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Biomedical subjects

R Lew

Publications and source records attributed to R Lew.

At least 91 records · Page 5Linked to original sources

Autoradiographic localization of beta-adrenoceptor subtypes in guinea-pig kidney.

The distribution of beta-adrenoceptor subtypes in slide-mounted sections of guinea-pig kidney has been examined by the technique of in vitro labelling combined with autoradiography. Binding of (-)-[125I]-cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with respect to the isomers of propranolol and pindolol. These characteristics were appropriate for binding to beta-adrenoceptors. Delineation of beta-adrenoceptor subtypes was achieved by use of betaxolol (beta 1-adrenoceptors) and ICI 118,551 (beta 2-adrenoceptors) and computer assisted curve fitting techniques. Both beta 1- and beta 2-adrenoceptors were present in the proportions 1:2. 3H-Ultrofilm images of (-)-[125I]-Cyp binding to guinea-pig kidney sections showed localized patches of binding in the cortex and concentrated binding in the outer stripe of the medulla. Cortical receptors were of the beta 1 subtype and those associated with the outer stripe of the medulla were of the beta 2-adrenoceptor subtype. beta 1-Adrenoceptors were concentrated over glomeruli and beta 2-adrenoceptors over the straight portion of the proximal tubule.

Animals↗

Genetic Analysis Workshop II: combined segregation, linkage, and association analysis.

A combined segregation, linkage, and association analysis using the program COMBIN was performed on the simulated pedigree data prepared for the Second Genetic Analysis Workshop. The model used in COMBIN is described and the presented results illustrate its effectiveness in the analysis of such data. Linkage analysis was performed and maps for each linkage group are presented.

Adult↗

Patterns of local-regional recurrence and results in Stages I and II breast cancer treated by irradiation following limited surgery. An update.

One hundred forty-six women with Stage I and Stage II breast cancer received radical radiotherapy after having excisional biopsy ( lumpectomy ) at Massachusetts General Hospital between 1956-1978. They were grouped according to age: those younger than 49 years and those older than 50 years. The 5-year survival rates were 93 and 73% for patients with Stage I and Stage II cancer, respectively; the corresponding 5-year relapse survival rates were 75 and 56%. The local recurrence rate was 8% in patients with Stage I disease and 17% in those with Stage II disease. Survival was not significantly affected by patients' age, by the presence or absence of blood vessel or lymphatic involvement, or by the addition of adjuvant chemotherapy. No major complications occurred. Modification in radiation dose and technique resulted in improved overall survival and local control. Limited surgery followed by radical radiation therapy offers a therapeutically effective, cosmetically acceptable alternative to radical surgery for early stage breast cancer.

Adult↗

Patterns of recurrence of rectal cancer after potentially curative surgery.

The results of surgical treatment alone for 142 cases of carcinoma of the rectum and rectosigmoid from the Massachusetts General Hospital were reviewed. The incidence of local failure as any component of failure was found to be strongly dependent on the pathologic stage, and for Dukes' A was 8.0% (3/39); Dukes' B, 31% (18/59), and Dukes' C, 50% (22/44). The incidence of local failure for tumors without lymph node metastasis was 17% with only microscopic extension through the wall (modified Astler-Coller Stage MAC-B2m), but increased to 54% in tumors that were adherent to or invading adjacent organs and structures (MAC-B3). Similarly, in tumors with positive lymph nodes, there was a 36% incidence of local failure for tumors confined to the wall or with only microscopic extension through the wall (MAC-C1/C2m), compared to a 67% incidence for tumors with adherence or involvement of adjacent organs (MAC-C3). Other predictors of local recurrence were the tumor location, grade, number of lymph nodes, and blood vessel invasion. The pathologic factors predicting distant metastasis are also presented. Five-year survival for Dukes' A was 77% (30/39); Dukes' B, 44% (26/59); and Dukes' C, 23% (10/44). The implications for future adjuvant therapy based on the identification of patients with the highest risk for local and distant failure are discussed.

Follow-Up Studies↗

Estimation of haplotype frequencies.

Maximum likelihood estimates of haplotype frequencies in multilocus systems are often zero and so may be genetically inacceptable. Estimation problems are discussed, and preferable estimates are derived.

Alleles↗

Favorable prognosis for malignant melanomas associated with acquired melanocytic nevi.

In a clinicohistopathologic study of 557 patients with primary cutaneous malignant melanoma, there were fewer metastases and/or deaths from melanoma when histologic evidence of a coexisting acquired melanocytic nevus was found. A total of 130 patients with melanocytic nevus and 427 cases of melanoma without histologic evidence of a nevus (denovo) were studied. Clinical follow-up evaluation for evidence of metastases and/or death was obtained. Only ten of the patients (7.7%) with nevus-associated melanoma had metastases and/or death v 78 (18.3%) with de novo melanoma. When stratified by lesion thickness, the logrank test for survival revealed a statistically significant difference between the two groups. An overall favorable outcome seen in patients with malignant melanomas associated with acquired melanocytic nevi was found, therefore, to be independent of lesion thickness as well as six other variables reported to be related to the biologic behavior of malignant melanoma. Thus, the presence of nevus cells in a specimen of malignant melanoma portends a better prognosis and may have important implications in the biology of this neoplasm.

Female↗

Cytogenetic surveillance of spontaneous abortions.

During the five years of a cytogenetic study on spontaneous abortions in Hawaii there have been significant increases in the frequencies of triploidy of maternal origin and trisomy 16, a significant decrease in sex chromosome monosomy, and variation without trend in the frequency of tetraploidy. Attempts to explain these results in terms of technical factors or changes in maternal and gestational age have been unsuccessful, as have preliminary attempts to identify viral, pharmacological, or other causes. Apparently the etiology of chromosomal abnormality is variable over a few years even in a stable population. Research to identify these causes is continuing on the supposition that variable risks can be reduced.

Abortion, Spontaneous↗

Ca2+-induced phase separation in phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine mixed membranes.

Ca2+-induced phase separation in phosphatidylserine/phosphatidylethanolamine and phosphatidylserine/phosphatidylethanolamine/phosphatidylcholine model membranes was studied using spin-labeled phosphatidylethanolamine and phosphatidylcholine and compared with that in phosphatidylserine/phosphatidylcholine model membranes studied previously. The phosphatidylethanolamine-containing membranes behaved in qualitatively the same way as did phosphatidylserine/phosphatidylcholine model membranes. There were some quantitative differences between them. The degree of phase separation was higher in the phosphatidylethanolamine-containing membranes. For example, the degree of phase separation in phosphatidylserine/phosphatidylethanolamine membranes containing various mole fractions of phosphatidylserine was 94--100% at 23 degrees C and 84--88% at 40 degrees C, while the corresponding value for phosphatidylserine/phosphatidylcholine membranes was 74--85% at 23 degrees C and 61--79% at 40 degrees C. Ca2+ concentration required for the phase separation was lower for phosphatidylserine/phosphatidylethanolamine than that for phosphatidylserine/phosphatidylcholine membranes; concentration to cause a half-maximal phase separation was 1.4 . 10(-7) M for phosphatidylserine-phosphatidylethanolamine and 1.2 . 10(-6) M for phosphatidylserine/phosphatidylcholine membranes. The phase diagram of phosphatidylserine/phosphatidylethanolamine membranes in the presence of Ca2+ was also qualitatively the same as that of phosphatidylserine/phosphatidylcholine except for the different phase transition temperatures of phosphatidylethanolamine (17 degrees C) and phosphatidylcholine (-15 degrees C). These differences were explained in terms of a greater tendency for phosphatidylethanolamine, compared to phosphatidylcholine, to form its own fluid phase separated from the Ca2+-chelated solid-phase phosphatidylserine domain.

Animals↗

Path analysis of qualitative data on pairs of relatives: application to schizophrenia.

Methods are developed for the resolution of cultural and biological inheritance based on qualitative data on pairs of relatives. Analysis of data on schizophrenia concluded in favor of significant cultural inheritance, assortative mating and familial environment unique to twins, in addition to biological inheritance. Genetic and cultural heritabilities were estimated as 0.707 +/- 0.077 and 0.203 +/- 0.120, respectively. Familial environmental component unique to twins was estimated as 0.090 +/- 0.040.

Adoption↗

The likely region of overlap (LRO) method for physical assignment of loci.

Numerical analysis is applied to physical assignments of loci, providing point estimates, an LRO confidence interval, and a chi(2) test of consistency whether there is a smallest region of overlap (SRO) or not. Results are given for two examples and summarized for 81 loci in man.

Chromosome Mapping↗

Genetic epidemiology of an institutionalized cohort of mental retardates.

By criterion scaling and principal component analysis of performance, social class, symptoms, institutionalization, and medical history, a cohort of mental defectives has been divided into medical, biological, and sociofamilial categories. This division, corresponding to differences in etiology and severity, reveals changing patterns of admission and provides evidence that male excess is not primarily due to sex linkage. The incidence of mental retardation increases about 5% with first-cousin marriage, in agreement with other studies. The decline of IQ with inbreeding appears to be due entirely to rare recessive genes, not to dominance deviations of polygenes.

Consanguinity↗

Major loci for lipoprotein concentrations.

In more than 500 families of Japanese ancestry, selected in part through fathers with hyperlipemia or coronary heart disease, a major locus for hyper-beta-cholesterolemia (hyperlipoproteinemia type IIa) is highly significant (chi22 = 24.02), with an allele frequency .002 in the general population. This gene is revealed with about the same power by fasting levels of LDL (low density lipoprotein) cholesterol and total cholesterol. However, VLDL (very low density lipoprotein) cholesterol, HDL (high density lipoprotein) cholesterol, and triglyceride give no convincing evidence for a major locus in this population, nor was a gene for combined hyperlipoproteinemia detected.

Female↗