PubMed Health⌕ Search

Biomedical subjects

D L Schaffner

Publications and source records attributed to D L Schaffner.

12 recordsLinked to original sources
PubMed1996

Unanticipated diagnoses found at autopsy in an urban public teaching hospital.

The authors set out to evaluate the use of the autopsy in an urban public teaching hospital setting during the AIDS era. Demographic and length of hospital stay data were obtained from weekly mortality review reports on all patients dying on the medicine service between 1/1/92 and 12/31/93. Clinical and autopsy diagnoses were compared for those patients who had autopsies. The autopsy rate was 16% (152/974). Significant, unsuspected diagnoses were found in 35% (53/152) of the cases, with infections, pulmonary emboli, and myocardial infarctions being most common. Human immunodeficiency virus-infected patients had a greater percentage of unsuspected findings (55%, 23/42), and many of these also were from an infectious etiology. The authors conclude that valuable, unsuspected information frequently can be obtained from autopsies in this clinical setting.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Retention of p53val135 wild-type function in transgenic mice.

We targeted a mutant p53 gene (val135), previously shown to cause tumors in transgenic mice, to the kidney and eye using a gamma-glutamyltranspeptidase promoter. Although transgene RNA was expressed in both tissues, and mutant protein could be detected at high levels in the kidney and was appropriately localized to the nuclei of proximal tubules, no gross or microscopic lesions developed, even when mice were held as long as 75 weeks. When these mice were crossed with transgenic mice carrying HrasT24 (containing a codon 12 mutation) driven by the same promoter, the p53val135 transgene partially suppressed the mutant ras phenotype (proximal tubular hyperplasia and adenomas and carcinomas of the ciliary body and retinal pigment epithelium). The kidneys of double transgenic mice younger than 25 weeks showed less tubular hyperplasia and cystic change than littermates carrying gamma-glutamyltranspeptidase(I)rasT24 alone. By 33 weeks, there was no difference in the severity of the kidney lesions. The eye lesions were less aggressive, and no malignant lesions were identified. Our findings are consistent with the work of others, indicating that p53val135 is not tumorigenic under all conditions; in fact, in some circumstances, it retains some of the suppressing activity of wild-type p53.

Alanine↗
PubMed1995

Leu-7 immunoreactivity in cytologic specimens of thyroid lesions, with emphasis on follicular neoplasms.

Anti-Leu-7 (HNK-1, CD 57) antibody, a marker for natural killer lymphocytes, was employed by Ghali et al. (Hum Pathol 1992;23: 21-25) to study surgically resected formalin-fixed, paraffin-embedded thyroid lesions. They demonstrated strong immunoreactivity of this antibody with thyroid carcinomas, both follicular and papillary, and only occasional weak immunoreactivity with colloid goiters and follicular adenomas. We studied cytologic specimens (primarily fine-needle aspiration biopsy specimens) from 44 thyroid lesions, including 10 follicular carcinomas, 14 follicular adenomas, seven adenomatous nodules, six papillary carcinomas, and seven cases of Hashimoto's thyroiditis. All follicular carcinomas exhibited immunoreactivity to anti-Leu-7 antibody, usually of a moderate to strong degree (9/10); however, six of 14 follicular adenomas yielded similar results. The patterns of immunoreactivity in the other lesions were similar to those previously described (Ghali et al., Hum Pathol 1992;23:21-25). It does not appear that anti-Leu-7 antibody can be used as a specific marker of malignancy in the cytologic assessment of follicular neoplasms of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1995

Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms.

BACKGROUND: Although prostate cancer is one of the most prevalent tumors in men, knowledge of its biology has been hindered by lack of animal models. We have attempted to develop a prostate cancer model utilizing transgenic mouse technology. EXPERIMENTAL DESIGN: Two lines of transgenic mice were derived from one cell stage embryos injected with a fusion gene consisting of a mutated (codon 12) ras gene driven by the human prostate specific antigen (PSA) promoter in an attempt to target the oncogene specifically to the mouse prostate gland. Nontransgenic FVB/N mice were used as controls. The animals were sacrificed for study between 4 and 55 weeks of age. RESULTS: All organs were normal except the salivary glands and gastrointestinal tracts, both of which developed carcinomas in animals older than 44 weeks. The salivary gland tumors were of ductal origin, exhibited a variable degree of differentiation, and were shown to contain abundant PSAras mRNA by in situ hybridization. The gastrointestinal tract tumors were undifferentiated but appeared to be of stromal origin. Both salivary gland and gastrointestinal tumors occasionally metastasized. No transgene expression could be demonstrated in the prostate gland by either reverse transcription-polymerase chain reaction or in situ hybridization. CONCLUSIONS: Lack of transgene expression by the prostate can be explained on the basis of the apparent species specificity previously observed for PSA. Expression in salivary gland is best attributed to identity between the nucleotide sequences of the PSA promoter and of a mouse glandular kallikrein normally secreted by the salivary gland.

Animals↗
PubMed1993

Targeting of the rasT24 oncogene to the proximal convoluted tubules in transgenic mice results in hyperplasia and polycystic kidneys.

Five families of transgenic mice were derived from one-cell-stage embryos injected with gamma GT-rasT24, a fusion gene consisting of the gamma-glutamyl transpeptidase (gamma GT) 5' flanking region containing promoter I linked to a mutated (codon 12) human H-ras oncogene. The transgene was expressed selectively in the kidneys, eyes, and brains of all families as determined by reverse transcription-polymerase chain reaction, nuclease protection assays, and in situ hybridization. In two of five families, kidney lesions consisting of proximal tubular hyperplasia, renal cysts, and microadenomas developed in male animals; males also expressed higher levels of gamma GT/rasT24 RNA. Early lesions consisted of proximal tubular hyperplasia as defined by alkaline phosphatase histochemistry, gamma GT immunohistochemistry, and electron microscopy and could be correlated with the presence of rasT24 RNA within the cystic proximal tubular epithelium by in situ hybridization. Advanced lesions also involved other segments of the nephron and consisted of cysts lined by a flattened unicellular layer of attenuated epithelium. No rasT24 could be identified within cystic lesions of the distal nephron and collecting tubules by in situ hybridization, and they most likely arise by external compression. Animals from the two transgenic strains exhibiting cystic lesions die of renal failure beginning at 8 months of age. No difference in cell-cycle parameters or DNA ploidy between transgenic and control kidneys was identified by flow cytometric analysis. No renal carcinomas developed. The primary renal effects of the H-rasT24 oncogene in this model system consist of proximal tubular hyperplasia and polycystic kidneys. This model appears to provide a useful in vivo system for the study of ras oncogene function and control of renal cell proliferation.

Animals↗
PubMed1993

Expression of the rasT24 oncogene in the ciliary body pigment epithelium and retinal pigment epithelium results in hyperplasia, adenoma, and adenocarcinoma.

We examined eye lesions in five lines of transgenic mice carrying the human rasT24 oncogene driven by the type I gamma glutamyl transferase (gamma GT) promoter. In three lines, hyperplasia developed as early as 11.5 days postconception in the outer neuroectodermal layer, which gives rise to ciliary body and retinal pigment epithelium. At birth, the eyes from many animals contained adenomas, and by day 27, mice developed invasive adenocarcinomas originating in the region of the ciliary body. Microphthalmia, cataracts, and chronic nongranulomatous inflammation involving the anterior and/or posterior segments of the eye were also found. gamma GT is detectable histochemically as early as 11.5 gestational days in the outer neuroectodermal layer and after birth is more abundant in the ciliary body than in the retinal pigment epithelium. Using a reverse transcriptase-polymerase chain reaction, we found that type I (but not types II or III) gamma GT RNA is made by the mouse eye; the gamma GT(I)rasT24 transgene transcription product was detected in the eyes of all five transgenic lines. The sequential progression of hyperplasia to invasive neoplasms in the ciliary body in response to gamma GT(I)rasT24 expression differs from the process in the kidney of these animals in which tubular hyperplasia and microadenomas with little evidence of progression are the major lesions.

Adenocarcinoma↗
PubMed1991

Coinjection strategy for visual identification of transgenic mice.

Transgenic mice were generated by coinjection of a dominant marker gene that induces fur and eye pigmentation (a tyrosinase minigene) plus an unrelated DNA construction that has a gamma-glutamyl transferase (gamma GT) promoter linked to a ras oncogene. Mice transgenic for gamma GT-ras could be identified in the first and all subsequent generations by simple visual inspection for pigmentation. Furthermore, the gamma-glutamyl transferase promoter was active in kidney but not skin of the transgenic mice, indicating that the cointegrated DNA was active and independently expressed. These results confirm that the tyrosinase minigene can be used for coinjections to allow rapid visual identification of transgenic mice.

Animals↗
PubMed1988

The glandular odontogenic cyst: an apparent entity.

This article reports 8 examples of a rare cyst of the jaws that appears to be a distinct entity and which we have named glandular odontogenic cyst because of its unusual histopathological features. This lesion occurs over a wide age range in both sexes, tends to recur, and may become very large. However, one example in this series remained small over a period of 9 years; another, somewhat atypical example, was associated with an ameloblastoma.

Adult↗
PubMed1982

Solitary neurofibroma of the maxilla.

A case of a large central neurofibroma of the left posterior maxilla is presented. This lesion was treated by a left radical maxillectomy because of the extensive nature of the tumor. The surgical defect was reconstructed with a latissimus dorsi myocutaneous flap. The incidence and clinical features of intraosseous benign nerve sheath tumors are discussed.

Adult↗
PubMedDate not supplied

Histopathologic effects of meconium on human umbilical artery and vein: in vitro study.

OBJECTIVE: To determine the histopathologic effects of meconium on human umbilical artery and vein. METHODS: Umbilical cords from six patients with uncomplicated, singleton, term gestations were obtained immediately after delivery. One centimeter segments from each cord were flushed, isolated, placed in either modified Krebs solution alone or modified Krebs solution with various concentrations (1%, 10%, or 25%) of fresh meconium, and then incubated at pH 7.2, temperature 37 degrees C, PCO2 50-55 mmHg, PO2 40-45 mmHg for 1, 6, 12, or 24 h. The specimens were then fixed, stained, and examined under light microscopy. RESULTS: Umbilical arteries exhibited focal vacuolation of the endothelium after exposure of the cord to meconium. Umbilical veins revealed: 1) endothelial loss proportionate to the meconium concentration at all intervals (P < 0.05), 2) increased density or focal absence of the internal elastic lamina, and 3) focal loss of myocyte nuclei. Rare nonpigmented macrophages and increased mast cells were identified in the Wharton's jelly. CONCLUSIONS: Exposure to meconium in vitro results in histopathologic changes in the umbilical artery and vein.

Cell Nucleus↗