Biomedical subjects
S C Bernstein
Publications and source records attributed to S C Bernstein.
Linear basal cell carcinoma: report of seventeen cases and review of the presentation and treatment.
BACKGROUND: Linear basal cell carcinoma was first described as a distinct clinical morphologic variant in 1985. Subsequently, twelve cases were reported. OBJECTIVE: To review and identify cases of linear basal cell carcinoma in our institutions and determine optimal treatment based on review of our cases and those in the literature. METHODS: Primary basal cell carcinomas treated at the three campuses of Mayo Clinic and the University of Montreal were reviewed retrospectively, as were the twelve cases in the literature. RESULTS: Seventeen cases of linear basal cell carcinoma were identified. The age and sex ratios were similar to those of patients with standard basal cell carcinomas. Based on the review of the few reported cases of linear basal cell carcinoma (29), the percentage of aggressive histologic subtypes (38%) was increased compared with that in a general population. The average number of Mohs layers required for treatment was higher than that reported for standard basal cell carcinoma, an indication of increased subclinical spread. CONCLUSION: Linear basal cell carcinoma is an uncommonly recognized morphologic variant. Based on the small number of cases, these tumors have more aggressive histologic subtypes. Because of the possibility for increased subclinical spread, Mohs micrographic surgery can be considered for treatment. Further studies are needed to confirm these findings.
The many faces of squamous cell carcinoma.
BACKGROUND: Cutaneous squamous cell carcinoma is a disease that has a multitude of clinical, histologic, and etiologic subtypes, all of which are of significance to the clinician. OBJECTIVE: Ten of the most common and clinically significant subtypes of squamous cell carcinoma are presented to emphasize the clinical importance of each and to emphasize and contrast their differences. METHODS: The literature of each subtype of squamous cell carcinoma is reviewed and capsulized. RESULTS: Appropriate diagnosis, therapy, and postoperative management of all subtypes of squamous cell carcinomas are dependent upon the understanding of their unique characteristics. CONCLUSION: The 10 common variants of squamous cell carcinoma presented in this paper: neurotrophic squamous cell carcinoma, Bowen's disease, squamous cell carcinoma in transplant patients, keratoacanthoma-like squamous cell carcinoma, squamous cell carcinoma of the lip, adenoid squamous cell carcinoma, spindle cell squamous cell carcinoma, radiation-induced squamous cell carcinoma, verrucous carcinoma, and Marjolin's ulcer, have unique etiologic, histologic, and clinical features that significantly influence their diagnosis, treatment, and subsequent management. It is imperative that physicians responsible for the care of these patients understand the implication of these unique characteristics.
Leiomyosarcoma of the skin. Treatment of 34 cases.
BACKGROUND: Leiomyosarcoma is a rare soft tissue sarcoma that is one of the least common malignant lesions found in the skin. OBJECTIVE: We discuss the clinical, histopathologic, and prognostic factors related to superficial leiomyosarcoma from cases reported in the literature as well as from the Mayo Clinic experience from 1964 through 1994 with 34 patients. CONCLUSIONS: The vast majority of tumors were treated by excisional surgery with wide margins, but conceptually, Mohs' micrographic surgery should prove useful for the treatment of this tumor as it has with other skin cancers displaying contiguous growth.
Surgical pearl: erythromycin ointment for topical antibiotic wound care.
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Chloroisothiocyanatoquinolines as fluorogenic derivatizing agents for primary and secondary amines.
Two new prechromatographic LC fluorogenic derivatizing agents, 2- and 4-chloro-3-isothiocyanatoquinoline (4 and 5) have been synthesized and shown to react smoothly with primary and secondary amines to produce fluorescent thiazoloquinolines. Compounds 4 and 5 hydrolyse in aqueous base and the rates of this reaction compared with the rates of derivatizations with amino acids indicate that the hydrolysis reaction interferes with derivatization when UV detection is used. The kinetics of derivatization with ordinary amines indicate that this reaction is quite facile, although less nucleophilic amines, e.g. aniline, react slowly. The pKas for first protonations indicate that derivatives of 4 would be unprotonated and those of 5 would be protonated with typical RP-LC mobile phases. The Stokes shift for protonated derivatives of 5 is nearly 200 nm. The excess of unreacted derivatizing reagent interferes with UV detection of some analytes; but when fluorescence detection is used this excess produces only a small negative peak. With fluorescence detection the sensitivity of this method is about 0.8 microM at S/N of 2, and the response of peak height to concentration is linear over at least two decades of concentration.
A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity.
A highly malignant human T-cell leukemia was identified by cell surface analysis as a member of the T-cell receptor (TCR) gamma delta lineage. Cytogenetic and molecular analysis showed a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on chromosome 14 and the distal end of chromosome 8 near the c-myc proto-oncogene locus. The gamma delta TCR of the leukemia blasts was functionally intact and could be activated to generate intracellular calcium flux and to target Fc receptor-mediated redirected tumor cell lysis. In addition, non-major histocompatibility complex restricted lysis of a limited target cell panel was shown by fresh leukemic blasts and by the in vitro-maintained leukemia cells that was comparable to known T-cell lines with natural killer-like activity. These data suggest that the T-cell leukemia potentially had in vivo functional cytolytic activity. However, whether this activity did contribute to the patient's clinical condition could not be determined.
Recombinant gene expression in pulmonary vascular endothelial cells: polarized secretion in vivo.
A unique, spontaneously immortalized rat pulmonary endothelial cell line was transfected with a human growth hormone (hGH) fusion gene generating a line of stably transfected cells that expresses high levels of hGH (Ec/XGH-1). These cells produced significant serum levels of hGH when implanted intraperitoneally, subcutaneously, or intravenously into nude mice. Implantation of Ec/XGH-1 cells under the renal capsule resulted in the formation of large cysts that contained concentrations of hGH that were several thousand times greater than those in serum assayed simultaneously from the same animals. This study presents a new technique for in vivo gene expression using a convenient line of pulmonary vascular endothelial cells as gene carriers. In addition, this system demonstrates the special physiological features of transfected endothelial cells in forming large cysts.
A rapid procedure for cell colony hybridization using DNA probes.
A rapid, direct method for screening single cell-derived colonies or foci is described. The method allows the screening of a large number of colonies or foci by nitrocellulose filter hybridization using DNA probes. This technique simplifies current screening procedures and is a reliable, rapid, and sensitive method for the selection of cell clones containing a desired transfected gene.
Separation of human from mouse and monkey adenosine deaminase by ion-exchange chromatography following retroviral-mediated gene transfer.
A method for the chromatographic separation of human adenosine deaminase (ADA) from murine and monkey ADA is described. This procedure was developed in order to detect the expression of low or moderate levels of human ADA following retroviral-mediated gene transfer of cloned human ADA gene sequences into both mouse and monkey cells. Protein separation was achieved on a Mono Q (HR 5/5) anion-exchange column using the Pharmacia fast protein liquid chromatography system and was found to be a highly reproducible method yielding enzymatically active protein. An increasing linear gradient extending from 0.05 to 0.5 M potassium chloride (pH 7.5) was used to elute the enzyme. Under these conditions, most human ADA does not bind to the column and elutes in the low-salt buffer (0.05 M KCl), while murine ADA elutes at 0.12 M KCl and monkey ADA at 0.15 M KCl. The column fractions were assayed for ADA activity, and the characteristic isozyme banding patterns for human, mouse, and monkey ADA were confirmed by starch gel electrophoresis. This procedure allows the rapid and reproducible separation of human ADA from that of other species and yields partially purified enzymatically active protein.
Multiple myeloma in a child.
A 12-year-old girl with the diagnosis of multiple myeloma is described. She presented with a nasopharyngeal mass which was histologically found to be a plasmacytoma. Serum immunoelectrophoresis revealed an IgA-kappa M-protein (4.9 g/dl). There were approximately 20% atypical plasma cells in a bone marrow biopsy specimen. The diagnosis was further supported by immunohistochemical demonstration of cytoplasmic monoclonal IgA-kappa in the tumor cells of both the nasopharyngeal and bone marrow biopsies. The patient was treated with chemotherapy for 1 year, at which time she became refractory to treatment, based on serum IgA levels. Five months after cessation of therapy, she continues to exhibit a significant objective response, remaining clinically well with a stable, elevated serum IgA level.
Expression of the metastatic phenotype in cells transfected with human metastatic tumor DNA.
NIH 3T3 mouse fibroblasts form nonmetastasizing fibrosarcomas upon transformation by the Ha-ras oncogene isolated from the EJ human bladder carcinoma cell line and subcutaneous inoculation into immunocompetent NFS/NCr mice. DNA from a human metastatic tumor was transfected into these Ha-ras transformants, and one of the resulting colonies yielded a lung metastasis after subcutaneous inoculation. DNA was isolated from this metastasis and subjected to a second round of transfer into Ha-ras-transformed NIH 3T3 cells. Inoculation of these transfected cultures into mice led once again to formation of metastases, this time at a higher frequency. Examination of four of the resulting metastases revealed discrete human DNA fragments that were common to all four. These findings demonstrate that the metastatic phenotype can be transferred via DNA from cell to cell and is associated with the presence of a discrete DNA segment. This segment is not identical to the myc oncogene or to any of the frequently detected ras tumor oncogenes.
Cutaneous "MAIS" infectious granuloma.
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G6PD/malaria hypothesis: a balanced or transient polymorphism.
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Genetic variation in Cameroon: thermostability variants of hemoglobin and of glucose-6-phosphate dehydrogenase.
The technique of heat denaturation was used in addition to electrophoresis for the detection of thermostability variants of hemoglobin and glucose-6-phosphate dehydrogenase in an attempt to measure the amount of genetic variability present in villages in the United Republic of Cameroon, Equatorial Africa. A minimum of three to a maximum of 13 thermostability variants were estimated for HbA and HbS, and a minimum of two to a maximum of ten thermostability variants were estimated for GdA, GdB, and GdA-. It is suggested that hemoglobin and glucose-6-phosphate dehydrogenase thermostability variants are genetically determined and that the sites of these variants are at the hemoglobin and glucose-6-phosphate dehydrogenase structural loci. The evidence for the existence of these hidden variants and their importance in the neutralist v. selectionist controversy are discussed.
Interaction of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency in Cameroon.
The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell trait was determined in 371 Cameroonian males and 668 male blood donors in Chicago. The number of males with both sickle cell trait and G6PD deficiency was significantly greater than expected (p less than 0.05) in Cameroon. The number of males with both sickle cell trait and G6PD deficiency in the Chicago population also exceeded the exptected number, although this was not statistically significant (p greater than 0.30). A young red cell population associated with the sickle cell gene leading to elevated G6PD levels in G6PD-deficient males suggests that sickle hemoglobin may exert a beneficial effect on G6PD deficiency, rather than the opposite, as had previously been proposed. These red cells may be better able to deal with oxidative stress, which can precipitate severe hemolytic disease in G6PD deficiency.
Population studies in Cameroon: hemoglobin S, glucose-6-phosphate dehydrogenase deficiency and falciparum malaria.
Examination of blood samples from 1,183 individuals from Cameroon indicates that sickle cell trait frequencies and G6PD deficiency frequencies were heterogeneous among villages as well as within geographic areas and ethnic groups. Mean parasite counts were significantly correlated with Hb AS frequencies for children 6 years of age and under, although no correlation was found for mean parasite counts and G6PD deficiency frequencies. The mean age of sickle cell trait individuals was found to be significantly greater than the mean age of Hb AA individuals. The mean age of G6PD-deficient males did not differ from the mean age of G6PD-normal males. Hb AA and Hb AS children did not differ significantly in mean positive parasite counts. Falciparum malaria appears to be a selective pressure keeping Hb S frequencies high; yet it may not be the major selective force maintaining the G6PD polymorphism.
Modification of the acid elution technique for quantitation of fetal hemoglobin in individual erythrocytes.
A modification of the acid elution procedure for the demonstration of fetal hemoglobin in red cells using fast green stain is described. This technique not only permits improved visual estimation of the amount of fetal hemoglobin in red cells, but allows for the direct quantitation of fetal hemoglobin content of individual cells, using a scanning and integrating microdensitometer. As an application of this method, the distribution of fetal hemoglobin in populations of red cells of individuals was determined. Distributions were examined in sickle cell anemia patients with different proportions of fetal hemoglobin.