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Biomedical subjects

J Reising

Publications and source records attributed to J Reising.

13 recordsLinked to original sources

Detection of P-glycoprotein with four monoclonal antibodies in normal and tumor tissues.

P-glycoprotein (Pgp), encoded by the multidrug-resistance gene (MDR1), is an active efflux pump for many structurally diverse lipophilic compounds. Using peroxidase-antiperoxidase immunohistochemistry technique and four anti-Pgp monoclonal antibodies directed against different epitopes of the molecule, we examined the distribution of Pgp in normal human tissues and squamous cell carcinomas of the head and neck. All four antibodies detected Pgp in bronchial cells, mammary ductal epithelium, gallbladder epithelium, epithelia of small and large intestine, bile canaliculi, dermal sweat glands, proximal tubules of kidney, endometrium, trophoblasts, adrenal gland, and capillaries of central nervous system, testis, and papillary dermis. Of the 23 head and neck squamous cell carcinomas, about 60% had detectable Pgp. It is possible that differences noticed between antibodies are due to cross-reactivity to proteins unrelated to MDR1. Care must be taken in interpreting staining results when only one or two monoclonal antibodies are used.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Detection of P-glycoprotein with JSB-1 monoclonal antibody in B-5 fixed and paraffin-embedded cell lines and tissues.

We analyzed the expression of P-glycoprotein (Pgp) by immunohistochemistry using JSB-1 monoclonal antibody (MAb) on paraffin-embedded sections of the multi-drug resistant (MDR) (CHrC5 and CEM-VLB), and sensitive (AuxB1 and CEM) cell lines, and also in normal kidney, colon, adrenal and in kidney and colon carcinomas. After comparing the sensitivity of three different immunohistochemical techniques the peroxidase-antiperoxidase method was found to be the best. We then tested six different fixation methods. The MDR cell lines and human tissues demonstrated the strongest staining with B-5 fixative. Both MDR cell lines, but not the tissues fixed in 1% paraformaldehyde and Zamboni's fixative demonstrated weak staining. No immuno- reactivity could be detected in MDR cell lines and tissues fixed in 10% buffered or nonbuffered formalin or by the AMeX method of tissue processing. The present study clearly shows that the type of fixative is critical for the preservation of Pgp epitope recognized by JSB-1 MAb, and that B-5 fixative is expected to be equally applicable for the detection of Pgp in normal and neoplastic tissues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Observations regarding DNA replication sites in human cells in vivo following infusions of iododeoxyuridine and bromodeoxyuridine.

In studies using bromodeoxyuridine (BrdUrd) and/or iododeoxyuridine (IdUrd) to label S phase cells in cancer patients, several unique observations were made regarding DNA replication sites and the organization of newly synthesized DNA in post-mitotic cells. While the majority of tumour specimens removed at the end of infusions demonstrated concentration of replication sites around the nuclear membrane, biopsies obtained in leukaemic patients 1 week later demonstrated several distinct patterns of labelling. For example, one, two or all lobes of granulocytes were labelled. Scavenger macrophages bearing labelled leukaemic cells in their cytoplasm were also seen. Sequential IdUrd/BrdUrd labelling of solid tumours showed various patterns of nuclear/nucleolar/membrane labelling, allowing more precise localization of early versus late replication sites.

Antibodies, Monoclonal↗

Immunohistochemical detection of c-myc oncoprotein in paraffin embedded tissues.

In almost all studies using paraffin embedded tissue, c-myc protein has been found in the cytoplasm of cells. Since the protein is normally localized in the nucleus it is difficult to determine which histochemical observations are real and which are artefactual. The study designed here evaluated several different methods of fixation prior to paraffin embedding in an attempt to identify which would prevent the diffuse of the protein out of the nucleus. Using various fixation procedures (formalin, paraformaldehyde, B-5, Zamboni and AMeX) we found that fixation in cold acetone (-20 degrees C) overnight followed by 2x15 min fixation in acetone at +4 degrees c and at room temperature, cleared in methyl benzoate and xylene (AMeX procedure) gives reproducible nuclear staining when a variety of normal and tumor tissues are treated with an anti c-myc protein antibody. This method was then compared to frozen sections. While there was no cytoplasmic staining in same tissue specimens in both AMeX processed and frozen sections, the tissue architecture was much better preserved in AMeX processed samples. Our data strongly suggest that AMeX fixation, originally developed for T and B lymphocyte antigens, should be used for immunolocalization of c-myc oncoprotein in paraffin embedded tissues.

Cell Nucleus↗

Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation.

Initial trials of irradiation and chemotherapy followed by operation for squamous carcinoma of the esophagus have produced encouraging results. Over the past three years, with palliative and curative intent, we have treated 27 unselected patients initially with two courses of chemotherapy (fluorouracil and either cisplatin, mitomycin, or cisplatin and vincristine sulfate) given 29 days apart and 3000 rad (30 Gy) of radiation. Ten patients have then undergone esophageal resection and two patients have undergone esophageal bypass. Results are compared with those of 70 unselected historical control patients treated since 1979. Survival at 30 months was significantly improved for multimodality-treated patients (21.4% +/- 10.1%, mean +/- SEM) when compared with historical control patients (4.8% +/- 2.7%). Twenty-four percent of multimodality-treated patients had complete remission of all tumor. These data indicate that overall therapy for carcinoma of the esophagus has been improved in our institutions.

Carcinoma, Squamous Cell↗

Fitts' principles still applicable: computer monitoring of fighter aircraft emergencies.

When examining the impact of automation in the cockpit, a careful distinction must be drawn between the role of a multi-crew civilian aircraft and a single-seat military aircraft. For the former, there are some concerns that automation can have a negative impact on the crew by reducing their proficiency. However, for a single-seat military aircraft on an attack mission, the role of automation is not only helpful to the pilot now but in the future may be necessary to achieve mission success. These distinctions must constantly be brought to mind in explaining the concepts of Fitts' principles. For a single-seat military aircraft, it is believed that these principles still apply, and that computer monitoring of system failures will further enhance their application. Three approaches to computer-augmented system monitoring are discussed.

Aerospace Medicine↗

Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters.

We have analyzed the expression of the p53 tumor suppressor gene in paraffin-embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas.

Biomarkers, Tumor↗

Seasonal variations of inflammation and ulcer incidence as assessed by upper digestive tract endoscopy.

A retrospective analysis of 3650 endoscopies shows that frequency of inflammation and ulcer incidence both in the stomach and the duodenal bulb were similar in consecutive seasons of the year. The conclusion is drawn that there may be seasonal (circannual) factors which predispose aggression to mucosa both in the stomach and duodenum, which in turn leads to seasonal occurrence of inflammation as well as to ulcer incidence.

Duodenal Diseases↗