Biomedical subjects

M Zatz

Publications and source records attributed to M Zatz.

256 records · Page 15Linked to original sources

PubMedDate not supplied

Further evidence for the organisation of the four sarcoglycans proteins within the dystrophin-glycoprotein complex.

Based on the pattern of distribution of the SG proteins in patients with LGMD2C and 2D, and on the observed decreased abundance of dystrophin through WB in some sarcoglycans (SG) patients, we have recently suggested that alpha, beta and delta subunits of sarcoglycan complex might be more closely associated and that gamma-SG might interact more directly with dystrophin. Two additional SG patients here reported give further support to these suggestions: an LGMD2F patient showed patchy labelling for gamma-SG, despite the lack of staining of the other three SG proteins; an LGMD2C boy showed deficiency in dystrophin by means of WB and IF, comparable with an DMD manifesting carrier. These two patients represent further evidence of a closer relation of alpha, beta and delta-SG than of gamma-SG and of the possible association of gamma-SG with dystrophin. In addition the LGMD2C patient illustrates the potential risk of misdiagnosis using only dystrophin analysis, in cases with no positive family history, or when DNA analysis is not informative.

Adolescent↗

PubMedDate not supplied

Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina.

The mRNAs encoding three enzymes of the melatonin synthesis pathway (tryptophan hydroxylase (TPH), arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyl-transferase (HIOMT)) are expressed with a day/night rhythm in the chicken pineal gland and retina. TPH and AANAT mRNA levels reach their peak at night. HIOMT mRNA levels peak at night in the retina, but during the day in the pineal gland. In this tissue, the rhythm of TPH, AANAT and HIOMT mRNA levels persisted in constant darkness (DD), both in vivo and in vitro, indicating that the three genes are controlled by the circadian oscillator of the chicken pineal. In the retina, the rhythms of TPH and AANAT mRNA levels also persisted in DD in vivo, suggesting that they are driven by a circadian oscillator. In contrast, the rhythm of HIOMT mRNA in the retina appeared to be controlled only by light. The clones of chicken AANAT and HIOMT genes that we have isolated should help us to understand the molecular mechanisms of: 1) their transcriptional regulation by circadian oscillators and by light; 2) their tissue-specific expression in the pineal gland and the retina.

ARNTL Transcription Factors↗

PubMedDate not supplied

Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases.

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

Age of Onset↗

PubMedDate not supplied

Regulation of protein kinase in rat pineal: increased Vmax in supersensitive glands.

Protein kinase activity was examined in supernatants from super-sensitive and subsensitive rat pineal glands both in the presence and absence of added cAMP. After a 20 min exposure to 1-isoproterenol, in vivo or in organ culture, supersensitive pineals displayed a greater decrease in protein kinase activity (in the absence of added cAMP) than did subsensitive glands. Furthermore, exposure of rats to 24 h light, a procedure which produces a supersensitive response to beta-adrenergic stimulation, results in a 50% increase in protein kinase activity (with or without added cAMP) as compared to the activity in pineals obtained after 12 h darkness, when the glands are subsensitive. Kinetic analysis revealed a 50-100% increase in the Vmax for ATP, histone, and cAMP. This increase in protein kinase was not prevented by prior treatment of rats with cycloheximide. The diminished kinase activity in subsensitive glands did not appear to be due to an increase in the heat-stable protein kinase inhibitor. Protein kinase activity also increased (in the presence or absence of added cAMP) after noradrenergic input to the gland was reduced by denervation or depletion of neurotransmitter. Thus, pineal protein kinase may participate in the effects of beta-adrenergic agonists (e.g. the induction of serotonin N-acetyltransferase) and in the regulation of the sensitivity of the gland to beta-adrenergic stimulation.

Adenosine Triphosphate↗