Biomedical subjects

A Rosenthal

Publications and source records attributed to A Rosenthal.

At least 145 records · Page 8Linked to original sources

PubMed1995

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.

Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Animals↗

PubMed1995

Control of neuronal diversity by the floor plate: contact-mediated induction of midbrain dopaminergic neurons.

The notochord and floor plate contribute to patterning the ventral neural tube in part by expressing a diffusible factor that induces motoneurons. To determine the mechanisms that direct the development of other classes of ventral neurons, we studied the development of dopaminergic neurons that reside near motoneurons in the ventral midbrain. We provide evidence that dopaminergic neurons develop in the vicinity of the floor plate and that they can be specified by the floor plate in vitro and in vivo. Unlike motoneurons, efficient induction of dopaminergic neurons requires contact with floor plate cells. These results suggest that neuronal diversification along the dorsal-ventral axis may be achieved partly through the concerted action of diffusible and contact-dependent signals from a single organizing center, the floor plate.

Animals↗

PubMed1995

Malnutrition in hospitalized children with congenital heart disease.

OBJECTIVE: To determine the prevalence of malnutrition among hospitalized children with congenital heart disease by age, disease process, and clinical status. DESIGN: Cross-sectional, retrospective chart review. SETTING: Pediatric cardiology units at a 150-bed tertiary care teaching hospital in Ann Arbor, Mich. PATIENTS: Patients (n = 160) were randomly selected from consecutive admissions to the Pediatric Cardiology and Thoracic Surgery Services during a 1-year period. INTERVENTION: None. MAIN OUTCOME MEASURES: Acute and chronic malnutrition, assessed by comparing the patients' weight and height with established means. RESULTS: Acute and chronic malnutrition occurred in 33% and 64% of the patients, respectively. Age, diagnostic category, and symptoms were associated with malnutrition. Eighty percent of infants presented with acute malnutrition compared with 18% of patients of other ages (P < .001). Malnutrition affected 60% of patients with left-to-right shunts, 53% of patients with complex heart disease, and no patients with primary rhythm disturbances. Acute malnutrition affected 11% and chronic malnutrition affected 50% of patients with left-sided heart obstruction. Acute or chronic malnutrition occurred in 70% or more of patients with cyanosis and/or congestive heart failure but in only 30% of patients with neither (P < .001). CONCLUSION: Malnutrition in hospitalized children with congenital heart disease remains common, highlighting the importance of nutritional screening and intervention.

Acute Disease↗

PubMed1995

Formulation and characterization of dry mixes based on dehydrated fresh high-lysine corn.

Fresh sweet corn pulp from high-lysine corn was dehydrated in a drum-dryer and utilized in the formulation of creamy instant soups. Studied formulas contained 27.5 to 67% dehydrated high-lysine corn pulp. The sensory profiles of the formulas improved with increasing proportion of dehydrated fresh corn pulp. Formula with 27.5% fresh corn pulp was rated lowest by the tasters on the basis of poor appearance, low characteristic fresh corn flavor and low overall impression. Formulas with 60 and 67% corn pulp rated highest in sensory quality and were nutritionally adequate. The PER for these formulas did not differ from casein control diet but nitrogen absorption and nitrogen retention was inferior for the formulas protein as compared to casein.

Animals↗

PubMed1995

Exon 2 of the gene for neural cell adhesion molecule L1 is alternatively spliced in B cells.

L1CAM is a neural cell adhesion molecule expressed mainly on neurones' cell surface and plays an important role in the developing fetal brain. Recently, we have shown that mutations in the gene encoding L1CAM are responsible for three related neurological disorders including the most common form of inherited hydrocephalus. During our genetic analysis, we have discovered that L1CAM is also expressed on the surface of B cells but that the messenger RNA in this tissue is different to that in brain through alternative splicing of the L1 gene. This indicates that this region of the L1 molecule has a distinct role in brain cells compared to B lymphocytes and confirms its importance in brain development.

Alternative Splicing↗

PubMed1995

Induction of midbrain dopaminergic neurons by Sonic hedgehog.

Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the amino-terminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can function in a dose-dependent manner to induce different cell types within the neural tube. Our results also provide the basis for a potential cell transplantation therapy for Parkinson's disease.

Animals↗

PubMed1995

GDNF is an age-specific survival factor for sensory and autonomic neurons.

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of two populations of CNS neurons: motoneurons and midbrain dopaminergic neurons. To see whether GDNF promotes the survival of PNS neurons, we studied embryonic chicken autonomic and sensory neurons in culture. We show that GDNF promotes the survival of sympathetic, parasympathetic, proprioceptive, enteroceptive, and small and large cutaneous sensory neurons. Whereas sympathetic, parasympathetic, and proprioceptive neurons become less responsive to GDNF with age, enteroceptive and cutaneous sensory neurons become more responsive. GDNF mRNA is expressed in the tissues innervated by these neurons, and developmental changes in its expression in several tissues mirror the changing responses of the innervating neurons to GDNF. These results show that GDNF promotes the survival of multiple PNS and CNS neurons and suggest that GDNF may be important for regulating the survival of various populations of neurons at different stages of their development.

Animals↗

PubMed1995

Passive immunization of rhesus macaques against SIV infection and disease.

To evaluate the role of humoral immunity against simian immunodeficiency virus (SIV), we tested whether passive immunization with plasma from SIVmac251 vaccine-protected or healthy infected animals would protect rhesus monkeys against intravenous infection with ten 50% animal infectious doses of the cell-free homologous virus. The challenge dose of this SIVmac251 virus stock had previously caused persistent infection in all (21 of 21) nonimmunized controls. A plasma pool was obtained from a donor that had been immunized with an inactivated whole SIVmac251 vaccine produced in human T cells. This plasma pool contained low levels of SIVmac binding and neutralizing antibody but had a high titer of antibodies recognizing human cell proteins. Given 4 or 18 hr before intravenous challenge, this plasma completely protected three of eight recipients from infection and delayed virus detection in one recipient. The five unprotected animals had only a transient or undetectable p27 antigenemia and low virus load in their PBMCs, and all survived at least 7 months after infection. By contrast, no protection was observed in 6 monkeys given inactivated, pooled plasma or purified immunoglobulin (Ig) from healthy SIVmac251-infected animals. This plasma pool and the Ig preparation contained high levels of SIV-binding and neutralizing antibody but no reactivity to human cellular components. Five of the six recipients had persistent antigenemia after challenge and four died acutely from simian AIDS in 4-7 months. These studies suggest that passive transfer of antibody to human cellular antigens can confer protection against SIVmac whereas passive transfer of neutralizing antibodies without human cellular antibodies does not protect against the homologous virus and may enhance infection.

Animals↗

PubMed1995

Scintigraphic cerebral spinal fluid leak study in a child with recurrent meningitis after resection of a frontal meningocele.

An In-111 DTPA cerebrospinal fluid (CSF) leak study was performed on a 3-year-old boy admitted with recurrent meningitis. He was born with a congenital encephalocele that was surgically resected at 7 days-of-age. A residual skull floor defect with a recurrent tumor of the nasal radix was clinically suspected. Computed tomography and MRI scans could not confirm or rule out the presence of a CSF leak. The scintigraphic study clearly demonstrated a leak into the left naris. A large leptomeningeal cyst extending down into the left nares was resected and a defect in the left frontal calvarium, identified as the source of the CSF leak, was repaired at surgery.

Arachnoid Cysts↗

PubMed1995

Predictors of 2-year mortality among older male veterans on a geriatric rehabilitation unit.

OBJECTIVE: To determine if nutritional parameters and discharge setting are associated with mortality in older male veterans on a Geriatric rehabilitation unit (GRU). DESIGN: Two-year follow-up of sequential admissions to the GRU who had laboratory studies completed on admission to the acute hospital and on transfer to and discharge from the GRU. SETTING: University-affiliated VA medical center. PATIENTS: Eighty-three consecutive older male veterans admitted to the GRU. MEASUREMENT: Mortality during a period of 2 years post-discharge. MAIN RESULTS: In a univariate analysis, predictors of mortality were serum albumin level < or = 3.5 g/dL on admission to the GRU (P = .01), moderate or severe Nutritional Status Score (P = .03), discharge to a place other than home (P = .01), and use of antibiotics while on the GRU (P = .05). Discharge albumin remained the single significant predictor of mortality in a multivariate analysis (P = .005). CONCLUSIONS: Serum albumin is the strongest predictor of 2-year post-hospitalization mortality of older patients cared for on a GRU. Other predictors were presence of infection, Nutritional Status Score of moderate or severe compromise, and discharge to a place other than home.

Aged↗

PubMed1995

Immunosuppressive agents and endothelial repair. Prednisolone delays migration and cytoskeletal rearrangement in wounded porcine aortic monolayers.

Endothelial denudation at areas of predilection to atherosclerosis is balanced by an active repair process that may be inhibited under conditions of accelerated atherosclerosis. After cardiac transplantation, the accelerated atherosclerotic process that develops may be enhanced by immunosuppressive agents that have nonspecific effects on cell signaling, proliferation, and response to injury. To study subtle effects of cyclosporine A, azathioprine, and 6 alpha-methylprednisolone on normal endothelial repair processes, confluent porcine endothelial monolayers were denuded in the presence of clinically relevant concentrations of these agents. The rate of endothelial wound repair was compared and the effects on cell spreading, proliferation, and the cytoskeleton assessed. 6 alpha-Methylprednisolone at concentrations of 1.25 to 50 mumol/L was associated with a transient 30% to 60% inhibition of endothelial wound repair. This was associated with increased cell size at the wound edge and a delay in centrosomal reorientation toward the wound, without any effect on cell proliferation. Cyclosporine and azathioprine in clinically relevant concentrations did not affect endothelial repair. Thus, corticosteroids transiently inhibit endothelial cytoskeletal alterations that are important in endothelial repair after a denuding injury.

Animals↗

PubMed1995

Individualized developmental care for very-low-birth-weight premature infants.

Forty very-low-birth-weight neonatal intensive care unit (NICU) infants with birth weights < or = 1,250 g were randomly assigned to treatment or control groups. Behavior of the treatment infants was systematically evaluated, and individualized developmentally oriented care plans were implemented to enhance stability. Treatment babies required fewer days of intermittent mandatory ventilation and continuous positive airway pressure and achieved full enteral feedings sooner. Length of hospital stay and hospital charges were less for treatment than control infants. There were favorable effects on treatment infants' behavioral performance at 42 weeks' postconceptional age. These results support the hypothesis that behaviorally sensitive, developmentally oriented care improves medical and neurodevelopmental outcome in the NICU.

Hospital Charges↗

PubMed1994

Neurons from mouse embryos with a null mutation in the tumour suppressor gene p53 undergo normal cell death in the absence of neurotrophins.

Cell death plays an important role in regulating cell numbers in a wide variety of tissues during development and throughout life. Cell death can be triggered by changes in the levels of hormones and growth factors and is regulated by the expression of the tumour suppressor gene p53 in many cells. To determine if p53 plays a role in neuronal death resulting from neurotrophin deprivation, we studied the survival of neurons obtained from normal mouse embryos and embryos with a null mutation in the p53 gene. Embryonic sensory and sympathetic neurons from mutant embryos survived in response to the appropriate neurotrophin and died normally in the absence of neurotrophins. These results indicate that neurotrophin-deprived neurons die by a p53-independent pathway.

Animals↗

PubMed1994

GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle.

For survival, embryonic motoneurons in vertebrates depend on as yet undefined neurotrophic factors present in the limb bud. Members of the neurotrophin family are currently the best candidates for such neurotrophic factors, but inactivation of their receptor genes leads to only partial loss of motoneurons, which suggests that other factors are involved. Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture. GDNF messenger RNA was found in the immediate vicinity of motoneurons during the period of cell death in development. In vivo, GDNF rescues and prevents the atrophy of facial motoneurons that have been deprived of target-derived survival factors by axotomy. GDNF may therefore be a physiological trophic factor for spinal motoneurons. Its potency and specificity in vitro and in vivo also make it a good candidate for treatment of motoneuron disease.

Animals↗

PubMed1994

Extension of incomplete cDNAs (ESTs) by biotin/streptavidin-mediated walking using the polymerase chain reaction.

In the last 2 years thousands of new partial cDNAs or expressed sequence tags (ESTs) have been identified by single pass sequencing methods. It is expected that this number will further increase in order to help to isolate all human genes. However, the scientific value of partial cDNA fragments is limited unless they are used as tools for isolating and sequencing their full length parent molecules. Conventional library screening methods are tedious and not very effective in achieving this goal. We present a modified PCR technique which allows rapid isolation of the ends of partial cDNA fragments in vitro using a biotin/streptavidin capture procedure. Our method has several advantages over the RACE technique, is very specific, and allows to frequently sequence the final product directly without subcloning. We also show that cDNA walks can be obtained from partial sequences as short as 26 bp.

Bacterial Proteins↗

PubMed1994

Neurotrophin 3 stimulates the differentiation of motoneurons from avian neural tube progenitor cells.

Neurotrophin 3 (NT-3) promotes differentiation of neural tube progenitors into motoneurons expressing the BEN/SC1 and islet-1 epitopes. A 1.75- to 6.7-fold increase in BEN-positive motoneurons was obtained when quail neural tube cells were cultured with NT-3 at 0.1-10 ng/ml, respectively. In contrast, the overall number of cells, as well as the proportion of motoneurons that developed from cycling precursors, did not change. Addition of NT-3 at 1 ng/ml to cells obtained from ventral half-neural tubes promoted a 2.5-fold stimulation in motoneuron number, confirming the specificity of the effect. Moreover, NT-3 had no significant effect on survival of differentiated avian motoneurons. The distribution of trkC mRNA, which encodes the high-affinity receptor for NT-3, is consistent with these findings. trkC expression is homogeneous in the embryonic day 2 (E2) neural tube, becomes restricted to the mantle layer on E3, where differentiation occurs, and disappears from the ventral third of the E4-E5 spinal cord right before the onset of normal motoneuron death. These results suggest that NT-3 and trkC regulate early neurogenesis in the avian central nervous system.

Amino Acid Sequence↗

PubMed1994

Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons.

The survival of developing motor neurons depends on factors secreted from skeletal muscles and from cells within the central nervous system. Although several members of the nerve growth factor protein family [neurotrophins (NTs)] are able to maintain developing rat motor neurons in vitro, only the brain-derived neurotrophic factor has been shown to have significant effects on the survival of motor neurons in vivo. In the present study, we demonstrate that NT-4/5 also prevents injury-induced death of facial motor neurons in neonatal rats. Furthermore, facial motor neurons express a functional receptor for NT-4/5, whereas mRNA-encoding NT-4/5 can be detected in their environment throughout embryonic and postnatal life. Thus, both NT-4/5 and brain-derived neurotrophic factor may be physiological survival factors for facial motor neurons and may serve as therapeutic agents for motor neuron disease.

Animals↗

PubMed1994

Neurotrophin-4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures.

Parkinson's disease is a prevalent neurological disease characterized by profound and incapacitating movement disorders. A common pathology in Parkinson's patients is degeneration of substantia nigra dopaminergic neurons that innervate the striatum and a corresponding decrease in striatal dopamine content. We now report that NT-4/5 can prevent the death of rat embryonic substantia nigra dopaminergic neurons in low density, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT-4/5 and transcripts for NT-4/5 are present in their environment. In addition, we demonstrate that NT-4/5 protects embryonic dopaminergic neurons from the toxic effects of the neurotoxin MPP+. Thus, NT-4/5 could be a physiological survival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for Parkinson's disease.

1-Methyl-4-phenylpyridinium↗