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M Grossman

Publications and source records attributed to M Grossman.

At least 19 recordsLinked to original sources
PubMed1997

Selective expression of insulin-like growth factor II in the songbird brain.

Neuronal replacement occurs in the forebrain of juvenile and adult songbirds. To address the molecular processes that govern this replacement, we cloned the zebra finch insulin-like growth factor II (IGF-II) cDNA, a factor known to regulate neuronal development and survival in other systems, and examined its expression pattern by in situ hybridization and immunocytochemistry in juvenile and adult songbird brains. The highest levels of IGF-II mRNA expression occurred in three nuclei of the song system: in the high vocal center (HVC), in the medial magnocellular nucleus of the neostriatum (mMAN), which projects to HVC, and to a lesser extent in the robust nucleus of the archistriatum (RA), which receives projections from HVC. IGF-II mRNA expression was developmentally regulated in zebra finches. In canary HVC, monthly changes in IGF-II mRNA expression covaried with previously reported monthly differences in neuron incorporation. Combining retrograde tracers with in situ hybridization and immunocytochemistry, we determined that the HVC neurons that project to area X synthesize the IGF-II mRNA, whereas the adjacent RA-projecting neurons accumulate the IGF-II peptide. Our findings raise the possibility that within HVC IGF-II acts as a paracrine signal between nonreplaceable area X-projecting neurons and replaceable RA-projecting neurons, a mode of action that is compatible with the involvement of IGF-II with the replacement of neurons. Additional roles for IGF-II expression in songbird brain are likely, because expression also occurs in some brain areas outside the song system, among them the cerebellar Purkinje cells in which neurogenesis is not known to occur.

Amino Acid Sequence↗
PubMed1997

Object recognition difficulty in visual apperceptive agnosia.

Two patients with visual apperceptive agnosia were examined on tasks assessing the appreciation of visual material. Elementary visual functioning was relatively preserved, but they had profound difficulty recognizing and naming line drawings. More detailed evaluation revealed accurate recognition of regular geometric shapes and colors, but performance deteriorated when the shapes were made more complex visually, when multiple-choice arrays contained larger numbers of simple targets and foils, and when a mental manipulation such as a rotation was required. The recognition of letters and words was similarly compromised. Naming, recognition, and anomaly judgments of colored pictures and real objects were more accurate than similar decisions involving black-and-white line drawings. Visual imagery for shapes, letters, and objects appeared to be more accurate than visual perception of the same materials. We hypothesize that object recognition difficulty in visual apperceptive agnosia is due to two related factors: the impaired appreciation of the visual perceptual features that constitute objects, and a limitation in the cognitive resources that are available for processing demanding material within the visual modality.

Aged↗
PubMed1997

Impairment in category fluency in ischemic vascular dementia.

The underlying mechanisms for impaired output on letter (F, A, and S) and category (e.g., animal) word list generation (WLG) tasks in subcortical ischemic vascular dementia (IVD) were investigated. Normal control (NC) and Alzheimer's disease (AD) participants were also studied. IVD and NC participants performed better on category than letter WLG tasks, whereas the opposite was observed among AD participants. IVD participants produced fewer responses than AD participants on letter WLG tasks, but there was no difference between AD and IVD participants on the "animal" WLG task. AD participants scored lower than IVD and NC participants on animal WLG indexes measuring semantic knowledge. There were few differences between IVD and NC participants. The reduced output on the animal WLG task for IVD participants is consistent with search-retrieval deficits. The reduced output of AD participants may be caused by degraded semantic knowledge.

Aged↗
PubMed1997

Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease.

OBJECTIVE: Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS: Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS: Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing. CONCLUSION: These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

Aged↗
PubMed1997

Nutrient flows in agriculture in The Netherlands with special emphasis on pig production.

Annual nitrogen (N), phosphorus (P), and potassium (K) flows in agriculture in The Netherlands were identified and quantified in 1990, with special emphasis on pig production. Also, the effects that various management strategies in pig production have on NPK emission in 1990 were compared using a static deterministic simulation model. Ammonia emission from pig production in 1990 (60.9 Gg N) exceeded the defined target for the year 2000 (12.7 Gg N). Measures that affect volatilization of ammonia directly (i.e., introduction of low-emission stables, manure storage facilities, or manure application techniques) reduced ammonia emission most effectively. These measures, however, should be combined with a reduction in application of artificial N fertilizer to avoid an increase in N losses through leaching, run-off, or denitrification. Targets for ammonia emission in the year 2010 require a reduction in the pig population of 24 to 62%, in addition to implications of measures described in this article. National NPK losses in 1990 through leaching, run-off, or denitrification, predicted at 223.5 kg/ha for N, 32.7 kg/ha for P, and 67 kg/ha for K, exceeded government targets for the year 2010 (185 kg N/ha; 8.7 kg P/ha; norm not set for K). Reducing application of artificial NPK fertilizer reduced national NPK losses most effectively. For P, use of phytase and feeding pigs in accordance with their P requirements is required, in addition to limited use of artificial P fertilizer to meet targets for the year 2010. Hence, from an environmental point of view, pig production in The Netherlands is limited primarily by ammonia emission targets for the year 2010.

Ammonia↗
PubMed1996

Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia.

We report the clinical, neuroimaging, and neuropathologic features of progressive nonfluent aphasia (PNFA), a rare neurodegenerative syndrome most notable for its distinct language disturbance. Longitudinal observations of 3 patients revealed progressively telegraphic speech and writing, followed by gradual deterioration of sentence comprehension, and finally, preterminal mutism and dementia. Magnetic resonance imaging revealed cortical atrophy most pronounced in anterior regions of the left hemisphere. Functional neuroimaging demonstrated reduced cerebral activity most prominently in left frontal and temporal regions. At necropsy, microscopic pathology of brain was most consistent with the diagnosis of "dementia lacking distinctive histology" (DLDH). A review of published primary progressive aphasia cases with adequate clinical and histopathological descriptions reveals that the most common pathology underlying PNFA is DLDH. PNFA is one example of a family of clinical syndromes with similar underlying histopathology that affects different regions of the frontal lobe.

Adult↗
PubMed1996

Verb comprehension deficits in probable Alzheimer's disease.

Studies of lexical comprehension in probable Alzheimer's disease (pAD) have focused almost exclusively on nouns. In the following preliminary study, we examined whether lexical comprehension for verbs is also impaired in 25 pAD patients. The semantic meaning of motion verbs, cognition verbs, and perception verbs was assessed with a triadic comparison task. Structural meaning associated with these verbs was evaluated by asking the patients to judge the coherence of sentence frames that accept these verbs naturally or awkwardly. We found that pAD patients are significantly impaired at identifying semantic relations among verbs. pAD patients also encountered significantly more difficulty judging the coherence of sentences than control subjects. Correlation and regression analyses demonstrated that semantic characteristics of verbs are projected from the verb's sentence frames in control subjects, but there was minimal evidence for such a structural-semantic relationship in pAD. We consider several possible explanations for our preliminary observations of an impairment that has consequences for processing both semantic and structural aspects of verb meaning.

Aged↗
PubMed1996

Anomaly judgments of subject-predicate relations in Alzheimer's disease.

Claims that patients with probable Alzheimer's disease (AD) have semantic memory difficulty have received equivocal support. A common assumption has been that defining or core information determines the truth value of word meaning on measures requiring semantic memory such as category membership judgments or confrontation naming, but this assumption may not be valid. In the present study, we assessed the comprehension of subject-predicate sentences independent of their truth value by asking AD patients to judge the coherence of statements such as "The tulip is tall" or "*The tulip is jealous." We found that AD patients are significantly more impaired than controls at judging the coherence of these simple subject-predicate sentences. Moreover, AD patients were more successful at judging the coherence of statements that contain attributes with a narrow scope of reference compared to attributes with a broad scope of reference. These findings support the hypothesis that AD patients have a semantic memory impairment and suggest a specific deficit processing the network of semantic relations underlying word meaning in semantic memory.

Aged↗
PubMed1996

Serial position and temporal cue effects in multiple sclerosis: two subtypes of defective memory mechanisms.

Neurocognitive studies of multiple sclerosis (MS) have identified a robust long-term memory deficit. We hypothesized that this is due in part to the limited representation and use of serial order information. MS patients and controls were studied with a supraspan list learning procedure with post-encoding retrieval and recognition trials. MS patients demonstrated post-encoding negative recency with normal recognition, and word order recall was impaired. These findings appear to be in part to difficulty using temporal order cues in long-term memory. Two dissociable memory deficits were identified, suggesting that there are at least two neurocognitive mechanisms underlying memory impairment in MS.

Adult↗
PubMed1996

The semantic memory impairment of Alzheimer's disease: category-specific?

We addressed the question of whether Alzheimer's Disease (AD) causes a selective impairment for knowledge of living things. Although we replicated a previous finding that AD subjects name pictures of living things less accurately than pictures of nonliving things, we also failed to observe this selective impairment when we used two new stimulus sets, which more tightly controlled the overall naming difficulty of the living and nonliving items. We conclude that, whereas some individuals may have bona fide selective impairments in semantic memory as a result of herpes simplex encephalitis or head injury, AD does not generally give rise to selective impairments in knowledge of living things.

Aged↗
PubMed1996

Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia.

OBJECTIVE: The purpose of this report was to provide detailed information on the safety and feasibility of surgical procedures associated with the first ex vivo liver-directed gene therapy trial for the treatment of vivo gene therapy for homozygous familial hypercholesterolemia (FH). SUMMARY BACKGROUND DATA: Familial hypercholesterolemia is an autosomal dominant disease in which the gene encoding the low density lipoprotein receptor is defective. Patients homozygous for this mutation have extraordinarily high levels of cholesterol and accelerated atherosclerosis and die prematurely of myocardial infarction. The concept of liver-directed gene therapy was based on the report of normalization of cholesterol levels by orthotopic cardiac/liver transplant in a child with homozygous FH. METHODS: Five patients with homozygous FH were selected for inclusion in this trial. The patients underwent hepatic resection and placement of a portal venous catheter. Primary hepatocytes cultures were prepared from the resected liver and transduced with a recombinant retrovirus encoding the gene for the human low density lipoprotein receptor. The genetically modified cells were then transplanted into the liver through the portal venous catheter. RESULTS: Numerous clinical, laboratory, and radiologic parameters were analyzed. Elevations of the hepatic transaminases and leukocyte counts and a decline in hematocrit count were noted. Transient elevations of the portal pressure were observed during cell infusion. No major perioperative morbidity--specifically, myocardial infarct, perioperative hemorrhage, or portal vein thrombosis--or death occurred as a result of this protocol. CONCLUSION: Liver-directed ex vivo gene therapy can be accomplished safely in humans and is appropriate for selected patients.

Adult↗
PubMed1996

Category-specific difficulty naming with verbs in Alzheimer's disease.

We studied 20 patients with Alzheimer's disease (AD) on a picture-naming task consisting of frequency-matched pairs of nouns and verbs that were homophonic and homographic (e.g., paint). Intragroup comparisons revealed that verb naming is significantly more difficult for patients with AD than noun naming. An error analysis demonstrated that patients with AD produce significantly more semantic and descriptive errors for verbs than nouns. We correlated verb naming and noun naming with measures of grammatical comprehension, lexical retrieval, and visuoperceptual processing, but there were no selective effects for verbs compared with nouns. Differences in the mental representation of concepts underlying verbs and nouns may account, in part, for the relative difficulty naming with verbs in AD.

Aged↗
PubMed1996

Language comprehension profiles in Alzheimer's disease, multi-infarct dementia, and frontotemporal degeneration.

We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimer's disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness.

Aged↗
PubMed1996

Multiphasic analysis of embryonic mortality in chickens.

Infertility and embryonic mortality are economically important for the commercial broiler industry because they are components of hatchability. Embryonic mortality in chickens is not uniformly distributed over the course of incubation; two phases of embryonic mortality are characteristic of chicken development. The objective of this paper was to develop a mathematical model to assess infertility and to characterize the distribution over time of embryonic mortality in chickens. A model was constructed based on evidence in the literature for multiple phases of embryonic mortality before and during incubation. A multiphasic model, with two phases, included parameters for the proportion of eggs that were infertile and the proportion that were fertile but the embryo died before or during incubation. For those eggs that were fertile but the embryo died, the model included the proportion of embryonic mortality during each phase, day of peak mortality, and duration of phase. Data on embryonic mortality for white Cornish chickens were used to illustrate the multiphasic model. Model parameters could be estimated easily and interpreted with clear biological meaning. Estimates of parameters, in general, were reasonably precise and consistent with the literature. With multiphasic analysis, one can assess infertility and characterize the distribution of embryonic mortality in chickens, which can lead to a useful understanding of management and genetic aspects of these components of hatchability.

Animals↗
PubMed1995

The neural basis of the central executive system of working memory.

Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.

Adult↗
PubMed1995

Parental relationships, coping strategies, received support, and well-being in adolescents of separated or divorced and married parents.

The purpose of this cross-sectional study was to examine the impact of the perceived quality of the parental relationship and family status on coping strategies, received support, and well-being in adolescents from separated or divorced and married parents. Two hundred forty-four matched adolescents from separated/divorced and married households were drawn from an initial sample of 1,044 students who were tested at five colleges and three high schools of a large metropolitan and rural area. Regression analyses supported the hypothesis that a perceived poor parental relationship, and not family status, was associated with low life satisfaction and sense of future, and high anxiety in adolescents of divorced and married households. Hierarchical regression techniques revealed that coping strategies and received support did not mediate the association between a perceived poor parental relationship and low levels of well-being in adolescents from divorced and married households. The findings underscore the importance of intervening with adolescents within the context of their family relationships.

Adaptation, Psychological↗
PubMed1995

A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia.

The outcome of the first pilot study of liver-directed gene therapy is reported here. Five patients with homozygous familial hypercholesterolaemia (FH) ranging in age from 7 to 41 years were enrolled; each patient tolerated the procedure well without significant complications. Transgene expression was detected in a limited number of hepatocytes of liver tissue harvested four months after gene transfer from all five patients. Significant and prolonged reductions in low density lipoprotein (LDL) cholesterol were demonstrated in three of five patients; in vivo LDL catabolism was increased 53% following gene therapy in a receptor negative patient, who realized a reduction in serum LDL equal to approximately 150 mg dl-1. This study demonstrates the feasibility of engrafting limited numbers of retrovirus-transduced hepatocytes without morbidity and achieving persistent gene expression lasting at least four months after gene therapy. The variable metabolic responses observed following low-level genetic reconstitution in the five patients studied precludes a broader application of liver-directed gene therapy without modifications that consistently effect substantially greater gene transfer.

Adult↗