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Biomedical subjects

R A Martinez

Publications and source records attributed to R A Martinez.

At least 19 recordsLinked to original sources
PubMed2001

Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a CAG repeat expansion. To determine the mechanism of neurotoxicity, we produced transgenic mice and observed a cone-rod dystrophy. Nuclear inclusions were present, suggesting that the disease pathway involves the nucleus. When yeast two-hybrid assays indicated that cone-rod homeobox protein (CRX) interacts with ataxin-7, we performed further studies to assess this interaction. We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. In SCA7 transgenic mice, electrophoretic mobility shift assays indicated reduced CRX binding activity, while RT-PCR analysis detected reductions in CRX-regulated genes. Our results suggest that CRX transcription interference accounts for the retinal degeneration in SCA7 and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disease.

Age Factors↗
PubMed2001

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗
PubMed2001

Genomic organization, chromosome location, and expression analysis of mouse beta-synuclein, a candidate for involvement in neurodegeneration.

The synuclein family of proteins is a group of primarily brain-expressed polypeptides that show a high degree of amino acid conservation. alpha-Synuclein is the best known of the synuclein family, as it is a major component of the Lewy body, a cytoplasmic inclusion characteristic of Parkinson's disease as well as a variety of related neurodegenerative disorders. With the discovery that mutations in alpha-synuclein can cause Parkinson's disease, a potential role for the other synuclein family members in neurodegenerative disease is being considered. beta-Synuclein in particular may deserve special attention, as it is co-expressed with alpha-synuclein at presynaptic nerve terminals, is subject to phosphorylation by Ca(2+) calmodulin protein kinase II, appears important for neural plasticity, and forms aggregates in the brains of patients with Parkinson's disease and a related disorder. To facilitate study of beta-synuclein, we have cloned the mouse beta-synuclein gene (Sncb) and determined its genomic organization, size, and intron-exon structure. Using an interspecific backcross mapping panel from The Jackson Laboratory, we were then able to localize Sncb to chromosome 13 at the MGD 35.0 cM position. Like the human beta-synuclein gene, Sncb appears to consist of six exons separated by five introns. Unlike the human beta-synuclein gene, the mouse ortholog possesses a variant GC 5' splice donor sequence at the exon 4 - intron 4 boundary in a highly conserved splice junction consensus. Northern blot analysis and Western blot analysis both indicate that Sncb is highly expressed in the brain. Knowledge of the genomic organization and expression pattern of Sncb will allow functional studies of its potential role in neurodegeneration to commence in the mouse.

Amino Acid Sequence↗
PubMed2000

Late-onset SCA2: 33 CAG repeats are sufficient to cause disease.

SCA-2 is an autosomal dominant inherited disorder characterized by ataxia, slow saccades, and hyporeflexia. The authors evaluated a patient with a mild balance problem with a SCA-2 allele sized at 33 CAG repeats. The authors then ascertained her 91 year-old mother, who showed disease onset at age 86 with an SCA-2 allele of identical size. Their study indicates that 33 CAG repeats can be pathogenic at the SCA-2 locus, though such an allele may produce an extremely late onset and gradual rate of disease progression.

Aged↗
PubMed2000

Low incidence of persistent tardive dyskinesia in elderly patients with dementia treated with risperidone.

OBJECTIVE: The authors studied the incidence of tardive dyskinesia in elderly institutionalized patients with dementia being treated with risperidone. METHOD: After participating in a 12-week multicenter double-blind study during which they received placebo or one of three doses of risperidone, 330 patients (mean age=82.5 years) with Alzheimer's, vascular, or mixed dementia were enrolled in a 1-year open-label study during which they received flexible doses of risperidone. Persistent emergent tardive dyskinesia was defined according to scores on the dyskinesia subscale of the Extrapyramidal Symptom Rating Scale. RESULTS: The mean modal risperidone dose was 0.96 mg/day (SD=0.53), and the median length of risperidone use was 273 days. The 1-year cumulative incidence of persistent emergent tardive dyskinesia among the 255 patients without dyskinesia at baseline was 2.6%. Patients with dyskinetic symptoms at baseline experienced significant reductions in the severity of dyskinesia. Patients who received 0.75-1.5 mg/day of risperidone showed a significant improvement in psychopathologic symptoms over the 1-year period. CONCLUSIONS: Although there was no control group, the observed incidence of persistent tardive dyskinesia with risperidone seemed to be much lower than that seen in elderly patients treated with conventional neuroleptics. The average optimal dose of risperidone in elderly dementia patients was found to be 0.75-1.5 mg/day.

Aged↗
PubMed1999

Relationship between physical and psychosocial dysfunction in Mexican patients with vertigo: a cross-cultural validation of the vertigo symptom scale.

The Vertigo Symptom Scale (VSS) was designed to assess and differentiate symptoms of: (a) balance disorder; and (b) somatic anxiety and autonomic arousal in patients complaining of dizziness and vertigo. Although it has been translated for use in countries other than the UK, where it was originally developed, its validity in different languages and cultures has not previously been evaluated. This study examined the structure, reliability, and discriminative power of a Spanish translation of the VSS administered to a Mexican sample of 172 dizzy patients and 40 healthy controls. Scores on the two subscales of the VSS not only discriminated between patients and controls, but were also sensitive to differences between patient groups classified on the basis of diagnosis, test results, and occupational disability. The pattern of intercorrelations between symptoms, anxiety, depression, and handicap in the Mexican sample was almost identical to that observed in the original UK sample.

Adult↗
PubMed1995

National Medical Association/National Institutes of Health Workshop on Violence and the Conduct of Research. Workgroup Proceedings, June 1-2, 1994.

The physical, economic, and mental toll caused by violence in the United States has put tremendous pressure on American medical, political, religious, and social institutions. The impact in urban neighborhoods has been especially harrowing, forcing African-American organizations to address this domestic problem with ideas and suggestions unique to their philosophies and collective talents. This article contains general perspectives and commentary from physicians and social science experts who participated in a workshop sponsored by the National Medical Association, the National Institute of Drug Abuse, and the National Institute of Mental Health to discuss topics on violence, its health consequences, and the conduct of research in the African-American community.

Black or African American↗
PubMed1993

Autonomic dysfunction in patients with dementia of the Alzheimer type.

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.

Aged↗
PubMed1993

CSF somatostatin in Alzheimer's disease and major depression: relationship to hypothalamic-pituitary-adrenal axis and clinical measures.

Patients with Alzheimer's disease (AD) and major depression have been shown to have overlapping clinical symptoms and biological markers, including decreased concentrations of cerebrospinal fluid (CSF) somatostatin-like immunoreactivity (SLI), which may be related to alterations in the hypothalamic-pituitary-adrenal axis activity. As in prior studies, we found that CSF SLI was significantly decreased in a group of AD patients (N = 49) and a group of elderly patients with major depression (N = 18), as compared with 13 age-matched controls (F[2, 77] = 12.9, p < .001). In the present study, CSF SLI and CSF corticotropin-releasing factor correlated significantly within the group of AD patients (r = 0.49, p < .0004) and almost attained significance in the depressed patients (r = 0.47, p < .07). CSF SLI correlated significantly with urinary free cortisol within each patient group (r = -0.51, p < .03). Clinical measures of dementia severity and depression did not consistently correlate with CSF SLI in either patient group.

Aged↗
PubMed1993

Familial alcoholism and ERPs: differences in probability sensitivity?

Event-related potentials (ERPs) were recorded from sons (age 11-14) of families that were positive (FH+) and negative (FH-) for alcoholism in response to circles, triangles and squares presented in four colors with a single central digit. A button was pressed for successive presentations of identical stimuli (target probability = 0.2). Reduced late positivity in FH+ boys has been previously reported. This positivity was shown to increase with the number of features that match target requirements. FH- boys responded more quickly, but no less accurately, than FH- boys, and were characterized by reduced ERP stimulus selectivity. That is, FH+ boys not only produced less P3 than FH- boys in response to targets, but generally produced more late positivity than FH- boys in response to nontargets. The pattern of group differences was most consistent with FH+ boys exhibiting both reduced ERP effects of target features in general, and a specific insensitivity to matching digits. It is hypothesized that these effects result from reduced sensitivity to information about the frequency with which categories of events occur, and that this may be characteristic of those at high risk for alcoholism.

Adolescent↗
PubMed1991

Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.

Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.

Aged↗
PubMed1991

CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression.

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.

Aged↗
PubMed1991

Lack of seasonal variation in the births of patients with dementia of the Alzheimer type.

Seasonal variation in the birth rates of patients suffering from dementia of the Alzheimer type (DAT) was investigated in 150 patients, aged 42-88 years, and in 132 normal control subjects of comparable age and gender. No seasonal variation or cyclic trend could be demonstrated in the DAT patients compared with control subjects. The exclusion from the analysis of the patients with a positive family history did not change the results of the study, which further suggests that a seasonality in DAT birth rates is unlikely.

Adult↗
PubMed1990

Reflections of the self: atypical misidentification and delusional syndromes in two patients with Alzheimer's disease.

Two patients with moderately severe AD, when asked directly, could identify their own images in a mirror, but also consistently misidentified their own reflections as that of another person. Both patients were paranoid and mildly depressed at times, but had no evidence of other concurrent psychotic symptoms. It appeared that mood substantially modified the nature of the symptom and the patients' reaction to it over time. These cases illustrate the ability of an organic symptom to be modified by a concurrent affective state, indicating the importance of the interaction between biological and psychological factors in the expression of such symptoms.

Alzheimer Disease↗
PubMed1989

Antigenic relationships of fractionated western diamondback rattlesnake (Crotalus atrox) hemorrhagic toxins and other rattlesnake venoms as indicated by monoclonal antibodies.

Seven hemorrhagic factors have been isolated from Crotalus atrox venom, but their antigenic relationships have not been well studied. In this study, two different monoclonal antibodies, C. atrox peak 8 (CA-P-8) and C. atrox subclone 5 (CA-5+), were produced against two C. atrox venom hemorrhagic fractions and used in an ELISA (enzyme-linked immunosorbent assay) to determine if the hemorrhagic factors in C. atrox venom are antigenically related. The same ELISA test was used to determine cross-reactivity of seven other crude Crotalidae venoms. The two monoclonal antibodies were tested for their ability to neutralize each hemorrhagic HPLC fraction separated from C. atrox venom. C. atrox venom was fractionated into 22 fractions using HPLC analytical DEAE ion exchange. Fractions 4-17 were hemorrhagic. The CA-P-8 monoclonal antibody reacted strongly with hemorrhagic fraction 8; CA-5+ had a broader reactivity and reacted with several HPLC hemorrhagic and non-hemorrhagic fractions. Crude venoms of C. adamanteus, C. scutulatus scutulatus and C. viridis lutosus reacted with CA-P-8, while C. viridis lutosus, C. viridis oreganus, C. scutulatus scutulatus and C. horridus horridus reacted with CA-5+. C. molossus molossus and C. lepidus lepidus did not react with CA-P-8 and CA-5+. Hemorrhagic HPLC fractions 6, 7, 8, were completely neutralized by monoclonal antibody CA-P-8; fraction 9 was partially neutralized. The present study indicated that some C. atrox venom HPLC hemorrhagic fractions have both common and unique epitopes. Antigenic determinants were also found to be shared among different Crotalus species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗