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Biomedical subjects

R L Teplitz

Publications and source records attributed to R L Teplitz.

At least 19 recordsLinked to original sources

The cytology of pediatric masses: a differential diagnostic approach.

In the United States, fine-needle aspiration biopsy (FNAB) and other cytodiagnostic methods have been underutilized in the evaluation of masses in the pediatric age group. Cytopathologists and cytotechnologists are therefore relatively unfamiliar with the cellular features of lesions that occur in children. On the basis of the cytologic findings from 64 pediatric cases, including 56 FNABs and 8 intra-operative imprints, a differential diagnostic approach to lesions in this age group is presented. The majority of cases can be placed into 1 of 5 cytomorphologic categories: (1) round-cell pattern, (2) mixed inflammatory pattern, (3) spindle-cell pattern, (4) epithelial pattern, and (5) cystic pattern. Once a cytomorphologic category is determined, evaluation for unique cellular features, special studies, and clinical correlation allows a specific diagnosis to be made in most cases. Pitfalls in pediatric cytopathology are illustrated by discussion of the following cases: a renal Burkitt's lymphoma mimicking a Wilms' tumor, a traumatic neuroma masquerading as a recurrent malignant schwannoma, Langerhans-cell histiocytosis resembling granulomatous inflammation, and a cystic granuloma that mimicked a branchial cleft cyst. Consideration of these problems and use of the recommended diagnostic approach will aid in interpretation in this difficult area.

Adolescent

Prenatal diagnosis by enzymatic amplification and restriction endonuclease digestion for detection of haemoglobins A, S and C.

The detection of the single base pair mutations at codon 6 of the beta-globin gene is important for the prenatal diagnosis of sickle-cell anaemia and SC disease. A novel procedure has been designed to create a restriction site at both the beta A and beta C alleles to facilitate the discrimination of haemoglobins A, S and C. The general principle of this procedure is to enzymatically amplify genomic DNA using a modified primer containing an altered 3'-terminal nucleotide to create these restriction sites. After this modified primer has been efficiently incorporated into amplified DNA, the PCR products are digested with the restriction enzymes Ava I and Sty I. Ava I recognizes a site in amplified DNA containing a beta A allele, and Sty I recognizes a site in DNA containing a beta C allele. Since the beta A and beta C alleles can be distinguished directly by the presence of a restriction site, the beta S allele can be identified indirectly. All three beta-globin alleles are easily distinguished by size and pattern of electrophoresed fragments on agarose gels. This procedure is specific and sensitive, thus permitting rapid, economical diagnosis of sickle-cell anaemia and SC disease.

Anemia, Sickle Cell

Metastases from fresh human non-small cell lung cancers propagated in nude mice.

Specimens from 69 freshly resected human non-small cell lung cancers (NSCLC) were transplanted into nude mice. Twelve mice died before the transplants were evaluable. There were 4 takes of 12 evaluable transplants into untreated athymic nude mice and 24 takes of 45 evaluable transplants into nude mice with decreased natural killer (NK) cell activity. Fourteen tumor lines were propagated into 2 or more successive transplant generations. Distant metastases occurred from the mid-dorsal transplant site in 8 of 81 (9.88%) recipients of 4 of those tumor lines, after 3-9 consecutive tumor growth cycles. Xenotransplantation of freshly resected human NSCLC provides a model with potential for serial assessment of cellular changes related to metastatic capability.

Adenocarcinoma

Lung cancer model for study of the metastatic process.

In our hamster model of focal, chemically induced nonsmall cell lung cancer (NSCLC), we studied metastases in autochthonous hamster hosts (n = 300) and in syngeneic hamster and nude mice recipients (n = 230) of serial tumor transplants. Metastases in autochthonous hosts and transplant recipients occurred in regional lymph nodes, liver, and adrenals. In autochthonous host hamsters no metastases were noted from microinvasive (n = 112) or visible cancer less than 3.0 mm in diameter (n = 66); the incidence of metastasis was 8.2% (4/49) from 3- to 10-mm cancers and 22% (16/73) from cancers 10 mm in diameter or larger (p less than 0.05). Serial transplants were used to evaluate the metastatic propensity of 20 primary and six metastatic NSCLCs. Six primary NSCLCs that metastasized in the autochthonous host and six metastatic NSCLCs all metastasized promptly in recipients. This expression of metastatic potential was significantly different (p less than 0.05) from 14 primary cancers without autochthonous host metastases. Eight of the 14 caused no metastases in recipients, even after 5 to 11 tumor growth cycles; metastases occurred from the other six primary NSCLC after 3 to 12 tumor growth cycles in transplant recipients. Primary hamster NSCLCs metastasize in the autochthonous host with a frequency and a distribution pattern similar to human NSCLCs. A new model to study serially the cellular changes that govern the process of metastasis in NSCLC has been developed.

Animals

Fine needle aspiration biopsy of superficial masses in children.

Fine needle aspiration biopsy (FNAB) is an underused diagnostic procedure in children, particularly in the evaluation of superficial masses. A total of 54 FNABs of superficial masses were performed in children aged 1 month to 15 years. Adequate material for diagnosis was obtained in 50 attempts. The cytologic diagnosis increased clinical understanding and provided a guide for treatment in 46 of the 50 cases. The cytologic diagnosis was confirmed in 15 of 19 patients who underwent an operation. Surgical intervention was obviated in 31 patients. There was one false-positive diagnosis of cancer. We describe the role of FNAB in children and its technique, accuracy, and diagnostic problems.

Adolescent

Variable regression of experimental bronchial preneoplasia during carcinogenesis.

It has been thought that squamous severe atypical metaplasia of the bronchus is reliably precancerous. The canine subcutaneous bronchial autograft model for studying the progression of epidermoid carcinogenesis (normal----regular squamous metaplasia----mild, moderate, and severe atypical metaplasia----squamous cell carcinoma) provides evidence that severe atypical metaplasia of the bronchial epithelium is reversible. Among 148 subcutaneous bronchial autografts that had serial sampling of the epithelium and exposure to implants of methylcholanthrene, severe atypical metaplasia was noted in 28 that received only a single implant. During the total carcinogen exposure (median 24.5 months), 9 of 28 (32%) developed squamous cell cancer, and 19 of 28 (68%) regressed toward normal. Severe atypical metaplasia was noted in 34 subcutaneous bronchial autografts that received two or more carcinogen implants: epidermoid cancer developed in 26 of 34 (76.5%), and regression toward or to normal occurred in 8 of 34 (23.5%). Severe atypical metaplasia was not detected in 53 subcutaneous bronchial autografts: 19 that received only a single implant and 34 that received two or more implants. Progression and regression occurred among these subcutaneous bronchial autografts in proportions similar to those found in subcutaneous bronchial autografts wherein severe atypical metaplasia was seen. Among 33 subcutaneous bronchial autografts initially studied after 6 months of exposure to carcinogen, progression to severe atypical metaplasia was seen 3 months later in 19 of 33 that had additional exposure; in the same interval regression of epithelial abnormalities occurred in 14 of 33 subcutaneous bronchial autografts that had no additional exposure (p less than 0.05). We have presented evidence that severe atypical metaplasia includes at least three cell populations: one committed to cancer without further stimulus, one that regresses despite further carcinogen exposure, and one that requires additional carcinogen to progress to cancer. At least in this model, severe atypical metaplasia is not inexorably precancerous. The subcutaneous bronchial autograft model is suitable for seeking biologic indicators of irreversibility.

Animals

Quantitative DNA alterations during 5-azacytidine-induced differential modulation of benzo(a)pyrene carcinogenesis in hamster bronchi.

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.

Animals

Genetics.

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DNA Repair

An enzyme-linked immunosorbent assay for antibodies to native and denatured DNA.

A modification of the enzyme-linked immunosorbent assay (ELISA) is described, that permits determination of antibodies to native DNA (nDNA). The same approach can be used to measure antibodies to denatured DNA (dDNA). Poor binding of nDNA to the polystyrene solid phase has presented difficulties in using the ELISA method for assaying anti-nDNA activity (Engvall, 1976), but we find that precoating of the solid phase with protamine sulfate circumvents this problem. Assays for anti-dDNA are also enhanced by the use of protamine sulfate coated tubes. We have used the ELISA method to assay 15 SLE and 27 non-SLE sera for anti-nDNA and anti-dDNA activity. The results are compared with those obtained using the GF/A glass fiber filter assay, previously described by Lewis et al. (1973).

Animals

Autosensitization to DNA: evidence for an immunologic basis.

A 59-year-old female with spontaneous painful ecchymoses developed ecchymoses after intracutaneous injection of washed autologous whole blood cells and calf thymus DNA. Immunofluorescent studies of the spontaneous lesions revealed granular deposits of IgM, C3, factor B and properdin at the dermal-epidermal junction but no deposits in her normal skin. T cells were decreased in number but responded normally to polyclonal mitogens and did not transform in response to DNA containing antigens. Repair of UV-damaged DNA by her lymphocytes appeared to be depressed. The findings presented here are the first immunologic abnormalities uncovered in this disorder and may help in understanding the pathogenesis of the inflammatory lesions seen in autosensitization to DNA.

Autoantibodies

Genetics.

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Animals

Ataxia telangiectasia.

Ataxia telangiectasia has been described as a single-gene autosomal recessive disorder. It affects multiple systems. Several attempts to present an etiological hypothesis that will account for the multisystem involvement have been made. Those reviewed haer are (1) aberration of inductive signaling, which is predicted on a deficient mesoderm, leading to vascular and thus multiorgan effects (a critical timing of events is a basic assumption); (2) developmental imbalance, based on multisystem supression of embryological development; (3) the autoimmune hypothesis, which requires the presence of a cell surface antigen on thymic and nerve cells analogous to the thy 1.1 antigen of mouse and rat. The development of cytotoxic autoantibody to this antigen is postulated as an explanation of the pathogenesis.

Ataxia Telangiectasia

Establishment and characterization of a cell line from the American opossum (Didelphys virginiana).

A permanent tissue-cultured cell line (designated OK) has been established from kidney tissue of an adult American opossum. The OK line has been characterized with respect to morphology, chromosome constitution, tissue-culture requirements, and attainable mitotic arrest. The cells are epithelial-like with a stable nondiploid chromosomal modal number of 23. Cells grown in Eagle's minimal essential medium with 10% fetal bovine serum have a mean doubling time of 18 hr. The cell line OK is potentially useful for the isolation and purification of the mammalian X chromosome because of the size differential between the smaller X's and the larger autosomes.

Animals

Solubilization and developmental distribution of embryonic antigen of the chick red blood cell plasma membrane.

An antigen(s) on the surface of embryonic and newly hatched chick red blood cells was studied with antiserum absorbed with adult red blood cells. Because of the reappearance of the antigen or some cross-reactive antigen during myeloblastosis, attempts at solubilization and characterization of the antigen were pursued. Antigen was solubilized from whole red blood cell lysates or from red blood cell ghosts with 0.01 M Tris:0.1% Nonidet P40, pH 8.0. Antigen was assayed with an enhancement of agglutination assay. Enhancement apparently occurs because of available specific receptors for the antigen on newly hatched chick red blood cells. Antigen was also found to be present in plasma, and both the membrane-derived antigen and the plasma antigen were excluded from Sephadex G-100. Isoelectric focusing of the antigen extract indicated the presence of more than one molecular species with antigenic activity.

Age Factors

NZB/WF1 hybrid autoimmune disease: a genetic analysis.

This study analyzes the role of genetic and/or viral factors as etiologic agents in systemic lupus erythematosus in NZB/NZW F1 hybrid mouse, first by a backcross within the NZ strains. A separate study involved an outcross, production of an F2 generation, and then backcross to both NZ parents. The results were assayed by histologic evaluation of renal disease. Assay techniques for anti-DNA and proteinuria showed no evidence for segregation and were not useful. Histology of the kidney showed distinct segregation patterns consistent with the interpretation of the etiology as co-dominant genetic factors. While the virus[es] was not considered etiologic, mechanisms for relating activity to the pathogenesis were discussed.

Animals