Translocation chromosome 7 of A431 cells contains amplification and rearrangement of EGF receptor gene responsible for production of variant mRNA

The epidermal growth factor (EGF) receptor, along with several oncogene protein products, possesses tyrosine-specific protein kinase activity. Furthermore, the EGF receptor has structural similarity to the putitive v-erb-B transforming protein. Because of these closely shared characteristics, it is important to elucidate the possible involvement of the EGF receptor in malignant transformation. The epidermal carcinoma cell line A431 exhibits an abnormally high number of EGF receptors, which is associated with the presence of translocation chromosome M4. Recently, A431 cells have been shown to contain amplified sequences for the EGF receptor gene(s) and also to produce a variant mRNA which diverges from the normal EGF receptor mRNA at the 3 end. Here we report, using the human EGF receptor cDNA probe pE7, that the chromosome M4 has a six-to sevenfold amplification of the EGF receptor gene. Furthermore, the presence of M4 in somatic cell hybrids correlates with the production of the variant 2.9-kb mRNA. This aberrant mRNA is apparently generated by an intrachromosomal rearrangement which was detected using as a probe a fragment of the pE15cDNA encoding the variant mRNA.     

Isolation and genetic characterization of human KB cell lines resistant to multiple drugs

Human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections. Most of these selection steps resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin; however, at the highest levels of colchicine resistance, increased cross-resistance to other drugs was not observed. There was no major change in protein synthesis or alteration in protein phosphorylation or [^14C]glucosamine labeling patterns accompanying the development of multiple drug resistance as measured by analysis of metabolically labeled proteins on SDS gels. Cell-cell hybridization experiments showed that the colchicine-resistant and multiple drug-resistant phenotypes were incompletely dominant. In addition, colchicine resistance was found to segregate independently from resistance to other drugs in one somatic cell hybrid, suggesting that complex genetic loci are involved in the development of the multiple drug-resistant phenotype. These mutants should be useful for the study of the clinically important problem of multiple drug resistance in human cancer.     

Disrespect and Abuse in Obstetric Care in Mexico: An Observational Study of Deliveries in Four Hospitals

Maternal and Child Health Journal - To identify and describe the frequency and characteristics of disrespect and abuse practices towards women during facility-based delivery in four hospitals in...     

Kidney transplant program waitlisting rate as a metric to assess transplant access

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = −.15, 95% CI, −0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.     

Targeting growth factor receptors with fusion toxins.

Recombinant toxins which bind to growth factor receptors have been prepared and used to kill cells responsible for malignant or autoimmune disease. Our strategy has been to genetically fuse ligands to different forms of Pseudomonas exotoxin which due to mutations or deletions do not bind to normal cells. The resulting recombinant chimeric toxins, in concentrations often less than 1 ng/ml, selectively kill cells expressing the appropriate growth factor receptor. The ligand may be a growth factor, such as transforming growth factor alpha (TGF alpha), interleukin 6 (IL6) or interleukin 2 (IL2), or single chain antigen binding proteins, such as the variable heavy and light regions of the monoclonal antibody anti-Tac. These chimeric toxins kill not only established cell lines but also fresh tumor cells from patients and display anti-tumor activity toward human malignant tumors in nude mice. While clinical trials are beginning with some of these agents, work continues to improve the effectiveness of recombinant chimeric toxins, and to widen the scope of disorders which might be treated by this approach.     

Emil Gruening

Emil Gruening was the first chief of ophthalmology at the Mount Sinai Hospital, in New York City. The hospital started in a couple of brownstone tenement buildings in lower Manhattan. Some eye patients were cared for there and many more after moving to much larger buildings at 66th Street and Lexington Avenue. Gruening came to the United States from Posen in Prussia and soon afterwards joined the Union army. From Appomattox he returned to New York for completion of his medical studies. He went to Europe and studied with such notables as von Graefe and Helmholtz. He did cataract surgery with a Graefe knife, with a nurse at times holding his beard out of the way. He also did ear, nose, and throat surgery. There is a drawing of him doing a mastoid operation on a child with Abraham Jacobi, the father of American pediatrics, watching him. While at Mt. Sinai, William Wilmer participated in the transplant of a rabbit eye into a patient, but went on to achieve greater things in the field. When Gruening died, Wilmer wrote that next to his own father he respected Gruening more than any man he knew. Emil's son Ernest became Governor of Alaska and Senator from Alaska. When Gruening retired the Eye service was jointly run by Charles H. May and Carl Koller, but those are other tales to tell. This revised version was published online in July 2006 with corrections to the Cover Date.     

Friday,December 8, 1995 8Th Annual San Antonio flow cytometry forum

Summary Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Clinical Guidelines Panel on Erectile Dysfunction: Summary Report on the Treatment of Organic Erectile Dysfunction

Purpose

The American Urological Association convened the Clinical Guidelines Panel on Erectile Dysfunction to analyze the literature regarding available methods for treating organic erectile dysfunction and to make practice recommendations based on the treatment outcomes data.

Materials and Methods

The panel searched the MEDLINE data base for all articles from 1979 through 1994 on treatment of organic erectile dysfunction and meta-analyzed outcomes data for oral drug therapy (yohimbine), vacuum constriction devices, vasoactive drug injection therapy, penile prosthesis implantation and venous and arterial surgery.

Results

Estimated probabilities of desirable outcomes are relatively high for vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis therapy. However, patients must be aware of potential complications. The outcomes data for yohimbine clearly indicate a therapy with marginal efficacy. For venous and arterial surgery, based on reported outcomes, chances of success do not appear high enough to justify routine use of such surgery.

Conclusions

For the standard patient, defined as a man with acquired organic erectile dysfunction and no evidence of hypogonadism or hyperprolactinemia, the panel recommends 3 treatment alternatives: vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis implantation. Based on the data to date, yohimbine does not appear to be effective for organic erectile dysfunction and, thus, it should not be recommended as treatment for the standard patient. Venous surgery and arterial surgery in men with arteriolosclerotic disease are considered investigational and should be performed only in a research setting with long-term followup available.