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Biomedical subjects

B F Atkinson

Publications and source records attributed to B F Atkinson.

At least 19 recordsLinked to original sources

The effects of short-term lansoprazole therapy on Helicobacter pylori infection and antral gastritis in duodenal ulcer patients.

BACKGROUND/AIMS: Lansoprazole is a new potent proton pump inhibitor that exhibits activity against Helicobacter pylori in vitro. This study endeavored to determine the effects of 4 wk of lansoprazole therapy upon H. pylori infection and antral gastritis in duodenal ulcer patients and to determine the relationship of the gastritis with Helicobacter infection and with ulcer activity. METHODS: Satisfactory antral biopsies were obtained from 119 duodenal ulcer patients before and after 4 wk of therapy with lansoprazole, ranitidine, or placebo. Sections were scored blindly for degree of active and chronic inflammation and extent of H. pylori infection. RESULTS: Four weeks of lansoprazole (30 mg daily) or ranitidine (300 mg daily) therapy produced a significant decrease in H. pylori infection. The reduction of H. pylori infection, but not ulcer healing per se, correlated with the decrease in active and chronic antral inflammation. Reduction of H. pylori infection, however, did not improve the good ulcer-healing rates already achieved at 4 wk by potent acid inhibition. CONCLUSIONS: Lansoprazole exhibits activity against H. pylori in vivo. Short-term improvement in antral gastritis is affected by reduction of H. pylori infection but not by ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles

Interobserver variability of cervical smears with squamous-cell abnormalities: a Philadelphia study.

The reproducibility of reporting squamous lesions by the Bethesda System (TBS) was evaluated by distributing 20 slides to be classified among 5 panelists considered experts in the field of cytopathology. Four cases were chosen for their classic morphology and the remainder were foreseen to produce possible discrepancies within one diagnostic category. For 7/20 (35%) cases there was unanimous agreement. Participants disagreed within one category of magnitude for seven (35%) cases. In six (30%) cases there was a range of more than one category disagreement. However, additional written comments modifying TBS diagnoses often diminished the clinical significance of these discrepancies. We conclude that despite the important role of TBS in standardization of Pap smear reports, a great degree of subjectivity exists in classifying squamous abnormalities without "classic" morphology. The lack of reproducibility should be taken into account in cytology proficiency testing.

Carcinoma, Squamous Cell

Monoclonal antibody-dependent, cell-mediated cytotoxicity against human malignant gliomas.

Two monoclonal antibodies (MAbs), IgG2a MAb ASHG4 and IgG2b MAb ASHE2, were produced in mice immunized with cultured human malignant glioma cells. Both MAbs bound strongly to the surfaces of long-term cultured glioma cells, and MAb ASHE2 also bound strongly to short-term cultured glioma cells. Sections of frozen glioma tissues bound both MAbs strongly, whereas normal brain tissues showed weaker reactivities, and tissues derived from carcinomas of various histological types were completely unreactive. Furthermore, the MAbs did not bind to peripheral blood cells or bone marrow cells. Although both MAbs bound to the same Mr 27,000-29,000 protein, they may detect different or overlapping epitopes on this antigen. Because MAbs ASHE2 and ASHG4 lysed cultured glioma cells with human peripheral blood lymphocytes as effector cells, they are promising reagents for approaches to immunotherapy of human malignant gliomas.

Antibodies, Monoclonal

Monoclonal antibodies with cytotoxic reactivities against human gliomas.

Monoclonal antibodies (MAb's) reactive with human malignant glioma cells were derived from mice inoculated with cells from fresh glioma tissue. Seven MAb's were selected for study based on their high-level binding in immunoperoxidase and immunofluorescence assay to most of the glioma tissues derived from various patients and based on the absence of binding to normal bone marrow cells. Four of the seven MAb's did not bind to any of the four normal brain tissues tested, whereas three MAb's bound to one or two of these tissues. Two MAb's bound to the surfaces of cultured glioma cells in radioimmunoassay. One of these MAb's (AS-AY1, immunoglobulin (Ig)(G1) lysed cultured glioma cells with human lymphocytes or murine macrophages as effector cells; the other MAb (AS-AY2, IgM) was reactive in complement-dependent cytotoxicity assay. These two MAb's therefore seem especially promising reagents in approaches to immunotherapy of human malignant glioma.

Antibodies, Monoclonal

Diagnosis of Pneumocystis carinii pneumonia by cytologic evaluation of Papanicolaou-stained bronchial specimens.

To evaluate the sensitivity and specificity of diagnosing Pneumocystis carinii pneumonia (PCP) by Papanicolaou-stained bronchial brushing and wash/lavage specimens obtained by fiberoptic bronchoscopy, the cytologic preparations and clinical records from 58 immunocompromised patients were reviewed. Bronchial brushings and wash/lavage specimens were examined using methenamine silver (Grocott) and Papanicolaou stains. Pneumocystis carinii pneumonia was recognized with Papanicolaou stain by identifying distinctive alveolar casts, which frequently contained collections of encysted sporozoites. Thirty cases of PCP were identified, and Grocott-stained bronchial wash/lavage specimens were positive in 29 instances (97%). Grocott staining of the transbronchial biopsy was positive for PCP in 18 of 22 specimens (82%). Bronchial brushings were insensitive, yielding a positive specimen in only 30% of cases of PCP. Alveolar casts of PCP were identified by Papanicolaou-stained slides of wash/lavage specimens in 83% of cases of Pneumocystis pneumonia. These proteinaceous alveolar casts were not seen in other pulmonary disorders. Encysted sporozoites were found in 56% of cases in which Papanicolaou-stained alveolar casts were identified. We conclude that the diagnosis of PCP can be made rapidly and reliably on the Papanicolaou-stained bronchial wash/lavage or bronchial brush specimens by detecting the characteristic alveolar casts, which contain P. carinii-encysted sporozoites. The presence of encysted sporozoites within alveolar casts is pathognomonic for PCP, and methenamine silver stains can be eliminated in those cases in which encysted sporozoites are identified.

Bronchoalveolar Lavage Fluid

The fibrolamellar variant of hepatocellular carcinoma. Its association with focal nodular hyperplasia.

A case of fibrolamellar hepatocellular carcinoma (FL-HCC) associated with adjacent focal nodular hyperplasia (FNH) is described. These two regions were adjacent but distinct, both on gross and microscopic examination. Currently, it is unclear whether FL-HCC rarely arises in preexisting FNH, or whether FNH is a typical response to this vascular variant of hepatocellular carcinoma (HCC). The FNH region, which is peripheral, may be biopsied to exclude the underlying carcinoma, and thus lead to inadequate therapy. Previous reports of this association are reviewed.

Adult

Purification and amino terminal sequencing of human melanoma nerve growth factor receptor.

The nerve growth factor (NGF) receptor, solubilized with Triton X-100 detergent, has been purified from human melanoma cell line A875. Purification to near-homogeneity was achieved by chromatography on wheat germ agglutinin-agarose, followed by immunoaffinity chromatography on Sepharose columns coupled with anti-NGF receptor monoclonal antibody (MAb). The purified receptor, a 75,000-dalton protein, retains the capacity to bind NGF as well as anti-receptor MAbs. Final purification was achieved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sequence of amino acid residues at the amino terminus has been determined. Possible sequence homology between the NGF receptor and several other proteins is discussed. Using the purified receptor as immunogen, new MAbs to the NGF receptor have been produced. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of dorsal root ganglia from monkeys.

Amino Acid Sequence

An antimelanoma monoclonal antibody and the histopathology of uveal melanomas.

Monoclonal antibody ME491 identifies a cutaneous melanoma-associated antigen in formaldehyde-fixed, paraffin-embedded tissues. This antibody was applied to tissue sections from 79 cases of formaldehyde-fixed, paraffin-embedded uveal melanomas. Sixty-nine (87.3%) of the 79 cases showed staining by monoclonal antibody ME491, thus demonstrating an antigen shared by cutaneous and uveal melanomas. No relationship between the staining pattern and the patient outcome was detected. Twelve (85.7%) of the 14 cases in which balloon cells were present stained with the antibody. The antibody stained the long posterior ciliary nerve in 12 (38.7%) of 31 cases in which the nerve was present in tissue sections. The antibody cross reacted with the retinal pigment epithelium (16.5% of cases) and a variety of normal nonocular tissues.

Antibodies, Monoclonal

Flow cytometric DNA analysis as a diagnostic aid for cervical condyloma and cancer.

Flow cytometric DNA analysis data (FCDA) were obtained from 324 samples provided through the Gynecology-Oncology Clinic. These samples consisted of 294 combined endoectocervical and vaginal smears and 30 peritoneal washings. Using a conventional scheme for G0/G1, S + G2/M and the coefficient of variation with computer correction for the cell-cycle kinetics, it was possible to assign a diagnostic Class I, II, III or V similar to that used by the Cytology Laboratory. These data were then compared with the histopathologic and colposcopic diagnoses. The correlation between FCDA and cytologic results were essentially similar to the previous data obtained from only endocervical sampling. The most interesting finding in this study was the recognition of an FCDA pattern showing a higher DNA content in the G0/G1 and the early S regions in 70 of 94 (74.5%) of samples from patients with condyloma acuminata. All condyloma samples were diagnosed either by cytologic, histopathologic, or colposcopic examination, or a combination of two or three. All biopsy specimens were then reviewed by one pathologist to verify any discrepancies. The relationship of this pattern to the viral etiology of this disease is discussed with the three methods of diagnosis and electron microscopic observations. It is suggested that, based on this study. FCDA analysis of pap smears may also be useful in determining the presence of condyloma in a gynecology clinic. The potential value of FCDA analysis from peritoneal washings for the diagnosis of gynecologic cancer can not be ascertained in this preliminary investigation because of insufficient samples.

Cell Cycle

A fetal glycolipid expressed on adenocarcinomas of the colon.

Reactivity of neuraminidase-treated colorectal carcinoma cells with antibodies that detect the X-carbohydrate structure was greater than the reactivity of untreated cells. The same results were obtained with glycolipid extracts of meconium, a colorectal carcinoma cell line, three freshly excised human adenocarcinomas, and normal bronchial mucosa. The glycolipid was either not expressed or expressed in smaller quantities on the corresponding normal colon tissue. Further study showed that the major sialo-X glycolipid has six sugars including a single sialic acid which blocks X-antigenicity. These glycolipids were further analyzed by ion-exchange high-pressure liquid chromatography and thin-layer chromatography. These monosialo-X glycolipid antigens might serve as potential tumor markers.

Adenocarcinoma

Differential reactivity of monoclonal antibodies with human colon adenocarcinomas and adenomas.

Monoclonal antibodies have been generated using membrane-enriched extracts of human metastatic mammary carcinoma lesions (Colcher et al., 1981), some of which demonstrated binding to the surface of human colon carcinoma cell lines. We report here an analysis of the reactivity of three of these monoclonal antibodies with formalin fixed tissue sections of human colon adenocarcinomas and adenomas. The three monoclonals employed were B72.3, which is reactive with a 220-400 kdal high molecular weight glycoprotein complex; B6.2, reactive with a 90 kdal glycoprotein, and B1.1, which is reactive with the 180 kdal glycoprotein CEA. B1.1 was least selective in its reactivity to colon carcinoma versus adenoma lesions. When 10 micrograms/ml of purified B1.1 IgG were used per slide, 94% (15 of 16) of carcinomas and 83% (15 of 18) adenomas showed reactivity. Monoclonal B72.3 demonstrated the most selective reactivity for carcinomas. Eighty-two percent (14 of 17) of carcinomas were positive while none of 18 adenomas examined showed reactivity with more than a few percent of adenoma cells positive. When a low concentration of purified B72.3 immunoglobulin was used per slide, 8 of 16 carcinomas and none of 46 adenomas or normal colon epithelium samples scored positive. Monoclonal B72.3 also reacted with cells in areas of "atypia" within adenomas. The reactivity of monoclonal B6.2 was intermediate as compared to B1.1 and B72.3 in its selectivity of reactivity for carcinoma cells. A heterogeneity in the populations of tumor cells showing reactivity with the three monoclonals was observed within many of the tumor masses. Both colon adenocarcinomas and adenomas can now be placed in several distinct groups based on their expression of antigens reactive with the three monoclonal antibodies employed.

Adenocarcinoma

Evaluation of a one-parameter flow analysis of cervical samples for gynecology cancer screening.

A total of 246 endocervical samples were collected for Papanicolaou staining and one-parameter flow cytometric DNA analysis (FCDA) using 4',6-diamidino-2-phenylindole as a DNA stain. Typical histograms derived from FCDA analysis were designated class I, II, III, and V. Two groups of patients were studied: 135 women referred for colposcopy (COLPO), and 79 women exposed to diethylstilbestrol (DES). The remaining 32 samples were evaluated and found unsatisfactory. In the colposcopy group FCDA assigned 38 patients normal, 62 mild to moderate dysplasia, 33 moderate to severe dysplasia, and 2 carcinoma in situ and invasive carcinoma. Agreement of Pap smear and FCDA occurred in 56, 59, 72, and 100%, respectively. In the diethylstilbestrol group 57 patients were normal and 12 had mild to moderate dysplasia according to Pap diagnosis. Agreement between FCDA and Pap diagnosis were 45 and 58%, respectively. However, FCDA did not falsely assign severe dysplasia or carcinoma in situ to any DES patient. This preliminary study based on FCDA appears to clearly differentiate patients with normal Pap smears from those patients with invasive cancer.

Carcinoma in Situ

Comparative study of the binding characteristics of monoclonal antimelanoma antibodies.

The binding specificities of monoclonal antibodies against human cutaneous malignant melanoma were analyzed using radioimmunoassay (RIA), mixed hemadsorption assay (MHA), and peroxidase-antiperoxidase assay on a variety of malignant and nonmalignant cells. Twenty-four of the 30 monoclonal antibodies bound to the majority of melanoma cell lines tested, and only two antibodies did not bind to any of the melanoma lines. Three antibodies bound to melanoma lines only, 13 antibodies reacted also with fetal cells, 21 antibodies bound to at least one carcinoma cell line and nine antibodies reacted with one or more cell lines of leukemic or lymphoid origin. The antibodies could be divided into seven groups based on their binding characteristics. These groups had been established by a panel of monoclonal antimelanoma antibodies produced and characterized at The Wistar Institute.

Antibodies, Monoclonal

Gastrointestinal cancer-associated antigen in immunoperoxidase assay.

A monosialoganglioside antigen of gastrointestinal adenocarcinomas defined by murine monoclonal antibody was demonstrated by immunoperoxidase (IP) assay in fixed paraffin-embedded tumors in 59% of colonic adenocarcinomas, 86% of pancreatic adenocarcinomas, and 89% of all gastric adenocarcinomas. In all patients with detectable levels of antigen in circulation, the resected tumors also expressed the antigen in IP assay. Six of eight individuals with no detectable levels of antigen in their serum samples expressed the antigen in the tumor tissue. Removal of the sialic acid residue of the antigen abolished the IP reaction. The successful use of the IP assay on fixed tissue to demonstrate the specific sites of gastrointestinal cancer antigen localization in human tumors and normal tissues provides an important tool for the study of developing neoplasia.

Adenocarcinoma