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Biomedical subjects

R Nass

Publications and source records attributed to R Nass.

At least 19 recordsLinked to original sources
PubMed2004

Life extension versus improving quality of life.

There are two principal directions in ageing research: (i) the quest for understanding the mechanisms that determine the length of life and the use of such knowledge in order to find a potentially life extending treatment and (ii) the attempt to improve the quality of life in the elderly by reversing or preventing functional decline of different tissues without primarily extending life span. This chapter addresses the importance of assessing the potential impact of interventions on quality of life rather than extending life.

Aging↗
PubMed2004

Chronic changes in peripheral growth hormone levels do not affect ghrelin stomach mRNA expression and serum ghrelin levels in three transgenic mouse models.

Ghrelin is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. Ghrelin is involved in feeding behaviour and is a potent stimulator of GH release. Chronically increased GH concentrations are known to negatively regulate the pituitary GHS receptor. This study tested whether chronic changes in peripheral GH levels/action affect ghrelin mRNA expression and circulating concentrations of ghrelin. Stomach ghrelin mRNA expression and serum concentrations of ghrelin were measured in three groups of transgenic mice and the respective control animals: group 1, GH-receptor gene disrupted mice (GHR/KO); group 2, mice expressing bovine GH (bGH); and group 3, mice expressing GH-antagonist (GHA). Ghrelin mRNA expression in the stomach, pituitary and hypothalamus of young adult male rats were measured using reverse-transcription-polymerase chain reaction. Ghrelin mRNA expression levels were approximately 3000-fold higher in rat stomach than in rat pituitary. Ghrelin mRNA expression in rat hypothalamus was below the detection limits of our assay. Stomach ghrelin mRNA expression, as well as serum concentrations of ghrelin, did not change significantly in any of the three mouse groups compared to the respective control group. These data support previous observations that the stomach is the main source of circulating ghrelin, and also indicate that stomach ghrelin mRNA expression and serum concentrations of ghrelin are not affected by chronic changes in peripheral GH/insulin-like growth factor-I levels/action.

Animals↗
PubMed2002

Impact of the GH-cortisol ratio on the age-dependent changes in body composition.

Aging is associated with a decrease in GH levels and this is paralleled by changes in body composition, i.e., increased visceral fat, and decreased lean body mass and bone mineral density. Similar changes in body composition are seen in the state of hypercortisolism. Increasing age has been shown to be associated with elevated evening cortisol levels in men. An increased exposure of several tissues to glucocorticoids with aging, i.e., visceral fat cells, in combination with the reduction of the lipolytic effects of declining GH levels, may contribute to the age-dependent increase of visceral fat accumulation. We hypothesize that the age-dependent changes in body fat are the result of an age-dependent decrease of the GH/cortisol ratio at the level of the adipocyte. This is caused by the decline in GH concentrations and the increase in cortisol levels and/or metabolism at the adipocyte.

Adipocytes↗
PubMed2001

Perfusion brain scintigraphy studies in infants and children with malformations of the vein of Galen.

Cerebral perfusion brain scintigraphy obtained in six unselected patients (age newborn to 14 years) from among 50 children with vein of Galen malformations was used in conjunction with magnetic resonance imaging to determine the basis of the neurological and cognitive abnormalities in patients with vein of Galen malformations (VGMs). Five had a hemiparesis - persistent, transient, or alternating. Four were developmentally delayed. Two had so far been cognitively normal and acquired a neurological deficit, following an embolization procedure. The school age patient had a nonverbal learning disability. Three had epilepsy and/or an abnormal electroencephalogram. Magnetic resonance imaging documented only the VGM, hydrocephalus and atrophy; one child with perinatal asphyxia had periventricular leukomalacia. Perfusion brain scintigraphy was normal in two (a normal infant, and a toddler with a hemiparesis and aphasia). Abnormal findings included: left parietal hypoperfusion, fronto-temporal atrophy, patchy flow; left fronto-temporal hypoperfusion, left hemiatrophy, bilateral medial temporal hypoperfusion, right cerebellar hypoperfusion; right temporal hypoperfusion, patchy flow; right hemiatrophy, occipital hypoperfusion. Perfusion brain scintigraphy findings correlated better with focal neurological and cognitive defects than did magnetic resonance imaging.

Adolescent↗
PubMed2001

C. elegans: a novel pharmacogenetic model to study Parkinson's disease.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the use of vertebrate and tissue culture systems continue to provide valuable insight into the pathology of the neurodegeneration, the molecular determinants involved in the etiology of the disease remain elusive. Because of the high conservation of genes and metabolic pathways between invertebrates and humans, as well as the availability of genetic strategies to identify novel proteins, protein interactions and drug targets, genetic analysis using invertebrate model systems has enormous potential in deducing the factors involved in neuronal disease. In this article, we discuss the opportunities for the use of the nematode Caenorhabditis elegans (C. elegans) for gaining insight into the molecular mechanisms and pathways involved in PD.

Journal Article↗
PubMed2001

Behavioural profiles of children and adolescents after pre- or perinatal unilateral brain damage.

Recent case reports of individuals with early-onset damage to the prefrontal cortex have suggested that such early insults could result in severely impaired social behaviour in later childhood and adolescence. The investigators speculated that the acquisition of complex social conventions and moral rules had been impaired. In a large cohort of children, we sought to determine whether early focal brain insults might result in clinically significant behavioural or emotional problems. This study reports on 39 children with pre- or perinatal-onset unilateral brain damage (focal lesion) from cerebral infarction or intraparenchymal haemorrhage, using the Achenbach Child Behavior Checklist to assess the presence or absence of behavioural and emotional difficulties. Two-thirds of the subjects had left hemisphere (LH) lesions and one-third had right hemisphere (RH) lesions. Age range was 4.0-15.4 years at the time of questionnaire completion. Their results were compared with those of 54 control children. Analyses were conducted on focal lesion versus controls, RH versus LH lesion, frontal versus non-frontal lesion, and seizure versus non-seizure groups. When the effect of IQ was partialled out, there were no significant differences on the nine Behavior Problem scales, the Internalizing-Externalizing dichotomy or the Total Problem score for any of the group comparisons. Our subjects showed no evidence of clinically significant behavioural or emotional problems, even when the frontal lobe was involved. Individuals with more extensive and bilateral damage may be at higher risk of significant behavioural and emotional dysfunction than were those in our study population. In future studies of brain-behaviour relationships in developing children, all potential causes for any observed behavioural abnormalities, such as genetic and environmental factors and toxin exposure, must be considered before concluding that specific anatomical lesions are causally related to specific behavioural outcomes.

Adolescent↗
PubMed2000

Acquired aphasia in children after surgical resection of left-thalamic tumors.

Five children (three males, two females; four right-, one left-handed; age range 6 to 14 years) who developed aphasia after gross-total excision of left predominantly thalamic tumors are reported. Three patients had Broca aphasia, one had mixed transcortical aphasia, and one patient had conduction aphasia. In the months after surgery, three children improved while receiving radiation and/or chemotherapy, although none recovered completely. Two patients with malignant tumors developed worsening aphasia when the tumor recurred, and later died. Two of three patients tested had visuospatial difficulties in addition to language deficits. Attention and executive functioning were affected in three of three patients tested. Memory, verbal and/or visual functioning, were affected in four of four patients tested. Both patients who were tested showed transient right hemineglect. Two of two patients tested were probably apraxic. The wide range of deficits in these children highlights the importance of the thalamus and other subcortical structures in developing cognition.

Adolescent↗
PubMed2000

Intracerebroventricular administration of the rat growth hormone (GH) receptor antagonist G118R stimulates GH secretion: evidence for the existence of short loop negative feedback of GH.

Pulsatile growth hormone (GH) secretion is regulated by three hypothalamic factors, growth hormone-releasing hormone (GHRH), somatostatin and the natural ligand for the GH secretagogue receptor (Ghrelin). These factors and their effects are, in turn, affected by short loop feedback of GH itself. To test the hypothesis that hypothalamic GH receptors are involved in the ultradian rhythmicity of pituitary GH secretion, the rat GH receptor antagonist (G118R) was administered to adult male rats by intracerebroventricular (i.c. v.) injection and the effects on spontaneous GH secretion were studied. Normal saline was administered i.c.v. to eight control rats. Mean GH concentrations increased significantly in the rat treated with G118R compared to rats that received normal saline. The pulse amplitude rose by a mean of 33.3 ng/ml and the total area under the curve increased by a mean of 15 061 ng/ml x min. The number of GH peaks did not change significantly following G118R. These data suggest that GH regulates its own secretion by acting directly on hypothalamic GH receptors.

Animals↗
PubMed2000

High plasma growth hormone (GH) levels inhibit expression of GH secretagogue receptor messenger ribonucleic acid levels in the rat pituitary.

Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that of GH-releasing hormone. The GHS-R has been cloned from the pituitary and is expressed not only in the pituitary but also in specific areas of the brain, including the hypothalamus. Recent studies suggest that hypothalamic GHS-R expression is regulated by GH. This study was designed to investigate whether pituitary GHS-R expression is modulated by GH. Female Wistar-Furth rats were injected sc with either saline (control) or GC tumor cells (GC) that secrete rat GH. The tumors were allowed to develop for 1-4 weeks. At weeks 1-4, control (n = 4-8) and GC rats (n = 3-8) were killed. Pituitary GHS-R messenger RNA (mRNA) was measured by a quantitative competitive PCR assay. The endogenous GHS-R mRNA levels were measured by determining the amount of competitive template RNA required to produce equimolar amounts of native and competitive template PCR products. The mean log plasma GH levels were significantly greater in the GC rat group than in the control group at weeks 2, 3, and 4. At these times, the mean log pituitary GHS-R mRNA contents were significantly lower in the GC rat group than in the control group. No relationship could be established between log estradiol levels and GHS-R levels. These data indicate that pituitary GHS-R expression is modulated by GH.

Animals↗
PubMed1999

Outcome of multiple subpial transections for autistic epileptiform regression.

Treatment options for atypical forms of Landau-Kleffner syndrome (LKS) are not well delineated. Many patients with typical LKS fail to respond to antiepileptic drug treatment, but some benefit from multiple subpial transections (MSTs). The authors report seven patients with autism or autistic epileptiform regression who responded in varying degrees to MSTs after failed medical management. These patients derived from an original cohort of 36 children (29 males, seven females, ranging from 2 years, 3 months to 11 years, 3 months, mean age = 5 years, 8 months) with a history of language delay or regression, as well as varying degrees of social and behavioral abnormalities, who were evaluated with video-electroencephalogram (EEG) monitoring over a 2-year period. Fifteen patients had clinical seizures (11 of the 19 children with autistic epileptiform regression and four of 12 autistic children). Epilepsy was refractory to medication in seven. Surgical treatment variously involved MSTs of the left neocortex in temporal, parietal, and frontal regions, often including regions within the classic perisylvian language areas. One patient also had a left temporal lobectomy. In all seven patients, seizure control or EEG improved after MSTs. Language, social, and overall behavior improved to a moderate degree, although improvements were temporary in most. Autistic epileptiform regression resembles LKS in that both may respond to MST. MST is used to treat epilepsy in eloquent regions. The responsiveness of autistic epileptiform regression to MST buttresses the argument that autistic epileptiform regression is a form of focal epilepsy.

Autistic Disorder↗
PubMed1999

Autistic regression with rolandic spikes.

OBJECTIVE: This study was designed to further define the electroencephalographic abnormalities seen in the Landau-Kleffner syndrome variants and the associated clinical features. BACKGROUND: Landau-Kleffner syndrome is rare, but its putative variants are more common. METHOD: We report two patients with centro-temporal spikes, autistic epileptiform regression, and variably prominent oro-motor symptoms. RESULTS: The epileptic aphasia pattern found among patients with prominent Rolandic spikes may more frequently involve expressive language than is seen in the typical Landau-Kleffner syndrome, where verbal auditory agnosia is the rule. CONCLUSIONS: This clinical difference likely reflects the location of the epileptiform activity (centrotemporal as opposed to anterior or mid-temporal) on buccal-lingual function, vocalization, and language production.

Autistic Disorder↗
PubMed1998

Novel localization of a Na+/H+ exchanger in a late endosomal compartment of yeast. Implications for vacuole biogenesis.

Na+/H+ exchangers catalyze the electrically silent countertransport of Na+ and H+, controlling the transmembrane movement of salt, water, and acid-base equivalents, and are therefore critical for Na+ tolerance, cell volume control, and pH regulation. In contrast to numerous well studied plasma membrane isoforms (NHE1-4), much less is known about intracellular Na+/H+ exchangers, and thus far no vertebrate isoform has been shown to have an exclusively endosomal distribution. In this context, we show that the yeast NHE homologue, Nhx1 (Nass, R., Cunningham, K. W., and Rao, R. (1997) J. Biol. Chem. 272, 26145-26152), localizes uniquely to prevacuolar compartments, equivalent to late endosomes of animal cells. In living yeast, we show that these compartments closely abut the vacuolar membrane in a striking bipolar distribution, suggesting that vacuole biogenesis occurs at distinct sites. Nhx1 is the founding member of a newly emergent cluster of exchanger homologues, from yeasts, worms, and humans that may share a common intracellular localization. By compartmentalizing Na+, intracellular exchangers play an important role in halotolerance; furthermore, we hypothesize that salt and water movement into vesicles may regulate vesicle volume and pH and thus contribute to vacuole biogenesis.

Amino Acid Sequence↗
PubMed1998

Conduction aphasia in a 3-year-old with a left posterior cortical/subcortical abscess.

A 3-year-old, right-handed girl developed a conduction-type aphasia following a second generalized seizure in the setting of a developing abscess involving left subcortical and cortical angular gyrus and arcuate fasciculus, and the posterior corpus callosum. The language disorder was fluent, characterized by age appropriate mean length of utterance and syntax, but with markedly reduced spontaneity of output, rapid rate of speech and mild dysarthria. Comprehension was relatively, but not completely spared. Naming, repetition, and reading (letters) were initially markedly impaired. Improvements in naming and repetition were associated with both literal and semantic paraphasias. Writing skills in the form of drawing were spared, but a mild apraxia to verbal command and imitation was initially present. Despite her young age, this child's fluent conduction aphasia and lesion localization were adult-like. Multimodal memory difficulties appeared to underlie what is best described as conduction aphasia.

Abscess↗
PubMed1998

Autism and autistic epileptiform regression with occipital spikes.

The electroencephalographic abnormalities seen in Landau-Kleffner syndrome (LKS) (language deterioration) are non-specific, and consist of a variety of epileptiform discharge patterns including continuous slow spike-wave discharges during sleep, focal sharp waves with spikes, and centrotemporal (rolandic) spikes. Similarly, the EEG abnormalities seen in autistic epileptiform regression (language and social/behavioral deterioration) are non-specific and overlap with those seen in LKS. By contrast, distinct epilepsy syndromes in otherwise normal children occur in the EEG-defined benign focal epilepsies of childhood. Occipital spikes or spike-wave present either in the older child with visual symptoms and headache or in the younger child with autonomic symptoms followed by brief or prolonged partial motor seizures. Seven young children (five from a consecutive series of 42) presenting clinically with autism or autistic regression and possible or definite seizures, whose EEGs revealed occipital spikes or spike-wave characteristic of the benign epilepsies, are reported. Although occipital spikes are commonly seen in young children as an age-dependent EEG-defined benign focal epilepsy, their high frequency in this population with cognitive difficulties suggests a possible causal relation. The effects of the epileptiform discharge on cognitive functioning presumably reflect extension into temporal and parietal lobes, rather than occipital disturbances per se.

Autistic Disorder↗
PubMed1998

Temperament profiles of children with vein of Galen malformations.

Unlike many brain injured children who are often rather difficult, toddlers and school-aged children with congenital vein of Galen malformations (n = 20; age range, 4 months to 12 years with a mean of 4 years) evidence a relatively positive temperament profile (based on the Temperament Scales of Carey, McDevitt, Fullard, Hegvik, Medoff-Cooper). They do not, however, differ from normal children with regard to the frequency of easy, difficult, slow to warm up, and intermediate temperament clusters. The temperament profile of children with vein of Galen malformations appears unaffected by additional neurologic abnormalities (hydrocephalus, abnormal developmental quotient, seizure disorder, focal cortical lesions) or other factors including age at testing, sex, or socioeconomic status. Contrary to the findings in adults of right hemisphere dominance for attention, presence of additional right-sided focal cortical pathology was not associated with greater activity level, distractibility, or impersistence. In contrast to the findings in adults and children of right hemisphere dominance for emotions in general, children with vein of Galen malformations and additional right hemisphere cortical damage are not more difficult than those with additional left cortical pathology or no additional focal cortical pathology. The fact that the pathology in vein of Galen malformations is subcortical may explain their relatively easier temperament and the absence of lateralization effects.

Analysis of Variance↗
PubMed1998

Growth hormone secretagogue receptor expression in human pituitary tumors.

The GH secretagogue (GHS) receptor (GHS-R) has been characterized and cloned. It is a member of a family of seven transmembrane receptors and is closely related to the neurotensin and TRH receptors. To determine the expression of this receptor in normal anterior pituitary and in 24 human pituitary adenomas, we analyzed GHS-R messenger ribonucleic acid (mRNA) using a RT-PCR assay. We found that normal human pituitary was positive for the GHS-R signal. In addition, all GH-secreting adenomas and the one TSH-secreting adenoma demonstrated the presence of GHS-R mRNA. Three of four ACTH-secreting tumors and three of nine gonadotroph adenomas were also positive for the GHS-R mRNA. To determine the amounts of GHS-R mRNA in normal pituitary and in representative tumors, semiquantitative competitive PCR was performed. We determined that normal pituitary had approximately 750 molecules/L GHS-R mRNA. The acromegalic tumor had approximately 1.5 x 10(5) molecules/L, and the TSH-secreting tumor had approximately 7.5 x 10(3) molecules/L. Other tumor types contained considerably less, with the ACTH-secreting and gonadotroph tumors expressing 7.5 x 10(2) and 3 x 10(2) GHS-R mRNA molecules/L, respectively. These results suggest that GH- and TSH-producing adenomas express GHS-R mRNA at levels 200 and 10 times higher, respectively, than the normal pituitary, and that this receptor expression may be involved in the pathogenesis and growth of these pituitary adenomas.

Adenoma↗
PubMed1998

Moyamoya syndrome associated with congenital heart disease.

OBJECTIVE: To describe the association between moyamoya syndrome and congenital heart disease and to discuss its clinical implications. Study Design. Retrospective analysis of a case series from two institutions. RESULTS: Five patients with moyamoya syndrome and structural congenital heart disease were identified. Coarctation of the aorta was present in 3 patients, in association with a ventricular septal defect (1 patient), aortic and mitral valve stenoses (1 patient), and tetralogy of Fallot (1 patient). Tetralogy of Fallot and a large paramembranous ventricular septal defect were found in the other 2 patients. Four patients underwent surgical repair of their congenital heart disease during the first year of life and 1 patient had balloon dilation of aortic coarctation at 5 years of age. In all patients, moyamoya syndrome was diagnosed after surgical intervention for congenital heart disease-at 6 months of age in 1 patient, at 2 years of age in 3 patients, and at 6 years in 1 patient. Strokes were the most common presenting sign (3 patients) followed by seizures (2 patients). By the age of 33 months, 4 of 5 patients had undergone cerebral revascularization surgery to halt the clinical progression of moyamoya syndrome. CONCLUSIONS: Moyamoya syndrome should be considered in the differential diagnosis of seizures and stroke in patients with structural congenital heart disease. Prompt diagnosis and surgical management of the occlusive cerebral angiopathy should lead to improved neurological outcome in these patients.

Diagnosis, Differential↗