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Biomedical subjects

D Carter

Publications and source records attributed to D Carter.

At least 19 recordsLinked to original sources
PubMed1992

Giant cell carcinoma of the lung.

BACKGROUND: Giant cell carcinoma of the lung has been described as an aggressive tumor characterized by extensive local and distant disease and extremely short survival. In 1981, the World Health Organization defined giant cell carcinoma as a variant of large cell carcinoma. Before then giant cell lung cancer was a descriptive term, but it was not considered a separate entity. METHODS: The authors retrospectively studied 16 cases of giant cell carcinoma of the lung. RESULTS: These cases had a prognosis that was not appreciably different from that for lung cancer of other non-small cell histologic types. Of those patients with pathologic Stage I or II at resection, five of nine are alive and disease-free from 20 to 116 months and one has died without evidence of disease at 15 months. CONCLUSIONS: Based on this series and a review of the literature, there appears to be an increased incidence of both clinical and subclinical gastrointestinal tract involvement in patients with this histology, compared with patients with other non-small cell histologic types. The authors conclude that patients with giant cell carcinoma of the lung have a prognosis similar to that of patients with other non-small cell histologic types, and that clinicians should be aware of the increased incidence of gastrointestinal tract involvement in this disease.

Adult↗
PubMed1992

NEU protein overexpression in benign, borderline, and malignant ovarian neoplasms.

In situ hybridization (ISH) analysis of 24 benign, borderline, and malignant ovarian tumor specimens revealed NEU transcript expression by epithelial elements in approximately two-thirds of the samples and high-level expression in 3 grade 3 adenocarcinomas. Immunohistochemical staining (IHC) of a total of 86 specimens (including 17 of those studied by ISH) localized NEU antigen expression to epithelial cells in 36 of 86 samples with strong membrane staining observed in 12, including 1 benign, 1 borderline serous carcinoma, 3 clear cell/endometrioid carcinomas, and 7 predominantly papillary serous carcinomas with areas of clear cell/endometrioid histology. Clinical correlation of the IHC results for the 72 Stage I-IV invasively malignant neoplasms revealed no statistically significant association of the intensity of NEU IHC staining with either relapse-free or overall survival. However, more of the patients whose tumors showed strong membrane staining for NEU antigen suffered relapses of disease by 3 and 4 years than did patients whose tumors showed weak or no membrane staining. These results suggest a role for the NEU gene product in the physiology of benign ovarian surface epithelium and the neoplastic epithelium of preinvasive borderline and some invasively malignant adenocarcinomas.

Adenocarcinoma↗
PubMed1992

Development of a shielded 241Am applicator for continuous low dose rate irradiation of rat rectum.

This paper describes the development of sources, applicators, and techniques that can be used to irradiate rat rectums with continuous irradiation at dose rates of interest in brachytherapy, either with the full circumference of the rectum irradiated, or with half of the circumference shielded from the radiation. The system uses encapsulated 241Am sources, to irradiate rat rectum with 60 keV photons continuously at a dose rate of up to 50 cGy/hr. Details of the design and fabrication of the 241Am sources, the rectal applicator, the dosimetry of the system, and the protocols for preparing and irradiating the rats, and for detecting early rectal injury using histological examination of irradiated rectum are presented. Highly effective shielding (attenuation factors as low as 0.04) of half of the circumference of the rat rectum was achievable. Unidirectional 241Am irradiators for intracavitary brachytherapy offer a unique tool for examining the effects of shielding a portion of the circumference of the rat rectum, on the radiation tolerance of the rectum.

Americium↗
PubMed1992

Transgenic approaches to modifying cell and tissue function.

As our knowledge of cell regulation pathways becomes increasingly sophisticated, the tools and techniques that have emerged from in vitro studies are being applied to the whole organism through transgenesis. With the development of new ways of modifying cellular signalling in intact animals comes the ability to analyse physiological systems and their pathologies with greater spatial and temporal precision.

Animals↗
PubMed1992

Neuropeptide gene expression in transgenic animals.

Transgenic animal techniques offer today's neuroscientist the ability to experimentally manipulate neurosecretory systems with a precision undreamt of by our predecessors. The range of techniques now available, building as it does on our growing knowledge of physiological systems at the inter- and intercellular level, allows us to critically define molecular lesions and ask about their consequences to the whole organism. Neuroscientist should grasp the opportunities afforded by these recent developments.

Animals↗
PubMed1992

Posttranscriptional regulation of rat growth hormone gene expression: increased message stability and nuclear polyadenylation accompany thyroid hormone depletion.

In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone-depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins.

Animals↗
PubMed1992

The relationship between large airway and alveolar space inflammation and airway metaplasia.

Bronchoscopy and bronchoalveolar lavage (BAL) yield important information about the lower respiratory tract of subjects who have been exposed to asbestos. Evidence of metaplasia is easily detected with random biopsies in large airways and a relationship with smoking status can be found. A significant finding, however, is that inflammatory cells recovered by late BAL aliquots which presumably reflect alveolar space inflammation are also importantly associated with the presence of metaplasia. Asbestos provides an important stimulus for recruitment of inflammatory cells. These cells release oxidants which can be responsible for direct or indirect mutagenesis. Our data suggest that this inflammatory cell recruitment may be an important additional factor predictive of airway metaplasia and perhaps subsequent carcinogenesis.

Asbestosis↗
PubMed1992

Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.

PURPOSE: This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS: Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS: At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS: DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.

Adult↗
PubMed1992

Association between acute inflammatory cells in lavage fluid and bronchial metaplasia.

In epidemiologic studies, airway disease and parenchymal injury are known morbid outcomes of occupational exposure to asbestos. However, the relationship of inflammatory events considered to be responsible for parenchymal injury to the subsequent development of airway injury is unknown. To assess this we performed bronchoalveolar lavage (BAL) and airway biopsies on a population of subjects with exposure to asbestos in the workplace. As an index of airway injury, we employed histologic metaplasia seen in mucosal biopsy specimens. Lung BAL fluid was analyzed for two potentially relevant protein markers and for inflammatory cells recovered from the lower respiratory tract. We related metaplasia to demographic features of this study population (eg, smoking history and asbestos exposure data) and also to the protein and cellular markers recovered by BAL. We studied 50 workers and detected keratinizing metaplasia in 15 and varying lesser abnormalities in the other 28. Cigarette smoking was not associated with the presence of metaplasia (p less than 0.2). Smoking status was associated with an increase in BAL cells (p less than 0.02); however, neither the percent nor concentration of acute inflammatory cells was significantly increased. Acute inflammatory cells (percent and cells per milliliter of BAL fluid) were significantly increased among the subjects with severe metaplasia compared with other study subjects. This increase was true of both neutrophils and eosinophils and the sum of these two (p less than 0.02). Stratification of subjects by smoking status demonstrated a persistent association of inflammatory cells with metaplasia. By logistic regression analysis, polymorphonuclear leukocytes per milliliter and eosinophils per milliliter were significantly related to the presence of metaplasia in two independent models (odds ratios, 9.9 and 7.6, respectively). Cigarette smoking and other demographic or BAL variables were not significantly associated with metaplasia in these models.

Asbestosis↗
PubMed1992

Human studies with the chelating agents, DMPS and DMSA.

Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.

Adult↗
PubMed1992

Neu proto-oncogene amplification and expression in ovarian adenocarcinoma cell lines.

In this communication, the authors summarize their characterization of eight ovarian adenocarcinoma-derived cell lines for level of neu gene amplification, expression of neu transcripts and protein, and intraperitoneal tumorigenicity in nude mice. Two of the eight cell lines in our study (SKOV3 and YAOVBIX1) exhibited five- to ninefold neu DNA sequence amplification, accompanied by up to 200-fold overexpression of transcripts and protein (p185). Both of these cell lines expressed a major approximately 7.5 kb neu-complementary transcript not previously reported in other neu-positive tumor cell lines. One pair of cell lines (YAOVBIX1 and YAOVBIX3), isolated from a single ovarian carcinoma patient's ascites sample differed dramatically in regard to level of neu gene amplification and expression. Immunohistochemical staining of the primary ovarian tumor from which these two lines were derived demonstrated populations of both neu-positive and neu-negative malignant epithelial cells. Seven of the eight ovarian carcinoma lines produced intra-abdominal tumors after intraperitoneal injection into nude mice, irrespective of level of neu gene expression. This study demonstrates tumor cell heterogeneity with regard to neu gene amplification and expression in an ovarian adenocarcinoma, reveals the overexpression of novel neu-complementary transcripts in two independently isolated ovarian adenocarcinoma cell lines, and suggests that neu gene expression is not required for intraperitoneal tumorigenicity of ovarian carcinoma xenografts in a nude mouse model system.

Adenocarcinoma↗
PubMed1991

The expression of class I patatin gene fusions in transgenic potato varies with both gene and cultivar.

Patatin is a family of glycoproteins that contributes about 40% of the total soluble protein in tubers of potato (Solanum tuberosum L.). The protein is encoded by a multigene family of 50-70 genes which have been divided into classes I and II on the basis of sequence homology. The promoters of two class I genes, PS20 and PS3/27, were transcriptionally fused to beta-glucuronidase and transformed into the potato cultivars Désirée and Maris Bard. Examination of the expression levels in large populations of microtubers indicated that the PS20 promoter produced beta-glucuronidase activities 5-fold lower in Désirée than Maris Bard whereas the PS3/27 promoter showed similar levels in both cultivars. Furthermore, the relative expression levels from the two promoters were reversed in the two cultivars. The beta-glucuronidase enzyme activity was correlated with the mRNA level but not the copy number of the introduced gene. The implications for the use of patatin promoters in the genetic modification of tubers is discussed.

Carboxylic Ester Hydrolases↗
PubMed1991

Expression of calcyclin, a calcium-binding protein, in the keratogenous region of growing hair follicles.

Changes in calcium levels control the differentiation of skin epithelial cells and thus may also affect the epithelial cells of the hair follicle. We have isolated a murine cDNA clone, pCAL-F559, for the calcium-binding protein calcyclin by differential screening of a cDNA library made from RNA isolated from hair follicles of 6-d-old mice. The identity of our cDNA clone was established by comparing the DNA sequence with the sequence of the human calcyclin gene. That the authentic calcyclin mRNA encoded by pCAL-559 is present in skin of 3-d-old mice was confirmed by S1 nuclease protection assays. As measured by RNA dot blots, calcyclin mRNA levels in the skin change in accordance with the hair cycle and reaches a peak a few days prior to the mRNA for structural hair proteins. Although we can demonstrate by in situ hybridization that mRNA for calcyclin is localized in the post-mitotic keratogenous region of the hair follicle we can only assume that this calcium binding protein is involved in the control of differentiation of these cells by regulating their Ca++ levels.

Animals↗
PubMed1991

Testicular oxytocin gene expression in seminiferous tubules of cattle and transgenic mice.

We are using transgenic mice to study the regulation of the bovine vasopressin (VP) and oxytocin (OT) genes. Prompted by the observation that mice bearing a bovine OT transgene express bovine OT RNA in their testes, we investigated the expression of the VP-OT locus in normal mice and cattle. Normal wild-type mice do not have detectable levels of either VP or OT RNA in their testes. Normal cattle are also devoid of detectable VP transcripts, but have relatively high levels of testicular OT RNA. Additionally, OT, but not VP, peptide is detectable by HPLC. In situ hybridization to RNA in bovine testicular tissue sections localized OT transcripts to seminiferous tubules, with a distribution similar to that of alpha-inhibin, suggesting expression in Sertoli cells. Interestingly, the bovine OT RNAs in the transgenic mouse testes were also shown by in situ hybridization to have the same distribution. These data suggest that the cis-acting regulatory sequences responsible for expression of the OT gene in bovine Sertoli testis reside within the limits of the transgene used in this study. Further, the trans-acting factors present in murine testicular cells are able to recognize these elements, although they do not express the endogenous mouse OT gene in this tissue.

Animals↗
PubMed1991

Vasopressin and oxytocin gene expression in rat testis.

The vasopressin (VP) gene is expressed as three different transcripts in the rat testis. Using polymerase chain reaction (PCR) analysis we have been able to identify a VP RNA that is identical in exonic structure to that found in the hypothalamus. However, the abundance of this form is very low, and it cannot be detected by Northern blotting. Two VP RNAs with a novel structure, as shown using exon-specific probes, are present in higher abundance. By differential hybridization, sequencing of a cDNA clone, and PCR we have deduced the structure of these novel transcripts. Both of the novel testicular VP RNA species share two exons with the classical hypothalamic RNA. However, the testicular VP gene-derived RNA lacks the first exon of the hypothalamic transcript, the exon that contains the sequence information for the VP nonopeptide hormone. Instead, it has novel sequence that are derived from at least two unique testis-specific exons, one of which is located 7-10 kilobase up-stream of the brain-specific start of transcription. These two unusual transcripts are probably derived by alternative splicing of at least two up-stream exons. Sequence and polysome analyses indicate that the testicular VP RNAs are probably not translated. Northern blotting revealed that the VP gene-derived RNA species are tightly regulated during postnatal development, becoming apparent by 40 days of age, although they subsequently fail to respond to a variety of physiological perturbations. Oxytocin gene transcripts are not detectable by Northern hybridization, but the authentic hypothalamic-type RNA can be detected in the rat testis using PCR analysis.

Adrenal Glands↗
PubMed1991

The relationship between large airway inflammation and airway metaplasia.

To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers.

Animals↗
PubMed1991

FMS (CSF-1 receptor) and CSF-1 transcripts and protein are expressed by human breast carcinomas in vivo and in vitro.

The expression in vivo of FMS transcripts and antigen by neoplastic epithelial cells was demonstrated immunohistochemically or by in situ hybridization in sixteen of seventeen human breast carcinoma specimens and one case of sclerosing adenosis. Expression of CSF-1 receptor (FMS) transcripts and protein was also observed in vitro in two or three breast carcinoma-derived cell lines and was dramatically increased by dexamethasone, a potent glucocorticoid and inducer of mammary epithelial cell differentiation. Immunohistochemical staining with an anti-CSF-1 antibody identified neoplastic epithelial cell co-expression of fms and CSF-1 antigens in more than one-third of the fms-positive invasive carcinoma specimens. These results suggest that autocrine and paracrine interactions of the lymphohematopoietic cytokine CSF-1 and its receptor may participate in the biology of human mammary neoplasms.

Blotting, Northern↗