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Biomedical subjects

J M Ward

Publications and source records attributed to J M Ward.

At least 325 records · Page 18Linked to original sources
PubMed1981

The tnpR gene product of TnA is required for transposition immunity.

A mutant of TnA no longer recognizing immune plasmids had been isolated. The mutation is complemented in trans by a functional tnpR gene. The requirement for wild type tnpR gene product for the establishment of transposition immunity was confirmed by the use of a derivative of transposon Tn3 in which both the tnpA and the tnpR genes are partly deleted. This deleted Tn3 was shown to transpose onto an immune plasmid in the presence of a wild type tnpA gene but not in the presence of both tnpA and tnpR genes.

DNA Transposable Elements↗
PubMed1981

Excision of chromosomal DNA sequences from Streptomyces coelicolor forms a novel family of plasmids detectable in Streptomyces lividans.

When strains of Streptomyces coelicolor A3(2) lacking the previously identified autonomous plasmids SCP1 and SCP2 are crossed with Streptomyces lividans 66, some of the S. lividans progeny are able to elicit zones of growth inhibition (lethal zygosis), previously associated with the transfer of conjugative Streptomyces plasmids, when grown in contact with S. lividans 66. Some such progeny yield covalently closed circular (CCC) plasmid DNA, the size and restriction endonuclease cleavage pattern of which is constant for a particular isolate, but varies among isolates. These plasmids, which have been named SLP1.1, SLP1.2, etc., all confer resistance to lethal zygosis elicited by the others. Genetic and molecular characterization of the plasmids reveals that they are derived from the strA region of the chromosome of S. coelicolor. It is proposed that, before or during mating with S. lividans, the SLP1 sequences are excised from the chromosome, bringing varying regions of the surrounding chromosome with them, and can circularize to yield the SLP1 family of plasmids. Autonomous SLP1 plasmids can also be generate by cleaving total DNA of S. coelicolor with certain restriction enzymes, ligating it, and transforming the DNA into S. lividans. The autonomous SLP1 plasmids exist within S. lividans in a few copies per chromosome, and act as fertility factors. They provide suitable vectors for DNA cloning since the segments of chromosomal DNA carried by the larger members of the family are dispensable.

Conjugation, Genetic↗
PubMed1981

Morphology of neoplastic lesions in the clitoral and prepucial gland of the F334 rat.

Three hundred fifty-nine neoplasms of the prepucial and clitoral glands of F344 rats were reviewed to classify the different types of tumors in relation to the normal anatomy and histology of the glands. Most tumors originated from the acinar of ductal cells, while only one tumor could be found originating from the mesenchymal tissue. They were classified as adenomas, adenocarcinomas, papillomas, squamous cell or basal cell carcinomas, and mixed cell carcinomas with different structural formations. Only one tumor metastasized to the lung.

Adenocarcinoma↗
PubMed1981

Morphology of foci of altered hepatocytes and naturally-occurring hepatocellular tumors in F344 rats.

The morphology of liver tumors of F344 rats used as controls in carcinogenesis bioassays were studied. Foci of cellular alteration composed of hepatocytes with basophilic cytoplasm were found commonly in F344 rats, 2 years of age. Eosinophilic and vacuolated foci were considerably less common. The morphology of 67 nodular hepatic lesions indicated that 54 were neoplastic nodules and 13 hepatocellular carcinomas. The majority of these tumors were composed of basophilic hepatocytes. Some of the carcinomas appeared to arise within neoplastic nodules. No tumors metastasized.

Animals↗
PubMed1981

Characteristics of proliferative lesions in the nasal cavities of mice following chronic inhalation of 1,2-dibromoethane.

Groups of 50 male and 50 female B6C3F1 mice inhaled 10 or 40 ppm 1,2-dibromoethane 6 h/day, 5 days/week, for 103 (10 ppm) or 90 (40 ppm) weeks. Focal epithelial hyperplasia was found in 1 (low dose group) and 10 (high dose group) males and 3 (low dose group) and 11 (high dose group) females. Squamous papillomas or adenomas were seen in 3 males and 7 females in the high dose groups. Squamous, adeno-, or mixed carcinomas were present in 7 females in the high dose group. One poorly differentiated sarcoma and 2 hemangiosarcomas were observed in females in the low and high dose groups, respectively.

Animals↗
PubMed1981

Quantitation of differences between spontaneous and induced liver tumors in mice with an automated image analyzer.

Spontaneous hepatocellular neoplasms of B6C3F1 mice (basophilic neoplasms) as well as those induced with the herbicide Nitrofen (eosinophilic neoplasms) were observed with an image analyzing computer to determine if quantifiable morphologic differences existed between them. Several morphologic parameters were measured on 5 liver sections from each of the following groups: (a) unexposed control liver; (b) non-trabecular basophilic neoplasms; (c) trabecular basophilic neoplasms; (d) small well circumscribed eosinophilic neoplasms; and large irregular eosinophilic neoplasms without (e) and with (f) pulmonary metastases. The total number of hepatocytes per unit area was significantly smaller in the eosinophilic neoplasms than in the basophilic neoplasms or the controls. This was the result of a greatly increased cell cross-sectional area in the eosinophilic neoplasms, caused predominantly by a larger cytoplasmic cross-sectional area. Nuclear cytoplasmic ratios of cells in eosinophilic neoplasms were lower than in the other groups for this reason. This demonstrates that quantitative morphologic differences exist between the spontaneous and induced neoplasms, which supports the conclusion that Nitrofen is a true carcinogen, and not a promoting agent.

Animals↗
PubMed1981

Effects of three retinoids on colon adenocarcinomas, sarcomas and hyperplastic polyps induced by intrarectal N-methyl-N-nitrosourea administration in male F344 rats.

Male F344 rats, 9 weeks of age, were given multiple intrarectal administrations of N-methyl-N-nitrosourea (NMU) at 0.5 mg/dose twice a week for a total of 8, 12, or 16 doses. Five days after the final NMU instillation, rats were placed on one of four diets; chow with retinoid vehicle, chow with 654 mg N-ethylretinamide per kg diet, chow with 686 mg N-(2-hydroxethyl)retinamide per kg diet, or 406 mg retinylidene dimedone per kg diet. Groups of 40--50 rats receiving 16, 12, or 8 total doses were sacrificed 32, 44, or 52 weeks after the initial NMU dose, respectively. The number of rats with colon tumors and the number of tumors per tumor bearing rat in each dosage regimen was compared to appropriate controls. Organ weights for testis, liver, and kidneys were similar for controls and retinoid treated animals and no histopathologic lesions indicative of retinoid toxicity were found. Unusual proliferative lesions of the colon in rats of all dosed groups included hyperplastic and inflammatory polyps and sarcomas. The feeding of diets containing these three retinoids did not significantly modify the incidence or multiplicity of colon tumors observed under these conditions.

Adenocarcinoma↗
PubMed1981

Variability in the rates of some common naturally occurring tumors in Fischer 344 rats and (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Variability inthe incidence rates of some common naturally occurring tumors for 72 inbred F344 rat and 54 (C57BL/6N x C3H/HeN)F1 (B6C3F1) mouse control groups used in carcinogenesis bioassays was evaluated. Significant heterogeneity of control rates was observed in at least two of six laboratories for lymphomas-leukemias, liver tumors, and pituitary tumors in the male rat and for pituitary tumors and endometrial stromal polyps in the female rat. Significant interlaboratory heterogeneity was observed for several tumor types in the F344 rat. In contrast, control incidence rates for tumors of the lung and liver and lymphomas-leukemias in B6C3F1 mice were relatively homogeneous within four of five laboratories. Significant interlaboratory heterogeneity was observed, however, for these mouse tumors. The causes of significant heterogeneity in naturally occurring tumor incidence rates within and among laboratories are unknown. Although the most appropriate and important comparison of an experimental group is with its matched control, there may be instances in which the historical control rates provide relevant data needed to clearly interpret carcinogenesis bioassay results. With the use of data from bioassays of 4-chloro-m-phenylenediamine and nitrilotriacetic acid, two examples are presented to demonstrate the usefulness of the historical control data.

Adrenal Gland Neoplasms↗
PubMed1981

Reduced expression of Tn 10-mediated tetracycline resistance in Escherichia coli containing more than one copy of the transposon.

In Escherichia coli a single copy of Tn10 confers high-level resistance to tetracycline. Resistance itself results from expression of three distinct mechanisms which normally act together (Shales et al., 1980). In cells containing two copies of Tn10, the level of resistance to tetracycline was reduced. This was not due to overproduction of the repressor which controls the resistance genes, because strains diploid for an operator-constitutive allele of Tn10 also exhibited reduced expression of resistance. The negative gene dosage effect resulted from decreased expression of two mechanisms (1 and 2) consequent on enhanced expression of the third mechanism. The net result of increasing the copy number was a decrease in resistance because mechanism 3 was less efficient than mechanisms 1 and 2 in protecting the cell against tetracycline. The DNA sequence responsible for the reduced expression of resistance was contained in the internal BglII fragment of Tn10. This sequence, which is probably unique to Tn10, may encode the protein which mediates mechanism 3. Elevated levels of this protein probably cause decreased expression of mechanisms 1 and 2.

DNA Transposable Elements↗
PubMed1981

Morphology of hyperplastic and neoplastic lesions in the clitoral and preputial gland of the F344 rat.

We reviewed 359 neoplasms of the preputial and clitoral glands of F344 rats to classify the different types of tumors, in relation to the normal anatomy and histology of the glands. Most tumors originated from the acinar or ductal cells; only one tumor originated from mesenchymal tissue. They were classified as adenomas, adenocarcinomas, squamous cell or basal cell carcinomas, and mixed cell carcinomas. Only one tumor metastasized to the lung.

Animals↗
PubMed1981

Aroclor 1254-induced intestinal metaplasia and adenocarcinoma in the glandular stomach of F344 rats.

Ingestion of diets containing Aroclor 1254, a mixture of polychlorinated biphenyls, for 2 years led to a dose-related increase in the incidence of focal lesions in the glandular stomachs of male and female F344 rats. The incidence of stomach lesions was 6% in control specimens and in specimens from rats fed a diet containing 25, 50, or 100 ppm Aroclor 1254, the incidences of stomach lesions were 10, 17, and 35%, respectively. The majority of gastric lesions in treated rats were histologically identified as intestinal metaplasia characterized by an architecture resembling that of intestinal crypts and particularly by goblet cells, which stained with Alcian blue and periodic acid-Schiff reagent. Adenocarcinomas were found in six specimens. Most (88%) of the lesions were located in the pyloric region of the glandular stomach. No multiple lesions were observed among 47 control specimens examined; however, nine cases of multiple lesions were observed in 30 lesion-containing specimens from Aroclor 1254-treated rats. Although the exact relationship between gastric intestinal metaplasia and adenocarcinoma remains to be established, they commonly coexist and may share initiating mechanisms.

Adenocarcinoma↗
PubMed1981

Detection of mutagens-carcinogens: carcinogen-induced lesions pinpointed by alkaline phosphatase activity in fixed gastric specimens from rats.

Alkaline phosphatase (AP) activity was not detectable by histochemical staining in the glandular stomachs of normal rats. However, AP activity was present at high levels in the brush borders of the intestine and persisted after fixation of the tissues in Formalin at room temperature. Foci of AP activity were detected in gross Formalin-fixed specimens of glandular stomachs of male and female inbred F344 rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and killed over 6 years ago. The incidence of AP-positive foci increased in proportion to the dose of the carcinogen MNNG. Histologically, most of the grossly visible AP-positive foci corresponded to areas of intestinal metaplasia and adenocarcinoma. AP-positive foci localized sites of pathologic significance for microscopic examination and pinpointed gastric sites containing very early tumors that were missed by standard examination.

Adenocarcinoma↗
PubMed1980

DNA cloning in Streptomyces: resistance genes from antibiotic-producing species.

The biochemical and morphological differentiation of actinomycetes makes them academically and economically interesting. Their secondary metabolites provide the majority of medically and agriculturally important antibiotics (streptomycete genes may also be the primary source of clinically important antibiotic resistance); their complex morphological developmental cycle involves a series of changes from vegetative mycelial growth to spore formation. Recombinant DNA technology would add a powerful new dimension to the analysis of these various aspects of actinomycete biology and would also facilitate the development of industrial strains with increased antibiotic yield, or capable of making new antibiotics. For most of these purposes, cloning of genes within and between actinomycetes is required to study the expression of particular genes in genetic backgrounds defined by mutations of the characters under study. To achieve this, we have now developed a method for molecular cloning involving the transfer of genes between unrelated streptomycetes.

Cloning, Molecular↗
PubMed1980

Respiratory pathology in rats and mice after inhalation of 1,2-dibromo-3-chloropropane or 1,2 dibromoethane for 13 weeks.

Seventy F344 rats and 144 B6C3F1 mice were subdivided into seven groups. Three groups were each exposed via inhalation to 1, 5, or 25 ppm of 1,2-dibromo-3-chloropropane (DBCP) for 6 h per day, 5 days per week for 13 weeks. Three additional groups were each similarly exposed to 3, 15, or 75 ppm of 1,2-Dibromoethane (EDB). The remaining group was exposed to room air under the same conditions. At 13 weeks, rats and mice showed severe necrosis and atrophy of the olfactory epithelium in the nasal cavity after inhalation of 5 or 25 ppm DBCP and 75 ppm EDB. Lower concentrations induced squamous cell metaplasia, hyperplasia and cytomegaly of the epithelium of the respiratory nasal turbinals. Squamous metaplasia, hyperplasia and cytomegaly of the epithelium was also seen in larynx, trachea, bronchi and bronchioles. Other compound related toxic lesions in rats were seen in the liver, kidney and testes.

Animals↗