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Biomedical subjects

M A Fishman

Publications and source records attributed to M A Fishman.

At least 19 recordsLinked to original sources
PubMed1995

Lymphocyte memory and affinity selection.

The persistence of antigen-specific immune memory appears to require the presence of antigen--suggesting that memory may be due to restimulation of "memory" lymphocytes by persisting antigen. Persistence of antigen, in a form capable of stimulating B cell proliferation, on long-lived, follicular dendritic cells of lymphoid tissue is well documented. Existence of an analogous mechanism for T cell memory maintenance is controversial but can not be ruled out. Here we examine the consequences of immune memory maintenance by antigen-specific lymphocyte restimulation, and estimate the duration of memory as a function of model parameters. We show that the competition for restimulation among memory cell populations results in the selection of the clone having the highest overall affinity for the retained antigen. Thus affinity selection, an important attribute of immunity, is a constitutive property of memory maintenance by antigen-specific restimulation. In the case of B cells, affinity selection is predicted to continue to increase antibody affinity even after somatic mutation stops, and thus may be an important component of affinity maturation. Finally, we discuss several other hypotheses proposed to explain immune memory, including T cell stimulation by cross-reactive antigens.

Animals↗
PubMed1994

Th1/Th2 cross regulation.

We present and analyze a model for the cross-regulation of the Th1 and Th2 helper cell subsets during an immune response by the regulatory cytokines interferon-gamma (IFN)-gamma) and interleukin-10 (IL-10). IFN-gamma, secreted by Th1 cells, can inhibit the proliferation of Th2 cells. Interleukin-10, secreted by Th2 cells, inhibits cytokine production by Th1 cells. Based on these properties, the model shows that responses are expected to be dominated by either Th1 cells or Th2 cells but not both. Which type dominates is shown to depend principally on the relative efficiencies of activation of the responding Th1 and Th2 cells. However, our model, as well as numerous experiments, show that perturbations of the system allow one to switch from a Th2 to a Th1 response, or vice versa. Our model can account for observed outcomes of parasitic infection and may also contribute to our understanding of immune responses to HIV infection as well as to tolerance to self components. It also predicts that in certain parameter ranges vaccination with low doses of live parasites can provide protection against subsequent encounters with high doses that normally induce disease. Experiments by Bretscher et al. (1992, Science 257, 539) on Leishmania major infection are consistent with this prediction. A similar strategy may also be relevant for the design of an AIDS vaccine. Lastly, our results indicate that Th1/Th2 cross-regulation is capable of generating a "sneaking through" phenomenon, and hence it may play a role in tumor immunity.

Animals↗
PubMed1994

Neurological complications from fat emulsion therapy.

Fat emulsion therapy is convenient for parenterally administering calories and essential fats. We report 2 children with neurological complications of fat emulsion therapy that arose before any systemic findings. The complications included focal and generalized seizures, weakness, and altered mental status. Biopsy and autopsy findings included cerebral endothelial and intravascular lipid deposition. Early recognition of fat emulsion therapy complications is essential as the neurological complications are potentially reversible with alteration of the parenteral diet.

Bone Marrow Transplantation↗
PubMed1994

Multicore myopathy, microcephaly, aganglionosis, and short stature.

Multicore myopathy, classified with the benign congenital myopathies, is manifest clinically as proximal muscle weakness, hypotonia, and delayed motor development. We report an unusual case of multicore myopathy with an expanded clinical syndrome involving the central nervous system, as well as additional congenital malformations. Clinical manifestations included microcephaly, mental retardation, spasticity with hyperreflexia, cerebellar dysfunction, short stature, Hirschsprung's disease, pharyngeal web, and facial dysmorphism.

Abnormalities, Multiple↗
PubMed1993

Modeling T cell-antigen presenting cell interactions.

We present and analyze a model for the interaction of naive T cells with antigen presenting cells (APCs) that results in T-cell activation. We use this model to examine delayed type hypersensitivity (DTH) reactions. We show that responses can be of two types; either the antigen is completely eliminated or the immune system fails to eliminate the antigen and chronic infection results. Both outcomes are characteristic of diseases in which delayed type hypersensitivity is the primary defense mechanism. We compare the effectiveness of two types of APCs macrophages and dendritic cells, in the generation of DTH responses. We conclude that dendritic cells are more suited to the task of stimulating naive T cells than are macrophages, as has recently been argued by Steinman and coworkers.

Antigen-Presenting Cells↗
PubMed1993

Hodgkin's disease associated with central pontine myelinolysis.

We describe a 12-year-old black male who presented with cervical lymphadenopathy, hepatosplenomegaly of 3 months duration, and ataxia and incoordination of recent onset. Hodgkin's disease, stage IVB, was diagnosed. An MRI of the head demonstrated a nonenhancing, well-defined pontine lesion. The pontine lesion and the associated neurologic symptoms were consistent with central pontine myelinolysis. Treatment of Hodgkin's disease resulted in complete remission and complete disappearance of the pontine abnormality.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Barbiturates and hyperventilation during intracranial hypertension.

OBJECTIVE: The purpose of this study was to determine the effect of hyperventilation alone and hyperventilation plus barbiturate therapy on intracranial pressure, global and regional cerebral blood flow rates, cerebrovascular resistance, and cerebral perfusion pressure in adult dogs with and without intracranial hypertension induced by epidural balloon. DESIGN: Prospective, randomized, controlled study. SETTING: An animal laboratory of a university hospital. Four sequential global and regional cerebral blood flow determinations were made in each animal during monitoring of heart rate and systemic arterial pressure, during respiratory control and arterial blood gas monitoring, intracranial pressure monitoring, and with or without inflation of an epidural balloon catheter. SUBJECTS: Acute mongrel dogs obtained from the Baylor Center for Comparative Medicine. Five groups of animals were studied. In group 1, the response to hyperventilation was assessed in dogs without increased intracranial pressure. In group 2, the response to hyperventilation was assessed in animals with acute intracranial hypertension. In group 3, the response to hyperventilation plus barbiturate therapy was assessed in dogs without increased intracranial pressure. In group 4, the response to hyperventilation plus barbiturate therapy was assessed in dogs with acute increased intracranial pressure. In group 5, a group of dogs with increased intracranial pressure was treated with neither hyperventilation nor barbiturates. INTERVENTIONS: Hyperventilation, hyperventilation plus barbiturate therapy, or no interventions were studied in these experimental paradigms. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were changes in intracranial pressure and/or changes in regional or total cerebral blood flow. A significant decrease in intracranial pressure and cerebral blood flow rate was produced by hyperventilation alone in groups with intracranial hypertension. Combined hyperventilation and barbiturate therapy resulted in a significant further decrease in cerebral blood flow rate in animals with normal and increased intracranial pressure, but no greater decrease in intracranial pressure was seen compared with treatment with hyperventilation alone. Cerebral perfusion pressures remained normal despite significant decreases in cerebral blood flow rates. CONCLUSIONS: These studies suggest that barbiturate administration in this model of intracranial hypertension was no more effective in reducing increased intracranial pressure than hyperventilation alone.

Acute Disease↗
PubMed1993

Strokes in children due to vertebral artery trauma.

Strokes due to vertebral artery lesions are rare in children. We describe three new patients and compare them with the 16 other patients described in the literature. All of these patients are boys. Traumatic vertebral artery lesion at C1-2 level was the most common cause of stroke, and the prognosis for neurologic recovery was good. We suggest that vertebral artery disease be considered in boys with posterior circulation ischemia.

Cerebral Angiography↗
PubMed1992

Brain biopsy in herpes simplex encephalitis.

Routine brain biopsy is often recommended in all patients suspected of having herpes simplex encephalitis (HSE). This approach is based upon the lack of ability to make the diagnosis of HSE on clinical grounds, the need to exclude other diseases for which there is specific therapy, and to stop empiric therapies. Acyclovir is a relatively safe, effective antiviral agent with little toxicity as currently used to treat HSE. Thus this is not a problem. Careful review of alternate diagnoses established at brain biopsy reveals few for which biopsy is the only and best way of making the diagnosis. Thus empiric therapy with acyclovir should be considered in some children in whom all appropriate diagnostic techniques fail to establish specifically treatable diseases. Early detection of HSV antigen in CSF may provide a non-invasive means of early diagnosis in the future.

Acyclovir↗
PubMed1988

Update on bacterial meningitis.

Recently, advances in identifying the etiologic agent, improving antibiotic therapy, and understanding the pathogenesis of complications of bacterial meningitis have been made. The acute and long-term sequelae and their courses have been documented. Acridine orange staining of the cerebrospinal fluid may identify bacteria in children with partially treated meningitis when gram-staining is not helpful. Monoclonal antibodies for meningococcus group B antigen have been developed and may prove useful for testing cerebrospinal fluid. Several newer cephalosporins have been shown to have excellent in vitro activity against the bacteria commonly associated with meningitis. They are indicated in the treatment of infants between 4 and 8 weeks of age, children in septic shock, children with liver disease, and children with infection with gram-negative enteric agents or bacteria resistant to ampicillin and chloramphenicol. Vasculitis and cerebral infarction may result in some of the complications, such as seizures and hemiparesis, noted in children, and their consequences can be documented by various neuroimaging procedures. The prognosis for ataxia is good, while that for sensorineural deafness is poor. The majority of children will have neither intellectual deficits nor difficulty with academic achievement. An effective vaccine against Haemophilus influenzae type b has been developed and is recommended for children between 18 and 60 months of age.

Adolescent↗
PubMed1988

Basal ganglia calcifications in a case of biotinidase deficiency.

Biotinidase deficiency leads to a biotin-deficient state, with cardinal symptoms of ataxia, alopecia, and skin rash presenting in infancy. Previous reports of head CTs in patients with biotinidase deficiency did not note basal ganglia calcifications. We report the first case of biotinidase deficiency with basal ganglia calcifications. There were no symptoms referable to basal ganglia dysfunction.

Amidohydrolases↗
PubMed1987

Encephalocraniocutaneous lipomatosis.

Encephalocraniocutaneous lipomatosis is a distinct clinical syndrome characterized by unilateral cerebral malformations and ipsilateral scalp, face, and eye lesions. The cutaneous lesions are confined to the head. The central nervous system lesions consist in part of cerebral hemiatrophy, porencephaly, and defective opercularization of the insula. The intracranial lesions and clinical symptomatology are progressive, and appear, in part, to have a vascular pathogenesis. This suggests that a primary defect in the formation of tissues derived from embryonic mesenchyme may be responsible for the syndrome and that tissues derived from ectoderm may be secondarily affected.

Adolescent↗
PubMed1986

Megalencephaly due to impaired cerebral venous return in a Sturge-Weber variant syndrome.

An infant with a Sturge-Weber variant syndrome developed progressive megalencephaly and eventual hydrocephalus, which required shunting. Cerebral angiography revealed absence of the deep cerebral venous system and the development of abnormal drainage channels via the periorbital veins. It is postulated that the abnormal enlargement of the brain was due to the impaired venous return. Resistance of the brain to continued expansion may have caused an increase in hydrostatic pressure and the development of hydrocephalus.

Angiomatosis↗