James W. Griffith

Histologic Development of the Sheath That Forms Around Long-Term Implanted Central Venous Catheters

BACKGROUND Chronically implanted catheters often become covered with a thin, white adherent covering of tissue that has been referred to as a fibrin sheath. This tissue often interferes with catheter function. METHODS To chronicle the development of this sheath, rats were implanted with silicone rubber central venous catheters. Five rats were euthanized at 3,7, and 60 days postimplantation so that gross necropsy and histology could be performed on the catheterized vessels. RESULTS The coating that developed around the external portion of the catheter started as a dark red thrombus containing fibrin and progressed into vascularized, fibrous connective tissue. CONCLUSIONS The translucent to white sheath that forms around chronically implanted catheters is not composed of fibrin and is therefore not likely to be dissolved by fibrinolytic agents such as urokinase, streptokinase, or tissue plasminogen activator.

Human melanoma metastasis is inhibited following ex vivo treatment with an antisense oligonucleotide to protein kinase C-α

To determine whether alteration of PKC alpha expression would affect the metastatic potential of human melanoma cells, replicate cultures of C8161 cells were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161 cultures were treated with a scrambled sequence ODN, cationic liposomes or were left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75% when ISIS-3521-treated cells were injected intravenously into athymic mice. These results show that PKC alpha expression is important in the regulation of human melanoma metastasis.

Spontaneous reproductive tract leiomyomas in aged guinea-pigs

Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47.6 months, and the mean age of the study population was 33.1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii.

Reproductive Failure Associated with Cystic Rete Ovarii in Guinea Pigs

Cystic ovaries were found at necropsy in 54 of 71 (76%) female guinea pigs between 18 and 60 months of age. Histologic appearance and location of the cysts within the ovary were consistent with cystic rete ovarii. Microscopic appearance of the large ovarian cysts suggested reproductive performance in these guinea pigs should be compromised. Breeding records indicated that fertility was markedly reduced in affected females over fifteen months of age. Cystic endometrial hyperplasia, mucometra, endometritis in appropriate placental tissue, or fibroleiomyomas were seen in 21 of 54 (39%) guinea pigs with cystic ovaries, but in only one of 17 (6%) guinea pigs without cystic ovaries.

Cilia-associated Respiratory (CAR) Bacillus Infection of Obese Mice:

Cilia-associated respiratory (CAR) bacillus was identified in respiratory tract lesions of obese mice dying of chronic respiratory disease. Neither Mycoplasma pulmonis nor pathogenic bacteria were isolated from cultures of the lesions at necropsy, but there was serologic and histologic evidence of respiratory virus infection. Cranial-ventral areas of lung were firm and demarcated from unaffected lung at gross examination, and representative tissue sank in water. Microscopically, there was suppurative bronchopneumonia with extensive peribronchiole lymphocyte and plasma cell proliferation. The affected bronchiole epithelium was covered with a sheet of slightly basophilic, filamentous, gram negative bacteria. Bronchioles with lesser amounts of lymphocyte accumulations contained lesser amounts of filamentous bacteria. Bronchioles without filamentous bacteria lining the respiratory epithelium lacked peribronchiole lymphocyte accumulations. There was a high correlation between CAR bacillus-positive serology and the identification of diagnostic histologic lesions. CAR bacillus was readily stained using immunohistochemical methods, and the ultrastructural features were similar to that described in rat infections.

Effects of α-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice

We have recently shown that administration of α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.

Cystitis, urolithiasis and cystic calculi in ageing guineapigs

Nineteen cases of cystitis were diagnosed at necropsy and/or by histology in a group of 170 (96 females, 74 males) guineapigs (11·2%). Seventeen of the 19 cases (89·4%) were females. The mean age of guineapigs with cystitis was 34·7 months, which was higher than the mean age of 24 months of the 170 members of the study group. In addition, 6 cases of urolithiasis and cystic calculi in 5 females and one male were also found in the 170 guineapigs (3·5%). The mean age of the 6 cases was 30 months, which was also higher than the mean age of the 170 animals. The study suggests that aged female guineapigs were much more predisposed to cystitis and urolithiasis or cystic calculi than male and young guineapigs. The cause may be related to infection with Escherichia coli and Staphylococcus sp, cystic calculi, diabetes mellitus and female guinea pig urogenital anatomy and function.

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Quantitative Trait Loci (QTL) analysis of longevity in C57BL/6J by DBA/2J (BXD) recombinant inbred mice

Background and aims: Genes associated with longevity have been identified using both single gene and genome-wide approaches in a variety of species. The aim of this study was to identify quantitative trait loci (QTLs) that influence longevity in male and female mice from twenty-three C57BL/6J by DBA/2J (BXD) recombinant inbred (RI) strains. Methods: Approximately 12 animals of each sex for each RI strain were maintained under standard conditions until natural death or moribundity criteria were met. Results: A number of life span-relevant loci previously reported on chromosomes (Chrs) 7,8, 10 and 11 were confirmed. In addition, 5 previously unre-ported QTLs for mouse life span on Chrs 1,2,6,11, and X were identified as significant and 3 QTLs on Chrs 5, 8, and 16 were suggestive. Conclusions: Several QTLs were coincident in males and females although the modest correlation between male and female median lifespans and the identification of sex specific QTLs provide evidence that the genetic architecture underlying longevity in the sexes may differ substantially. The identification of multiple QTLs for longevity will provide valuable resources for both reductionist and integrationist research into mechanisms of life span determination.

Osseous choristoma of the ciliary body in guinea pigs.

ronts have many organisms. The multinucleate meronts of References the organisms in the calf are distinct from Toxoplasma and Besnoitia, because the latter divided by endodyogeny (division into two). No species of Isospora has been known to develop in tissues of ruminants (cattle, sheep, goat^).^ Thus, by exclusion, the organism may be Eimeria, although sexual stages were not seen. Lesions in the present study were considered to be due to the coccidium because the infection was localized in the small bile ducts and protozoa were seen in lesions. Moreover, the hepatobiliary lesions were similar to those caused by Eimeria hiepei in mink3 and Eimeria stiedae in rabbits.’ Intestinal coccidiosis due to Eimeria is among the most common of parasitic infections of cattle, sheep, and goats.5 Although species of Eimeria occasionally invade the gallbladder of goats’ and mesenteric lymph nodes of sheep and goats,6 none have been reported to do so in cattle. The parasite of cattle in the present case was similar to that in the gallbladder of a goat, but sexual stages were not observed.