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Biomedical subjects

J J Berman

Publications and source records attributed to J J Berman.

At least 55 records · Page 3Linked to original sources

DNA analysis of cardiac myxomas: flow cytometry and image analysis.

Cardiac myxoma is the most common primary tumor of heart, but there is a longstanding controversy over whether it is a true neoplasm or a reactive lesion. We analyzed 24 cardiac myxomas from 22 patients: 22 by DNA flow cytometry and five by image analysis. Two myxomas were aneuploid; one of those analyzed by flow cytometry, and the other by image analysis. Proliferative fractions (S + G2/M) were high in three tumors from patients with multiple myxomas (mean, 15.9%; SD, 4.0%) as compared with 12 solitary uncomplicated myxomas (mean, 7.7%; SD, 6.0%). S-phase and proliferative fractions were low in embolic, recurrent, and solitary myxomas. The presence of aneuploidy in some myxomas supports a neoplastic origin for this tumor.

Adult↗

Cell growth simulations predicting polyclonal origins for 'monoclonal' tumors.

Studies showing the clonal identity of various tumors have led to the belief that most tumors originate from a single cell. It is shown by Monte Carlo computer simulations that monoclonality can evolve from minor differences either in cell cycle time or in the probability of cell death in a polyclonal 'founder' population. If cells divide continuously without cell death (exponential clonal growth), a triclonal population with three starting cells (cell cycle times 0.9 days, 1 day and 1.1 days) converges to near-monoclonality in 100 generations. For cell cycle times of 0.9 days, 1.1 days and 1.1 days, and cell death probabilities of 0.45 and 0.46, populations tend toward monoclonality while the tumor is still small (less than 3 mm3).

Cell Cycle↗

Clear cell dysplasia of the bladder. Report of a case with flow cytometric analysis.

Clear cell dysplasia of the bladder is a well-described morphologic entity that has been found in association with transitional cell carcinoma of the bladder. Its biologic role in bladder tumorigenesis is unknown, and no instances of its polidy analysis have been reported. The authors describe a case of clear cell dysplasia of the bladder found in association with a primary adenocarcinoma of the bladder. Flow cytometric analysis of bladder tissue involved by clear cell dysplasia, adenocarcinoma and cystitis cystica (all from the same bladder) demonstrated no DNA aneuploid populations. Cells from the area of clear cell dysplasia had an S + G2 + M fraction of 7%, indicating that it was a proliferative lesion. Cells from the adenocarcinoma had an S + G2 + M phase of 18%, and cells from an area of cystitis cystica had an S + G2 + M phase of 4%.

Adenocarcinoma↗

Object-oriented controlled-vocabulary translator using TRANSOFT + HyperPAD.

Automated coding of surgical pathology reports is demonstrated. This public-domain translation software operates on surgical pathology files, extracting diagnoses and assigning codes in a controlled medical vocabulary, such as SNOMED. Context-sensitive translation algorithms are employed, and syntactically correct diagnostic items are produced that are matched with controlled vocabulary. English-language surgical pathology reports, accessioned over one year at the Baltimore Veterans Affairs Medical Center, were translated. With an interface to a larger hospital information system, all natural language pathology reports are automatically rendered as topography and morphology codes. This translator frees the pathologist from the time-intensive task of personally coding each report, and may be used to flag certain diagnostic categories that require specific quality assurance actions.

Algorithms↗

PRELOG: precedence logic inference software for blood donor deferral.

Blood collection facilities have recently witnessed a substantial increase in the complexity of tests used to detect infectious disease in donor populations, and there is a stringent regulatory effort by the Food and Drug Administration (FDA) to validate the software for managing this information. PRELOG is precedence-based inference software used to determine a donor's suitability for continued donations and whether the donation can be released for transfusion. PRELOG accepts ternary input for test results (positive, negative, or undetermined), and solves the logic rules sequentially, so that the rulebase can be validated in a concise and consistent manner.

Blood Banks↗

Basal cell carcinoma: importance of histologic discontinuities in the evaluation of resection margins.

Pathologists frequently need to judge whether basal cell carcinomas have been excised adequately. Traditionally, excision adequacy is assessed by looking for the presence of tumor at the margins of resection. This time-honored activity has questionable value, since it has been demonstrated that the majority of tumors with positive margins do not recur, and a substantial minority of tumors with negative margins do recur. It is proposed that excision adequacy can be evaluated by considering the pattern of tumor growth. Tumors composed of widely dispersed nests need wider margins than tumors that grow as tight clusters of tumor nests, and this assertion can be evaluated statistically. A morphometric study of 28 basal cell carcinomas (BCCs) was performed, in which the distribution of tumor cell nests seen in cross-section was analyzed. The average distance from the center varied greatly (272 to 2273 microns) among these tumors. Standard deviations were calculated from distances between the tumor center to each nest within the tumor, and one-tailed Student's t tests were used to obtain 90%, 95%, and 99% confidence limits for distances beyond which no additional tumor nests are expected. These distances, in tumor radii, ranged from 0.8 to 1.9 and from 1.03 to 4.89, for 90% and 99% confidence limits, respectively. Conventional methods used to determine margin adequacy do not account for the discontinuous appearance of BCC in histologic sections. This theoretical model demonstrates that an alternate way of assessing excision adequacy can be achieved with a statistical analysis of the pattern of tumor growth, rather than looking for absence of tumor at the resection margin.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Cell Carcinoma↗

Adenocarcinoma of the ileostomy: the latent risk of cancer after colectomy for ulcerative colitis and familial polyposis.

A case of a primary adenocarcinoma of an ileostomy is reported along with 15 other cases collected from the literature. These rare tumors are seen on the average 24 years after colectomy with ileostomy and in all cases are associated with a past history of ulcerative colitis or familial polyposis. Most of the reported cases of these tumors have appeared in the literature within the past 5 years, suggesting that there is a rising incidence of this disease corresponding to completion of a biologic latency period that began when the Brooke ileostomy was introduced for ulcerative colitis in 1951. In our case a mucinous adenocarcinoma occurred at the ileostomy site 34 years after colectomy. Adjacent to the tumor was mucosa showing colonic metaplasia and focal dysplasia. Subsequent biopsy specimens of the revised stoma showed inflammatory lesions morphologically suggestive of inflammatory (pseudo) polyps. The clinical and morphologic features in this case suggest that there is transition from ileal mucosa to colonic mucosa to colonic dysplasia to adenocarcinoma. Annual evaluation of the ileostomy for colonic metaplasia, inflammatory lesions consistent with ulcerative colitis and dysplasia, is recommended. In the presence of dysplasia, stomal revision is advised. Wide local excision is advised for adenocarcinoma.

Adenocarcinoma↗

Cytologic evaluation of Papanicolaou-stained bone marrow aspirates.

Aspirates obtained from bone marrow were prepared for routine Papanicolaou staining and screened by a cytologist. As a preliminary study, 100 consecutive bone marrow aspirations were examined. It was shown that metastatic carcinoma and primary bone marrow disorders (including leukemia, myelodysplastic syndromes, and multiple myeloma) can be recognized on Papanicolaou-stained marrow aspirates using the same cytologic criteria employed in the evaluation of cells from any site. Evaluation of bone marrow aspirates in the cytology laboratory is feasible and can be used to augment parallel services employing air-dried Wright-Giemsa-stained specimens in the hematology laboratory.

Biopsy, Needle↗

Amsacrine-induced cytoplasmic rods.

Amsacrine induces cytoplasmic rods in cultured epithelial cells derived from adult rat liver hepatocytes (ARL6T). Rods become visible two hours after treatment of cells with 10 microM amsacrine. At 24 h, multiple rods are present in nearly every cell. Ultrastructural examination of treated cells reveals structures 5-10 microns in length and 0.2 to 0.3 micron in width. These rods are not found in untreated ARL6T cells. This consistently-induced morphologic finding represents a newly described drug effect. The mechanism of formation of these rods and their role in amsacrine cytotoxicity is at present unknown.

Amsacrine↗

Colonic metaplasia of ileostomies. Biological significance for ulcerative colitis patients following total colectomy.

Two patients who had undergone proctocolectomy for ulcerative colitis developed lesions in their ileal stoma that appeared to be inflammatory polyps morphologically similar to those encountered in the large intestine of ulcerative colitis patients. One of these patients eventually developed mucinous adenocarcinoma in the ileal stoma. The ileal mucosa adjacent to the neoplasm had morphologic features of large-bowel mucosa and was richly populated by sulfomucin-containing goblet cells, which are characteristic of large-bowel mucosa. Sulfomucin-containing goblet cells were also found in the inflammatory lesions biopsied from the ileal stomas of both patients, as well as from the adenocarcinoma found in one patient. These findings support the hypothesis that colonic metaplasia can occur in ileal stomas of ulcerative colitis patients. Furthermore, the metaplastic colonic tissue is the site of origin of lesions typically found in ulcerative colitis. Colonic metaplasia occurring in ileal stoma should be recognized by pathologists as a clinical entity. When colonic metaplasia is identified in the ileal stoma of an ulcerative colitis patient, biopsy surveillance of stomal mucosa is recommended.

Adenocarcinoma↗

Epithelial repair versus carcinoma in esophageal brush cytology.

The distinction between repair atypia and carcinoma in esophageal brushings is often difficult. To establish criteria for making this distinction, the cytologic smears from 121 consecutive esophageal brushings and the companion biopsies were reviewed. The most reliable criteria for malignancy included sharply angulated nuclear rims, a high nuclear/cytoplasmic ratio, and coarsely granular chromatin. Nuclei bearing these features were not numerous and had to be carefully sought. Nuclear pleomorphism was a more consistent feature, but it showed considerable overlap with epithelial repair. Cytologic features of multiple nucleoli, macronucleoli, and loss of polarity were common to both repair and carcinoma. Adherence to the criteria established in this study permits the distinction between repair atypia and carcinoma in almost all cases; however, there are lesions of the esophagus with such overlap between the features of repair and carcinoma that it may not be possible to reach a definitive diagnosis. Specific examples, with illustrations, are discussed as diagnostic guides.

Carcinoma, Squamous Cell↗

Ethidium bromide resistance in a rat liver epithelial cell line: association with enhanced drug efflux.

Ethidium bromide-resistant cell strains were obtained by continuous selection of an adult rat liver-derived cell line (ARL6T) grown in the continuous presence of 200 ng/ml ethidium bromide. Comparison of resistant strains and parental (sensitive) cells was made for uptake and binding of ethidium bromide, visualized as fluorescent ethidium bromide-nucleic acid complexes. Although uptake of ethidium bromide was similar in parental and resistant cells, efflux kinetics were markedly different. Over a three-hour period, parental (sensitive) cells maintained fluorescence following a short ethidium bromide pulse (100 micrograms/ml ethidium bromide). In contrast, ethidium bromide-resistant cell lines eliminated photographically detectable fluorescent complexes within three hours following pulse exposure to ethidium bromide. The rapid elimination of ethidium bromide-fluorescent complexes in all (5) resistant cell strains examined supports an efflux mechanism as contributing to the resistance of ethidium bromide cytotoxicity in these cells.

Animals↗

Cell proliferation and the aetiology of hepatocellular carcinoma.

The liver is, under normal conditions, mitotically inactive and relatively resistant to chemical carcinogenesis. When rat or mouse hepatocytes are stimulated to divide, however, the liver becomes exquisitely sensitive to carcinogenesis. The heightened sensitivity of dividing liver cells to carcinogens is one of the most dramatic phenomena in the field of experimental chemical carcinogenesis and is reproducible with a wide variety of chemical agents and experimental conditions. This same phenomenon seems to apply to humans, as circumstances that produce a sustained hepatocellular proliferation in man are associated with an increased risk of hepatocellular carcinoma (HCC). These include inborn errors of metabolism (e.g., haemochromatosis, Wilson's disease, hereditary tyrosinaemia) as well as alcoholism. A recent editorial in this Journal suggested that any condition resulting in cirrhosis is also associated with an increased risk of HCC, and this may in turn be due to regenerative hyperplasia always present in cirrhotic liver (Johnson PJ, Williams R. J Hepatol 1987; 4: 140-147). In the case of HCC associated with hepatitis B virus (HBV) infection, the possibility must be entertained that chronic HBV infection serves to produce a sustained hepatonecrosis with concurrent (regenerative) hyperplasia. This proliferative state would in theory serve to increase the liver's susceptibility to environmental dietary carcinogens and may tend to increase the risk of HCC by this indirect mechanism. Until a molecular mechanisms is demonstrated whereby HBV produces a defined cellular lesion that endows hepatocytes with a malignant phenotype, it should not be assumed that HBV is a direct cause of HCC.

Animals↗

Using the day treatment appropriateness scale with rural, alcoholic clients.

Inadequate selection of patients is one factor in the underutilization of day-treatment programs. The Day Treatment Appropriateness Scale (DTAS; Lefkovitz, P. M., Int. J. Part. Hosp. 1:45-47, 1982) is one of only two reported instruments designed to assist in patient selection; it has been shown to predict validly successful completion of a day-treatment program for chronic, psychiatric patients. This report addresses the use of the DTAS in an alcohol day-treatment program located in a rural, midwestern, community mental-health center. The DTAS was not found to predict accurately successful program completion among alcoholic clients in day treatment. Possible explanations of the findings and additional predictive variables are reported.

Alcoholism↗

Toxicity of 6-thioguanine and 8-azaguanine to non-dividing liver cell cultures.

8-azaguanine and 6-thioguanine were both toxic to non-dividing liver cells in primary cultures. In addition, these agents were toxic to an established line of liver-derived epithelial cells brought to growth arrest by serum deprivation. These observations demonstrate that the toxicity of 8-azaguanine and 6-thioguanine can occur at least in part through mechanisms that do not involve effects on DNA synthesis or incorporation of the analogs into DNA.

Animals↗

The function of gamma-glutamyl transpeptidase as a determinant in cell sensitivity to azaserine toxicity.

The enzyme gamma-glutamyl transpeptidase (GGT) is characteristically present at high levels in mammalian cells that are vulnerable in vivo to the selectively toxic and carcinogenic effects of the naturally occurring diazo amino acid L-azaserine. The possible role of GGT as a determinant of cellular sensitivity to azaserine toxicity was investigated. No correlation was found between GGT activity and the abilities of different cell lines or GGT-deficient cell strains of TuWi, a human nephroblastoma-derived line high in GGT, to accumulate azaserine. However, the thiols glutathione and cysteine were found to inhibit the toxicity of azaserine in cultures of TuWi. In addition, maleate lowered both intracellular and extracellular glutathione levels and enhanced sensitivity of TuWi cells to azaserine, while serine-borate, a potent inhibitor of GGT, increased extracellular glutathione levels and inhibited azaserine toxicity. Since extracellular glutathione accumulation, which may reflect the rate of cellular glutathione turnover, is increased in cultures of azaserine-resistant, GGT-deficient strains of TuWi, we propose that GGT enhances cellular sensitivity to azaserine primarily by increasing the rate of glutathione turnover, thus removing the glutathione from detoxification pathways.

Animals↗