the molecular basis for the previously described defect in bacterial killing that is present in the cystic fibrosis (CF) lung. Airway surface fluid from CF grafts contained abnormally high NaCl and failed to kill bacteria, defects that were corrected with adenoviral vectors. A full-length clone for the only known human beta-defensin (i.e., hBD-1) was isolated. This gene is expressed throughout the respiratory epithelia of non-CF and CF lungs, and its protein product shows salt-dependent antimicrobial activity to P. aeruginosa. Antisense oligonucleotides to hBD-1 ablated the antimicrobial activity in airway surface fluid from non-CF grafts. These data suggest that hBD-1 plays an important role in innate immunity that is compromised in CF by its salt-dependent inactivation.

Amino Acid Sequence↗
PubMed1995

Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect.

We have developed a model of gene therapy for cystic fibrosis (CF) lung disease, based on growth of human CF bronchial xenografts in nu/nu mice. We now report an evaluation of the primary abnormalities in CF lung epithelia--defective Cl secretion and Na hyperabsorption--in xenografts following adenovirus-mediated gene transfer. In vivo infection of CF xenografts with a cystic fibrosis transmembrane regulator (CFTR) recombinant adenovirus, at a multiplicity of infection equal to 100, was sufficient to reconstitute near normal levels of cAMP-stimulated Cl transport, despite transducing only 5% of cells in the pseudostratified epithelium. Correction in sodium hyperabsorption was partial and variable. These experiments define aspects of adenovirus-mediated gene therapy relevant to CF protocols based on intrapulmonary genetic reconstitution.

Absorption↗
PubMed1995

Transfer of the CFTR gene to the lung of nonhuman primates with E1-deleted, E2a-defective recombinant adenoviruses: a preclinical toxicology study.

This paper describes a preclinical toxicology study designed to investigate the biological efficacy and safety profile of second-generation adenovirus for CFTR gene transfer into the baboon lung. This second-generation virus is deleted of E1 and contains a temperature-sensitive mutation in the E2a gene, which encodes a defective DNA-binding protein. Two distinct projects were undertaken. Group A animals received a first-generation adenovirus (i.e., deleted of E1) in an upper lobe at the time a second-generation virus was instilled into the contralateral upper lobe. The goal of study A was to compare the biology of each construct directly and to determine if an immune response to the first-generation virus affected the performance of the second-generation virus. Group B animals received a lacZ second-generation virus in an upper lobe at the same time the CFTR second-generation virus was instilled in the other upper lobe. Necropsies were performed 4 or 21 days after gene transfer and tissues were evaluated for recombinant gene expression and histopathology. Using a second-generation adenovirus, recombinant gene stability was prolonged and associated with a diminished level of perivascular inflammation as compared to first-generation vectors. Markedly diminished levels of hexon protein were present in tissues infected with second-generation as compared to first-generation virus. No evidence of viral shedding was evident. Furthermore, coadministration of first- and second-generation adenovirus did not affect the stability of transgene expression from the second-generation virus. These data suggest that second-generation adenoviral vectors provide an improved gene delivery vehicle, and thus may be useful in gene therapy for cystic fibrosis.

Adenoviridae↗
PubMed1995

Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway.

Recombinant adenoviruses are being evaluated for gene therapy of cystic fibrosis lung disease with the goal of reconstituting the expression of the cystic fibrosis transmembrane conductance regulator in pulmonary epithelia by direct administration of the virus into the airway. The therapeutic potential of recombinant adenoviruses is limited in part by the relative inefficiency by which gene transfer occurs. This study uses a human bronchial xenograft model to study adenovirus infection in the human airway in an attempt to define the molecular events that limit gene transfer. Our studies of the human airway confirm previous observations of cell lines that have indicated a two-step process for adenovirus entry, which begins with the binding of the virus to the cell through the fiber protein and continues with internalization via interactions among cellular integrins and an RGD motif (Arg-Gly-Asp) in the penton base. Furthermore, the level of maturity of the epithelia in xenografts has a major impact on gene transfer. Undifferentiated epithelia express high levels of alpha v beta 5 integrins and are easily infected with recombinant adenoviruses; gene transfer is completely inhibited with excess fiber and partially inhibited with RGD peptide and alpha v beta 5 integrin antibody. Pseudostratified epithelia do not express alpha v beta 5 integrin in differentiated columnar cells and are relatively resistant to adenovirus-mediated gene transfer; what little gene transfer occurs is inhibited by fiber but not by RGD peptide or alpha v beta 5 integrin antibody. These studies suggest that the expression of integrins in human airway epithelia limits the efficiency of gene transfer with recombinant adenoviruses. However, low-level gene transfer can occur in fully mature epithelia through alpha v beta 5 integrin-independent pathways.

Adenoviridae↗
PubMed1994

Mucogingival orthodontic and periodontal problems.

The absence of keratinized gingiva alone is not an indication for a periodontal surgical procedure. However, if recession increases during orthodontic treatment, then a gingival graft may be indicated. Orthodontic therapy and removal of a mandibular incisor where excessive gingival recession is present may be the indicated treatment.

Adolescent↗
PubMed1994

The misperceived duty to report patients' past crimes.

A questionnaire survey revealed that a number of mental health professionals believed that they had a duty to report a hypothetical patient's past criminal act. The authors examine the legal context of this misperceived reporting duty and discuss its implications for training and practice.

Adult↗
PubMed1992

On kleptomania.

Explore the source record for details and available documents.

Disruptive, Impulse Control, and Conduct Disorders↗
PubMed1992

The dissolution of the dyad in psychiatry: implications for the understanding of patient-therapist sexual misconduct.

Psychiatry has undergone multiple changes in this century. Some twenty years ago, Kubie describe a move away from patients, particularly in those practitioners involved in academic psychiatry. His concern was warranted; such a trend appears to have involved much of psychiatry. There has been a markedly decreased emphasis in viewing the operative unit of psychiatric inquiry as a dyad of the physician and patient, in which the parties inescapably influence each other. Newer treatments tend to employ the physician as a more independent entity that applies necessary treatment to the patient. Concomitantly, we have seen a trend toward a diminishing focus on sexuality as a primary motivating force in all areas of human endeavor. Freud proposed that libidinal impulses dominated much of our behavior; later psychoanalytic theorists and founders of other modalities of treatment have focused on other sources of motivation. Within the context of a psychiatry less focused on the physician and patient in a dyadic sense, and less focused on sexuality as a universal source of motivation, we have witnessed a marked increase in interest in the sexual misconduct of psychiatrists. Comprehension of this disturbing issue in the service of prevention rests upon reversing these trends. We must attend to the dyad as a bipersonal field serving as the arena for misconduct. We must also parallel our strident disapproval of misconduct with an objective exploration of the dynamics of both parties and the human commonality of sexual feelings. This special section represents such an exploratory effort.

Ethics, Professional↗
PubMed1992

Bone regeneration around a failing implant using guided tissue regeneration. A case report.

An implant was determined to be clinically and radiographically failing. The implant was treated as if it were a natural tooth with periodontal disease. The defect around the implant was degranulated and a polytetrafluoroethylene periodontal membrane placed over the implant to cover the defect. The membrane was removed 6 weeks later. A 5-month re-entry found new bone around the implant and the implant could then be used as a prosthetic abutment. Further case studies may prove this to be a predictable procedure to save failing implants.

Bone Regeneration↗
PubMed1991

Kleptomania: making sense of the nonsensical.

OBJECTIVE: Kleptomania, or the irresistible impulse to steal unneeded objects, is a poorly understood disorder. The objectives of this paper are to critically review and integrate existing data and to make suggestions for further research. DATA COLLECTION: Information was gathered by reviewing the English-language literature on kleptomania. Cases were chosen for review that approximated the diagnosis as defined in DSM-III-R. These cases were analyzed in terms of their relationship to previous theories about the disorder, and larger relevant studies were examined. Using the data organized into a table, the author explores areas of convergence and disagreement and discusses the methodological difficulties of the different studies. FINDINGS: Kleptomania is more common than previously thought. The "typical" individual with kleptomania is a 35-year-old woman who began to steal when she was 20 years old. Her thefts bring both relief and guilt. She probably has not sought treatment on her own but suffers from a necessary, pervasive, repetitive, and self-destructive act. She may have a history of sexual dysfunction or sexual preoccupation and may be unhappily married to an emotionally unsupportive husband. She has been labile and dysphoric for many years and may have a personality disorder. She has probably had a tumultuous, stressful childhood and may dissociate. CONCLUSIONS: The author proposes a biopsychosocial model of the etiology of kleptomania based on data from the literature. This model emphasizes possible childhood abuse as a precipitating factor in later development of kleptomania. More complete research is needed in the study of kleptomania.

Adolescent↗
PubMed1990

An objective appraisal of the role of computed tomographic (CT) guided drainage of intra-abdominal abscesses.

Computed tomographic (CT) guided drainage is an important tool in the treatment of intra-abdominal abscess. Its most important role is in the treatment of small, unilocular, well-placed abscesses. Success rates in our experience diminish considerably in abscesses involving necrotic tumors or those infected with yeast. As is frequently characteristic of new technologic procedures, the initial evaluation of the success rate of the procedure is overly optimistic. The procedure carries a considerable complication rate (13%) and mortality rate (15%). Most importantly, success is usually evident early; within the first 24 to 48 hours. After this length of time, careful evaluation to consider further treatment should be contemplated.

Abdomen↗