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Biomedical subjects

G L Bratthauer

Publications and source records attributed to G L Bratthauer.

At least 19 recordsLinked to original sources
PubMed1994

Expression of LINE-1 retrotransposons in human breast cancer.

BACKGROUND: Several diseases have been linked to the insertion of human LINE-1 retrotransposons (L1Hs) into structural genes. Recently, the element has been shown to be expressed in a variety of adult and pediatric germ cell cancers, leading to speculation that L1Hs-induced insertion mutations may play a role in the etiology of some neoplasias. METHODS: An L1Hs-encoded protein (p40) was assayed in breast cancer cell lines by Western blotting and in solid tumors by immunohistochemical staining and Western blotting. RESULTS: L1Hs retrotransposons are expressed in a significant number of human breast cancers: expression was detected in 7 of 8 malignant cell lines and in 9 of 12 primary infiltrating ductal carcinomas. No expression was detected in two nonmalignant breast epithelial cell lines, five malignant B- or T-cell lines, tissue from a normal breast, a primary breast sarcoma, or a primary medullary carcinoma of the breast. CONCLUSIONS: These results raise the possibility that L1Hs expression may contribute to the origin or progression of some breast cancers.

Breast↗
PubMed1994

Squamous cell papillomas of the esophagus: a study of 23 lesions for human papillomavirus by in situ hybridization and the polymerase chain reaction.

This study assessed squamous cell papillomas of the human esophagus for the presence of human papillomavirus (HPV) and correlated the results with histological features. Twenty-three lesions obtained by endoscopic biopsy from 17 patients were studied, first by in situ hybridization (ISH) for HPV types 6-11, 16-18, 18, and 31-33-51, and second by the polymerase chain reaction (PCR) with amplification of multiple HPV types and demonstration of amplified product by ethidium bromide staining and Southern blot hybridization for HPV types 6-11, 16, and 18 in each case. Evidence of HPV DNA was found in only one lesion, which showed HPV type 6-11 by ISH and HPV positivity by Southern blotting of the amplified product after the PCR. This case exhibited histological features suggestive of HPV infection, although no morphological changes specific to the lesion were identified. The remaining 22 lesions, including those from cases in which multiple papillomas were present, were negative for HPV. The results show that HPV DNA is frequently not detectable in esophageal squamous cell papillomas, even when highly sensitive techniques are used. These findings are consistent with the hypothesis that other pathogenetic mechanisms, such as mucosal injury and repair, are important in the etiology of these lesions.

Adult↗
PubMed1993

LINE-1 retrotransposon expression in pediatric germ cell tumors.

BACKGROUND: Human LINE-1 (L1Hs) is a retrotransposon that is known to cause insertion mutations. Previous work demonstrated that at least 10% of adult testicular germ cell cancers expressed the L1Hs element. METHODS: Pediatric germ cell tumors were assayed for L1Hs expression by in situ immunohistochemical methods using an antibody directed against one of the L1Hs-encoded proteins. RESULTS: Approximately 10% of pediatric germ cell tumors express abundant amounts of the L1Hs protein. The element was expressed in 1 of 19 ovarian tumors, 1 of 20 testicular tumors, and 4 of 19 extragonadal tumors. The reactive cells in all cases appeared to be embryonal carcinoma or yolk sac tumor cells. None of 32 ovarian immature teratomas gave positive results, suggesting that more differentiated tissues do not express L1Hs abundantly. CONCLUSIONS: It appears that neither the age nor sex of the patient, nor the location of the tumor, has a significant influence on the degree of L1Hs expression.

Adolescent↗
PubMed1993

Immunohistochemical profile and differential diagnosis of microglandular adenosis.

Twelve examples of microglandular adenosis (MA) were evaluated immunohistochemically using a panel of antibodies directed against actin, S-100 protein, collagen type IV, the c-erb-B2 gene product, and the progesterone receptor, as well as antibodies BER-EP4 and B72.3. The results were compared with the reactions observed in 15 cases of tubular carcinoma and 11 examples of sclerosing adenosis. Three examples of secretory adenosis were also evaluated, but only for S-100 protein and actin. The results confirmed the absence of a myoepithelial cell layer and the presence of basal laminar investiture in MA. Tubular carcinoma lacked a myoepithelial cell layer and basal laminar investiture. Sclerosing adenosis, in contrast, had both a myoepithelial cell layer and displayed basement membrane around the tubules. Secretory adenosis also had a myoepithelial cell layer; the presence of basement membrane could be confirmed easily using periodic acid-Schiff reaction in the three cases of secretory adenosis. An interesting and unexpected finding was the presence of an intensely positive reaction in the epithelial lining cells of the tubules in microglandular adenosis for S-100 protein. A far less intense positivity for S-100 protein was observed sporadically in many normal myoepithelial and some epithelial cells in the adjacent breast lobules. The intensely positive reaction suggests that the proliferating cells in MA correspond to an S-100-positive epithelial cell type that is often present in a small number and in a sporadic manner in the normal breast. The epithelial cells in tubular carcinoma, sclerosing and secretory adenosis were negative for S-100 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/16/18.

A recent study has shown that human papillomavirus (HPV) types 16 and 18 can immortalize normal breast epithelium, and raised the possibility that HPV may be etiologically related to some cases of breast cancer. In order to investigate this possibility, we performed polymerase chain reaction (PCR) assays for HPV types 6, 11, 16 and 18 in 15 papillomas, 15 papillary carcinomas, and 13 infiltrating ductal carcinomas of the breast. No HPV-related DNA sequences were identified by Southern blotting of the PCR products. It therefore seems unlikely that a significant percentage of human breast carcinomas is etiologically related to infection with one of these HPV types.

Base Sequence↗
PubMed1992

Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter.

BACKGROUND: Gene transfer into the arterial wall may provide a novel therapeutic strategy for the treatment of coronary artery restenosis. Previously described methods for gene transfer into the arterial wall require total vessel occlusion for 30 minutes. We sought to develop a protocol for gene transfer within a more clinically relevant time frame. METHODS AND RESULTS: We used a perforated balloon (Wolinsky) catheter to inject retroviral vector-containing virions into rabbit aortas in vivo. The virions were injected within 1 minute. Aortas were removed 5-14 days after injection and analyzed for evidence of gene transfer. In initial studies, nine rabbits were injected with a vector expressing the beta-galactosidase gene, and nine rabbits were injected with either non-beta-galactosidase-containing vectors or with a vehicle control. Histochemical staining of aortic tissues revealed blue (positive) cells in eight of nine experimental rabbits and six of nine controls. Because of the lack of specificity of the beta-galactosidase detection system, we adopted a polymerase chain reaction-based protocol in which oligonucleotide primers were used to amplify specific vector-related sequences from aortic tissue extracts. The polymerase chain reaction protocol, calibrated with standards containing known numbers of transduced cells, revealed low amounts of vector-related sequences in six of 12 vector-injected rabbits and in one of 13 controls (p less than 0.03). Comparison with standards indicated that fewer than 100 transduced cells were present in a 2-cm length of the injected aortic tissue. CONCLUSIONS: Although in vivo gene transfer through an infusion balloon catheter can be accomplished within 1 minute, the therapeutic use of this protocol is limited by the small number of cells that are transduced.

Animals↗
PubMed1992

Active LINE-1 retrotransposons in human testicular cancer.

An antibody to the protein encoded by the first open reading frame of the human LINE-1 (L1Hs) element was used to examine immunohistochemically 59 formalin-fixed, human testicular germ cell tumors. Six tumors were positive for L1Hs expression. In all cases the L1Hs-positive cells were epithelial and most had the very characteristic, undifferentiated appearance of embryonal carcinoma or yolk sac tumor cells. One L1Hs-positive tumor had metastasized to the lung and lymph nodes and the metastatic cells also expressed L1Hs. This is the first observation of widespread retrotransposon expression in human tissue. These observations raise the possibility that L1Hs-encoded proteins may function as oncoproteins in some cancers.

DNA Transposable Elements↗
PubMed1991

Retroviral vector-mediated in vivo expression of low-density-lipoprotein receptors in the Watanabe heritable hyperlipidemic rabbit.

We have achieved in vivo expression of recombinant low-density-lipoprotein (LDL) receptors in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for the human disease familial hypercholesterolemia. A retroviral vector was constructed containing the human LDL receptor cDNA and was used to stably transduce primary skin fibroblasts from WHHL rabbits. The integrity and function of the introduced LDL receptor was established by immunoprecipitation, by a fluorescent LDL binding assay, and by the ability of the transduced cells to suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity in response to exogenous cholesterol. Autologous transduced fibroblasts were reimplanted into donor rabbits; in vivo LDL receptor expression and the survival of the transduced cells were analyzed by immunohistochemistry and by LDL binding assays performed on cells recovered from the implants. LDL receptor-bearing cells could be identified on tissue sections and recovered from implants for up to four weeks. Total and LDL cholesterol levels decreased significantly after implantation of the transduced cells; however, control experiments indicated that the decreases were not mediated through the recombinant LDL receptor. While in vivo stable expression of recombinant LDL receptors in Watanabe rabbits is possible, consequent changes in lipid levels must be interpreted with caution. This system of site-specific in vivo expression of recombinant LDL receptors permits further evaluation of the role of LDL receptor-gene replacement in the therapy of hypercholesterolemia.

Animals↗
PubMed1991

Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma).

Twenty-six cases of malignant peripheral nerve sheath tumor with a predominant epithelioid pattern were studied to determine the range of its histologic patterns, immunophenotype, and biologic behavior. The tumor presented as an asymptomatic mass either in superficial (16 cases) or in deep soft tissue (10 cases) of the extremity. Characteristically, those in deep soft tissue were composed of vague nodules of varying cellularity made up of cords or strands of rounded epithelioid cells with prominent nucleoli. Those in superficial soft tissue were uninodular masses composed of tight clusters of cells showing cell-to-cell molding but possessing the same prominence of nuclei and mitotic activity as those in deep soft tissue. Several were associated with a preexisting benign nerve sheath tumor. A number of cases deviated from the above description, including cases that resembled a clear cell carcinoma, a malignant rhabdoid tumor, and a pleomorphic sarcoma. The majority of cases (80%) strongly expressed S-100 protein and neuron-specific enolase, but all lacked a melanoma-associated antigen (as defined by HMB-45) and cytokeratin. Stains for type IV collagen defined linear immunoreactivity around single cells and groups of cells. This pattern did not differ substantially from that of melanomas and therefore did not serve as a reliable discriminant. Follow-up information indicated a more favorable course for those in superficial soft tissue compared with those in deep sites. Two of 16 patients in the former group developed metastatic disease compared with three of 10 in the latter group. Tumors in superficial soft tissue may be eminently treatable and curable, depending on size.

Adolescent↗