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Biomedical subjects

C F Moniz

Publications and source records attributed to C F Moniz.

12 recordsLinked to original sources
PubMed1999

Genetic studies of a family with hereditary hyperparathyroidism-jaw tumour syndrome.

BACKGROUND AND OBJECTIVES: Familial hyperparathyroidism may occur as familial isolated hyperparathyroidism (FIHP) or as part of an inherited syndrome, in particular multiple endocrine neoplasia types 1 and 2A (MEN1, MEN2A) and hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The localization of the genes responsible for these syndromes has enabled genetic screening of families with primary hyperparathyroidism (PHPT) to be carried out. This has important clinical implications in terms of individual follow-up and management. We previously reported a large FIHP family with an increased risk of parathyroid cancer and excluded its linkage to MEN1, MEN2 and PTH genes. Here we re-analysed this family and performed genetic linkage to the HPT-JT locus in chromosome 1q21-q32. Loss of heterozygosity studies of 1q21-q32, 11q13 and X chromosome were also performed. PATIENTS AND DESIGN: We studied 19 family members, aged 6-63 years. High molecular weight DNA was isolated from peripheral blood samples from 17 family members. For the two deceased individuals, DNA was extracted from normal paraffin embedded tissues. MEASUREMENTS: All individuals (except two deceased patients) had serum corrected calcium, inorganic phosphate, intact PTH, prolactin and various pancreatic hormones, measured on fasting blood samples. Twenty microsatellite markers were examined for the 1q21-q32 region, the locus for the HPT-JT gene. Genetic polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and genetic linkage analysis was performed. Loss of heterozygosity studies were performed using paraffin-embedded parathyroid tissues from four affected members. RESULTS: Seven of the eight affected family members included in this study had biochemical evidence of PHPT and surgically proven parathyroid tumours. Indication of linkage of the disease to the HPT-JT locus was demonstrated with a maximum lod score of 2.32 by two-points linkage analysis. Linkage data were supported by multi-point analysis which gave a maximum lod score of 2.7. Meiotic recombinations detected in one affected individual narrowed the region to 26 cM. As a result of the genetic findings, we re-screened the living family members by orthopantomograph and renal ultrasound, and identified two jaw lesions in two gene carriers. One affected family member demonstrated polycystic kidney disease, thus establishing the association between the two conditions. A reduced penetrance of HPT in females was evident, in agreement with our previous study. No allelic deletion was detected in any tumour at 1q21-q32, 11q13 or X chromosome. CONCLUSIONS: This study illustrates the usefulness and importance of genetic studies in familial isolated hyperparathyroidism families. Our clinical and genetic findings indicate that this previously reported familial isolated hyperparathyroidism family has hyperparathyroidism-jaw tumour syndrome.

Adolescent↗
PubMed1996

Two nuclear proteins bind to the promoter P3 region of the human parathyroid hormone-related peptide gene.

We have used a 5' regulatory sequence fragment of the human parathyroid hormone-related peptide (PTHrP) gene to identify nuclear DNA-binding proteins (DBP), using South-Western analysis. The PTHrP 549 bp DNA fragment was amplified from a human genomic DNA, and composed of 5' non-coding exon Ic, the intervening intron and 5' non-coding exon II. The DNA fragment bound very specifically to a 70 kDa and a 65 kD protein from the nuclear extract of human hepatocyte, HepG2, and keratinocyte, SVK-14, cell lines. This is the first evidence of a physical binding between nuclear protein and the human PTHrP gene. The 70 kDa and 65 kDa nuclear proteins may have a role in the regulation of human PTHrP gene expression.

Base Sequence↗
PubMed1993

Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer.

Familial isolated hyperparathyroidism (FIHP) is a rare heritable disorder characterized by hypercalcemia, inappropriately high PTH levels, and isolated parathyroid tumors with no evidence of hyperfunction of any other endocrine tissues. To establish whether FIHP exists as a distinct disease entity or represents a variant of any of the known multiple endocrine neoplasia (MEN) syndromes, we tested 19 members of a large, well characterized family with FIHP in which the disease is transmitted through 4 generations in an autosomal dominant fashion. Fourteen DNA markers at 10 polymorphic loci closely linked to the MEN1 locus on the long arm of chromosome 11 and 5 markers close to the MEN2A gene on chromosome 10 were tested using Southern blot analysis and polymerase chain reaction-based techniques. Additionally, two polymorphic markers (Mir1 and Mir2) within the prepro-PTH gene on the short arm of chromosome 11 were analyzed using denaturant gradient gel electrophoresis. Linkage was clearly excluded between FIHP and the MEN1 and MEN2A loci as well as to the PTH gene. Comparison of constitutional and tumor genotypes showed that constitutional heterozygosity was retained for markers in the MEN1 and MEN2A regions as well as to the PTH gene in 4 tumors from 3 affected members. In 1 individual, a parathyroid carcinoma was found after recurrence of hypercalcemia. We, therefore, propose that autosomal dominant FIHP can occur as a genetically and clinically distinct entity with an increased risk of malignant transformation of parathyroid tumors.

Adolescent↗
PubMed1992

Fetal urine biochemistry in the assessment of obstructive uropathy.

In 60 fetuses with obstructive uropathy, sodium, total calcium, urea, and creatinine were measured in samples obtained by "urodochocentesis" or pyelocentesis at 16 to 36 weeks' gestation. The patients were retrospectively assigned into two groups on the basis of outcome. Group 1 (n = 20) included infants who either had normal postnatal renal function or absence of prenatal renal dysplasia. Group 2 included infants who either had histologic evidence of renal dysplasia or subsequently developed renal failure. In group 1 the urinary sodium decreased and creatinine increased with gestation, demonstrating maturation in fetal renal function. In group 2 the urinary sodium and calcium were higher and the urinary urea and creatinine were lower than in group 1. The best predictor of outcome was the combination of either high calcium or high sodium with a positive predictive value of 91.3% and negative predictive value of 77.7%. In the antenatal evaluation of obstructive uropathy, fetal urinary biochemistry provides useful information for more accurate counseling of the parents and a rational basis for selecting patients who may benefit from intrauterine therapeutic interventions.

Creatinine↗
PubMed1987

Skin collagen changes in post-menopausal women receiving oestradiol gel.

Sixteen post-menopausal women who had never previously received any hormonal treatment applied Oestrogel cream 1.5 mg/day percutaneously for 1 yr. Skin biopsies were taken from the abdomen and from the lateral aspect of the thigh at 0, 3, 6 and 12 mth, and the changes in skin collagen content were noted. The abdominal skin collagen content increased significantly (P less than 0.001) over the 1-yr treatment period. The thigh skin collagen content also increased, but did not reach significant levels. There was a strong correlation between the change in skin collagen content (in both the abdomen and the thigh) and the original skin collagen content, indicating that the change in collagen content in response to oestrogen therapy is dependent on the original level. There is no further increase once an 'optimum' skin collagen level has been reached.

Administration, Topical↗
PubMed1987

Decline in skin collagen content and metacarpal index after the menopause and its prevention with sex hormone replacement.

The thigh skin collagen content and the metacarpal index were measured in 69 untreated postmenopausal women and in 37 postmenopausal women who had been receiving oestradiol and testosterone implants for 2-10 years. There was a significant positive correlation between the skin collagen content and the metacarpal index in both groups of patients. In the untreated group, there was a statistically significant decrease both in the thigh skin collagen content and in the metacarpal index with the years since the menopause. This decrease was preventable in women who were on sex hormone replacement therapy.

Collagen↗
PubMed1987

A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman.

The skin collagen content, skin thickness, metacarpal index, and forearm bone mineral content in postmenopausal women showed a similar decline of between 1-2% per year after the menopause. All four parameters showed a decline that was significant when compared with the years from the menopause. Significant correlations between all four parameters suggest that a similar pathology causes the decrease in bone mass and skin thickness--a decline in the connective tissue element that is common to both bone and skin.

Bone and Bones↗
PubMed1987

Skin collagen changes in postmenopausal women receiving different regimens of estrogen therapy.

Collagen is a widespread body constituent that is affected by estrogen status in women. Its decrease after menopause can be prevented and/or restored by estrogen treatment. We explored the effect of four different hormonal replacement regimens on total skin collagen content by measuring hydroxyproline in skin biopsy specimens taken from postmenopausal women. All regimens showed increases in skin collagen levels proportionate to the levels at the start of the treatment. Estrogen replacement therapy is shown to be prophylactic in women who have higher skin collagen levels and both prophylactic and therapeutic in women with lower skin collagen levels.

Administration, Cutaneous↗
PubMed1986

Calcium homeostasis in second trimester fetuses.

The concentrations of ionised calcium ions (Ca++), total calcium, parathyroid hormone, pH, total protein, albumin, sodium, and potassium were measured in paired fetal and maternal blood from pregnancies at 15 to 24 weeks' gestation. Pure fetal blood samples were obtained fetoscopically. The concentrations of fetal ionised calcium ions (n = 26); mean (SD) 1.33 (0.12) mmol/l (5.32 (0.48) mg/100 ml) and those of parathyroid hormone (n = 9); 68 (19) pmol/l (58 (16) micrograms/100 ml) were significantly higher than those of the mothers: 1.18 (0.09) mmol/l (4.7 (0.4) mg/100 ml), and 40 pmol/l (less than 34 micrograms/100 ml), respectively. There was no difference between measured fetal and maternal total calcium, pH, and electrolytes. The fetal total protein and albumin concentrations increased with gestation but were always lower than the equivalent maternal values. The calculated total calcium was 0.23-0.45 mmol/l (0.9-1.8 mg/100 ml) higher in the fetal than in maternal blood from the same pregnancy. There were no fetal arteriovenous differences in ionised calcium ions despite higher venous pH.

Blood Proteins↗
PubMed1985

Normal reference ranges for biochemical substances relating to renal, hepatic, and bone function in fetal and maternal plasma throughout pregnancy.

Normal reference ranges for sodium, potassium, urea, creatinine, calcium, phosphate, total protein, albumin, bilirubin, alkaline phosphatase, and aspartate transaminase were determined from 344 fetal and maternal plasma samples between 15 and 38 weeks' gestation. Pure fetal blood was obtained by fetoscopy in the second trimester and in the third trimester by umbilical cord puncture at delivery. All biochemical substances were measured by continuous flow (SMAC, Technicon) except albumin, which was measured by turbidimetry (CobasBio, Roche). The resulting data were analysed on an AMDAHL 470A computer and reference ranges covering 2.5 to 97.5 percentiles were defined. Analysis of variance was performed to examine the overall effect of gestational age on the analytes measured and on the changes in the fetal compartment relative to the mothers'. A paired t test was performed to examine how these biochemical substances in fetal plasma related to maternal plasma from the same pregnancy.

Alkaline Phosphatase↗
PubMed1983

Sex hormones and skin collagen content in postmenopausal women.

Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.

Adult↗