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Biomedical subjects

R L Teplitz

Publications and source records attributed to R L Teplitz.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Rapid alkaline transfer of low molecular weight DNA from NuSieve GTG agarose gels.

The rapid alkaline transfer of high molecular weight DNA from agarose gels to nylon membranes has greatly decreased the time required for setup of Southern transfers. This technique has been used to resolve genomic DNA greater than 1000 base pairs by conventional electrophoresis on 1% agarose gels followed by alkaline transfer to nylon membrane. Now we report that this rapid alkaline method can be used for the transfer of low molecular weight DNA fragments (10 to 1000 base pairs) from NuSieve GTG agarose gels to nylon membrane.

Alkalies↗
PubMed1990

Quantitative DNA patterns in human preneoplastic breast lesions.

In 12 cases of human mammary carcinoma in which a preneoplastic atypical ductal hyperplasia was also identified, quantitative DNA (QDNA) measurements of thionein-stained samples from both lesions were performed using the Cell Image Analysis 100 system. The QDNA values in the preneoplastic and neoplastic lesions from each case showed concordance (six as euploid and six as aneuploid/hyperdiploid). Such congruence suggests a stable inheritance of the somatic mutation(s) that is involved in carcinogenesis and that affects ploidy. If this relationship between concurrent preneoplasia and neoplasia in the ipsilateral breast is confirmed, it offers the possibilities of (1) identifying individuals at risk for developing neoplasias with defined biologic characteristics and (2) developing therapeutic regimens more appropriate to the risk assessment of each patient. It may be possible to conceive of a rational preventive regimen for cancer of the breast.

Breast↗
PubMed1989

Papillary carcinoma of prostatic ductal origin: a cytologic case report with immunohistochemical and quantitative DNA correlation.

This report describes the aspiration biopsy cytology (ABC) of a case of papillary carcinoma of ductal origin, an uncommon malignant tumor of the prostate. Only one case has been previously reported in the cytology literature. Atypical papillary fragments are the distinctive cytologic findings. Similar to well-differentiated acinar carcinoma of the prostate, the cytologic features of malignancy in this lesion may be subtle, and diagnosis is based on the presence of the cytologic pattern. Positive immunohistochemical staining with prostate-specific acid phosphatase confirms the prostatic origin. Application is made of quantitative DNA analysis for prognostic determination.

Acid Phosphatase↗
PubMed1989

Factors involved in macrophage: immune complex binding.

The interaction of the immune complex (IC) composed of DNA and monoclonal anti-DNA antibody with thioglycollate-stimulated mouse peritoneal macrophages was investigated. The immune complex: macrophage interaction was shown to be highly time and temperature dependent; at 37 degrees C it proceeds faster than at 0 degrees C, although there is higher overall binding of IC to macrophages at 0 degrees C. The maximum bound IC detected was at a DNA/antibody ratio of 6.2ng/ml to 7.3 micrograms/ml. Higher densities of either DNA or antibody inhibited IC: phagocyte interaction. Binding of the IC to macrophages is through cell surface Fc receptors and is enhanced in the presence of 40 mg/ml albumin. Fresh human and mouse sera at the concentration of 10 percent, inhibited the IC binding to mouse peritoneal macrophages. Macrophage receptors for IC are not saturated even after 60 minutes. Addition of either chloroquine or cytochalasin B, resulted in increased binding of IC to macrophages.

Animals↗
PubMed1988

Biochemical and cytogenetic studies of human lung cancers.

In ongoing studies, we have tested resected lung cancers from 41 men and 49 women; of those with primary lung cancer, 46 patients are free of disease and 35 have died of cancer or have persistent disease. Measurements and studies were as follows: total cellular deoxyribonucleic acid content by image analysis (n = 77); total genomic deoxyribonucleic acid methylation state and banding patterns from probed Southern blots (n = 36); radioimmunoassay for motilin, bombesin, gastrin, vasoactive intestinal peptide, and cholecystokinin (n = 18); and cytogenetic analysis (n = 39). All lung cancers were hyperploid. Adenocarcinomas and epidermoid carcinomas were generally hexaploid to nearly septaploid; comparisons by stage and histologic features suggested potential prognostic correlations. There was general hypomethylation of deoxyribonucleic acid (p less than 0.001). Deoxyribonucleic acid digests from restriction endonuclease Hpa II, when probed with deoxyribonucleic acid homologous to KPN, showed banding patterns that separated histologically indistinguishable primary adenocarcinomas and metastatic adenocarcinomas from one another. Cancers studied with radioimmunoassay were all negative for polypeptide hormones. Five cancers grew adequately in vitro to permit study of 190 detailed karyotypes (20 to 50 per tumor). Chromosome modal numbers ranged from 49 to 109. There were from 4 to 20 clearly abnormal marker chromosomes per tumor; abnormality derived from chromosome 1 was prevalent. Ten of 19 tumors xenotransplanted to nude mice were carried through two to five transplant generations without a change in histologic patterns.

Animals↗
PubMed1987

Analysis of DNA extracted from formalin-fixed, paraffin-embedded tissues by enzymatic amplification and hybridization with sequence-specific oligonucleotides.

The "polymerase chain reaction" (PCR) procedure for amplifying specific gene sequences has recently been combined with sequence-specific oligonucleotide (SSO) probe hybridization to develop a highly sensitive, rapid, and simple method for analyzing allelic variations in genomic DNA. In the present study we have used PCR/SSO to analyze partially purified DNA extracted from formalin-fixed, paraffin-embedded tissue specimens. We report that this DNA, including samples that were partially degraded, proved to be suitable for analysis by the PCR/SSO procedure.

Base Sequence↗
PubMed1987

Effect of levamisole on binding of immune complex to mouse peritoneal macrophages.

Levamisole at the concentrations of 240 and 500 micrograms/ml increased DNA-anti-DNA immune complex (IC) binding to thioglycollate-stimulated mouse (CBA) peritoneal macrophages. Reduced IC binding by macrophages of (NZB/NZW)F1 a mouse model for systemic lupus erythematosus occurs as a consequence of disease and was partially corrected after inclusion of levamisole into the reaction mixture in vitro. However, in vivo administration of 2.5 mg/kg of levamisole, the therapeutic dose, did not alter IC binding to CBA macrophages.

Animals↗
PubMed1986

Quantitative nuclear DNA analysis of human ovarian adenocarcinoma: compared before and after chemotherapy and correlated with clinical response.

Quantitative DNA measurements on 18 human ovarian adenocarcinomas were made by computerized image analysis. The DNA content of the tumor cells was measured on specimens of tumor obtained at the initial diagnostic surgery and at second-look surgery after treatment with chemotherapy. The mean DNA content of the specimens and the ploidy pattern of the tumor cells were determined. With the exception that borderline tumors had near normal ploidy patterns and mean DNA content, there was no consistent correlation between the stage of disease, grade, or histiologic character of the tumor and either the DNA content or ploidy pattern. But it was noteworthy that all three of the patients who had complete responses (negative second-looks), also had tumors with DNA content and ploidy patterns near triploid. When the ratio of mean DNA content before and after chemotherapy was determined for each ploidy group, there was an apparent correlation between this ratio and clinical status of the patient 10 month after chemotherapy. That is, patients with low ploidy tumors and high DNA content ratio (greater than 1.25) had a better prognosis than patients with high ploidy tumors and lower DNA content ratios (less than 1.25). Thus, although the mean DNA content of the tumor at the initial surgery was not in itself of sufficient prognostic value, when the mean DNA content of the tumor after chemotherapy is also known, an accurate picture of the patients clinical response could be determined.

Adenocarcinoma↗
PubMed1986

Carcinogenesis in heterotopic respiratory epithelium in canine subcutaneous bronchial autografts.

Short bronchial segments obtained by pneumonectomy were implanted, 9-12 per dog, in the subcutaneous tissues of the back of seven dogs. These subcutaneous bronchial autografts (SBA) became vascularized, and they contained viable, histologically normal respiratory epithelium 4 wk after implantation. From 1-3 mo after implantation, 10% methylcholanthrene in steroid suspension medium was instilled into 21 SBAs, and 10% methylcholanthrene in a silicone polymer sustained release implant was placed in 22 SBAs. Ten SBAs were left carcinogen free as controls. SBA contents were examined cytologically at 3-mo intervals. Biopsies were done from 2-32 mo after carcinogen implantation. Progressive preneoplastic changes were noted in all five dogs which received carcinogen. Curetments of five SBAs after 14-mo exposure to methylcholanthrene yielded 10(4)-10(5) cells from each SBA; 40-70% of the cells obtained were at the same stage of atypical squamous metaplasia. At least one SBA in each dog yielded cancer cells by cytological criteria by 19-29 mo after instillation. Biopsy of a grossly abnormal SBA revealed well-differentiated epidermoid carcinoma at 32 mo. The multiple SBA method provides isolated portions of canine respiratory epithelium for the study of chemical carcinogenesis and for the production of sizable preneoplastic cell populations.

Animals↗
PubMed1986

Endobronchial carcinogenesis in dogs.

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.

Adenocarcinoma↗
PubMed1985

A method for binding specificity analysis of anti-DNA autoantibodies in SLE.

A pattern of differential binding between an NZB/NZW mouse-derived monoclonal anti-ssDNA antibody, V'D2, and restriction fragments of plasmid pBR322 DNA was shown by electrophoresis of the fragments through a denaturing agarose gel followed by their transfer onto nitrocellulose membrane and subsequent reaction of the immobilized DNA with the antibody and 125I-protein A. The antibody showed preferential binding to a 328 base pair Alu I + Hinf I fragment (denoted FD) (AT content, 60%), compared with the other fragments (AT contents, 40-56%). In dot blot assays the antibody bound only to poly(dT) and poly(dA,dT), failing to bind to other synthetic deoxyribopolynucleotides even at the highest concentration tested (300 ng). In competition experiments, the ability of unlabeled DNA to inhibit binding of V'D2 to FD increased with AT content of the DNA. It is concluded that V'D2 has preference for AT-rich DNA. In addition, poly(dA,dT) inhibited binding to a greater extent than either poly(dA) or poly(dT), indicating that base sequence may be important in defining the antigenic determinant. The method, appropriately modified, may be applicable to a wide range of natural nucleic acids and monoclonal antibodies, allowing detection and isolation of specific DNA fragments for detailed studies of antigenic determinants.

Animals↗
PubMed1985

Bronchopulmonary Kulchitzky cell carcinomas. A new classification scheme for typical and atypical carcinoids.

Typical and atypical carcinoids constitute less than 5% of lung tumors. They and small cell undifferentiated lung cancers (SCLC) belong to the same family of apudomas arising from bronchopulmonary Kulchitzky cells. To reflect the overlap among these cancers, the authors suggest calling them Kulchitzky cell carcinomas (KCC); to indicate their spectrum of aggressiveness, the authors suggest calling typical carcinoids KCC-I, atypical carcinoids KCC-II, and small cell cancers KCC-III. One hundred fifty-six KCCs were reviewed: 115 were KCC-I and 41 were KCC-II. The ratio of women to men equals 2:1. At time of initial diagnosis, all patients with KCC-I, except one patient, were in Stage I. Among patients with KCC-II, 16 (39%) were in Stages II or III at time of presentation. The incidence of carcinoid syndrome was 1.9%. Treatment was lobectomy in 112 (72%) of patients, the remainder having lesser resections or pneumonectomy in approximately equal distribution. Our data cannot support the use of radical resection in the treatment of KCC because none of the patients died of local recurrence. The mean diameters of KCC-I and -II tumors were 1.5 and 2.8 cm, respectively. Increased mitotic activity and tumor necrosis were reliable criteria for diagnosing KCC-II. Electron microscopic examination did not help in differentiating KCC-I and KCC-II. Thorough sampling of the entire tumor was found to be mandatory for precise diagnosis and for differentiation from KCC-III (SCLC). Measurement of nuclear DNA was done using integrated optical density (IOD) by image analysis. The IODs of KCC-I, -II and -III were 1.36, 1.55 and 1.94, respectively. These significant differences (P less than 0.001) correlated with the aggressiveness of the cancers. Of patients with KCC-I, 1.7% succumbed to KCC; this included one patient reported to have died of KCC-III (SCLC). Of 41 patients with KCC-II, 11 (27%) died of KCC; this includes at least 3 deaths from KCC-III.

Adolescent↗
PubMed1985

Effects of serum and serum components on the binding of DNA to thioglycollate-stimulated mouse peritoneal macrophages.

Binding of ssDNA and dsDNA to thioglycollate-stimulated peritoneal macrophages derived from normal CBA mice was increased not only by ssDNA-specific antibody but also by albumin and gamma-globulin preparations. Fresh mouse serum inhibited ssDNA binding, even if the ssDNA and serum were preincubated at 37 degrees C. Heat decomplemented mouse serum also depressed DNA binding. These results are significant to interpretations of DNA clearance rate data from serum or blood, and subsequent inferences concerning blood DNA levels, autoimmune response, and systemic lupus erythematosus.

Animals↗