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Biomedical subjects

G Reznik

Publications and source records attributed to G Reznik.

At least 19 recordsLinked to original sources

The Rhodobacter capsulatus genome.

The genome of Rhodobacter capsulatus has been completely sequenced. It consists of a single chromosome containing 3.5 Mb and a circular plasmid of 134 kb. This effort, started in 1992, began with a fine-structure restriction map of an overlapping set of cosmids that covered the genome. Cosmid sequencing led to a gapped genome that was filled by primer walking on the chromosome and by using lambda clones. Methods had to be developed to handle strong stops in the high GC (68%) inserts. Annotation was done with the ERGO system at Integrated Genomics, as was the reconstruction of the cell's metabolism. It was possible to recognize 3709 orfs of which functional assignments could be made with high confidence to 2392 (65%). Unusual features include the presence of numerous cryptic phage genomes embedded in the chromosome.

Journal Article↗

Non-protein thiols flux to S-nitrosothiols in endothelial cells: an LPS redox signal.

Lipopolysaccharide (LPS) injures blood vessels by activating pathways in the endothelium that lead either to cell survival and proliferation or apoptosis. It has been suggested that these outcomes are determined when reactive oxygen and nitrogen intermediates oxidize low molecular weight non-protein thiols (NPSHs) such as glutathione (GSH) and cysteine (Cys), which serve as major intracellular reducing agents. The oxidoreduction of NPSHs could be an important redox signal if it were shown to occur rapidly following injury. Towards that end, cultured bovine aortic endothelial cells were stained with the thiol fluorescent probe, monobromobimane (MBB). Most of the acid extractable MBB-reactive adducts are GSH (approximately 90%) and Cys (approximately 90%). Within 1 min of LPS exposure, 50-70% of the MBB-reactive NPSHs are consumed without evidence for concomitant net generation of superoxide, hydrogen peroxide, singlet oxygen, or glutathione disulfide (GSSG). Although LPS induces an increased rate of thiol-disulfide exchange, the slight increase does not explain the magnitude of NPSH consumption. Within the first 10 min of recovery from LPS exposure, the MBB-reactive NPSH fluorescence returns at or slightly above baseline values. When HgCl2 was added to the acid extract, one mole of S-nitrosothiol oxidizing equivalent was found for every mole of MBB-reactive NPSH consumed. It is suspected that the rapid flux of MBB-reactive NPSHs and Hg2+-inducible oxidants reflects transition of GSH to GSNO (S-nitrosoglutathione) and could be an important redox signal in endothelial cells exposed to LPS.

Animals↗

Percutaneous endoscopic implantation of Automatic Implantable Cardioverter/Defibrillator (AICD): an animal study of a new nonthoracotomy technique.

The Automatic Implantable Cardioverter/Defibrillator (AICD) prevents death due to malignant ventricular arrhythmias but requires thoracotomy for the implantation of the preferred two-patch lead system. The purpose of this study was to develop and test a new percutaneous endoscopic method of the AICD lead implantation without the need for open chest surgery. A high resolution video endoscopy system and currently available endoscopic instrumentation were used to develop pleural-pericardial dissection technique in 7 pigs and to endoscopically implant custom-made AICD patches in 20 pigs. An examining 10 mm rigid endoscope inserted in the 6th intercostal space in the anterior axillary line provided direct visual control for endoscopic dissection of the parietal pleura from the pericardium, delivery, and implantation of the AICD patches. This was successfully carried out through two trocars (10 and 11 mm) inserted into the pleural-pericardial space via the subxyphoid approach in 18 of 20 pigs. Effective patch positioning was confirmed by attaining a defibrillation threshold of 20J or less in 13 pigs. Of those, three required lead polarity reversal, and three others required lead repositioning to lower defibrillation thresholds to 20J or less. In three pigs, defibrillation thresholds of 30J or higher were required. Defibrillation was unsuccessful in two pigs due to patch malfunction. The authors conclude that percutaneous endoscopy is a feasible method of AICD lead implantation.

Animals↗

Mouse hepatoblastomas: a histologic, ultrastructural, and immunohistochemical study.

Hepatoblastomas from B6C3F1 and BALB/c mice were examined by light and electron microscopy and by immunohistochemical reactions for alpha-fetoprotein, keratin, and vimentin. Tumors occurred in one group of a chronic bioassay for the interaction of diet, genetic strain, and the carcinogen, 2-acetylaminofluorene. Tumors had several populations (including epithelial and mesenchymal cells) in various stages of differentiation. Neoplastic epithelial cells had features of embryonal hepatocytes, such as sparse cytoplasmic organelles, absence of glycogen, abundant free ribosomes, occasional bile canaliculi, and peroxisome-like dense bodies. Embryonal fibroblast-like cells had pleomorphic and folded nuclei with prominent perinuclear chromatin and dispersed cytoplasmic organelles. Fibroblast-like cells were surrounded by bundles of collagen fibrils. Intermediate or transitional types of cells were seen. No tumor cells were immunoreactive for mouse alpha-fetoprotein (AFP) antibody, unlike those in hepatocellular adenomas or carcinomas. Epithelial and mesenchymal tumor cells contained intermediate filaments throughout the cytoplasm; some of these cells stained for keratin but not for vimentin. These findings suggest that mouse hepatoblastomas are derived from bipotential liver blastema cells and are composed of a mixture of several cell populations.

Animals↗

Spindle cell carcinoma of the hamster trachea induced by N-methyl-N-nitrosourea.

The tracheas of 63 male Syrian golden hamsters were exposed once each week for 12 weeks to a flowing stream of 0.5% N-methyl-N-nitrosourea in phosphate-buffered saline (pH 4.5) with a specially designed intratracheal cannula. The animals were killed when moribund or 6 months after the final exposure, and the respiratory tracts were examined grossly, histologically, and ultrastructurally for tumor formation. A total of 13 neoplasms was found in the larynx or trachea. Six were papillomas, 3 were carcinomas, and 4 were diagnosed as spindle-cell carcinomas. The average time of observation of the various tumor types was 33, 31, and 21 weeks, respectively. The spindle cell carcinomas contained an exophytic portion protruding into the tracheal or laryngeal lumen and an infiltrating portion growing circumferentially between the intact mucosa and the cartilage rings or plates. They were composed of sheets of elongated and spindle-shaped cells. Ultrastructurally, the cells contained bundles of tonofilaments and keratohyalin, and were connected by numerous desmosomes. These findings are consistent with a squamous origin of the tumor cells and a diagnosis of spindle cell carcinoma.

Animals↗

Prostatic hyperplasia and neoplasia in aging F344 rats.

The prostates of 1775 (614 control and 1161 experimental) 2-year-old F344 rats from 12 different carcinogen bioassays conducted by the Bioassay Program of the NCI and the NTP were evaluated histologically. The incidence of prostatic lesions including (atypical) hyperplastic foci, adenomas, and carcinomas was 6.8%. There was no difference in the type or incidence of the lesions between treated and untreated animals. Adenomas or carcinomas were found in 71 (4.0%) of the rats, primarily as incidental findings. The number of tumors and hyperplastic foci varied from laboratory to laboratory depending on the anatomical localization of the plane of the section. Most of the neoplasms were found in the ventrolateral lobes of the prostate (ventral prostate). When adequate sections were prepared of the ventral lobe, 10-20% of the prostates had these proliferative lesions. The lesions were usually small and originated in the epithelium of the alveoli and small ducts and were usually small and originated in the epithelium of the alveoli and small ducts and were not associated with the common inflammatory lesions of the rat prostate. Thin fibrous capsules were formed in a few of the larger tumors. Metastases were not observed but there was local invasion into alveoli, ducts and interstitial connective tissue. Evidence is presented that the atypical hyperplasias progress to adenoma and carcinoma. The F344 rat offers a potential model for the study of latent prostatic preneoplastic and neoplastic lesions.

Aging↗

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↗

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↗

Chordoma of the spinal cord in a F344 rat.

A chordoma arose in the lumbar region of the vertebral column from the last two vertebrae of a 112 week old female control F344 rat. Macroscopically it was a mass measuring 32 by 22 mm reaching the pelvic region and pressing against the colon and urinary bladder. Histologically the tumor cells were arranged into lobules and the cells grew in cords. Vacuolated large cells infiltrated the bone and surrounding muscles. This is the first reported case of chordoma in a rodent.

Animals↗

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↗

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↗

Effect of three retinoids on tracheal carcinogenesis with N-methyl-N-nitrosourea in hamsters.

Male Syrian golden hamsters received 12 weekly intratracheal exposures to 0.5% N-methyl-N-nitrosourea with a special catheter. Following exposures, animals were randomized into 4 groups of 63 hamsters and placed on diets of lab meal or meal with 120 mg 13-cis-retinoid acid (CRA)/kg, 327 mg ethyl retinamide (ER)/kg, or 343 mg N-(2-hydroxyethyl)retinamide (HR)/kg for 6 months at which time all hamsters were killed. The observed incidences of tracheal epithelial neoplasms (No. of animals with tumors/total No. of animals) were 10/63 (lab meal), 22/61 (CRA), 24/63 (ER), and 17/62 (HR). The incidence of carcinomas (No. of animals with tumors/total No. of animals) were 4/63 (lab meal), 12/61 (CRA), 12/63 (ER), and 11/62 (HR). The weight loss and mortality relative to those in the group fed the lab meal were significantly in the group fed HR but not in the other retinoid-treated groups.

Amyloidosis↗

Unusual sites of lung tumor metastases in B6C3F1 mice and F344 rats.

Three male control B6C3F1 mice, one male and one female F344 rat were found to have lung tumours with unusual sites of distant metastases. The neoplasms spread to the regional lymph nodes, left heart, kidney, prostate and testes. One mouse showed metastases to the brain. Each had a metastasizing lung tumor in the medulla and cortex of the right adrenal gland and one neoplasm had spread to the heart, pancreas and kidney.

Adenocarcinoma↗