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B A Brody

Publications and source records attributed to B A Brody.

At least 19 recordsLinked to original sources
PubMed1992

A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein.

The envelope glycoprotein precursor of retroviruses undergoes proteolytic cleavage in the Golgi complex to yield the mature surface and transmembrane (TM) glycoproteins of the virus. We report here that the TM glycoprotein of Mason-Pfizer monkey virus undergoes a second proteolytic processing event during a late maturation step that can follow virus release and Gag polyprotein cleavage. Cleavage results in the conversion of the cell-associated TM glycoprotein (gp22) to a virus-associated gp20. Processing continues after virus release and yields virions that contain predominantly gp20. A mutation within the active site of the Mason-Pfizer monkey virus aspartyl protease was shown to block both TM glycoprotein cleavage and the processing of the Gag polyprotein precursor. The role of the viral protease in cleavage of the TM glycoprotein localizes the cleavage site to the cytoplasmic domain of this protein. Surprisingly, point mutations within the matrix (MA) coding region of the gag gene can affect the extent to which gp22 is processed to gp20 and in one case [p10(MA)-A79V] results in greater than 90% inhibition of gp22 cleavage. The data provide genetic evidence of a specific interaction between the capsid proteins and the cytoplasmic domain of the TM glycoprotein of a retrovirus. This interaction is required for cytoplasmic domain cleavage to occur and may play a critical role in virus assembly and viral infectivity.

Amino Acid Sequence↗
PubMed1992

Mutations within the env gene of Mason-Pfizer monkey virus: effects on protein transport and SU-TM association.

By deletion mutagenesis analyses, we have examined the contribution of the immunosuppressive peptide (ISP) region within the transmembrane (TM) protein of Mason-Pfizer monkey virus to viral maturation and infectivity. Deletion of the entire region (mutant D105) results in the production of an Env precursor that is transport defective and therefore unable to be processed to mature glycoproteins. This mutation results in the release of noninfectious virions devoid of surface glycoproteins. A second deletion that removes the most highly conserved 11 amino acids of the ISP (mutant D33) does not affect the production, transport, or processing of the Env precursor yet produces virions that are noninfectious. The mutation was shown to cause the loss of interaction between the surface (SU) and TM proteins and result in the efficient shedding of gp70 into the culture medium. The released gp70 protein was biologically active and could still bind with high specificity to susceptible target cells. Since the ISP domain may represent an area of contact between SU and TM, it could provide an additional explanation for the amino acid sequence homology observed within this region of a variety of retroviruses.

Amino Acid Sequence↗
PubMed1992

Protection of macaques against infection with simian type D retrovirus (SRV-1) by immunization with recombinant vaccinia virus expressing the envelope glycoproteins of either SRV-1 or Mason-Pfizer monkey virus (SRV-3).

Rhesus macaques were immunized with live vaccinia virus recombinants expressing the envelope glycoproteins (gp70 and gp22) of simian type D retrovirus (SRV), serotype 1 or 3. All of the animals immunized with either the SRV-1 env or the SRV-3 env vaccinia virus recombinant developed neutralizing antibodies against the homologous SRV. In addition, both groups developed cross-reactive antibodies and were protected against an intravenous live-virus challenge with SRV-1. The four control animals immunized with a vaccinia virus recombinant expressing the G protein of respiratory syncytial virus were not protected against the same SRV-1 challenge. Although SRV-1 and SRV-3 immune sera showed cross-neutralization, they failed to neutralize a separate, more distantly related serotype, SRV-2, in an in vitro assay. These findings are consistent with the known degree of serologic and genetic relatedness of these three SRV strains.

Animals↗
PubMed1992

MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review.

Findings on cranial magnetic resonance (MR) images were correlated with known histopathologic findings in 42 patients with tuberous sclerosis (TS), 17 of whom received gadopentetate dimeglumine, to extend the range of signs on MR images. Four neuroradiologists recorded the number, sites, configurations, and relative signal intensities of intracranial abnormalities. White matter lesions, found in 39 patients (93%), showed four distinct patterns: (a) straight or curvilinear bands extending radially from the ventricle through the cerebral mantle toward the cortex, (b) wedge-shaped lesions, (c) nonspecific conglomerate foci, and (d) cerebellar radial bands. It is concluded that cortical tubers, white matter lesions, subependymal nodules, and sub-ependymal giant cell astrocytomas (SGCAs) may be enhanced after administration of gadopenetetate dimeglumine. Enhancement of a TS lesion does not indicate neoplastic transformation into SGCA. Imaging surveillance every 12 months appears indicated during the peak ages (8-18 years) of occurrence of SGCA. The appearance of white matter lesions supports the theory that the cerebral lesions of TS may be caused by disordered migration of dysgenetic cells.

Adolescent↗
PubMed1992

The efficacy of image-guided stereotactic brain biopsy in neurologically symptomatic acquired immunodeficiency syndrome patients.

A prospective series of 50 neurologically symptomatic human immunodeficiency infected patients with intracranial lesions who underwent image-guided stereotactic brain biopsy is presented. Patients were diagnosed with primary central nervous system lymphoma (14 patients), progressive multifocal leukoencephalopathy (14 patients), toxoplasmosis (13 patients), human immunodeficiency virus encephalitis (3 patients), infarction (2 patients), and 1 patient each with metastatic adenocarcinoma, metastatic melanoma, cryptococcoma, and atypical mycobacterial infection. Two of the patients with toxoplasmosis had a second intracranial abnormality. Two biopsies resulted in either descriptive diagnosis only or were nondiagnostic; the definitive diagnostic efficacy of image-guided stereotactic biopsy was thus 96%. No deaths were incurred as a result of biopsy. Four intraoperative or postoperative hemorrhages occurred; in only 1 patient was there a residual neurological deficit related to the surgery. Image-guided stereotactic biopsy may thus be considered both safe and effective in this patient population.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Use of the Natural Death Act in pediatric patients.

OBJECTIVE: To review the use of Natural Death Act declarations (living will procedures) in pediatric patients. The implementation of such declarations for children is now possible in six states, including Texas, by specific statutory provisions. DESIGN: Retrospective study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Records of patients who had a Texas Natural Death Act declaration, either discussed and signed or discussed only, were studied. Patients who had another vehicle of limiting care (e.g., a do-not-resuscitate order) were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Reviewed characteristics included age, primary diagnosis, and concurrent complications. Also examined were who raised the issue of limiting care (parent or physician), the initial reaction of the other party, what support was withdrawn, what support was added, the final outcome (including the time from implementing limited care to death), and the description of witnesses. Discussions were held with parents of 17 patients, and 13 Natural Death Act declarations were actually implemented. In all but three instances, the patient died within 4 hrs from the time support was withdrawn. The main supports that were withdrawn were ventilators and catecholamines. In half of the cases, morphine sulfate was added for anticipated pain relief and sedation. All decisions were reached by close consultation between the family and the physicians, with the physicians raising the issue in 11 of the 17 cases and the family raising the issue in six cases. In 15 of the 17 patients, consultation with the Bioethics Committee was not necessary. The majority of difficulties involved resolving issues that beset patients with HIV infections, and finding appropriate witnesses as prescribed by the statute. CONCLUSIONS: We conclude that the Natural Death Act works well in situations involving dying children and their parents.

Adolescent↗
PubMed1991

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Birth Weight↗
PubMed1991

Spinal cord compression from a thoracic paraganglioma: case report.

A 34-year-old man with a 4-month history of midthoracic back pain sought treatment for a recent onset of lower extremity paresthesia and stiffness. A myelogram and computed tomographic myelogram disclosed an extradural block at the level of the 8th thoracic vertebral body with involvement of the pedicles, lamina, and spinous process. A posterior decompression of the spinal cord with subtotal resection of a highly vascular tumor was performed. The tumor was identified as a paraganglioma. In a second stage, the remainder of the tumor was embolized preoperatively, and gross total excision and sequential stabilization of the spine with a Luque rectangle and sublaminar wires were performed. The patient has been symptom free and without signs of a recurrence in the spine for over 13 months. A large abdominal paraganglioma was recently resected from its probable origin from the adventitia of the abdominal aorta.

Abdominal Neoplasms↗
PubMed1991

Physicians and rationing.

Current cost-containment pressures seem to be leading American health care into a world of rationing. Many people have urged that we resist rationing on the grounds that it would compromise the integrity of the patient-physician relation. I shall argue that rationing is in fact both inevitable and appropriate, but the world of rationing is one in which the role of the moral physician involves complex balancing of moral obligations.

Cost Control↗
PubMed1990

Quality of scholarship in bioethics.

This paper identifies four major forms of scholarship in bioethics: empirical research, the articulation of mid-level principles of bioethics, the relating of these principles to fundamental moral theories, and discussions of the bioethical implications of legal principles and health delivery policies. It develops a reflective equilibrium approach to the relation between these four forms of scholarship. It then presents, in light of this approach, criteria for quality research in each of these forms of scholarship in bioethics.

Bioethical Issues↗
PubMed1990

Fetal globoid cell leukodystrophy.

The early lesions of globoid cell leukodystrophy in a 110-g, 18-week-old fetus were characterized in relation to fetal myelination, and comparisons made to the animal models of this disease. Uninucleated and binucleated periodic acid-Schiff-positive cells were present in the spinal cord but not in ventral roots within regions at very early stages of myelination. These cells stained with the lectin Ricinus communis agglutinin, which preferentially binds to beta-D-galactosyl residues as found in stored metabolites of globoid cell leukodystrophy. Ultrastructural examination of the spinal cord revealed typical tubular spicular cytoplasmic inclusions in cells corresponding to the periodic acid-Schiff-positive cells. The degree and distribution of myelin tubules and myelination glia was similar to that in weight- and size-matched control fetuses. These results indicate that the first appearance of inclusion-bearing cells is closely associated with the onset of myelination in the central nervous system, apparently earlier in the stage of myelination than occurs in the central nervous system of the mouse model. Characteristic tubular inclusions are also present in renal epithelium in animal models but have not been seen in the human kidney. We have since identified noncharacteristic crystalline inclusions in the kidney of this human fetus.

Epithelium↗
PubMed1989

The President's Commission: the need to be more philosophical.

This paper argues, contrary to what has sometimes been claimed, that public commissions need to be more philosophical than they have been in analyzing crucial bioethical issues. It argues (a) that the failure of the President's Commission to develop and use even simple distinctions between life and personhood led to flaws in both its discussion of death and its discussion of persistent vegetative patients, and (b) that its treatment of access to health care fails to develop a coherent approach precisely because it is based on no serious philosophical reflections about justice in health care.

Advisory Committees↗
PubMed1989

The Baylor experience in teaching medical ethics.

This paper describes the activities of the Center for Ethics, Medicine, and Public Issues, a joint project of Baylor College of Medicine, the Institute of Religion of the Texas Medical Center, and Rice University. The center focuses on the clinical teaching of medical ethics, collaborative teaching and research involving ethicists and clinicians, and the training of future practitioners in the field. Problems as well as achievements in each of these areas are discussed.

Bioethical Issues↗
PubMed1989

Selective distribution of the 57 kDa neural intermediate filament protein in the rat CNS.

In order to determine the CNS distribution of the 57 kDa neural intermediate filament protein (NIFP), a specific antiserum was used in immunofluorescence studies on serial sections taken from each spinal cord level and at 300-microns intervals through the rat brain. The labeling pattern was recorded onto camera lucida tracings of adjacent sections stained with hematoxylin and eosin/luxol fast blue. Three major immunolocalization patterns were revealed. (1) Both large-caliber and fine-caliber axons of optic and all brain stem cranial nerves and their tracts except for the auditory portion of the VIIIth nerve. (2) An extensive array of fine-caliber fibers in the cerebellar white matter and brain stem with region-specific variation in pattern and density. Prominent among the regions with dense arrays of labeled processes were selective cerebellar afferent systems, particularly olivocerebellar fibers, visual afferents arising in the retina, and selective regions of reticular formation. In contrast to the brain stem, the telencephalon contained rare label. (3) Filamentous labeling of neuronal cytokarya in sensory ganglia and a small number of CNS nuclear groups, including all autonomic nuclei and the cholinergic pontine nuclei. On sections of selected CNS regions, distribution patterns of the 57 kDa NIFP were correlated to results obtained by in situ hybridization of a cDNA probe for the 57 kDa NIFP. The data suggest the possible existence of neuronal IF proteins specifically related to selective anatomic and/or neurotransmitter systems.

Animals↗
PubMed1988

Justice in the allocation of public resources to disabled citizens.

This paper examines several crucial questions concerning justice in the allocation of public resources to disabled citizens. It challenges the current failure to means-test certain programs, and it argues that fundamental choices about levels of funding and about priorities in nonentitlement programs cannot be justified without a better theory of social justice.

Persons with Disabilities↗
PubMed1987

Justice and competitive markets.

This essay challenges the view that the provision of health care must take place within a competitive-free system. The author argues that, presuming that there is a requirement to meet the demands of those who cannot pay for health care, a competitive market provides a good way to deal with injustices within the health care system. The author concludes that the demands for justice are best met when indigent individuals use some portion of the funds they receive from the government to purchase one of the many competing forms of health care. This scheme requires a competitive market in the delivery of health care.

Economic Competition↗