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Biomedical subjects

S Rehm

Publications and source records attributed to S Rehm.

At least 73 records · Page 4Linked to original sources
PubMed1988

N-nitrosocimetidine as a modifier of chemically-initiated tumors in mice.

N-Nitrosocimetidine (NCM) is a nitrosation product of cimetidine, a commonly-prescribed pharmaceutical agent. In spite of its known genotoxicity, NCM has failed to cause tumors in assays with rats and mice, but has given indications of enhancing or suppressive effects on tumor development. This possibility was tested by administering NCM topically to the skin or in the drinking water to mice in which tumors had been initiated by treatment with chemical carcinogens. Sencar mouse skin papillomas initiated by 7,12-dimethylbenzanthracene (DMBA) and promoted by 12-O-decanoylphorbol-13-acetate (TPA), progressed more rapidly to carcinoma on mice given treatment during stage 3 (after TPA) with NCM (1 mg/week) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 120 micrograms/week) [corrected] than on stage 3 acetone controls. Oral NCM (1 g/l drinking water) did not have this effect but rather suppressed development of keratoacanthomas, as did stage 3 MNNG or TPA. Primary lung tumors initiated in BALB/c mice by i.p. injection of urethane; and tumors of forestomach, lung, mammary, lymphoid and skin tissues caused in (C57BL/6 X DBA/2)F1 mice by oral DMBA were not markedly affected by NCM given in drinking water (1000-1800 ppm) until 14-16 months of age. These results confirm NCM's general lack of activity as an in vivo toxicant, but show that under certain circumstances it may enhance or suppress tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Metal-binding proteins of the Syrian hamster ovaries: apparent deficiency of metallothionein.

A deficiency of metallothionein, a high-affinity metal-binding protein thought to detoxify cadmium, has been observed in rat and mouse testes, tissues that are highly susceptible to the necrotizing and carcinogenic effects of cadmium. Like the testes, the ovaries undergo a hemorrhagic necrosis when exposed to cadmium, and female Syrian hamsters have recently been shown to be highly susceptible to cadmium. However, the nature of cadmium-binding proteins in the ovary is unknown; thus, this study was undertaken to define the nature of any such proteins in the Syrian hamster ovary. A low molecular weight (Mr) zinc- and cadmium-binding protein was detected in cytosol derived from the ovaries after gel filtration that eluted with a relative elution volume similar to authentic metallothionein. This protein was extractable by heat-treatment and sequential acetone precipitation. When such extracts were further purified with a reverse phase high performance liquid chromatography (HPLC) technique developed for the isolation of metallothionein isoforms, two forms were separated. However, neither of these could be classified as metallothionein on the basis of amino acid composition, since both were particularly low in cysteine, a very common amino acid in metallothionein. The ovarian protein also contained significant amounts of aromatic amino acids, unlike metallothionein--which is devoid of aromatics, and contained much more glutamate than metallothionein. Hamsters were also made resistant to cadmium-induced ovarian necrosis by zinc treatment. Such zinc treatment, however, did not alter levels of this protein, yet caused a marked induction of hepatic metallothionein. Likewise, cadmium treatment did not increase the levels of the ovarian metal-binding protein yet markedly induced hepatic metallothionein.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Aspergillus rhinitis in Wistar (Crl:(WI)BR) rats.

In two separate 24 month studies on the carcinogenic effect of single cadmium chloride injections in male Wistar (CRl:(WI)BR) rats, a total of 22% (129/597) of animals studied histologically were found to have chronic suppurative rhinitis caused by Aspergillus fumigatus. The diagnosis was based on characteristic conidial heads present in the sections, and positive methenamine-Grocott (GMS) staining of septate hyphae with dichotomous branching at angles of 45 degrees. Fungal hyphae balls, surrounded by a wall of neutrophilic granulocytes, were found in areas of the naso- and maxilloturbinates and occasionally caused complete blockage of the nasal passages. The underlying tissue showed an inflammatory response. In sections from 32 of the 129 cases (25% of the cases), epithelial necrosis and hemorrhage were indicative of fungal tissue invasion, but without dissemination to other organs. The infection rate was unaffected by the cadmium treatment or the location of rats in different cages. Positive antibody titers to Sendai and sialodacryoadenitis viruses suggested that transient inflammation of the upper respiratory tract rendered the mucosa susceptible to the fungal infection. The infection appeared to be sustained by growth around foreign bodies (hairs and plant material). Although focal squamous cell metaplasia of the respiratory epithelium with hyperplasia and hyperkeratosis occurred more frequently in rats with Aspergillus rhinitis, the incidence of tumors of the nasal cavities was not affected.

Animals↗
PubMed1987

Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats.

During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcomas) was diagnosed in 168 rats. Histologically, almost 90% of the rats in this study (henceforth referred to as Study I) showed some significant lesion at the tag site including various degrees of chronic inflammation, chondrous hyperplasia, and osseous metaplasia of the pinnal cartilage. In marked contrast, only two tumors were detected in 193 animals in a second study (Study II) in the same strain of rats, and only 56% of the rats had lesions at the tag site. A high incidence (greater than 25%) of clinically severe inflammation at the tag site was seen early in Study I and persisted during the first 6 mo of the study, while the incidence of such reactions in Study II was never more than 1%. Elemental analysis of the tags provided no explanation for the differences between the two studies, as tags used in both studies were of the same composition, predominantly nickel and copper. Metallic internal prostheses have induced local malignancies in humans and animals, and the present observations provide further evidence of the hazard posed by such devices at the site of prolonged contact with tissues. These findings suggest that a persistent tissue reaction may be an important factor in tumor development.

Alloys↗
PubMed1987

Serious infections caused by Bacillus species.

Thirty-eight patients with serious infections caused by organisms belonging to the genus Bacillus are described. Our experience, and that reported in the literature, indicates that, in most cases, isolated Bacillus bacteremia is not a particularly serious disease. Therefore, under most circumstances, empiric antibiotic therapy designed specifically for treatment of Bacillus is probably not necessary. Endocarditis can occur, but apparently follows bacteremia only infrequently. When these bacteria cause localized infection such as pneumonia, pan-ophthalmitis, visceral abscess, or musculoskeletal infections, tissue necrosis and profound morbidity are the rule. The frequency of these complications following bacteremia appears to be low but cannot be estimated from our experience or that reported in the literature reviewed. The role of intravascular devices and trauma as predisposing factors is emphasized. Immunocompromised hosts and intravenous drug abusers appear predisposed, but intravascular devices in the former group may play an important role in the pathogenesis of Bacillus infections. Antibiotics which appear especially useful in the treatment of Bacillus infections are clindamycin and vancomycin, to which the vast majority of strains are susceptible in vitro. Beta-lactam antibiotics, including the new cephalosporins and penicillins, are of little value in this setting.

Adult↗
PubMed1987

Spontaneous nonneoplastic gastric lesions in female Han:NMRI mice, and influence of food restriction throughout life.

A life span study of 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline, and 300 of a lean subline) was done to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. Major nonneoplastic lesions in the glandular stomach were erosions, ulcers and adenomatous hyperplasia of the fundus. Ulcers, ranging in incidence with ad libitum feeding from 5 to 9% and with food restriction from 13 to 34%, either occurred secondary to other diseases or were due to stress associated with food restriction, causing death mainly in the lean subline. Adenomatous hyperplasia was most common in the control group (41%); the frequency increased with age and was significantly reduced by food restriction. The etiology of adenomatous gastric hyperplasia is yet unknown. However, a lack of antiparietal cell antibodies, as determined by an immunofluorescent technique, indicates that an autoimmune disorder is not involved and an increase in antral gastrin cells, as determined by avidin-biotin peroxidase immunocytochemistry, suggests a hormonal involvement in pathogenesis.

Animals↗
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

Differences in the pattern of endogenous lectins from spontaneous rat mammary tumors.

Three spontaneously occurring rat mammary tumors, a fibroadenoma and two tubulopapillary adenocarcinomas, differing in their degree of histologic differentiation and malignancy, were investigated. They revealed significant differences in the pattern of carbohydrate-binding proteins with specificities for alpha- and beta-galactosyl, alpha-mannosyl, and alpha-fucosyl moieties, respectively. Analysis was performed by affinity chromatography on resins with immobilized sugars or glycoproteins and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The patterns were divided into categories according to the dependence of binding activity on the presence of Ca2+ and to dependence on extraction conditions. In comparison with both adenocarcinomas, the fibroadenoma contained alpha- and beta-galactoside-binding proteins at apparent molecular weights of 74,000 and 130,000. These proteins were not found in either adenocarcinoma. Comparison between the two adenocarcinomas revealed qualitative differences for all classes of carbohydrate-binding proteins under investigation. These differences between tumors of the same tumor class (mammary tumors) and tumor type (tubulopapillary adenocarcinoma) allow for the proposal that the pattern of endogenous carbohydrate-binding proteins may be potentially useful as a diagnostic marker.

Adenocarcinoma↗
PubMed1985

Vertebral osteomyelitis: assessment using MR.

Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, or histologic diagnoses. Based on the results of these latter studies, 23 patients were believed to have osteomyelitis. MR examinations consisted of at least a sagittal image (TE = 30 msec, TR = 0.5 sec) and an image obtained at TE = 120 msec, TR = 2-3 sec. All patients underwent radiographic and MR examinations, 36 underwent technetium 99m-HDP bone scanning, and 20 patients underwent gallium 67 scanning. Nineteen patients underwent both bone and gallium scanning. The imaging studies were reviewed independently by investigators blinded to the final diagnoses. MR had a sensitivity of 96%, specificity of 92%, and accuracy of 94%. Combined gallium and bone scan studies (19 cases) had a sensitivity of 90%, specificity of 100%, and accuracy of 94%. Bone scans alone had a sensitivity of 90%, specificity of 78%, and accuracy of 86%. Plain radiographs had a sensitivity of 82%, specificity of 57%, and accuracy of 73%. The MR appearance of vertebral osteomyelitis in this study was characteristic, and MR was as accurate and sensitive as radionuclide scanning in the detection of osteomyelitis.

Adult↗
PubMed1985

Non-neoplastic lesions of female virgin Han:NMRI mice, incidence and influence of food restriction throughout life span. I: Thyroid.

A life span study with 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline and 300 of a lean subline) was carried out to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. The major age-dependent non-neoplastic alteration of the thyroid was a cystic distension of the ultimobranchial bodies (up to 90% in the oldest age groups). Most of the severely cystic thyroids were found in animals of the fat sublines and development seemed to be slightly delayed by food restriction. The cyst walls were composed of ciliated and non-ciliated granular or highly attenuated cells. The cysts contained Alcian blue and periodic acid Schiff positive substances.

Age Factors↗
PubMed1985

Non-neoplastic lesions of female virgin Han:NMRI mice, incidence and influence of food restriction throughout life span. II: Respiratory tract.

A life-span study with 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline and 300 of a lean subline) was carried out to determine the occurrence of spontaneous diseases with ad libitum or restricted feeding. Rare non-neoplastic lesions of the lungs (1-8%) were secondary inflammations, focal ossification and subintimal arterial 'plaques'. More frequent were age-dependent pulmonary mineralizations similar to psammoma bodies (3-18%) and crystal formations (4-22%). Food restriction did not affect the incidence of these lesions directly. Crystals were observed furthermore within infoldings of the tracheobronchial mucosa and intra- as well as extracellularly in the nasal cavities.

Animal Feed↗
PubMed1985

Spontaneous urinary bladder tumors in DA/Han rats: a feasible model of human bladder cancer.

In a life-span study of virgin DA/Han inbred rats, 53.9% of the males and 14.4% of the females developed spontaneous urinary bladder tumors. A peak incidence was noted between the ages of 25 and 30 months. With the exception of 1 leiomyosarcoma, all neoplasms were of epithelial origin. After the papilloma, the majority of tumors were classified as transitional cell carcinoma of the papillary, solid, or mixed type. Less frequent were unclassified microcarcinoma, squamous cell, adenoid, and undifferentiated carcinomas. A sexual difference was found for almost every tumor type. Of the rats bearing tumors, 3.5% of the males and 64.4% of the females also were affected with urinary bladder stones. Squamous cell and glandular metaplasias of the tumors commonly were observed, and invasive growth into the bladder wall occurred frequently in less-differentiated tumors. Metastases were rare. The DA/Han rat strain is discussed as a suitable animal model for human urinary bladder cancer.

Age Factors↗