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Biomedical subjects

S Mora

Publications and source records attributed to S Mora.

At least 37 records · Page 2Linked to original sources
PubMed2001

A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease.

OBJECTIVE: Because osteopenia is a frequent complication of celiac disease, we evaluated the impact of a long-term gluten-free diet (GFD), initiated during childhood, on bone density. study design: Patients with celiac disease (n = 19; mean age, 14.2 +/- 2.6 years) were studied after 4.3 +/- 0.6 years of GFD. Bone density had been measured at diagnosis and after 1 year of GFD. We also studied 211 healthy children as a control group. Bone mineral density was measured by dual-energy x-ray absorptiometry. Intact parathyroid hormone (PTH) and bone-specific alkaline phosphatase (BALP) levels were measured in serum, and N-terminal telopeptide of type I collagen (NTx) was measured in urine. RESULTS: Although at diagnosis bone mineral content, bone area, and bone mineral density were significantly lower than in control subjects, the 3 measurements were normal after GFD. None of the patients on a GFD showed elevated values of PTH. Patients on a GFD had BALP (110.2 +/- 67.2 U/L) and NTx levels (261.9 +/- 187.8 nmol bone collagen equivalents/mmol creatinine) that were significantly higher than those of control subjects. The levels of BALP and NTx were significantly higher in patients with good compliance with the GFD, compared with patients with poorer compliance. CONCLUSIONS: This study shows that bone mineral content, bone area, and bone mineral density improve significantly with a GFD.

Absorptiometry, Photon↗
PubMed2001

VAMP3 null mice display normal constitutive, insulin- and exercise-regulated vesicle trafficking.

To investigate the physiological function of the VAMP3 vesicle SNARE (v-SNARE) isoform in the regulation of GLUT4 vesicle trafficking, we generated homozygotic VAMP3 null mice by targeted gene disruption. The VAMP3 null mice had typical growth rate and weight gain, with normal maintenance of fasting serum glucose and insulin levels. Analysis of glucose disposal and insulin sensitivity demonstrated normal insulin and glucose tolerance, with no evidence for insulin resistance. Insulin stimulation of glucose uptake in isolated primary adipocytes was essentially the same for the wild-type and VAMP3 null mice. Similarly, insulin-, hypoxia-, and exercise-stimulated glucose uptake in isolated skeletal muscle did not differ significantly. In addition, other general membrane trafficking events including phagocytosis, pinocytosis, and transferrin receptor recycling were also found to be unaffected in the VAMP3 null mice. Taken together, these data demonstrate that VAMP3 function is not necessary for either regulated GLUT4 translocation or general constitutive membrane recycling.

Adipocytes↗
PubMed2001

Early fractures and occult hyperthyroidism: McCune-Albright syndrome?

McCune-Albright syndrome (MAS) is a sporadic disease characterized by fibrous bone dysplasia, café-au-lait spots and hyperfunctional endocrinopathies. We report a 2.5-year-old child with MAS with an early and nonclassic onset. He was admitted to our attention for frequent fractures without clinical signs of endocrinopathies, found to have asymptomatic, nonautoimmune hyperthyroidism. The diagnosis of MAS was based on RX and MR imaging associated with hyperthyroidism. It is not clear if there was a correlation between the severity of bone disease and the presence of thyroid disorder. At the moment no standard treatment exists for bone fibrous dysplasia and hyperthyroidism in children before the age of 6 years.

Child, Preschool↗
PubMed2001

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4(+/-) mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.

Adipocytes↗
PubMed2001

Pediatric calcaneal fractures.

Calcaneal fractures in pediatric patients are seen infrequently. We retrospectively reviewed 22 skeletally immature patients with 23 fractures of the calcaneus before their distal tibial physis had fused. Eighteen (78%) of these fractures were intraarticular and five (22%) were extraarticular. Nine patients were followed for an average of 4.4 years. Of these nine fractures, 8 were treated non-operatively and one was treated with open reduction and internal fixation. A modification of the American Orthopaedic Foot and Ankle Society scoring system, which focuses on residual complaints of pain, work or sports restrictions, ability to walk on different surfaces and gait abnormalities, was employed to assess their outcome. Seven of the nine patients were free of pain, had unrestricted foot function, and possessed no apparent gait abnormalities. Two patients had activity related and cold weather related pain. We believe that the excellent prognosis for both intraarticular and extraarticular fractures, seen in this study is multi-fold. First, the immature talus and calcaneus have a superior capacity to remodel. Second, pediatric calcaneal fractures are usually consequence of low energy trauma. Lastly, a favorable intraarticular fracture pattern, unique to the skeletally immature calcaneus may exist, rendering a good prognosis.

Adolescent↗
PubMed2001

Skeletal age determinations in children of European and African descent: applicability of the Greulich and Pyle standards.

This study assesses the value of the Greulich and Pyle method in determining the skeletal ages of healthy American children of European and African descent born after the year 1980. The hand and wrist radiographs of 534 children (265 boys, 269 girls; 260 European-Americans [EA], 274 African-Americans [AA]), ages 0 to 19 y, were analyzed by two experienced pediatric radiologists blinded to the chronological age of the subjects. A difference score was calculated for each subject by subtracting chronological age from the mean bone ages scores provided by the two raters. One group t-tests were performed to verify the hypothesis that the mean difference score was equal to zero. Skeletal age determinations by the two radiologists showed a high degree of agreement by intraclass correlation coefficient (r = 0.994). The range of values for differences in skeletal and chronological ages was very wide, indicating great individual variability. Comparisons between skeletal and chronological age only reached statistical significance in EA prepubertal girls, whose skeletal ages were delayed, on average, by three months (t = -2.9; p = 0.005). Mean difference between skeletal and chronological age in prepubertal children of African descent was 0.09 +/- 0.66 y, while that in children of European descent was -0.17 +/- 0.67 y; (t = 3.13; p = 0.0019). On average, the bone ages of 10% of all prepubertal AA children were 2 SD above the normative data in the Greulich and Pyle atlas, while the bone ages of 8% of all prepubertal EA children were 2 SD below. In contrast to the racial differences observed in prepubertal children, EA postpubertal males had significantly greater values for bone age than AA postpubertal males (t = 2.03; p = 0.05). In conclusion, variations in skeletal maturation in prepubertal children are greater than those reflected in the Greulich and Pyle atlas; prepubertal American children of European descent have significantly delayed skeletal maturation when compared with those of African descent; and, postpubertal EA males have significantly advanced skeletal maturation when compared with postpubertal AA males. New standards are needed to make clinical decisions that require reliable bone ages and to accurately represent a multiethnic pediatric population.

Adolescent↗
PubMed2001

The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose tissue during states of insulin deficiency.

Previously we have demonstrated that striated muscle GLUT4 gene expression decreased following streptozotocin-induced diabetes due to a loss of MEF2A transcription factor expression without any significant effect on the MEF2D isoform (Mora, S. and J. E. Pessin (2000) J Biol Chem, 275:16323-16328). In contrast to both cardiac and skeletal muscle, adipose tissue displays a selective decrease in MEF2D expression in diabetes without any significant alteration in MEF2A protein content. Adipose tissue also expresses very low levels of the MEF2 transcription factors and nuclear extracts from white adipose tissue exhibit poor in vitro binding to the MEF2 element. However, addition of in vitro synthesized MEF2A to adipose nuclear extracts results in the formation of the expected MEF2/DNA complex. More importantly, binding to the MEF2 element was also compromised in the diabetic condition. Furthermore, in vivo overexpression of MEF2A selectively in adipose tissue did not affect GLUT4 or MEF2D expression and was not sufficient to prevent GLUT4 down-regulation that occurred in insulin-deficient states.

Adipose Tissue↗
PubMed2000

Certain cardiac risk factors predict risk factor interventions and influence communication between physicians and patients.

We assessed predictors of cardiac risk factor testing and services and the degree of concordance among patients, physicians, and the medical records for these services, and found considerable variability among different risk factors. The data suggest that baseline risk factors influence communication and performance of interventions and that physicians appear to be underestimating the importance of treating multiple risk factors simultaneously.

Adult↗
PubMed2000

CAP defines a second signalling pathway required for insulin-stimulated glucose transport.

Insulin stimulates the transport of glucose into fat and muscle cells. Although the precise molecular mechanisms involved in this process remain uncertain, insulin initiates its actions by binding to its tyrosine kinase receptor, leading to the phosphorylation of intracellular substrates. One such substrate is the Cbl proto-oncogene product. Cbl is recruited to the insulin receptor by interaction with the adapter protein CAP, through one of three adjacent SH3 domains in the carboxy terminus of CAP. Upon phosphorylation of Cbl, the CAP-Cbl complex dissociates from the insulin receptor and moves to a caveolin-enriched, triton-insoluble membrane fraction. Here, to identify a molecular mechanism underlying this subcellular redistribution, we screened a yeast two-hybrid library using the amino-terminal region of CAP and identified the caveolar protein flotillin. Flotillin forms a ternary complex with CAP and Cbl, directing the localization of the CAP-Cbl complex to a lipid raft subdomain of the plasma membrane. Expression of the N-terminal domain of CAP in 3T3-L1 adipocytes blocks the stimulation of glucose transport by insulin, without affecting signalling events that depend on phosphatidylinositol-3-OH kinase. Thus, localization of the Cbl-CAP complex to lipid rafts generates a pathway that is crucial in the regulation of glucose uptake.

3T3 Cells↗
PubMed2000

The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter.

Previously, we have demonstrated that an MEF2 consensus sequence located between -473/-464 in the human GLUT4 gene was essential for both tissue-specific and hormonal/metabolic regulation of GLUT4 expression (Thai, M. V., Guruswamy, S., Cao, K. T., Pessin, J. E., and Olson, A. L. (1998) J. Biol. Chem. 273, 14285-14292). To identify the specific MEF2 isoform(s) responsible for GLUT4 expression, we studied the pattern of expression of the MEF2 isoforms in insulin-sensitive tissues. Both heart and skeletal muscle were found to express the MEF2A, MEF2C, and MEF2D isoforms but not MEF2B. However, only the MEF2A protein was selectively down-regulated in insulin-deficient diabetes. Co-immunoprecipitation with isoform-specific antibodies revealed that, in the basal state, essentially all of the MEF2A protein was presented as a MEF2A-MEF2D heterodimer without any detectable MEF2A-MEF2A homodimers or MEF2A-MEF2C and MEF2C-MEF2D heterodimers. Electrophoretic mobility shift assays revealed that nuclear extracts from diabetic animals had reduced binding to the MEF2 binding site compared with extracts from control or insulin-treated animals. Furthermore, immunodepletion of the MEF2A-MEF2D complex from control extracts abolished binding to the MEF2 element. However, addition of MEF2A to diabetic nuclear extracts fully restored binding activity to the MEF2 element. These data strongly suggest that the MEF2A-MEF2D heterodimer is selectively decreased in insulin-deficient diabetes and is responsible for hormonally regulated expression of the GLUT4 gene.

Animals↗
PubMed2000

Cognitive function and neurophysiological evaluation in early-treated hypothyroid children.

In this study, we assessed cognitive function and neurophysiological development in congenitally hypothyroid (CH) children. We performed a cross-sectional study at the outpatient Pediatric Clinic and Department of Neurophysiology at San Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of age) detected by neonatal screening, and 34 healthy control children (4-11 years of age). Patients and controls had comparable scores at neuropsychological tests (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after birth showed lower scores at neuropsychological tests, but not at neurophysiological tests, compared to patients who started the replacement therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and similar neurophysiological results, compared with patients with moderate fetal hypothyroidism. The severity of fetal hypothyroidism and early treatment influence the mental outcome of CH patients. Neurophysiological results show that central nervous system damage occurs in some patients despite early treatment.

Child↗
PubMed2000

Gender, estrous cycle, ovariectomy, and ovarian hormones influence the effects of diazepam on avoidance conditioning in rats.

This study examines whether the hormonal condition of the rat modifies the effects of diazepam (0.25 and 1.0 mg/kg) on avoidance conditioning and other behavioral responses. Acquisition of a conditioning avoidance response (CAR) and spontaneous motor behaviors were assessed in intact male, in intact diestrous and estrous females, and in ovariectomized (OVX) rats injected with estradiol (2 microg/rat, SC) or progesterone (5 mg/rat, SC). A higher dose (1.0 mg/kg) of diazepam significantly impaired the acquisition of CARs in diestrous, OVX, OVX + progesterone, and male rats. Conversely, both doses of diazepam significantly improved the acquisition of CAR in estrous rats and in OVX rats injected with estradiol. These effects on conditioning avoidance were not accompanied with equivalent changes in spontaneous motor behaviors. Motor activity and grooming behavior decreased in all experimental groups after administration of 1.0 mg/kg of diazepam. On the contrary, diazepam 0.25 mg/kg increased motor activity in estrous, OVX + estradiol, and OVX + progesterone rats after, whereas grooming behavior was not affected in any group. These findings suggest a physiological influence of ovarian steroid hormones in modifying the benzodiazepine effects on conditioning avoidance and motor activity. The results are discussed considering that ovarian steroids may interact with diazepam on the GABA(A)/benzodiazapine/chloride ionophore complex, modifying the coupling between benzodiazepine sites and GABA(A) receptors.

Animals↗
PubMed2000

Body composition in children with celiac disease and the effects of a gluten-free diet: a prospective case-control study.

BACKGROUND: Celiac disease is the most common cause of malnutrition in children of Western countries. OBJECTIVE: The objective was to measure body composition in children at the time celiac disease was diagnosed and after consumption of a gluten-free diet (GFD). DESIGN: We assessed body composition by dual-energy X-ray absorptiometry in 29 children and adolescents with a mean (+/-SD) age of 9.5 +/- 3.4 y at the time celiac disease was diagnosed and in a subset of 20 patients after 1.2 +/- 0.2 y of a GFD. We also studied 23 patients aged 21.2 +/- 4.6 y who consumed a GFD for 10.6 +/- 4.5 y. Each patient was matched with a healthy control subject of the same age and sex. RESULTS: Untreated patients weighed less than control subjects (P = 0.04). Fat mass and bone mineral content were lower in the patients than in the control subjects (P < 0.01), as was lean mass of the limbs (P = 0.0013). After approximately 1 y of the GFD, there were no significant differences in body-composition values between patients and control subjects. Similarly, body-composition values of celiac disease patients who consumed the GFD long term were comparable with those of healthy subjects. CONCLUSIONS: Remarkable abnormalities in body composition were found in children at the time of diagnosis of celiac disease. Appropriate dietary treatment reverses body-composition abnormalities quickly and the beneficial effects of gluten withdrawal are persistent. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made.

Absorptiometry, Photon↗
PubMed1999

Behavioral effects of dopamine agonists and antagonists: influence of estrous cycle, ovariectomy, and estrogen replacement in rats.

The influence of the hormonal condition on the reactivity of central dopamine (DA) receptors was studied in male and in intact and ovariectomized (OVX) female rats. They were injected with selective DA agonists, acting either on D1 (SKF 38393, 2.5 or 10 mg/kg) or D2 receptors (PPHT, 31.3 or 125 microg/kg), or with selective DA antagonists, acting either on D1 (SCH 23390, 6.25 or 25 microg/kg), or D2 receptors (sulpiride, 10 or 40 mg/kg). The acquisition of an avoidance conditioning response (CAR) and the performance of some spontaneous motor behaviors were tested. Both D1 and D2 agonists and antagonists impaired the acquisition of CARs in diestrous, OVX, and male rats. Nevertheless, the effects of these drugs during estrus and in estradiol-primed OVX rats were different according to the drug and the dose injected. Whereas SKF 38393 failed to induce significative changes, PPHT and low doses of SCH 23390 and sulpiride improved the acquisition of CARS in those groups. The effects on conditioning were not accompanied with equivalent changes in spontaneous motor activity. Estradiol level fluctuations that occur in female rats within the estrous cycle or in OVX rats primed with estradiol would be responsive of changes in the response to DA agents. Although the reactivity of central DA systems is differentially affected by the hormonal condition of the rat, the precise mechanism of this modulatory action remains unknown.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients.

OBJECTIVES: Osteoporosis and alterations of bone metabolism are frequent complications of celiac disease. We evaluated the impact of long-term gluten-free diet (GFD) initiated during childhood and adolescence on bone mineralization and bone metabolism. METHODS: We studied 30 celiac patients on GFD for > or = 5 yr. The mean age at diagnosis was 11.4+/-5.0 yr, and the mean duration of GFD was 10.7+/-4.3 yr. Results were compared with those obtained in 240 healthy controls. Bone mineral density (BMD) was measured in the lumbar spine and in the whole skeleton by dual-energy x-ray absorptiometry. Serum levels of bone-specific alkaline phosphatase (BALP) and N-terminal propeptide of type I procollagen (PINP) were measured as bone formation indices, and urine levels of N-telopeptide of type I collagen (NTx) as bone resorption index. RESULTS: BMD measurements of celiac patients (lumbar spine: 1.131+/-0.121 g/cm2; total body: 1.145+/-0.184 g/cm2) did not differ from those of control subjects (lumbar spine: 1.131+/-0.184 g/cm2; total body: 1.159+/-0.118 g/cm2). The levels of BALP, PINP, and NTx of celiac patients did not differ from those of controls. Patients who started GFD before puberty had BMD and bone metabolism measurements comparable to those of patients who started GFD during puberty. CONCLUSIONS: Our data show that long-term dietary treatment ensures normal mineralization and bone turnover.

Absorptiometry, Photon↗
PubMed1999

Prolactin is an autocrine or paracrine growth factor for human myometrial and leiomyoma cells.

OBJECTIVE: To test the hypothesis that prolactin (PRL) acts as a mitogenic growth factor for human leiomyoma and myometrial cells. METHODS: To test this hypothesis, we performed three different types of experiments. First, we assessed whether exogenous PRL acted as a mitogen for cultured uterine smooth muscle cells. Second, we examined the role of endogenous PRL by assessing the cell number after exposure of the cultures to a neutralizing antibody to PRL. Finally, we examined both fresh tissues and cultured cells for expression of the PRL receptor messenger ribonucleic acid using the techniques of reverse-transcriptase polymerase chain reaction and Southern blotting. RESULTS: A significant suppression in cell number was seen after 5 days of culture for leiomyoma cells but not for myometrial cells after treatment with exogenous PRL. Both cell types showed a significant decrease in cell number after treatment with anti-PRL antibody. A 893-bp segment consistent with the cytoplasmic domain of the long form of the PRL receptor was amplified from both fresh and cultured tissues and confirmed by Southern blotting and sequencing. CONCLUSIONS: PRL appears to be an autocrine or paracrine growth factor for both leiomyoma and myometrial cells. However, there are some differences between tissues in their sensitivity to this growth factor.

Antibodies↗