Tumor necrosis factor alpha interferes with the cell cycle of normal and papillomavirus-immortalized human keratinocytes

We have shown that normal and human papillomavirus (HPV) type 16 immortalized human foreskin keratinocytes are growth inhibited by tumor necrosis factor alpha (TNF-alpha), whereas HPV-18- and SV40-immortalized keratinocytes are resistant to this cytokine (1). In this report, we investigated the expression of mitotic regulatory proteins, such as cyclin A, cyclin B, and p34cdc2. After exposure to TNF-alpha, normal and HPV-16-immortalized cells exhibited a dramatic decrease in the expression of these proteins. In contrast, no alteration in the levels of these proteins was observed after treatment of the resistant cell lines, as well as two HPV-positive cervical carcinoma cell lines. Expression of cyclin E does not seem to be modulated by TNF-alpha in any of the cells tested. On the other hand, cyclin D1, expression is slightly increased in normal keratinocytes and in the HPV-16-immortalized cells, whereas no alteration was observed in the HPV-18-transfected cells. The phosphorylation state of pRb correlated with cell growth; sensitive cells, which accumulate in G0-G1, after exposure to TNF-alpha, exhibited an accumulation of hypophosphorylated pRb, whereas no effect on pRb phosphorylation was observed for HPV-18-immortalized cells. These results clearly correlate with TNF-alpha-induced growth arrest in G0-G1.     

Experimental determination of NH<Subscript>4</Subscript>NO<Subscript>3</Subscript>-KNO<Subscript>3</Subscript> binary phase diagram

The solid-state phase transitions in ammonium nitrate (AN)-potassium nitrate (KN) system, and the equilibrium AN-KN phase diagram have been determined by using differential scanning calorimetry and high-temperature in situ x-ray diffractometry. Sample preparation was performed in a special “dry room” with very low humidity. A single phase region (AN III) with no phase transitions to 373 K was observed in the composition range 5 to 20% KN; this is critical for use in air bag gas generators. The high-temperature KN phase (KN I) has a wide range of stability from 20 to 100 wt.% KN. There are one eutectic, two eutectoid, three peritectoid, and one congruent transformations in this phase diagram. Two new nonstoichiometric phases were found at lower temperatures in the mid-composition range between the AN and KN terminal solid solutions. Details of the phase equilibria are presented.     

Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990

Cytomegalovirus (CMV) is the leading cause of congenital viral infection in the United States. To prevent damaging congenital CMV infections, it is necessary to have accurate population estimates of prevalence and to identify maternal factors associated with an elevated risk of congenital infection in the newborn. From 1980 through 1990, 17,163 offspring of predominantly low-income nonwhite women who delivered at a public hospital and 9892 newborns of predominantly mid- to upper-income white women who delivered at a private hospital were screened for congenital CMV infection. Women < 20 years old (adjusted prevalence odds ratio [POR], 4.8; 95% confidence interval [CI], 2.6-8.9) at the public hospital and all nonwhite women (adjusted POR, 1.6; 95% CI, 1.1-2.2) had an increased risk of delivering an infected newborn. Newborns of adolescent women in both populations had the highest prevalence of clinically apparent infection. Offspring of nonwhite low-income adolescents are at greatest risk for congenital CMV infection and more damaging sequelae.     

Predicting compliance with annual follow-up evaluations in persons with spinal cord injury

In this study a representative sample of German acute care hospitals is used to describe the effects of dementia within acute care hospitals. Data from hospital patients above age 60 with the diagnosis dementia (ICD 290, 293, 294 and 310), collected over an observation period of 12 years, are compared with nondemented hospital patients at the same ages. The differences in the average length of stay between demented and nondemented patients are only relatively small in German acute care hospitals. The degree of multimorbidity is higher and hospital infections are more frequent for demented patients. The main differences occur with mortality: demented inpatients of both sexes experience a hospital mortality which is about twice as high as for nondemented patients at the same ages.     

Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users

Seven cardiac electrophysiology stimulators from four manufacturers (Biotronik, Bloom, Digitimer and Medtronic) in common current use are reviewed. The stimulators differ in the features provided and the design adopted to achieve these features. The number of output channels ranges from one to four, the number of extra-stimuli available ranges from two to six, and these can be delivered as a variety of sequences. Some of the stimulators (Digitimer and Bloom) are modular while others (Biotronik and Medtronic 532 series) are of an integrated design comprising a single physical unit. The design of the Medtronic EP-2 has both integrated and modular characteristics. The features of the stimulators associated with input, output, control and the user interface are specifically reviewed. The features are also compared against the published recommendations of the American Heart Association. In addition, a summary of stimulator user comments from a number of electrophysiology centres is presented. All of the stimulators fulfil, or are close to fulfilling, basic electrophysiological requirements, but some provide more complex facilities such as would be required by specialist centres.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition

OBJECTIVE: The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA: The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. METHODS: Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. RESULTS: Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. CONCLUSIONS: Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.