PubMed Health⌕ Search

Biomedical subjects

D Devor

Publications and source records attributed to D Devor.

14 recordsLinked to original sources
PubMed1994

Rat gonadotropin-releasing hormone (GnRH) receptor: tissue expression and hormonal regulation of its mRNA.

The binding of gonadotropin-releasing hormone (GnRH) to its receptor in the anterior pituitary gland is the key molecular interaction regulating the reproductive process of mammals. Here, we report the isolation of a cDNA representing this receptor from rat anterior pituitary and the regulation of expression of its mRNA. The rat GnRH receptor cDNA was composed of 2909 nucleotides and encoded a protein containing 327 amino acids having a seven transmembrane topology. Northern blot analysis on RNA from rat pituitary, ovary and testis showed four different transcripts (5.0, 4.5, 2.5 and 1.3 kb) of which the 5.0 kb form was most abundant. The levels of expression of the transcripts were found to be highest in the pituitary followed by the ovary and the testis (about 40% and 5% compared to pituitary, respectively). Using the more sensitive reverse transcriptase/PCR technique, we also detected GnRH receptor mRNA in the adrenal and the hypothalamus. Measurement of pituitary GnRH receptor mRNA levels (the 5.0 kb form) during the estrous cycle showed the lowest levels at estrus (1.0-fold), a 2.2 +/- 0.57 (mean +/- SEM) -fold increase at diestrus I, a 3.5 +/- 0.41-fold increase at diestrus II, a 2.6 +/- 0.34-fold increase on the morning of proestrus, and a 1.9 +/- 0.25-fold on the afternoon of proestrus. Removal of the ovaries led to a 2.7 +/- 0.29-fold increase in GnRH receptor mRNA levels in the pituitary gland; treatment of ovariectomized rats with estrogen resulted in a significant decrease in GnRH receptor mRNA levels. Our studies demonstrate ovarian regulation of GnRH receptor mRNA expression in the anterior pituitary gland.

Amino Acid Sequence↗
PubMed1991

Proliferation of carcinogen-damaged hepatocytes during cell-cycle-dependent initiation of hepatocarcinogenesis in the rat.

Hepatocyte proliferation and damage to DNA were characterized during the initiation phase of carcinogenesis in livers of rats that had received a single administration of the methylating agent methyl(acetoxymethyl)nitrosamine (DMN-OAc). Quiescent non-proliferating hepatocytes in intact livers did not appear to be susceptible to initiation by DMN-OAc, whereas proliferating hepatocytes in the S phase appeared to have greatest risk. To characterize the phenomenology of S-phase-dependent initiation further, the fractions of hepatocytes in the S and M phases of the cell cycle were enumerated at various times after treatment with DMN-OAc. Hepatocytes treated when in G1 experienced a delay of up to 20 h in the onset of S phase and a reduced rate of entry into the S and M cycle phases. Hepatocytes treated when in S phase experienced considerable delay in progression to mitosis due to part to inhibition of DNA replication. Hepatocytes treated when in late S/G2 also demonstrated a delay in progression into mitosis. The levels of 7-methylguanine and O6-methyldeoxyguanosine were quantified in the nuclear DNA of proliferating hepatocytes. The kinetics of removal of these lesions appeared to be first-order (half-life = 24 h). Hepatocyte risk of initiation was modeled by a function which summed over time the product of the fraction of hepatocytes in the S phase and the fraction of residual, unrepaired damage to DNA. For hepatocytes treated when in early G1, the time-weighted frequency of premutagenic DNA damage that was present during DNA replication was estimated to be less than half of that for hepatocytes treated when in early S. The results suggest that cell-cycle-dependent variation in sensitivity to initiation of hepatocarcinogenesis may be, in part, due to efficient removal of potentially carcinogenic lesions from DNA during an extended G1. The apparent high sensitivity of hepatocytes in late S/G2 suggests the contribution of additional factors.

Animals↗
PubMed1987

Cell cycle-dependent initiation of hepatocarcinogenesis in rats by methyl(acetoxymethyl)nitrosamine.

Hepatocyte sensitivity to initiation of carcinogenesis was studied as a function of the cell cycle phase in which damage was incurred. Hepatocytes were stimulated to proliferate by a two-thirds partial hepatic resection, and their proliferation was synchronized further by postsurgical treatment with hydrocortisone. Groups of male F344 rats were given a single administration of methyl(acetoxymethyl)nitrosamine, a highly reactive methylating agent, at various times after two-thirds partial hepatic resection when hepatocytes were in defined phases of the cell cycle. Beginning 3 wk after the treatment and for 37 wk thereafter, rats were fed a diet containing 0.05% phenobarbital to promote the expression of initiated hepatocytes. At 45 wk after treatment with carcinogen hepatocytic neoplasms were enumerated. The greatest yield of neoplasms (5.4 per liver) was observed in the group treated 16 h after two-thirds partial hepatic resection or at the time when proliferating hepatocytes began to enter the S phase of the cell cycle. The least yield of neoplasms (0.8 per liver) was identified in the group treated with methyl(acetoxymethyl)nitrosamine when hepatocytes were early in G1. In the proliferating hepatocytes sensitivity rose continuously during G1 to a peak at the G1-S border and then fell continuously as hepatocytes traversed S, G2, and M. This pattern of response could not be attributed to variation in hepatic esterase which activates methyl(acetoxymethyl)nitrosamine or to variation in methylation of DNA. The results support a model in which carcinogen-induced genetic alterations, occurring at the time of or soon after damaged cells enter the S phase, represent irreversible events that contribute to the initiation of carcinogenesis.

Animals↗
PubMed1987

Oral cholecystography and sonography of gallbladder in cholecystectomy patients.

In comparing the diagnostic specificity and sensitivity of oral cholecystography with that of sonography in 479 patients in a community hospital, the oral cholecystogram, when used with a double dose of contrast agent, showed greater specificity (1.00) and sensitivity (0.99) than the sonogram (0.54 and 0.94, respectively). Because of lower cost, the oral cholecystogram should be used as the initial diagnostic study when cholelithiasis is suspected, unless specific contraindications exist.

Adolescent↗
PubMed1986

Differential carcinogenic effects of intraperitoneal initiation with 7,12-dimethylbenz(a)anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice.

Groups of female SENCAR or BALB/c mice were initiated once intraperitoneally with 300 micrograms/mouse of 7,12-dimethylbenz(a)anthracene (DMBA) or 20 mg/mouse of urethane at 7 weeks of age. Beginning one week later, mice received topically applied acetone or 12-O-tetradecanoylphorbol-13-acetate (TPA), once weekly, at 2.5 micrograms/mouse for weeks 1 through 6 and 1.25 micrograms/mouse for weeks 7 through 52. The skin lesions were evaluated clinically. A complete necropsy was performed on all mice at week 52. SENCAR mice exposed to DMBA/TPA and urethane/TPA had more skin tumors than SENCAR mice exposed to DMBA or urethane alone and more than BALB/c mice in any treatment group. Of all skin carcinomas diagnosed histologically in DMBA/TPA-exposed mice, less than one-third had been identified clinically while the mice were alive. Most of the carcinomas arose within papillomas. BALB/c mice developed more vascular and uterine tumors than did SENCAR mice injected with DMBA and more lung and vascular tumors than did SENCAR mice injected with urethane. TPA exposure after treatment with either initiator had no significant effect on internal tumor development in either SENCAR or BALB/c mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Malignant conversion and metastasis of mouse skin tumors: a comparison of SENCAR and CD-1 mice.

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of SENCAR and Charles River CD-1 mice, using a three-stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (DMBA) (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) (stage II), papilloma-bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-n-oxide (R-NQO), the promoter TPA, or solvent (acetone). Similar final carcinoma yields were found in the mice treated in stage III with TPA or acetone, although carcinomas developed earlier in the TPA-treated mice. In contrast, treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both SENCAR and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of TPA treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The heterogeneity of papillomas with regard to progression to carcinomas is demonstrated by the low rate of conversion of TPA-dependent papillomas and the high rate of conversion of persistent papillomas in CD-1 mice. The carcinomas that develop using the three-stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with MNNG, urethane, 4-NQO, TPA, or acetone, but treatment with urethane substantially increased metastases to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies.

The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors included histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.

Acetone↗
PubMed1981

Comparison of two-stage epidermal carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine in newborn and adult SENCAR and BALB/c mice.

In order to define factors which determine susceptibility to chemical carcinogenesis, mice sensitive (SENCAR) and resistant (BALB/c) to epidermal carcinogenesis were studied under several treatment conditions for sensitivity to initiation by 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine and promotion by 12-O-tetradecanoylphorbol-13-acetate. In newborns of both strains, topical application of initiator was much less effective than in adults. However, initiation by i.p. injection of 7,12-dimethylbenz(a)anthracene is at least as effective in newborns as in adults, which may indicate that topically applied carcinogen is not delivered effectively to target cells in newborns. Thus, newborn epidermis can respond to 7,12-dimethylbenz(a)anthracene as well as adult epidermis when the initiator is appropriately administered. SENCAR mice are much more sensitive than are BALB/c mice to both initiators, which suggests that enhanced metabolic activation of hydrocarbon carcinogens by SENCAR mice is unlikely to account for their sensitivity. Newborn male SENCAR's developed approximately 50% more papillomas than did females in all groups. BALB/c newborn mice developed so few tumors that a meaningful comparison of sensitivity of males and females could not be made. Thus, the increased sensitivity of SENCAR's was apparent regardless of route of administration of initiator or the age or sex of the mice. SENCAR mice also developed a significant number of papillomas and squamous cell carcinomas with 12-O-tetradecanoylphorbol-13-acetate promotion in the absence of an exogenous initiator. Therefore, the skin of SENCAR mice may contain an initiated population of cells capable of responding to tumor promoters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1971

Abdominal aortic aneurysmectomy, 1968-1969. A review of recent experience of the Southern California Permanente Medical Group.

Seventy-three aneurysmectomies were done in the two-year period 1968-1969 for a Health Plan population of 771,000. The mortality in the elective cases was nine percent and in the emergency cases 44 percent. An analysis of the complications and causes of death reveals them to be essentially the same as reported by others. Bleeding and myocardial infarction are the two most common causes of death in emergency operations. Pneumonia and urinary tract infections are the most common complications in successful cases. Comparison of this report of recent experience with reports of cumulative series is difficult. The morbidity and mortality reported here is felt to be representative of current practice.

Aged↗
PubMedDate not supplied

Ingested asbestos and intestinal carcinogenesis in F344 rats.

The effect of oral exposure to amosite or chrysotile on azoxymethane-induced intestinal carcinogenesis was investigated in male F344 rats. In two separate experiments, F344 rats, 6 weeks of age, were given ten weekly subcutaneous injections of azoxymethane, and intragastric administration of amosite or chrysotile three times weekly during this period. In experiment 1, rats were sacrificed at 34 weeks. The incidence rates and mean number of intestinal tumors per rat were similar in all groups. However, a slightly higher incidence, not significant, of metastatic intestinal carcinomas was seen in rats exposed to asbestos. In the second experiment, rats were allowed to live out their life span. The incidence of intestinal tumors was similar in the rats receiving amosite with azoxymethane and azoxymethane alone. Thirty-two percent of the rats receiving amosite alone had colon tumors; these tumors are usually rare in F344 rats. It was concluded that the experimental evidence suggested but did not prove that oral asbestos exposure in F344 rats may have increased the incidence of intestinal tumors occurring naturally.

Animals↗