Conformal proton therapy for prostate carcinoma

The suppression of apoptosis may contribute to the carcinogenicity of the peroxisome proliferators (PPs), a class of non-genotoxic rodent hepatocarcinogens. Our previous work demonstrated that the PP nafenopin suppressed both spontaneous and transforming growth factor beta1 (TGFbeta1)-induced hepatocyte apoptosis both in vivo and in vitro. Here, we extend these observations by demonstrating the ability of nafenopin to suppress apoptosis induced by other major candidates for the signalling of cell death in the liver. Treatment of rat or mouse hepatocyte monolayers with TGFbeta1 or the DNA damaging drugs etoposide or hydroxyurea induced high levels of apoptosis. Western blot analysis did not support a role for either p53 or p21waf1 in etoposide-induced apoptosis in rat hepatocytes. Treatment of mouse hepatocytes with an agonistic anti-Fas antibody also resulted in an induction of high levels of apoptosis. Pre-addition and continued exposure to nafenopin suppressed apoptosis induced by all three stimuli. Overall, our studies demonstrate that the ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus. It is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways. However, it seems more likely that nafenopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism.     

Oceanic protection of prebiotic organic compounds from UV radiation

It is frequently stated that UV light would cause massive destruction of prebiotic organic compounds because of the absence of an ozone layer. The elevated UV flux of the early sun compounds this problem. This applies to organic compounds of both terrestrial and extraterrestrial origin. Attempts to deal with this problem generally involve atmospheric absorbers. We show here that prebiotic organic polymers as well as several inorganic compounds are sufficient to protect oceanic organic molecules from UV degradation. This aqueous protection is in addition to any atmospheric UV absorbers and should be a ubiquitous planetary phenomenon serving to increase the size of planetary habitable zones.     

Testing cord blood human chorionic gonadotropin as a surrogate marker for early identification of human immunodeficiency virus-1 infection in children

We measured human chorionic gonadotropin (hCG) in cord sera of 22 infants born to women infected with the human immunodeficiency virus-1 (HIV-1). hCG was also determined in cord sera from 173 infants born at a suburban hospital to HIV-1-seronegative women. The findings indicate that 16 (9%) of 173 HIV-1-seronegative samples had hCG levels greater than 90 IU/L (values were distributed as a Poisson curve). In contrast, 8 (36%) of the 22 infants born to HIV-1-infected women had hCG levels in excess of 90 IU/L, and 7 (88%) of these were shown to be HIV-infected. The remaining 14 infants born to HIV-1-infected women had low hCG levels, and 3 (21%) of the 14 had HIV infection. Mean follow-up time for HIV-uninfected infants was 17.5 months (range 9 months to 3 years). A statistically significant association between maternal-fetal HIV-1 transmission and hCG levels > or = 90 IU/L in cord sera was observed (p = 0.02). The difference between CD4 counts among mothers who transmitted HIV and those who did not was also statistically significant (p = 0.025). On the basis of this study's findings, we propose that cord blood hCG may serve as a surrogate marker for HIV-1 infection. Testing hCG levels in cord sera is an inexpensive and readily available screening test for early identification of infants at increased risk for getting HIV-1 from their mothers.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992

BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.     

Gastrointestinal tract symptoms and self-reported abuse: a population-based study

BACKGROUND/AIMS: A link between abuse and irritable bowel syndrome (IBS) has been reported in outpatients but remains controversial. No population-based studies have investigated this issue. The aim of this study was to determine the prevalence of abuse and its association with symptoms in a representative community sample. METHODS: An age- and sex-stratified random sample of residents of Olmsted County, Minnesota ranging in age from 30 to 49 years was mailed a valid self-report symptom questionnaire. Abuse was assessed by standard published criteria. RESULTS: Of the 919 responders (74%), the age-adjusted prevalence of any abuse was 41% in women and 11% in men, resulting in an age- and sex-adjusted prevalence of 26%. Symptoms of IBS, dyspepsia, and frequent heartburn were reported by 14%, 23%, and 12%, respectively. There was a significant association between IBS and sexual abuse, emotional or verbal abuse, and abuse in childhood and adulthood. Similarly, dyspepsia and heartburn were both significantly associated with abuse. In the population, 31% had visited a physician for gastrointestinal symptoms; the odds of visiting a physician were highest in those reporting abuse in adulthood and childhood. CONCLUSIONS: Self-reported abuse is common in middle-aged subjects; those who report abuse are more likely to have symptoms consistent with IBS, dyspepsia, or heartburn and to visit a physician for bowel symptoms.     

Determination of the in situ forces and force distribution within the human anterior cruciate ligament

The in situ forces and their distribution within the human anterior cruciate ligament (ACL) can clarify this ligament's role in the knee and help to resolve controversies regarding surgical treatment of ACL deficiency. We used a universal force-moment sensor (UFS) to determine the magnitude, direction, and point of application of the in situ forces in the ACL in intact human cadaveric knees. Unlike previous studies, this approach does not require surgical intervention, the attachment of mechanical devices to or near the ACL, or a priori assumptions about the direction of in situ force. Anterior tibial loads were applied to intact knees, which were limited to 1 degree of freedom at 30 degrees flexion. The in situ forces developed in the ACL were lower than the applied force for loads under 80 N, but larger for applied loads of more than 80 N. The direction of the force vector corresponded to that of the anteromedial (AM) portion of the ACL insertion on the tibial plateau. The point of force application was located in the posterior section of the anteromedial portion of the tibial insertion site. The anterior and posterior aspects of the anteromedial portion of the ACL supported 25% and 70% of the in situ force, respectively, with the remainder carried by the posterolateral portion. We believe that the data obtained with this new UFS methodology improves our understanding of the role of the ACL in knee function, and that this methodology can be easily extended to study the function of other ligaments.     

Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting

DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.     

Chemical constituents of Luffa cylindrica (L.) Roem

Six compounds were isolated from the fruits of Luffa cylindrica. They were identified as lucyosides C, E, F, H, a mixture of alpha-spinasterol and stigmasta-7,22,25-trien-3 beta-OH and a mixture of alpha-spinasteryl glucoside and delta 7,22,25-stigmasteryl-beta-D-glucoside by means of chemical evidence and spectral analysis.