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Biomedical subjects

J S Green

Publications and source records attributed to J S Green.

At least 19 recordsLinked to original sources
PubMed1999

Genetic heterogeneity of Bardet-Biedl syndrome in a distinct Canadian population: evidence for a fifth locus.

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disease characterized by retinal dystrophy, renal structural abnormalities, obesity, dysmorphic extremities, and hypogenitalism in males. BBS is genetically heterogeneous with four known loci: BBS1 (11q), BBS2 (16q), BBS3 (3p), and BBS4 (15q). The prevalence of BBS in Newfoundland is approximately 10-fold greater than in Switzerland (1:160,000) and similar to the prevalence among the Bedouin of Kuwait (1:13,500). A population-based genetic survey was performed on 17 BBS families from the island portion of the province of Newfoundland, a comparatively isolated region of Canada. The families in the study had a total of 36 well-documented, affected individuals with 12 families having 2 or more affected individuals. Linkage at each of the four known loci was tested with two-point linkage and haplotype analysis. Three of the 17 kindreds showed linkage to 11q, 1 to 16q, and 1 to 3p. The latter is the first BBS3 family identified in a population of northern European descent. Six families remain undetermined because of poor pedigree structure or inconclusive haplotype analyses. Six families were excluded from all four known BBS loci, indicating that there is at least a fifth BBS locus (BBS5).

Abnormalities, Multiple↗
PubMed1998

Canadian Bardet-Biedl syndrome family reduces the critical region of BBS3 (3p) and presents with a variable phenotype.

There are at least five distinct Bardet-Biedl syndrome (BBS) loci, four of which have been mapped: 11q (BBS1), 16q (BBS2), 3p (BBS3), and 15q (BBS4). A comparative study of the three Arab-Bedouin kindreds used to map the BBS2, BBS3, and BBS4 loci suggests that the variability in the number and severity of clinical manifestations, particularly the pattern of polydactyly, reflects chromosome-specific subtypes of BBS [Carmi et al., 1995a; Am J Med Genet 59:199-203]. We describe a Newfoundland kindred of northern European descent and confirm the initial finding of a BBS locus on chromosome 3. However, the "BBS3 phenotype," which includes polydactyly of all four limbs and a progression to morbid obesity, was not observed. Rather, four of the five BBS patients in this family had polydactyly restricted to their feet. The obesity in these patients was reversible with caloric restriction and/or exercise. Mental retardation has been considered a major symptom of BBS. However, formal IQ testing shows that these patients are of average intelligence. Haplotype analysis reduces the BBS3 critical region to a 6-cM interval between D3S1595-D3S1753.

Adult↗
PubMed1998

Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN1 (MEN1Burin) in four kindreds from Newfoundland.

Familial multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with affected individuals developing parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tumors. Four large kindreds from the Burin peninsula/Fortune Bay area of Newfoundland with prominent features of prolactinomas, carcinoids, and parathyroid tumors (referred to as MEN1Burin) have been described, and they show linkage to 11q13, the same locus as that of MEN1. Haplotype analysis with 16 polymorphic markers now reveals that representative affected individuals from all four families share a common haplotype over a 2.5 Mb region. A nonsense mutation in the MEN1 gene has been found to be responsible for the disease in the affected members in all four of the MEN1Burin families, providing convincing evidence of a common founder.

Alleles↗
PubMed1998

Rothmund-Thomson syndrome complicated by osteosarcoma.

We describe the radiological features of Rothmund-Thomson syndrome, a rare condition of autosomal recessive inheritance, which is commonly associated with a generalised skeletal dysplasia. The condition has an increased incidence of malignancy, which occasionally manifests in the musculoskeletal system.

Child↗
PubMed1998

MRI in the assessment of a newborn with cervical teratoma.

Teratoma of the head and neck is a rare lesion comprising 6 % of all teratomas, with only 3 % occurring in the cervical region [1]. Most are non-malignant lesions consisting of a variety of tissues of variable maturity, commonly with neuroepithelial and thyroid elements. They often present as a large cystic mass in the neck of a neonate or infant and frequently cause respiratory embarrassment due to local mass effect necessitating urgent surgical intervention. They may be difficult to distinguish from cystic hygromas, both clinically and radiologically. Imaging plays an important role in the assessment of these lesions, especially in preparation for surgery. We present a case of cervical teratoma and emphasise the role of MRI.

Female↗
PubMed1998

Accumulated clonal genetic alterations in familial and sporadic colorectal carcinomas with widespread instability in microsatellite sequences.

A subset of hereditary and sporadic colorectal carcinomas is defined by microsatellite instability (MSI), but the spectra of gene mutations have not been characterized extensively. Thirty-nine hereditary nonpolyposis colorectal cancer syndrome carcinomas (HNPCCa) and 57 sporadic right-sided colonic carcinomas (SRSCCa) were evaluated. Of HNPCCa, 95% (37/39) were MSI-positive as contrasted with 31% (18/57) of SRSCCa (P < 0.000001), but instability tended to be more widespread in SRSCCa (P = 0.08). Absence of nuclear hMSH2 mismatch repair gene product by immunohistochemistry was associated with germline hMSH2 mutation (P = 0.0007). The prevalence of K-ras proto-oncogene mutations was similar in HNPCCa and SRSCCa (30% (11/37) and 30% (16/54)), but no HNPCCa from patients with germline hMSH2 mutation had codon 13 mutation (P = 0.02), and two other HNPCCa had multiple K-ras mutations attributable to subclones. 18q allelic deletion and p53 gene product overexpression were inversely related to MSI (P = 0.0004 and P = 0.0001, respectively). Frameshift mutation of the transforming growth factor beta type II receptor gene was frequent in all MSI-positive cancers (85%, 46/54), but mutation of the E2F-4 transcription factor gene was more common in HNPCCa of patients with germline hMSH2 mutation than in those with germline bMLH1 mutation (100% (8/8) versus 40% (2/5), P = 0.04), and mutation of the Bax proapoptotic gene was more frequent in HNPCCa than in MSI-positive SRSCCa (55% (17/31) versus 13% (2/15), P = 0.01). The most common combination of mutations occurred in only 23% (8/35) of evaluable MSI-positive cancers. Our findings suggest that the accumulation of specific genetic alterations in MSI-positive colorectal cancers is markedly heterogeneous, because the occurrence of some mutations (eg, ras, E2F-4, and Bax genes), but not others (eg, transforming growth factor beta type II receptor gene), depends on the underlying basis of the mismatch repair deficiency. This genetic heterogeneity may contribute to the heterogeneous clinical and pathological features of MSI-positive cancers.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Distal forearm fractures in children:the role of radiographs during follow up.

There is no consensus on the frequency of radiographic examination in the routine follow up of distal forearm fractures in children. This study was undertaken in an attempt to rationalize and optimize the use of ionizing radiation in these circumstances. The radiographs and clinical notes of 325 distal forearm fractures in children were retrospectively studied. Degrees of initial angulation were measured from all of the radiographs performed during follow up. Comparisons of outcome were made between the fractures with initial angulation under 10 degrees and over 10 degrees, types of fracture and the degree of reduction. Fractures with initial angulation of < 10 degrees had no clinically significant evidence of re-angulation and should be considered stable requiring only an initial diagnostic radiograph. Complete fractures, displaced fractures and fractures involving both the radius and ulna require more careful follow up. Residual angulation after manipulation under anaesthetic (MUA) of 5-10 degrees was not associated with an increased rate of re-angulation in this study. There is no apparent advantage in performing more than three radiographs in the majority of cases. The authors make recommendations concerning the optimal frequency of radiography in the follow up of forearm fractures in children.

Adolescent↗
PubMed1998

Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. As reported elsewhere, we mapped the human HPS gene to chromosome segment 10q23, positionally cloned the gene, and identified three pathologic mutations of the gene, in patients from Puerto Rico, Japan, and Europe. Here, we describe mutation analysis of 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication, the result of an apparent founder effect, is nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. We also describe six novel HPS mutations: a 5' splice-junction mutation of IVS5, three frameshifts, a nonsense mutation, and a one-codon in-frame deletion. These mutations define an apparent frameshift hot spot at codons 321-322. Overall, however, we detected mutations in the HPS gene in only about half of non-Puerto Rican patients, and we present evidence that suggests locus heterogeneity for HPS.

Albinism, Oculocutaneous↗
PubMed1998

Peak exercise hemodynamics in exercising postmenopausal women taking versus not taking supplemental estrogen.

The purpose of this study was to determine whether supplemental estrogen influences cardiovascular hemodynamics at peak exercise in endurance trained and sedentary postmenopausal women. Subjects were 22 women between 3 and 10 yr past menopause who had engaged in endurance exercise at least three times per week for one or more years. Twelve of the women had taken estrogen replacement for at least 1 yr (ER) while the other 10 had never taken supplemental estrogen (NOER). Peak cardiac output (Qpeak) and, subsequently, peak cardiac index (QIpeak) were calculated by regressing submaximal cardiac output values on corresponding oxygen consumptions and extrapolating to peak exercise. Peak oxygen consumption in the two groups were almost identical; however, the ER group demonstrated a higher QIpeak in conjunction with a lower arteriovenous oxygen difference and a lower peripheral resistance. It was concluded that estrogen supplementation may be associated with higher peak cardiac outputs in exercise trained postmenopausal women via alterations in the peripheral vascular and oxygen kinetic responses to maximal exercise.

Cardiac Output↗
PubMed1998

Cement as a risk factor for deep-vein thrombosis. Comparison of cemented TKR, uncemented TKR and cemented THR.

A total of 110 total knee replacements (TKRs) was randomised to receive either a cemented or an uncemented prosthesis. Postoperative venography at five to seven days was used to compare the prevalence, site and size of deep-vein thrombosis (DVT). We also compared the findings with those of postoperative venography in a group of patients with cemented total hip replacements (THRs). The total prevalence of DVT was significantly greater after uncemented (81%) than after cemented TKR (55%). Both knee groups had a significantly higher prevalence of DVT than in cemented hip replacements (32%). We found no difference in the proportion with proximal DVT in the three groups (14%, 15% and 16%). The median length of the thrombi was significantly greater after cemented (26.5 cm) than after uncemented TKR (11 cm) or after cemented THR (7 cm). This difference was mainly due to greater lengths of distal rather than proximal thrombi. We conclude that the use of cement may affect the formation of DVT after joint replacement, but does not appear to lead to an increased incidence.

Arthroplasty, Replacement, Hip↗
PubMed1997

Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states.

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior pituitary and other tissues. We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1. We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism. There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands). One case of sporadic MEN1 was proven to be a new MEN1 mutation. Eight different mutations were observed more than once in FMEN1. Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene. Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene. No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).

Adult↗
PubMed1997

Mutation of RET codon 768 is associated with the FMTC phenotype.

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are inherited cancer syndromes resulting from mutations in the RET proto-oncogene. Missense mutations of five codons in exons 10 and 11 are found in both MEN 2A and FMTC families, while mutations at codon 768 in exon 13 have been identified in three FMTC families. We report here the results of mutation analysis on a large multi-generation family with multiple cases of medullary thyroid carcinoma (MTC) or C-cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, which alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to segregate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 mutation does not predispose to adrenal medullary hyperplasia, but is an accurate predictor of the MTC phenotype in this family.

Carcinoma, Medullary↗
PubMed1997

Training intensity, blood lipids, and apolipoproteins in men with high cholesterol.

Twenty-six hypercholesterolemic men (mean cholesterol, 258 mg/dl; age, 47 yr; weight, 81.9 kg) completed 24 wk of cycle ergometer training (3 days/wk, 350 kcal/session) at either high (n = 12) or moderate (n = 14) intensity (80 and 50% maximal O2 uptake, respectively, randomly assigned) to test the influence of training intensity on blood lipid and apolipoprotein (apo) concentrations. All physiological, lipid, and apo measurements were completed at 0, 8, 16, and 24 wk. Lipid data were analyzed via two x four repeated-measures analysis of variance (alpha = 0.0031). Training produced a significant decrease in body weight and increase in maximal O2 uptake. No interactions between intensity and weeks of training were noted for any lipid or apo variable, and no between-group differences were significant before or throughout training. Therefore, intensity did not affect the training response. Regardless of intensity, apo AI and apo B fell 9 and 13%, respectively, by week 16 and remained lower through week 24 (P < 0.0003). Total cholesterol fell transiently (-5.5%) by week 16 (P < 0.0021) but returned to initial levels by week 24. Triglyceride, low-density-lipoprotein cholesterol, and high-density-lipoprotein (HDL) cholesterol did not change with training. In contrast, HDL2 cholesterol rose 79% above initial levels by week 8 and 82% above initial levels by week 24 (P < 0.0018); HDL3 cholesterol fell 8 and 13% over the same training intervals (P < 0.0026). These data show that changes in blood lipid and apo concentrations that accompany training in hypercholesterolemic men are not influenced by exercise intensity when caloric expenditure is held constant.

Adult↗