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Biomedical subjects

D Heller

Publications and source records attributed to D Heller.

At least 19 recordsLinked to original sources

Effect of intracoronal bleaching on external cervical root resorption.

The purpose of this study was to examine histologically and radiographically the effect of a bleaching agent, a mixture of sodium perborate and superoxol (30% hydrogen peroxide), without a heat source on the cervical root surface and periodontal tissue of endodontically treated teeth of dogs. Endodontic treatment was performed on anterior teeth of dogs. The endodontically treated teeth were then divided into two groups. One group received walking bleach procedures, while the other group did not. The animals were killed at intervals of 1 and 3 months after bleaching for histological and radiographic examination. External cervical root resorption was only observed in bleached teeth at 3-month but not at 1-month observation.

Animals

Two types of endometrial papillary neoplasm. A morphometric study.

Fourteen cases of Papillary Endometrial Carcinoma (EC) were analyzed by Interactive Computerized Morphometry. Seven cases were diagnosed as well differentiated adenocarcinomas with papillary features (PF) and belonged to a group of EC with associated adenomatous hyperplasia (AH). Seven cases were diagnosed as uterine papillary serous carcinomas (PA) and belonged to a group of EC without associated AH. Two morphometric procedures were used. DRAW for the characterization of individual nuclei (area, perimeter, chord) and NU-MEAS for tissue architectural features (crowding and stratification). Using a stepwise discriminant multifactorial analysis, both methods proved to be accurate for the two diagnostic categories, as shown by the 100% posterior probabilities and by the two diagnostic categories, as shown by the 100% posterior probabilities and by the distances between group means. A doubtful case was analyzed and classified using a K-nearest neighbor procedure, compared to the individual case in the database. The distinction between the two types of papillary EC is important for the differential diagnosis of the two lesions. Well differentiated adenocarcinoma with papillary features is seen usually in the context of a well-differentiated adenocarcinoma, in a group of patients known to have estrogen-related less aggressive tumors. Uterine papillary serous carcinoma was described to have a biological behavior similar to that of papillary ovarian carcinoma and is encountered in a group of patients with more invasive and less differentiated EC2. Computerized interactive morphometry is a valuable method to use for the accuracy of this differential diagnosis in doubtful cases.

Adenocarcinoma

Epidermal growth factor and its receptor in human implantation trophoblast: immunohistochemical evidence for autocrine/paracrine function.

Epidermal growth factor (EGF) and its receptor (EGF-R) were immunohistochemically localized in trophoblast during human implantation from intrauterine and ectopic pregnancies. EGF immunostaining was absent to light in the cytotrophoblast (CT), light to moderate in intermediate trophoblast (IT), and intense in the syncytiotrophoblast (ST). In ST, EGF immunostaining was found mostly in the cytoplasm; however, staining of the plasma membrane was also noted. Immunostaining for the EGF-R was absent to light in the CT and moderate to intense in the IT. Immunostaining for the EGF-R was intense in the ST, with moderate staining in the cytoplasm and intense staining in the plasma membrane. Staining was most intense on the microvilli of the ST. Additionally, EGF-R immunostaining could be demonstrated on nuclear membranes. The increase in the intensity of the immunostaining for both EGF and EGF-R noted in CT, IT, and ST suggests a differentiated expression of this receptor-ligand system in human trophoblast and provides evidence for an autocrine/paracrine role for EGF in trophoblast function. The presence of this receptor-ligand system during early human implantation strongly supports a role for EGF and the EGF-R in embryo-uterine signalling and the implantation process.

Embryo Implantation

Letter visibility and word recognition: the optimal viewing position in printed words.

It has repeatedly been shown that the time and accuracy of recognizing a word depend strongly on where in the word the eye is fixating. Word-recognition performance is maximal when the eye fixates a region near the word's center, and decreases to both sides of this "optimal viewing position." The reason for this phenomenon is assumed to be the strong drop-off of visual acuity: the visibility of letters decreases with increasing eccentricity from fixation location. Consequently, fewer letters can be identified when the beginning or ending of a word is fixated than when its center is fixated. The present study is a test of this visual acuity hypothesis. If the phenomenon is caused by letter visibility, then it should be sensitive to variations of visual conditions in which the letters are presented. By increasing the interletter distances of the word (e.g., a_t_t_e_m_p_t), letter visibility was decreased. As expected from our hypothesis, the viewing-position effect became more exaggerated. An additional experiment showed that destroying word-shape information (e.g., aTtEmPt) decreased overall word-recognition performance but had no influence on the viewing-position effect. Varying the viewing position in words might thus be used as a paradigm, allowing one to separate out the contribution of letter information and supraletter information to word recognition.

Adult

Identifying human papillomavirus subtypes in cervical biopsies with in situ DNA hybridization with biotinylated probes.

To test the utility of biotinylated DNA probes against various subtypes of human papillomavirus (HPV), we performed in situ DNA hybridization on routinely processed archival material from 30 patients with serial cervical biopsies including conization (group I) and a prospective group of 35 patients whose cervical biopsies showed various degrees of koilocytotic atypia and/or dysplasia (group II). Commercially available biotinylated probe cocktails against HPV types 6 and 11, 16 and 18, and 31, 35 and 51 were detected via the avidin-biotin horseradish peroxidase technique. Virus was found in 87% (26/30) of group I and 57% (20/35) of group II. Almost exclusively, viral types 16, 18, 31, 35 and 51 were detected in group I; 54% (19/35) of group II stained for types 16, 18 or 31, 35 and 51; 2.9% (1/35) stained for types 6 and 11. Nine percent of group II (3/35) showed coinfection with types 16, 18 and 31, 35 and 51. Three of six vulvar condylomata (50%) stained for types 6 and 11. In general, weaker staining was associated with greater dysplasia. In situ hybridization using biotinylated DNA probes is useful in identifying patients infected with dysplasia/carcinoma-associated HPV subtypes and can be performed easily on routine surgical specimens.

Adult

Human papillomavirus-associated lesions of the vagina and cervix. Treatment with a laser and topical 5-fluorouracil.

Twenty women with cervical and vaginal human papillomavirus-associated lesions were treated with CO2 laser ablation followed by eight weekly applications of 5-fluorouracil. Viral subtyping in a majority of patients and histology were obtained before and after treatment. After treatment 88% (15 of 17) had normal vaginal biopsies, and 59% (10 of 17) had normal cervical biopsies. There were no treatment failures with subtype 6/11 infection of the cervix or vagina. All the failures were with viral subtypes 16/18 and 31/35/51. The protocol was effective in treating patients with cervical and vaginal human papillomavirus-associated lesions.

Administration, Topical

Nitrosation of tertiary aromatic amines related to sunscreen ingredients.

Possible routes to the formation of the sunscreen contaminant, 2-ethylhexyl 4-N-methyl-N-nitrosoaminobenzoate, have been investigated in a study of the nitrosation chemistry of 2-ethylhexyl 4-N,N-dimethylaminobenzoate (Padimate-O) and related tertiary and secondary amines. Padimate-O and the corresponding ethyl ester nitrosate rapidly at 25 degrees C in either N2O3:ether or HNO2:HOAc to produce a mixture of alkyl 4-N-methyl-N-nitrosoaminobenzoate and alkyl 4-N,N-dimethylamino-3-nitrobenzoate, the former of which is the major product. The nitrosative dealkylation of these amines at this low temperature is unusual. Asymmetrical amines exhibit a preference for nitrosative demethylation (methyl versus ethyl or benzyl), but the cleavage ratios in N2O3:ether are time-dependent, suggesting competing mechanisms with different reactant kinetic orders. A radical cation route would explain the unusual reactivity, which may compete with the established nitrosative dealkylation mechanism. 2-Ethylhexyl 4-N-methyl-N-nitrosoaminobenzoate was mutagenic in two strains of Salmonella typhimurium in the Ames assay.

4-Aminobenzoic Acid

The proto-oncogene c-ros codes for a transmembrane tyrosine protein kinase sharing sequence and structural homology with sevenless protein of Drosophila melanogaster.

Our earlier study predicted that proto-oncogene c-ros codes for a receptor-like tyrosine protein kinase (TPK). To further understand its protein structure and physiological function, we have analysed its expression in various tissues of chicken and have isolated and sequenced cDNA clones containing the entire coding region of the gene. Confirming our earlier study, we found that kidney is the organ that expresses the highest level of c-ros mRNA, in addition, we found a lower level of expression in gonad, thymus, bursa and brain. A distinctive 8.3 kb c-ros mRNA is present in kidney. No detectable amount of c-ros mRNA was found in the rest of tissues examined. Nucleotide sequence of the c-ros cDNA predicts that it codes for a transmembrane (TM) TPK molecule of 2311 amino acids (aa). The extracellular domain consists of 1873 amino acids which share 20 to 43% homology with that of the Drosophila sevenless protein and TPK domains of the two genes have 58 to 74% homology. The extracellular domain containing 37 potential N-linked glycosylation sites is preceded by a 5' hydrophobic sequence resembling a typical signal peptide. An internal hydrophobic domain of 26 amino acids, the presumed transmembrane domain, is followed by a spacer sequence of 58 amino acids, a TPK domain of 270 amino acids and a carboxyl tail of 84 amino acids. Overall, our result indicates that c-ros codes for a glycosylated transmembrane TPK molecule which shares a remarkable sequence and structural homology with that of Drosophila sevenless protein.

Amino Acid Sequence

Interactive morphometry of normal and hyperplastic peritoneal mesothelial cells and dysplastic and malignant ovarian cells.

This study used computerized interactive morphometry to evaluate the differential characteristics of mesothelial normal cells, mesothelial hyperplastic cells, and carcinomatous cells, and also compared hyperplastic mesothelial cells with ovarian dysplastic cells from a previous study. The procedure included extraction of multiple descriptors of the nuclear profile: perimeter length, area, longest chord, circularity factors, standard deviations of these characteristics, and a 10-bin size distribution table of the nuclear area. The final classification is achieved by stepwise discriminant analysis of these variables. The analysis classified all cases correctly with high posterior probabilities.

Cystadenocarcinoma

Somatic diversification of chicken immunoglobulin light chains by point mutations.

The light-chain locus of chicken has 1 functional V lambda 1 gene, 1 J gene, and 25 pseudo-V lambda-genes (where V = variable and J = joining). A major problem is which somatic mechanisms expand this extremely limited germ-line information to generate many different antibodies. Weill's group [Reynaud, C. A., Anquez, V., Grimal, H. & Weill, J. C. (1987) Cell 48, 379-388] has shown that the pseudo-V lambda-genes diversify the rearranged V lambda 1 by gene conversion. Here we demonstrate that chicken light chains are further diversified by somatic point mutations and by V lambda 1-J flexible joining. Somatic point mutations were identified in the J and 3' noncoding DNA of rearranged light-chain genes of chicken. These regions were analyzed because point mutations in V lambda 1 are obscured by gene conversion; the J and 3' noncoding DNA are presented in one copy per haploid genome and are not subject to gene conversion. In rodents point mutations occur as frequently in the V-J coding regions as in the adjacent flanking DNA. Therefore, we conclude that somatic point mutations diversify the V lambda 1 of chicken. The frequency (0-1%) and distribution of the mutations (decreasing in number with increased distance from the V lambda 1 segment) in chicken were as observed in rodents. Sequence variability at the V lambda 1-J junctions could be attributed to imprecise joining of the V lambda 1 and J genes. The modification by gene conversion of rearranged V lambda 1 genes in the bursa was similar in chicken aged 3 months (9.5%) or 3 weeks (9.1%)--i.e., gene conversion that generates the preimmune repertoire in the bursa seems to level off around 3 weeks of age. This preimmune repertoire can be further diversified by somatic point mutations that presumably lead to the formation of antibodies with increased affinity. A segment with structural features of a matrix association region [(A + T)-rich and four topoisomerase II binding sites] was identified in the middle of the J-C lambda intron (where C = constant).

Animals

Infarction of intestine with massive amyloid deposition in two patients on long-term hemodialysis.

Two patients undergoing hemodialysis for 19 and 13 yr, respectively, developed intestinal infarction with extensive amyloid deposits in the muscle layer and blood vessels. In 1 patient the deposit reacted positively with antiserum to beta 2-microglobulin by immunohistochemical stain, and therefore was classified as beta 2-microglobulin in origin. The amyloid protein of the other patient remains unclassified. In patients with gastrointestinal symptoms who have been undergoing hemodialysis for long periods of time, amyloidosis of the intestine should be considered.

Amyloidosis

Prenatal diagnosis of fetal brain tumors.

Two cases of congenital brain tumors were detected during routine antepartum sonography at the Mount Sinai Medical Center Perinatal Ultrasound Unit. In both cases, diagnosis was made during the third trimester at 31 and 33 weeks, respectively. In one of these patients, no intracranial abnormalities were noted on a sonogram performed in conjunction with genetic amniocentesis at 18 weeks gestation. The histologic diagnosis of both tumors was glioblastoma multiforme grade III. Previous reports describing the prenatal sonographic diagnosis of intracranial tumors have been in cases with fetal intracranial teratomas.

Adult

Transcriptional measurements of mouse repeated DNA sequences.

We have carried out transcriptional measurements on several families of repeated sequences to define their expression in mouse cells. The majority of Alu family transcripts result from read-through from adjacent structural gene promoters while 20% are discrete RNA polymerase III products. Alu repeat members show preferential orientation within RNA polymerase II transcription units as evidenced by asymmetric representation of the complementary strands of the Alu family in hnRNA. We assessed whether 3 non-Alu repeated sequence families had their own promoters by strand symmetry measurements and size distribution analysis of repeat-homologous newly synthesized nuclear RNA. Transcription homologous to the R family is totally symmetric and is likely due to read-through from adjacent structural gene promoters. LLRep1 and Bam5 repeats, in contrast, exhibit consistent strand asymmetry which is suggestive that at least some members may be transcribed by their own promoters. Among 3 mouse tissues and 1 cultured cell line analyzed, no quantitative variation in the expression of any of these sequences was observed.

Animals

Organization and expression of non-Alu family interspersed repetitive DNA sequences in the mouse genome.

The mouse genome is complex with regard to DNA sequence organization and transcriptional activity. To more fully understand the role of interspersed repetitive DNA sequences we have isolated and characterized five different mouse non-Alu DNA sequence families. We have found that: (1) the distribution of repetitive sequences is non-random in the genome; (2) two of the five families (Bam5 and R) were previously described by Fanning (1982) and Gebhard et al. (1982), respectively. We found that these two families are linked to each other and are found adjacent to seven of seven studied structural genes but in randomly selected DNA fragments showed much less significant linkage. (3) The position of the Bam5 and R family repeat units relative to beta-globin and relative to a housekeeping gene has been evolutionarily conserved in mice and humans. (4) Three previously undescribed families representing from 200 to 40,000 copies per genome have been characterized and shown to have equivalent human sequences. (5) All five families studied are represented in RNA polymerase II transcripts. Little RNA polymerase III transcription homologous to these three families could be detected. The structural and functional features of these five families defined in this paper provide a basis for studies on the functional role of interspersed repetitive DNA in the mouse.

Animals