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Biomedical subjects

R J Pegoraro

Publications and source records attributed to R J Pegoraro.

At least 19 recordsLinked to original sources
PubMed2000

Apolipoprotein E polymorphism in South African Zulu women with preeclampsia.

OBJECTIVES: Apolipoprotein E may contribute to the hypertiglyceridemia and consequent endothelial dysfunction of preeclampsia. We carried out a study to determine whether the apolipoprotein E genotype plays any role as a risk factor for preeclampsia in a black South African population with a high incidence of preeclampsia. DESIGN: A descriptive, prospective study design was used. SETTING: King Edward VIII Hospital, a tertiary care, referral academic hospital in Durban, South Africa. PATIENTS AND PARTICIPANTS: One hundred three South African Zulu women with preeclampsia and 110 healthy normotensive women attending the antenatal clinic were recruited. MAIN OUTCOME MEASURES: The relationship between the apolipoprotein E allele and genotype frequencies to preeclampsia as well as adverse perinatal outcome. RESULTS: The frequencies of varepsilon2 and varepsilon4 alleles (0. 19 and 0.25, respectively) were much higher than those reported in other population groups. However, there was no significant difference in the apolipoprotein E genotype and allele frequencies between the study and the control groups. The varepsilon2/2 genotype was associated with increased risk of perinatal death (p = 0.047). CONCLUSION: The study suggests that, despite the high incidence of both preeclampsia and the varepsilon2 and varepsilon4 alleles in South African Zulu women, apolipoprotein E genotype does not appear to be a risk factor for preeclampsia in this population.

Adolescent↗
PubMed1999

5,10 methylenetetrahydrofolate reductase polymorphism in black South African women with pre-eclampsia.

The polymorphic C677T mutation in the gene encoding 5,10 methylenetetrahydrofolate reductase has been shown to be a risk factor for pre-eclampsia in Japanese and European women when inherited as a homozygous trait. We attempted to verify these findings in a black African population with a high incidence of pre-eclampsia. No difference in frequency of the T-allele was observed in 105 women with pre-eclampsia, compared with 110 healthy pregnant normotensive women. Only one woman with pre-eclampsia was TT homozygous, suggesting that methylenetetrahydrofolate reductase polymorphism is not an important factor in the pathogenesis of pre-eclampsia in black South African women.

Adolescent↗
PubMed1998

Molecular diagnosis of multiple endocrine neoplasia type 2A.

OBJECTIVE: To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. SUBJECTS: A three-generation kindred with clinically and biochemically diagnosed medullary thyroid cancer. METHOD: Identification of a heterozygote mutation by nucleic acid sequencing and restriction analyses. RESULTS: A heterozygote T-->C (Cys-->Arg) mutation at codon 618 in exon 10 of the RET proto-oncogene was identified in 4 family members who had previously been diagnosed with medullary thyroid cancer. The same mutation was also found in one of the proband's presymptomatic children who subsequently underwent a pre-emptive thyroidectomy. The genetic diagnosis was confirmed by histology. No mutations were detected in any other family members. CONCLUSION: Identification of heterozygote germline mutations in multiple endocrine neoplasia is direct, highly accurate and cost-effective. This study demonstrates that, appropriately used, molecular diagnosis can supersede conventional biochemical methods in the management of patients with inherited cancers.

Adult↗
PubMed1998

HMG-CoA reductase is not the site of the primary defect in phytosterolemia.

Phytosterolemia is an autosomal recessive disorder characterized by the excessive absorption, reduced excretion, and consequent high tissue and plasma levels of plant sterols, by the presence of tendon xanthomas, and by premature atherosclerosis. Low HMG-CoA reductase (HRase) activity and mass have been reported in liver and mononuclear leucocytes and low mRNA levels in liver from phytosterolemic subjects. These results led to the proposal that the primary defect in this condition involves the HRase gene locus. We examined this hypothesis in phytosterolemic subjects and heterozygous parents from four unrelated families. A variable number tandem repeat (VNTR) polymorphism of the HRase gene in the three informative families and a ScrFI restriction fragment length polymorphism (RFLP) within intron 2 of the gene in one of these families, segregated independently of the disease phenotype. Biological parentage was confirmed in the family in whom both polymorphisms failed to segregate with the disorder. These results conclusively exclude the HRase gene locus as the site of the primary defect in phytosterolemia. The study was extended by examining plasma levels of mevalonic acid and lathosterol, both markers of cholesterol biosynthesis, in response to cholestyramine, a bile acid sequestrant that is known to up-regulate HRase. Oral administration of cholestyramine resulted in a substantial (7.7-fold) increase in mevaIonic acid levels in two phytosterolemic subjects, compared with a 2.2-fold rise in their obligate heterozygote parents and a 2.3-fold increase in three healthy control subjects. The lathosterol/cholesterol (L/C) ratio showed a quantitatively similar response. Baseline levels of mevalonate and the L/C ratio were low in the phytosterolemic patients in conformity with reports of reduced cholesterol biosynthesis and HRase activity in this disorder. These functional data provide support for the concept that the primary defect in phytosterolemia does not affect a trans gene locus responsible for the constitutive expression or regulation of HMG-CoA reductase.

Adolescent↗
PubMed1997

Relation between retinoblastoma and p53 proteins in human papilloma viruses 16/18 positive and negative cancers of the uterine cervix.

AIM: To ascertain the extent of retinoblastoma protein (pRB) expression in comparison to p53 protein and human papilloma viruses (HPV) 16/18 status in cervical carcinomas. METHODS: Fifty cases of invasive cervical carcinoma were HPV typed for genotypes 16 and 18 using consensus primers by polymerase chain reaction (PCR). Immunohistochemistry for pRB and p53 was done on formalin fixed tissue using microwave antigen retrieval and commercially available antibodies. RESULTS: Forty five cases were squamous carcinomas, three were adenocarcinomas, and two were adenosquamous carcinomas. Thirty one cases were HPV 16 positive and one was HPV 18. Sixteen cases showed +4 pRB expression and a further 11 were +3 positive. Seven cases were negative. Only five cases (10%) showed +4 p53 immunostaining, while seven were negative and 15 were +1. Of the 16 pRB +4 positive cases, one was negative for p53 and a further seven were +1 positive. This inverse pattern of staining between pRB and p53 had a p value of < 0.001. No correlation was observed between HPV 16/18 status and p53 and/or pRB staining. CONCLUSIONS: pRB is expressed in the majority of cases of cervical cancer (86%), with more than 75% (+4) of the tumour cell population being positive in 16 cases (32%). There appears to be a general inverse pattern of staining between pRB (high) and p53 (low) in cervical cancer. The expression of both pRB and p53 proteins is independent of the HPV 16/18 status of the tumour.

Adenocarcinoma↗
PubMed1996

Variations in c-erbB-2 proto-oncogene status in breast cancer tumors as detected by two different cDNA probes.

We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis using two different cDNA probes. Using these same probes, 95 of these tumors were also examined for mRNA expression by Northern analysis. Amplification was detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204, respectively, but only 10% showed amplification with both probes. A significantly higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2 probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors demonstrating overexpression with both probes. A total of 10 tumors (11%) exhibited amplification as well as overexpression with pHER 2, whereas significantly fewer (3%) manifested both abnormalities with the larger pCER 204 probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe but not with the pCER 204 probe, was significantly associated with the absence of both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively). No relationship was found with other clinical prognostic indicators, such as nodal involvement and metastases. As determined by either probe, overexpression was not associated with prognostic indicators. There was no significant difference in the c-erbB-2 status of tumors from different racial groups.

Breast Neoplasms↗
PubMed1995

Apolipoprotein E allele frequencies in a South African Indian female population.

Coronary heart disease is common amongst South Africans of Indian (Asian) ancestry. As part of an investigation into risk factors in premenopausal and post-menopausal Indian nurses, we determined the apolipoprotein E genotype by means of restriction isotyping on 173 healthy nurses between the ages of 25-55 years. The apolipoprotein E allele frequencies on 346 chromosomes were: epsilon 2, 1.2% (95% confidence interval 0.06-2.66); epsilon 3, 87.6% (95% confidence interval 84.1-91.1 and epsilon 4, 11.3% (95% confidence interval 7.94-14.60). No epsilon 2/2 homozygotes were encountered. Our results demonstrate an extremely low frequency of the epsilon 2 allele, a low-normal apo epsilon 4 and a high epsilon 3 allele frequency. It is unlikely that apolipoprotein E polymorphism contributes to the high incidence of coronary heart disease in this population.

Adult↗
PubMed1990

Enzyme immunoassay of oestrogen and progesterone receptors in uterine and intrauterine tissue during human pregnancy and labour.

Oestrogen and progesterone receptors were studied in the non-pregnant state, in early pregnancy and at term using monoclonal antibody enzyme immunoassays. Receptors for both steroids were found in tissues from non-pregnant patients and patients in early pregnancy. At term oestrogen receptors were undetectable in all tissues studied. Progesterone receptors were undetectable in chorion, amnion and placenta at term, while present in extremely low concentrations in decidua and myometrium.

Amnion↗
PubMed1989

Changes in the binding characteristics of oestrogen and progesterone in uterine and intrauterine tissue with the progression of human pregnancy.

The binding characteristics of oestrogen and progesterone in intrauterine tissue were studied in the non-pregnant state and throughout pregnancy using sucrose density gradient centrifugation and titration analyses. High affinity receptors for these steroids which were present in high concentrations in tissue from non-pregnant patients and patients in early pregnancy, decreased with the advance of pregnancy to undetectable levels at term. Non-saturable binding to progesterone detected in term tissue was identified as albumin and cortisol binding globulin.

Centrifugation, Density Gradient↗
PubMed1987

Decreased concentrations and affinities of oestrogen and progesterone receptors of intrauterine tissue in human pregnancy.

Cytoplasmic and nuclear receptors for oestrogen and progesterone were measured in non-pregnant myometrium and endometrium and compared to concentrations found in decidua of ectopic pregnancy (6-8 weeks gestation) and therapeutic abortions (8-16 weeks). Amnion, chorion, placenta, decidua and myometrium at full term pregnancy were also assayed for the same receptors. High affinity binding was confirmed in the non-pregnant tissue; in early pregnancy, decreases in concentrations of cytoplasmic receptors were demonstrated, these decreases becoming more marked as pregnancy progressed in the 1st trimester. Nuclear receptor concentrations were not significantly different. Significant decreases in the occurrence of positive receptors with the progression of pregnancy were also demonstrated for cytoplasmic and nuclear oestrogen and nuclear progesterone receptors. Tissue at full term pregnancy had no detectable receptors, irrespective of whether the patients were in labour or not. Increasing the range of the labelled steroids failed to demonstrate any low affinity binding sites and pre-assay removal of endogenous hormones also had no effect on receptor status. When endogenous hormones were removed, displaceable binding was demonstrated in the presence of excess unlabelled ligand. However, this binding did not conform with receptor dynamics on Scatchard analysis. Heating the cytosol prior to assay or failure to remove endogenous steroid hormones eliminated this binding. Cytosolic oestrogen and progesterone levels increased significantly in the decidua of therapeutic abortions, whilst term pregnant tissue had the highest concentration of endogenous hormones.

Adult↗
PubMed1986

Breast cancer prognosis in three different racial groups in relation to steroid hormone receptor status.

Follow-up studies on 466 patients over a 5-year period showed Whites to have an overall significantly longer disease-free interval and survival than Blacks and Asians. No racial differences in prognosis were seen in patients with Stage II disease (p greater than 0.2) but in Stage III, White patients had significantly longer disease-free periods than Blacks or Asians; the same was not true of survival. Whites had a 67% incidence of cytoplasmic estrogen receptor (CER) positive tumors compared with only 49% in Blacks and 41% in Asians. When tumors were assayed for CER, nuclear estrogen receptor (NER), and cytoplasmic progesterone receptor (CPR), there were no racial differences in the proportions of tumors containing all 3 receptors, but significant variations were found in neoplasms with no receptors and in those with apparently defective receptors. In White patients receptor status had no influence on prognosis (p greater than 0.3). Black patients whose tumors contained both CER and NER had a significantly better time to recurrence than those whose tumors lacked these receptors, while in Asian women the presence of CER alone, or CER together with NER, or CER, NER, and CPR, was indicative of a significantly longer disease-free period.

Breast Neoplasms↗
PubMed1986

Estrogen and progesterone receptors in breast cancer among women of different racial groups.

No differences in steroid hormone receptor status were detected in premenopausal breast cancer patients of different races. In postmenopausal women, 65% of Whites were found to have tumors positive for cytoplasmic estrogen receptors (CER) compared with 58, 52, and 41% in women of mixed race, Blacks, and Asians, respectively. The proportions of tumors which contained a full complement of receptors (CER, nuclear estrogen receptors, and cytoplasmic progesterone receptors) were similar in Blacks, Whites, and Asians in each menopausal group. In postmenopausal patients, significantly fewer White women had tumors devoid of all receptors, while having a higher incidence of tumors with an abnormal or defective receptor distribution. Neither the stage of the disease nor the degree of nodal involvement appeared to affect receptor status in any population group, but very large tumors had fewer receptors. White patients with large neoplasms had a significantly higher incidence of CER than Blacks or Asians. Similar observations were made for White patients presenting with Stage III disease, whose tumors were greater of histological Grade I tumors were positive for CER, compared with Grade III neoplasms. Indications are that receptor status is inherent to the natural history of the disease and is not influenced by clinical features.

Adult↗
PubMed1985

Clinical patterns of presentation of breast cancer in women of different racial groups in South Africa.

The ages at presentation of white patients with breast cancer were found to be significantly higher than those of blacks, Indians and coloureds; 73% of white women fell into the postmenopausal group, in marked contrast to only 35% of Indians, while blacks and coloureds had similar proportions of pre- and post-menopausal patients. A significantly higher incidence of poorly differentiated tumours was seen in Indian and black patients. Blacks showed a significant tendency to present with more advanced disease, while whites were generally diagnosed at a much earlier stage.

Adult↗
PubMed1983

The sex hormone profile of male patients with breast cancer.

The mean total serum oestradiol level was found to be significantly increased in 8 patients with carcinoma of the breast when compared with 8 healthy reference subjects matched for race, sex and age. The calculated mean free oestradiol index was also higher in these patients. There were no significant differences, however, between the levels of LH, FSH, prolactin. DHEA-S, testosterone and SHGB in the 2 groups. The patients showed a significantly increased LH response to GnRH while there was no difference in the FSH response. Only 1/7 patients had a tumour devoid of steroid hormone receptors. It may be that an increased level of circulating oestradiol-17 beta is an important factor in the aetiology of hormone-dependent male breast cancer.

Adult↗
PubMed1982

Cytoplasmic and nuclear estrogen and progesterone receptors in male breast cancer.

Cytoplasmic estrogen receptors were detected in 12 of 13 male breast cancer tumors. There was no significant correlation of receptor levels with the age of the patient, size and histological grading of the tumor, and stage and nodal involvement of the disease. Nuclear estrogen receptors were found in eight of 10 tumors and six of nine patients had tumors positive for cytoplasmic progesterone receptors, two of which were also found to contain nuclear progesterone receptors. The presence of cytoplasmic progesterone receptors, in addition to cytoplasmic and nuclear estrogen receptors, may be indicative of truly hormone-dependent tumors in male breast cancer. Treatment offered to patients included surgery, X-ray therapy, chemotherapy, and orchiectomy, but as yet, no general conclusions of the efficacy of the therapeutic regime can be drawn.

Adult↗
PubMed1981

Nuclear and cytoplasmic oestrogen receptors in squamous carcinoma of the cervix.

Nuclear and cytoplasmic oestrogen receptors (REN and REC) were sought in 5 normal cervices and in 43 specimens of squamous carcinoma of the cervix. All 3 tissues components of the 5 normal cervices contained both REN and REC. Thirty-five (81%) of the tumours contained receptors, but in only 9 (21%) were they found in both subcellular compartments. Twenty-four tumours (56%) had only REC and 2 had only REN. The potential therapeutic significance of these findings is not yet known, but it seems possible that tumours with an intact receptor mechanism might benefit from oestrogen therapy and have a more favourable prognosis.

Carcinoma, Squamous Cell↗