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S A Rubin

Publications and source records attributed to S A Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of the neurovirulence of a vaccine and a wild-type mumps virus strain in the developing rat brain.

Prior to the adoption of widespread vaccination programs, mumps virus was the leading cause of virus-induced central nervous system (CNS) disease. Mumps virus-associated CNS complications in vaccinees continue to be reported; outside the United States, some of these complications have been attributed to vaccination with insufficiently attenuated neurovirulent vaccine strains. The development of potentially neurovirulent, live, attenuated mumps virus vaccines stems largely from the lack of an animal model that can reliably predict the neurovirulence of mumps virus vaccine candidates in humans. The lack of an effective safety test with which to measure mumps virus neurovirulence has also hindered analysis of the neuropathogenesis of mumps virus infection and the identification of molecular determinants of neurovirulence. In this report we show, for the first time, that mumps virus infection of the neonatal rat leads to developmental abnormalities in the cerebellum due to cerebellar granule cell migration defects. The incidence of the cerebellar abnormalities and other neuropathological and clinical outcomes of mumps virus infection of the neonatal rat brain demonstrated the ability of this model to distinguish neurovirulent (Kilham) from nonneurovirulent (Jeryl Lynn) mumps virus strains. Thus, this neonatal rat model may prove useful in evaluating the neurovirulence potential of new live, attenuated vaccine strains and may also be of value in elucidating the molecular basis of mumps virus neurovirulence.

Animals↗
PubMed1998

Clinical, serologic, and histopathologic characterization of experimental Borna disease in ponies.

Borna disease was originally described as an equine neurologic syndrome over 200 years ago, although the infectious etiology of the disorder was unproven until the early 20th century. Borna disease virus (BDV) was finally isolated from horses dying of the disorder, and that virus has been used to experimentally reproduce Borna disease in several species of laboratory animals. However, BDV has never been inoculated back into horses to experimentally and etiologically confirm the classic clinical, pathologic, and serologic characteristics of the disease in that species. Three ponies were intracerebrally inoculated with different amounts of BDV and were evaluated clinically, serologically, and neurohistopathologically. All 3 animals developed the clinical signs characteristically described for naturally occurring Borna disease, including ataxia, torticollis, postural unawareness, rhythmic repetitive motor activities, muscle fasciculation, and cutaneous hyperesthesia and hypoesthesia over several body surfaces. Two ponies died after rapid onset of these signs 28-30 days postinoculation. The third animal made a nearly complete clinical recovery. Seroconversion occurred only after the onset of signs and to a marked degree only in the convalescent animal. Virus was recovered postmortem from 2 of the 3 ponies, and a BDV-specific nucleic acid sequence was detectable in all 3 animals using a reverse transcription-polymerase chain reaction procedure. Gross neural lesions were absent, but histopathologically there was generalized intense mononuclear perivascular cuffing, glial nodule formation, and astrocytosis in all 3 brains. Confirming a diagnosis of Borna disease is difficult and perhaps best accomplished using a combination of the clinical, serologic, and histopathologic indicators of this unusual disease supported by positive reverse transcription-polymerase chain reaction findings.

Animals↗
PubMed1997

Borna disease virus antibodies and the deficit syndrome of schizophrenia.

We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p < 0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia.

Adult↗
PubMed1997

Flow cytometric analysis of major histocompatibility complex (MHC) class II antigen expression on brain cells from Borna disease virus-infected rats without an intervening in vitro culture step.

Borna disease virus (BDV) infects astrocytes in the Lewis rat brain. BDV-infected astrocytes have been shown to express MHC class II in vitro but not in vivo. Using a sensitive fluorescence-activated cytometric technique, we now report the detection of MHC class II on freshly harvested S100-positive cells from BDV-infected rat brain, without an intervening in vitro culture step. These data support the hypothesis that astrocytes from BDV-infected rats express MHC class II on their surface and, thus, are potential participants in the encephalitic response to BDV infection.

Animals↗
PubMed1997

Molecular and cellular prospects for repair, augmentation, and replacement of the failing heart.

Molecular and cellular biology offer the promise of new approaches to the treatment of heart failure. This article discusses the basic science background, the current state of investigation, and the potential for therapeutic application of these new sciences. It also emphasizes the limitations and unknowns in this frontier. Three approaches are presented: First, increasing the number of myocytes in the heart, previously held to be untenable because postnatal cardiomyocytes do not divide, may be possible by regulating the cell cycle to reinduce cardiac growth. Also, nonmyocytes extant in the heart may be coaxed into differentiating into cardiomyocytes, or exogenous muscle cells may be grafted into the myocardium. Second, cardiac function may be augmented by molecular therapies that increase contractile protein function or regulate beta-adrenergic receptors or Ca++ channels. Third, improved prospects for transplantation of the failed heart may occur by genetic modification of a xenograft donor heart that reduces the chance of immune rejection by the human recipient. The formulation for the successful application of any of these therapies depends on not only the creativity of scientists but also the wisdom of physicians.

Animals↗
PubMed1997

Human intestinal folate transport: cloning, expression, and distribution of complementary RNA.

BACKGROUND & AIMS: Despite intensive investigations, very little is known about the molecular identity(ies) of the intestinal folate transport system(s), especially in humans. The aim of this study was to isolate a functional human intestinal folate carrier complementary DNA (cDNA) clone and determine the distribution of complementary RNA at the tissue and cellular levels. METHODS: Hybridization screening, modified Marathon cDNA amplification, expression in Xenopus oocytes, Northern analysis, and in situ hybridization were used. RESULTS: The hIFC-1 cDNA contains an open reading frame for 591 amino acids (relative molecular mass = 64,826, pI = 9.4, 12 transmembrane domains, three protein kinase C phosphorylation sites, and one N-glycosylation site) with 74% DNA and 66% amino acid sequence homologies with the mouse cDNA counterpart. Xenopus oocytes injected with hIFC-1 cRNA show induced folate uptake that was (1) saturable with substrate concentration (apparent Michaelis constant = 0.71 +/- 0.06 micromol/L; maximum velocity = 128 +/- 3 fmol x h(-1) x oocyte(-1)), (2) inhibited by methotrexate, folinic acid, and folic acid (Ki = 0.84 micromol/L, 0.71 micromol/L, and 10 micromol/L, respectively), and (3) sensitive to 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (Ki = 0.29 mmol/L). Northern analysis showed wide distribution of hIFC1-complementary messenger RNA species in various human tissues. In situ hybridization on sections of human jejunum showed preferential hIFC-1 expression in epithelial cells, especially in the upper half of the villi. CONCLUSIONS: These results represent the first molecular characterization of a human small intestinal folate carrier.

Amino Acid Sequence↗
PubMed1997

Pulmonary complications in children with hematologic malignancies: accuracy of diagnosis with chest radiography and CT.

PURPOSE: To determine the diagnostic accuracy of chest radiography and computed tomography (CT) in patients with complications during treatment for hematologic malignancies. MATERIALS AND METHODS: CT scans were obtained 1 week or less before bronchoscopic sampling or biopsy in 48 pediatric patients (age range, 8 months to 18 years at diagnosis) undergoing treatment for leukemia, lymphoma, or myeloproliferative disease. Radiographs were obtained less than 1 week before CT. Pulmonary complications comprised fungal (n = 11), viral (n = 4), and bacterial (n = 5) pneumonias; cryptogenic organizing pneumonia ([COP] n = 4); and pulmonary tumor (n = 4). Chest radiographs and CT scans were rated independently by three radiologists who were unaware of these diagnoses. RESULTS: Satisfactory diagnostic accuracy, defined by the area under the receiver operating characteristic (ROC) curve, was noted for fungal pneumonia (radiography, ROC area = 0.82; CT, ROC area = 0.78), COP (radiography, ROC area = 0.75; CT, ROC area = 0.75), and pulmonary tumor (radiography, ROC area = 0.73; CT, ROC area = 0.83). Generalizability was good for fungal pneumonia (radiography, generalizability coefficient [GC] = 0.84; CT, GC = 0.84) and COP (radiography, GC = 0.75; CT, GC = 0.99). There was no statistically significant difference in diagnostic accuracy between radiography and CT for any of the diagnoses. CONCLUSION: Radiography and CT have satisfactory accuracies for fungal pneumonia and COP. For these conditions, CT identified more true-positive cases than did radiography.

Adolescent↗
PubMed1996

Intestinal folate transport: identification of a cDNA involved in folate transport and the functional expression and distribution of its mRNA.

Although the mechanism of folate intestinal transport has been the subject of intensive studies, very little is known about the molecular identity of the transport system(s) involved. In this investigation, we screened a mouse intestinal cDNA library using as probe the cDNA clone of a reduced folate carrier (RFC1) of mouse leukemia L1210 cells, and identified a positive clone, IFC1(RFC1). The cloned cDNA consisted of 2274 base pairs with an open reading frame that encodes a putative polypeptide of 512 amino acids with a predicted molecular mass of 58,112 daltons and 12 putative transmembrane domains. The polypeptide appears to carry a net positive charge (pI = 8.6) which may be important for its interaction with the negatively charged substrate. Functional identity of the IFC1(RFC1) clone was established by expression in Xenopus oocytes. An 11-fold increase in 5-methyltetrahydrofolate (5-MTHF) uptake was observed in oocytes injected with 10 ng IFC1(RFC1) cRNA compared to water-injected controls. The expressed folate uptake in the cRNA injected oocyte was (1) 4,4'-diisothiocyanatosilbene-2,2'-disulfonic acid (DIDS)-sensitive; and (2) saturable with an apparent Km of 1.99 +/- 0.32 micrometers and a V(max) of 3782 +/- 188 fmol/oocyte per h. The distribution of mRNA species complementary to IFC1(RFC1) in different mouse tissues was examined by Northern blot analysis. In addition to the small intestine, expression of such mRNA species were also found in the kidney, large intestine, brain, heart and liver. Furthermore, mRNA species complementary to IFC1(RFC1) were also detected by Northern blot analysis in the small intestine of human and other animal species (rat and rabbit). Expression of mRNA complementary to IFC1(RFC1) was markedly higher in rat intestinal villus cells than in crypt cells. These results represent the first identification of a folate transporter in mammalian intestine.

Animals↗
PubMed1996

Escherichia coli lobar pneumonia: fatal infection in a patient with mental retardation.

Lobar pneumonia due to Escherichia coli is rare. Most lobar pneumonias are caused by either Streptococcus pneumoniae or Klebsiella pneumoniae, and most E coli pneumonias are bronchopneumonias. We report an acute fulminant course of E coli lobar pneumonia in a 37-year-old patient who was profoundly retarded, institutionalized, and nonimmunosuppressed and who died within 2 days of developing initial symptoms. Antemortem blood and postmortem blood and lung specimens isolated pure cultures of E coli. The source of infection in E coli lobar pneumonia is not clear in this patient or in the few cases that have been reported. We postulate that nasopharyngeal colonization of E coli in those who are institutionalized with mental retardation may predispose these patients to E coli pneumonia. Our case illustrates features of pneumonias that are unique in the institutionalized, mentally retarded patient population (ie, the relatively high prevalence of nasopharyngeal colonization of E coli, a higher incidence of E coli pneumonia than in other institutionalized populations, the often fulminant course of the disease), as well as the need for early, aggressive treatment including antibiotics effective against gram-negative bacteria.

Adult↗
PubMed1995

Developmental injury to the cerebellum following perinatal Borna disease virus infection.

In rats infected as neonates, Borna disease virus (BDV) infection causes neuroanatomical, behavioral and physiological abnormalities without encephalitis. Neonatal infection with BDV provides a powerful model for studying the effects of virus replication on brain development without inflammation-induced brain damage. Here we report that neonatal BDV infection interfered with cerebellar development in the Lewis rat. Based on cerebellar cross-sectional area measurements, abnormal cerebellar growth was first noted between 7 and 14 days after infection. Reactive astrocytosis was evident by three days after infection, even without encephalitis, and even before identification of viral proteins in the cerebellum. While neonatal BDV infection caused a significant loss in granule cells, infected granule cells were not identified. BDV proteins were readily detected in the Purkinje cells. Thus, persistent BDV infection of Purkinje cells, but not granule cells, was associated with loss of granule cells during cerebellar development, in the absence of encephalitis.

Age of Onset↗
PubMed1995

Hematologic consequences of Borna disease virus infection of rat bone marrow and thymus stromal cells.

Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system. BDV has recently been identified by a reverse transcription-polymerization chain reaction-enzyme immunosorbent assay (RT-PCR-EIA) in bone marrow cells and peripheral blood mononuclear cells (PBMC) in BDV-infected Lewis rats. We now report the identification of BDV RNA and infectious virus in thymus cells from rats infected either as neonates (PTI-NB) or as adults (4 weeks of age). Based on in vitro studies, we determined that the BDV-infected cells in bone marrow and thymus tissue are fibroblastic stromal cells. Bone marrow stromal cells are nonhematopoietic, fixed-tissue elements that support hematopoiesis, and, thus, it was not surprising that BDV infection altered the recovery from granulocytopenia and leukocytopenia after myelosuppressive treatment. Notably, unlike other immunotropic and neurotropic viruses, BDV does not appear to infect cells of myeloid or lymphoid lineages. We also report the association between BDV in the thymus with the lack, or loss, of encephalitis in neonatally inoculated rats or adult-inoculated rats during the chronic stage of disease.

Alkaline Phosphatase↗
PubMed1995

Borna disease virus and schizophrenia.

The development of a new serological assay method to detect antibodies in human sera recognizing Borna disease virus (BDV) proteins and a clinical pilot study are presented. Psychiatric patients from a schizophrenia research clinic in Baltimore, Maryland, were examined for antibodies to BDV antigen with traditional indirect immunofluorescence assays (IFA) that used both single and double labeling techniques and also with a Western blot assay capable of detecting antibodies to the three BDV proteins from a human neuroblastoma cell line. Thirteen of 90 (14.4%) patients and 0/20 control subjects had antibodies that recognized more than one BDV protein on the Western blot. Three patients had antibodies that recognized all three BDV proteins. Magnetic resonance imaging assessments of the volume of the putamen (with controls for total cranial volume) differentiated BDV+ from BDV- patients, and there were trend differences for bilateral amygdalae and the left amygdala-hippocampal process. We conclude that: (1) the Western blot assay is superior to IFA assays in BDV serology studies, (2) detection of antibodies to more than one BDV protein is a useful working criterion for seropositivity, (3) the 14.5 kDa BDV protein is 10 times more predictive of seropositivity than either the 38/40 kDa or the 24 kDa protein, (4) there is tentative evidence for a schizophrenia-control difference in the prevalence of anti-BDV antibodies, and (5) it is likely that there are neuroanatomical/behavioral features that differentiate seropositive from seronegative schizophrenic patients.

Adult↗
PubMed1995

Childhood lymphoma: diagnostic accuracy of chest radiography for severe pulmonary complications.

INTRODUCTION: We sought to determine whether chest radiography can be reliably used to distinguish persistent or relapsing pulmonary lymphoma from a variety of infectious and noninfectious pulmonary conditions that can occur in children receiving treatment for lymphoma. METHODS: We studied chest radiographs of 37 patients (30 with non-Hodgkin's lymphoma, and seven with Hodgkin's disease) who died of paediatric lymphoma or of treatment complications. Pulmonary findings at autopsy comprised lung tumour (n = 14), pleural tumour (n = 12), pneumonia (n = 22), adult respiratory distress syndrome (ARDS; n = 16), haemorrhage (n = 27), and infarction (n = 13). Using a 4-point scale and without knowledge of autopsy findings, three radiologists independently rated antemortem radiographs for the presence of pulmonary tumour, pleural tumour, pneumonia in general, pneumonia caused by viral, bacterial, fungal, and protozoan pathogens, ARDS, pulmonary haemorrhage, and pulmonary infarction. Diagnostic accuracy was defined by the area under the receiver-operating-characteristic curve (AZ). RESULTS: Diagnostic accuracy was good for pulmonary tumour (AZ, 0.71 +/- 0.6), protozoan pneumonia (AZ, 0.77 +/- 0.06), and ARDS (AZ, 0.86 +/- 0.07) but poor for all other conditions. The absence of both pleural effusions and mediastinal/right hilar lymphadenopathy was significantly associated (P < or = 0.04) with the absence of lung tumour. DISCUSSION: The pulmonary processes in these patients can all demonstrate diffuse airspace opacification, and many patients had multiple lung abnormalities at autopsy. The radiologist-readers were unable to identify which pulmonary conditions were responsible for radiographic findings in most patients. The readers were able to identify patients who did not have pulmonary lymphoma. If pulmonary involvement with lymphoma is unlikely, bronchoscopy with bronchoalveolar lavage may be sufficient to establish a diagnosis. When pulmonary lymphoma is a clinical consideration, open lung biopsy is usually required for diagnosis.

Adolescent↗
PubMed1995

The molecular and cellular biology of heart failure.

We review recent publications that use molecular and cellular biology to explore the diagnosis and treatment of cardiovascular diseases that have relevance to heart failure. Familial hypertrophic cardiomyopathy has now been shown to be due to mutations not only in the previously described beta myosin heavy chain gene, but also in the troponin T and alpha-tropomyosin genes, thus providing some symmetry to the idea that this is a molecular disease of the sarcomere. The basis for a type of familial dilated cardiomyopathy without substantial skeletal muscle involvement, caused by a mutation in the dystrophin gene, has been explored. However, by-and-large, the disease basis for most patients with dilated cardiomyopathy remains a molecular mystery. The role of a polymorphism in the angiotensin-converting enzyme gene was examined as a risk factor for a number of cardiovascular diseases. In animal models, the hypothesis that the devolution from hypertrophy to heart failure includes alterations in the molecular direction of extracellular matrix production gained some support. The experimental foundation was laid this year for the concept of and approach to cardiomyocytoplasty--the molecular and cellular treatment of heart failure by augmentation, repair, or replacement of cardiac myocytes--by experiments in cardiac gene transfer and transgenic animals. Gene causes and cures for restenosis after angioplasty garnered considerable attention. As we gain greater understanding of the molecular basis for disease, we will also have to increase our wisdom in the application of genetic testing.

Animals↗
PubMed1995

Tuberculosis. Captain of all these men of death.

The intent of this review was to familiarize the reader with the fascinating history of TB. I quote from Robert Louis Stevenson: "It is not a hard thing to know what to write; the hard thing is to know what to leave out." Also, this review by its very nature must be incomplete. It is certain that TB was present before the beginning of recorded history; it also is certain that we have not yet seen the end of the white plague. In the United States, the number of reported cases of TB decreased from 84,304 in 1953 to 22,201 in 1985, an average annual decline of 5.8%. Unfortunately, however, the number of cases has been increasing since 1985. These cases are predominantly in racial/ethnic minorities, persons from 25 to 44 years of age, men, and immigrants. Human immunodeficiency virus infection is at least partly responsible for the increasing number of cases. Additionally, new strains of M. tuberculosis that are resistant to multiple antituberculous drugs are being seen more and more frequently. In the mid-twentieth century, it was widely believed that advances in antituberculous chemotherapy and radiographic diagnosis might result in eradication of TB; this hope has not been realized. It is obvious that new challenges exist, and that others may lie ahead. One hopes that further advances will be made that will enable us to control this greatest killer of mankind, "The Captain of All These Men of Death."

Famous Persons↗
PubMed1995

Diagnostic imaging of pneumonia and its complications in the critically ill patient.

Chest radiography and other radiographic imaging techniques often are extremely useful in the differential diagnosis of chest diseases in ICU patients. It should be remembered, however, that the findings on these imaging studies often are nonspecific. Also, different pathologic processes may be present in a patient's lungs at the same time. Clinical parameters, medical diagnostic studies, and laboratory studies are important in the differentiation of disease processes in these patients. The radiologist should work closely with the clinician to provide optimal care for patients in the ICU setting.

Adolescent↗