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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 595 records · Page 33Linked to original sources
PubMed1983

Limb salvage procedures for children with osteosarcoma: an alternative to amputation.

Amputation remains the standard surgical management for patients with osteosarcoma. However, in carefully selected patients, eradication of the primary tumor can be achieved by En-Bloc resection of the affected bone preserving both anatomical and functional status. Our criteria for limb salvage procedures are that patients must: (1) be age 12 years or older, (2) have no angiographic or clinical evidence of neurovascular involvement, (3) have low-grade osteosarcoma and/or good response to preoperative chemotherapy, and (4) be compliant. Between November 1980 and October 1982, 32 patients with osteosarcoma of an extremity were seen. Eight patients ranging in age from 13 to 21 years underwent limb salvage procedures. Five of these had Tikhoff-Linberg procedures for upper extremity lesions, two had En-Bloc resections for distal femur lesions, and one patient had a segmental arthrodesis for a distal tibial lesion. Of these eight patients, two had low-grade parosteal osteosarcoma. Follow-up ranged from 10 to 28 months (median 16 months). The two patients with parosteal osteosarcoma received no further therapy, while the other six patients received multiple agent chemotherapy. One patient died at 18 months with bilateral pulmonary disease. None have had local recurrences. Two of the eight patients had minor skin necrosis, requiring revision subsequently. Three patients have had transient nerve palsy. All have had good functional results. With careful selection of patients by rigid criteria, limb salvage procedures can be a viable alternative to amputation.

Adolescent↗
PubMed1983

Surgicopathologic staging of neuroblastoma: prognostic significance of regional lymph node metastases.

Of 254 children with neuroblastoma treated at St. Jude Children's Research Hospital, 102 (40%) had clinically localized tumors. Using a surgicopathologic staging system, 66 of these 102 children had localized tumor and 36 had tumor dissemination to regional lymph nodes. Survival of these two groups has been markedly different; 57 of 66 (87%) with localized tumor survive, compared with 11 of 35 (33%) with node dissemination, five of whom are less than two years from diagnosis. Our data indicate that the prognosis for children with neuroblastoma metastatic only to regional lymph nodes is no different from that of patients of similar age with widely disseminated tumor.

Age Factors↗
PubMed1983

Characteristics of binding of a low affinity, noncooperative insulin [( LeuB25]insulin) to IM-9 lymphocytes.

[Leu-B25]insulin is a low affinity insulin analog which does not increase the rate of dissociation of 125I-insulin from insulin receptors (i.e. does not display negative cooperativity). We have studied the characteristics of binding of this analog to IM-9 cultured lymphocytes, in order to determine the contribution of negative cooperativity to the curvilinear nature of Scatchard plots typical of insulin binding data. The affinity of [LeuB25]insulin for receptors was approximately 1% that of insulin, as determined by its ability to inhibit 125I-insulin binding. Monoiodinated preparations of insulin and of [LeuB25]insulin were produced, labeled in the tyrosine at position 14 of the A chain. These 125I-TyrA14-labeled species were used in all studies. Both native insulin and a serum containing antiinsulin receptor antibodies were equally potent at inhibiting binding of 125I-[LeuB25]insulin and 125I-native insulin, suggesting that they bind to the same population of receptors. Native insulin (100 ng/ml) increased the rate of dissociation of both 125I-insulin and 125I-[LeuB25]insulin. However, [LeuB25]insulin (2.5 micrograms/ml) did not increase the rates of dissociation of either 125I-insulin or 125I-[LeuB25]insulin (i.e. it did not display negative cooperativity). Competition curves and Scatchard plots were constructed using 125I-[LeuB25]insulin and unlabeled analog. Half-maximal inhibition of 125I-[LeuB25]insulin binding was seen at a [LeuB25]insulin concentration of approximately 500 ng/ml. More importantly, the Scatchard plot of these binding data was markedly curvilinear, as is typical of insulin binding data. In summary, a non-cooperative insulin analog, [LeuB25]insulin, yielded curvilinear Scatchard plots, indicating that negative cooperativity is not the full explanation of the curvilinear nature of Scatchard plots of insulin binding data. Therefore, an alternative explanation, such as the existence of heterogeneous receptor states, with differing affinities for the hormone, must contribute to the nonlinearity of these plots.

Cell Line↗
PubMed1983

The diagnosis of Hutchinson's melanotic freckle (lentigo maligna) in Queensland.

Following an increase in the reported incidence of melanoma of Hutchinson's melanotic freckle type (HMFM) in Queensland, a review of its histological diagnosis was undertaken. Ninety-nine pigmented lesions reported by 13 different pathology laboratories throughout Queensland as having an in-situ component of Hutchinson's melanotic freckle (HMF) were reviewed by 2 pathologists with an interest in malignant melanoma. This diagnosis was confirmed in 76 cases while in a further 3 the reviewers regarded the in-situ component as indeterminate. It would seem that the level of agreement among pathologists reporting HMF(M) should be considered in any assessment of incidence patterns of melanoma.

Diagnosis, Differential↗
PubMed1983

Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system.

HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. This evidence favors interaction of unlinked IDDM determinants to produce affection in a small proportion of heterozygotes for an HLA-linked determinant. Partition of data by HLA type of the propositus (ideally by DR and the complement types jointly) is a powerful method to resolve etiological heterogeneity for HLA-associated diseases.

Adult↗
PubMed1983

Fertility and mortality 1950-1974 in the Upernavik district, Greenland.

A descriptive study of fertility and mortality in a Greenlandic whaling and sealing community of approximately 1 800 individuals during the period 1950-74 was performed on the basis of data from parish records and medical reports. Fertility was on the increase until approximately 1960 after which it declined considerably. No significant reduction in the high stillbirth and infant mortality rates could be demonstrated. A considerable reduction in overall mortality was observed and could be attributed to the eradication of tuberculosis as a cause of death. The results are discussed in the light of data from Greenland as a whole, which in general has been characterized by intense industrialization and social development. Further comparative studies in Arctic communities characterized by varying degrees of socio-economic development are recommended.

Adolescent↗
PubMed1982

A sensitive micromethod for the routine estimation of methylmalonic acid in body fluids and tissues using thin layer chromatography.

A routine method for the rapid estimation of methylmalonic acid (MMA) has been developed using thin-layer chromatography (TLC) on cellulose, locating the separated MMA zones by coupling with a diazo reagent and quantitating the results by densitometric scanning of a photocopy of the chromatogram on transparency film. The method can detect as little as 25 pg MMA in small volumes of urine, plasma and other body fluids or tissue homogenates, has potential for the simultaneous estimation of MMA, other organic acids, methylmalonyl coenzyme A and creatinine and should be of particular value in the investigation of occult cobalamin deficiency or suspected errors of vitamin B12 or intermediary metabolism.

Adolescent↗
PubMed1982

Evidence for insulin-induced internalization and degradation of insulin receptors in rat adipocytes.

We have investigated the theory that the insulin-induced loss of insulin binding from adipocytes is due to internalization of insulin receptors. Cell-surface receptors were assessed by the binding capacity of intact cells at 16 degrees C. Total (i.e., cell-surface plus intracellular) receptors were assessed by solubilizing the cells in 1% Triton X-100 and then measuring binding by the solubilized extract. Intracellular receptors were measured by treating the cells with trypsin before solubilizing them. The trypsin treatment removed greater than 90% of the cell-surface binding, so that any significant binding by soluble extracts of these cells must represent intracellular receptors. Adipocytes were incubated with insulin (100 ng/ml) with or without chloroquine (0.2 mM) for 4 hr. Insulin alone resulted in a 62% loss of cell-surface receptors, but only a 46% loss of total receptors, and a 170% increase in intracellular receptors, suggesting that the lost cell-surface receptors were internalized, where some were degraded. Insulin in the presence of chloroquine resulted in a 34% loss of cell-surface receptors, but no loss of total receptors, and a 300% increase in intracellular receptors. Thus, in the presence of chloroquine receptors were internalized but not degraded. The loss of cell-surface receptors and appearance of intracellular receptors were time and dose dependent and were linearly related. These results demonstrate that insulin causes translocation of insulin receptors from the cell surface to the cell interior, where they can be degraded (or inactivated) by a chloroquine-sensitive process.

Adipose Tissue↗
PubMed1982

Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses.

The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA-DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.

Adolescent↗
PubMed1982

The epidemiologic approach to studies of association between HLA and disease. I. The basic measures, concepts and estimation procedures.

The present report describes the basic epidemiological measures and concepts used in association studies, i.e. measures of disease frequency and the concept of risk, together with their internal relationships. Further, the different types of designs for HLA and association studies are reviewed with particular reference to estimation of association strength. It is shown that the odds ratio from a 2 x 2 table estimates the incidence density ratio which again under certain conditions estimates the relative risk, if the study is based on incident (new) cases. However, most HLA and association studies are prevalence-based, which implies that the relative risk and incidence density ratio cannot be estimated unless a series of conditions is fulfilled. Finally, it is stressed that a detailed description of study design and the age classes studied as well as the procedure of case ascertainment should be mandatory before comparisons between and pooling of estimates from different studies are performed.

Adolescent↗
PubMed1982

The epidemiologic approach to studies of association between HLA and disease. II. Estimation of absolute risks, etiologic and preventive fraction.

It is the aim of the present report to review principles and measures which are fundamental in modern epidemiology and happen to be closely related to expressions used in studies of association between HLA and disease. These measures, the etiologic and the preventive fractions, may easily be estimated from the traditional 2 x 2 table. Furthermore, the practical procedures leading to estimates of the absolute frequency measures for individuals with and without a given HLA factor are presented; these estimates may also be obtained from the 2 x 2 table, supplemented with data on the disease frequency in the general population. The estimation procedures are simple in all the subtypes of the association study design, but especially in prevalence-based association studies some important limitations as to the interpretation and generalization should be kept in mind. A subsequent report will use the measures and principles, outlined here, in order to facilitate an extension of the perspectives of the results and establish a connection between this field of HLA research and clinical and genetic epidemiology.

Disease↗