Biomedical subjects

A Mariash

Publications and source records attributed to A Mariash.

6 recordsLinked to original sources

PubMed2005

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Aging↗

PubMed2001

Spot 14 gene deletion increases hepatic de novo lipogenesis.

Previous studies have investigated the relationship between the Spot 14 gene and hepatic lipogenesis. Those studies found that the Spot 14 protein was induced when lipogenesis was induced and suggested that induction of the Spot 14 protein was required for induction of hepatic lipogenesis by thyroid hormone and dietary carbohydrate. Analysis of those findings led us to hypothesize that the Spot 14 gene is required for induced hepatic de novo lipogenesis in vivo. To test this hypothesis, we created an in vivo deletion of the Spot 14 gene in mice using gene-targeting technology. Southern blot analysis showed that the Spot 14 gene was disrupted. Northern blot analysis showed that this disruption ablated expression of intact hepatic Spot 14 mRNA. In contrast to our hypothesis, acute thyroid hormone administration led to comparable induction of hepatic lipogenic enzyme mRNAs between the wild-type and knockout mice. Furthermore, long-term treatment with both thyroid hormone and a diet promoting lipogenesis led to enhanced lipogenic enzyme activity and a greater rate of hepatic de novo lipogenesis in the knockout, compared with the wild-type, mice. Although these data indicate that the Spot 14 protein is not required for induced hepatic de novo lipogenesis, they also suggest that Spot 14 plays some role in this process. It is possible that alternative pathways that complement the loss of the Spot 14 protein are present, and in the absence of Spot 14, these alternative pathways overcompensate to produce an enhanced rate of induced lipogenesis.

Animals↗

PubMed1999

Induction of bone formation in rat osteoprogenitor cell culture by sera of climacteric women before and after hormone replacement therapy.

OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on growth and differentiation of cultured osteoprogenitor cells. DESIGN: Prospective clinical study. SETTING: Outpatients in a menopause clinic. PATIENT(S): Women with climacteric symptoms. INTERVENTION(S): Daily oral conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 2.5 mg, for 7-12 months. Bone density measurement before HRT and blood sampling before and after HRT. MAIN OUTCOME MEASURE(S): Sera of climacteric women were added to the culture of rat osteoprogenitor cells, and indices of cell proliferation and differentiation (alkaline phosphatase activity and mineralization) were measured before and after HRT. RESULT(S): Sera after HRT significantly decreased cell counts but not alkaline phosphatase activity or mineralization as compared with sera before HRT. However, mineralization induced in the bioassay by both sera showed a positive correlation (r = 0.56) with E2 levels before treatment and a negative correlation (r = -0.6181) with time in menopause of serum donors. The change in mineralization showed a significant correlation with hip bone mineral density z scores (r = -0.67) but not with spine z scores (r = -0.1915), whereas the change in cell count correlated with spine bone mineral density z scores (r = 0.49) only. CONCLUSION(S): Changes in serum-induced cell proliferation and mineralization may be helpful in studying the response to HRT in climacteric women. Serum-induced mineralization is more efficient in diagnosing osteopenia than in monitoring HRT effects.

Adult↗

PubMed1997

Cloning, expression and regulation of the human S14 gene.

The rat S14 gene has been a useful model to study carbohydrate and triiodothyronine (T3) regulation of hepatic gene expression. To gain insight into the regulation and function of the S14 gene, we isolated the human S14 gene and studied its sequence, tissue specific expression, and transcriptional regulation by glucose and T3. The deduced amino acid sequence of the human S14 protein is 78% identical to that of the rat. Northern blot analysis showed that the S14-mRNA is a single species in human liver and is not present in human brain or HepG2 cells. Transfection studies in primary hepatocytes revealed that transcription of the human S14 gene is regulated by glucose and T3 in a similar manner to that of the rat gene. However, in HepG2 cells, T3 and glucose did not affect the transcription of the human S14 gene. These observations suggest that the S14 gene is highly conserved in mammals and is similarly regulated by carbohydrate and T3 in vivo. More importantly, the function of the human S14 gene may be critical in lipid metabolism in human liver as the rat S14 gene is in rodents.

Amino Acid Sequence↗

PubMed1996

Differential induction of cell-mediated mineralization in rat marrow stroma by sera from women of low and high risk for vertebral fracture.

The purpose of this study was to analyze the ability of sera to reflect the state of bone metabolism by testing the osteogenic response of mesenchymal cells in culture. Sera of 20 peri- and postmenopausal women were tested before the initiation of hormone replacement therapy. The responding cells were osteoprogenitors (OPC) of rat marrow stroma which normally respond to dexamethasone (DEX) and beta-glycerophosphate (beta GP) by proliferation, differentiation, and mineralization in culture. Instead of DEX, diluted sera (1:50) were applied to rat stromal cell cultures for analysis of their ability to affect cell proliferation, specific alkaline phosphatase (ALP) activity, and cell-mediated mineralization. The results were compared individually with the respective values of vertebral bone mineral density (BMD), expressed as the number of standard deviations above or below the mean BMD of reference populations (positive or negative Z-score). Serum donors were divided in two; the group with positive Z-scores was considered to have a low risk, and that with negative Z-scores was considered to have a higher risk for vertebral fractures. No significant difference was found between the two groups in the ability of their sera to induce cell proliferation or specific ALP activity. However, sera representing negative Z-scores induced sixteenfold less mineralization than those of positive Z-scores. The scatter of individual mineralization values was highly discriminatory between the two groups (alpha < 0.00). These results indicate that the serum-induced, cell-mediated mineralization in culture might be suitable for initial evaluation of fracture risk and thus deserve further investigation.

Alkaline Phosphatase↗

PubMed1996

Insulin increases the processing efficiency of messenger ribonucleic acid-S14 nuclear precursor.

Feeding a lipogenic diet increases transcription and enhances processing of the rat hepatic messenger RNA (mRNA)-S14 gene. To determine the separate roles of insulin and increased glucose in these processes, we used the streptozotocin-induced diabetic rat model. Diabetes caused a reduction in mature mRNA-S14 in chow- and lipogenic diet-fed animals (P < 0.006 and P < 0.001, respectively). Insulin restored these levels to normal. Despite the known effects of insulin and carbohydrate on the transcription of this gene, we were unable to demonstrate significant changes in the nuclear proteins that bind to carbohydrate response regions. Yet, insulin restored the content of the mRNA by increasing the ratio of mature to precursor mRNA-S14. Insulin significantly increased this ratio (P < 0.0001) independent of diet and diabetes, further supporting the action of insulin on increasing processing from precursor to mature mRNA. The mechanism of the enhanced processing was studied by ribonuclease mapping and primer extension analysis. Ribonuclease mapping showed that lipogenic diet feeding increases the efficiency of processing at a step before formation of the branched form of the precursor mRNA. Taken together, our data demonstrate for the first time that insulin significantly enhances the efficiency of processing of a pre-mRNA.

Animals↗