Topics in perinatal genetics. Prader Willi syndrome in a newborn infant.
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Biomedical subjects
Publications and source records attributed to S Olson.
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A 5.5-kilobase (kb) single sequence DNA fragment (G8) reveals the DNA polymorphic locus D4S10 on Southern blot analysis. This locus is closely linked to Huntington disease and has been mapped to chromosome 4 short arm using human-mouse somatic cell hybrids, and specifically to chromosome 4 band p16 using DNA from individuals with deletions of chromosome 4 short arm who exhibit Wolf-Hirschhorn syndrome. With in situ hybridization techniques, we have confirmed the location of D4S10 on chromosome 4 and further localized it within band p16 utilizing five patients, four with overlapping chromosome 4 short-arm aberrations. The DNA segment G8 was hybridized to the mataphase chromosomes of the five patients. Two of them have different interstitial deletions of one of the chromosome 4 short arms (TA and BA), two have different chromosome 4 short-arm terminal deletions (RG and DQ), and one has a normal male karyotype. By noting the presence or absence of hybridization to the partially deleted chromosomes with known precise breakpoints, we were able to more accurately localize probe G8 to the distal half of band p16.1 of chromosome 4.
Celebes black macaques (Macaca nigra) with a history of diabetes mellitus, recurrent bacterial and protozoal infections, diarrhea, anemia, weight loss, anorexia, and a high mortality were studied to determine their immune status. Two groups of monkeys, healthy and unhealthy, were formed on the basis of a clinical assessment. The proliferative response and the pokeweed-mitogen-induced polyclonal IgG response of peripheral blood mononuclear cells of unhealthy monkeys were significantly less than the responses of healthy monkeys. The percentage of HLA-DR+ cells varied greatly in unhealthy monkeys. The OKT4/OKT8 ratios of unhealthy monkeys were generally greater than the ratios of healthy monkeys. Unhealthy monkeys usually had smaller percentages of OKT8+ cells than did healthy monkeys. The two groups of monkeys were examined for the presence of a syncytial forming retrovirus by a coculture assay involving Raji cells, a human B lymphoblastoid cell line. A type D retrovirus was detected in the unhealthy group but not in the healthy group. Retroperitoneal fibromatosis was detected in several monkeys in the unhealthy group.
During the past decade, there has been a thrust, both socially and legally, to integrate adults with developmental disabilities, particularly those with mental retardation, into community life. Libraries, which are resources in the community for all citizens, can play a significant role in this integration. This article describes the format and outcome of a California-based library program for mentally retarded adults. It describes the materials developed, gives the contributions made by an interdisciplinary team, and discusses occupational therapy's role in the implementation of this community program.
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We have utilized a human tumor clonogenic assay to grow, and subsequently cytogenetically analyze, tumor colony forming cells from human urologic malignancies. Results following chromosome banding analysis are presented from 4 cases of transitional cell carcinoma and 1 case of renal cell carcinoma. Preliminary evidence suggests a possible association between the loss of chromosome 8 and progression or recurrence of transitional cell carcinoma. Additionally, we have utilized the technique of premature chromosome condensation to identify the interphase chromatin profile of urothelial cells obtained by cystoscopy from 8 patients with transitional cell carcinoma and compared these results to urothelial cells obtained from 7 control patients. This study demonstrates that cells obtained from urologic cancers contain a high proportion of cells in late G1, while normal urothelial cells are usually found in the early G1 phase of the cell cycle. Statistical correlation of premature chromosome condensation analysis suggests this method may be a useful adjunct to routine histopathology in discriminating between normal and cancerous urothelium.
The effects of interferons on the radiosensitivity of in vitro human bronchogenic carcinoma cells was investigated. Human fibroblast-derived interferon (IFN-beta) was found to sensitize cells to gamma irradiation while either HuIFN-alpha or mouse IFN-alpha/beta did not. The observed radiosensitization was supra-additive and resulted in a decrease in the shoulder width of the radiation dose-cell survival curve but did not affect the slope. The degree of radiosensitization of the various IFNs tested paralleled the antiproliferative effects of these IFNs on this cell line.
To analyze if methotrexate (MTX) resistance arises from gene amplification in a patient treated clinically with MTX, the cytogenetic and drug sensitivity profile of the tumor colony forming units (TCFUs) from a 58-year-old woman with stage III well-differentiated ovarian serous adenocarcinoma was studied. This patient had not received treatment directed against her tumor for nine months before this study, but had received oral-dose MTX (2.5 mg, twice weekly) for three years for the treatment of psoriasis. Analysis of TCFUs grown in nucleoside-free media demonstrated MTX resistance at concentrations of up to 100 micrograms/mL (2.2 X 10(-4)M). Cytologic evidence for dihydrofolate reductase (DHFR) gene amplification in TCFUs was determined by in situ hybridization, using radiolabeled cDNA to DHFR mRNA. Results localized the DHFR sequences to an abnormally staining region present on chromosome 4q. This study supports the notion that alterations in gene dosage (that is, gene amplification) play a role in the development of drug resistance in spontaneous human cancers.
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Recombinant plasmids containing cDNA inserts from human leukocyte interferon (IFN-alpha), fibroblast interferon (IFN-beta), or immune interferon (INF-gamma) genes were radiolabeled and hybridized in situ to human metaphase chromosome preparations. The results localized the human IFN-alpha and IFN-beta genes to the short arm of chromosome 9(p21-->pter) and localized the IFN-gamma gene to the long arm of chromosome 12(q24.1).
Exogenously administered heme is incorporated into rat hepatic cytochrome P-450 in vivo (Correia, M. A., Farrell, G. C. Schmid, R. S., Ortiz de Montellano, P. R., Yost, G. S., and Mico, B. A. (1979) J. Biol. Chem. 254, 15-17). This was demonstrated in allylisopropylacetamide (AIA)-treated rats by the formation of a radioactive adduct derived from the porphyrin of the administered [3H]heme and AIA. Formation of such adducts requires catalytic participation of cytochrome P-450 in oxidative metabolism of AIA to an active species which subsequently alkylates the prosthetic heme moiety of the cytochrome. These results suggested that the exogenous heme had been incorporated prosthetically into cytochrome P-450 prior to generation of the adduct. However, the possibility remained that a minute portion of the inactivating AIA-species escaped the catalytic site of the generating hemoprotein and alkylated the nonprosthetically bound isotopic heme. To examine this critical possibility, we have employed a chemical derivative of heme which binds to the microsomal membrane. Although this heme derivative is a structurally suitable target for attack by the inactivating drug species, we found that it was unsuitable for incorporation into the prosthetic site of cytochrome P-450. The findings of this study provide irrefutable evidence that the label recovered in drug-porphyrin adducts is derived exclusively from radioactive heme incorporated prosthetically into cytochrome P-450. Drug-porphyrin adducts can therefore be used as reliable probes to follow the transfer of heme from the hepatic "free" heme pool into cytochrome P-450.
A prospective study was performed on 196 consecutive patients undergoing elective colonic surgery to evaluate the prophylactic effect of a single dose of doxycycline. The patients were randomized into four groups: group I 200 mg i.v. preoperatively, group III 600 mg i.v. preoperatively, group III 600 mg i.v. postoperatively, and group IV 200 mg i.v. preoperatively and 200 mg i.v. daily 3 days postoperatively. The rate of septic complications for the different groups were: I 13 per cent, II 7 per cent, III 20 per cent, and IV 19 per cent. There was no statistically significant difference in occurrence of septic complications between the groups. The degree of bacterial contamination during operation was estimated by culture from wound irrigation fluid and from cotton swabs. Bacteria were recovered from the irrigation fluid in 97 per cent, while culture from cotton swabs proved to be much less sensitive. A high number of bacteria in the irrigation fluid was significantly correlated to a high complication rate. It is suggested that direct plating from irrigation fluid can be used for defining a high risk group of patients in colonic surgery.
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