Plasma concentration of Propionibacterium acnes antibodies and prostate cancer risk: results from an Australian population-based case-control study.

BACKGROUND: Recent studies in prostatic tissue suggest that Propionibacterium acnes (P. acnes), a bacterium associated with acne that normally lives on the skin, is the most prevalent bacterium in the prostate and in men with benign prostatic hyperplasia. Its prevalence is higher in samples from patients subsequently diagnosed with prostate cancer. The aim of our study was to test whether circulating levels of P. acnes antibodies are associated with prostate cancer risk and tumour characteristics using plasma samples from a population-based case-control study. METHODS: We measured plasma concentration of P. acnes antibodies for 809 cases and 584 controls using a recently developed ELISA assay. We compared antibody titres between cases and controls using unconditional logistic regression adjusted for batch and variables associated with the study design (i.e., age, year of selection and centre). The primary analysis included P. acnes titres in the model as a dichotomous variable using the median value for controls as the cut-off value. RESULTS: P. acnes antibody titres for both cases and controls ranged from 1 : 16 (i.e., low concentration) to 1 : 65,536 (i.e., high concentration; median value=1 : 1024). The odds ratio for prostate cancer associated with titres at or above the median value was 0.73 (95% CI 0.58-0.91, P=0.005). The association appeared to be particularly strong for advanced prostate cancer (AJCC Stage grouping III-IV) for which the odds ratio was 0.59 (95% CI 0.43-0.81, P=0.001) but there was insufficient evidence that the association differed by tumour stage (p heterogeneity=0.07). CONCLUSION: These results need to be confirmed in prospective studies but they are consistent with the hypothesis that P. acnes has a role in prostate cancer.

Esophageal motion during radiotherapy: quantification and margin implications.

The purpose was to evaluate interfraction and intrafraction esophageal motion in the right-left (RL) and anterior-posterior (AP) directions using computed tomography (CT) in esophageal cancer patients. Eight patients underwent CT simulation and CT-on-rails imaging before and after radiotherapy. Interfraction displacement was defined as differences between pretreatment and simulation images. Intrafraction displacement was defined as differences between pretreatment and posttreatment images. Images were fused using bone registries, adjusted to the carina. The mean, average of the absolute, and range of esophageal motion were calculated in the RL and AP directions, above and below the carina. Thirty-one CT image sets were obtained. The incidence of esophageal interfraction motion > or =5 mm was 24% and > or =10 mm was 3%; intrafraction motion > or =5 mm was 13% and > or =10 mm was 4%. The average RL motion was 1.8 +/- 5.1 mm, favoring leftward movement, and the average AP motion was 0.6 +/- 4.8 mm, favoring posterior movement. Average absolute motion was 4.2 mm or less in the RL and AP directions. Motion was greatest in the RL direction above the carina. Coverage of 95% of esophageal mobility requires 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margins. In all directions, the average of the absolute interfraction and intrafraction displacement was 4.2 mm or less. These results support a 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margin for internal target volume (ITV) and can guide margins for future intensity modulated radiation therapy (IMRT) trials to account for organ motion and set up error in three-dimensional planning.

Evidence for mediated protein uptake by amphibian oocyte nuclei.

The objective of this investigation was to determine whether there is mediated transport of endogenous proteins across the nuclear envelope. For this purpose, we studied the nuclear uptake of a 148,000-dalton Rana oocyte polypeptide (RN1) and compared its actual uptake rate with the rate that would be expected if RN1 crossed the envelope by simple diffusion through the nuclear pores. Nuclear uptake was studied in two ways: first, oocytes were incubated in L-[3H]leucine for 1 h and, at various intervals after labeling, the amount of 3H-RN1 present in the nucleoplasm was determined. Second, L-[3H]leucine-labeled nuclear extracts, containing RN1, were microinjected into the cytoplasm of nonlabeled cells, and the proportion of 3H-RN1 that subsequently entered the nucleus was measured. It was found that RN1 can readily penetrate the nuclear envelope; for example, after 6 h, approximately 36% of the newly synthesized RN1 and 17% of the injected RN1 had entered the nucleus. The diffusion rate through pores having a radius of 45 A was calculated for several possible molecular configurations of RN1. Using axial ratios of 34, 7.5, 2, and 1, the estimated times required to reach 63% of diffusion equilibrium are 757, 468, 6,940 h, and infinity, respectively. Even assuming an axial ratio of 7.5 (the most diffusive configuration) and an equilibrium distribution of 45, simple diffusion through the pores could account for only approximately 1/20 the observed nuclear uptake of RN1. This and other comparisons indicate that some form of mediated transport is involved in the nucleocytoplasmic exchange of this polypeptide.

A molecular defect in virally transformed muscle cells that cannot cluster acetylcholine receptors.

Muscle cells infected at the permissive temperature with temperature-sensitive mutants of Rous sarcoma virus and shifted to the non-permissive temperature form myotubes that are unable to cluster acetylcholine receptors (Anthony, D. T., S. M. Schuetze, and L. L. Rubin. 1984. Proc. Natl. Acad. Sci. USA. 81:2265-2269). Work described in this paper demonstrates that the virally-infected cells are missing a 37-kD peptide which reacts with an anti-tropomyosin antiserum. Using a monoclonal antibody specific for the missing peptide, we show that this tropomyosin is absent from fibroblasts and is distinct from smooth muscle tropomyosins. It is also different from the two previously identified striated muscle myofibrillar tropomyosins (alpha and beta). We suggest that, in normal muscle, this novel, non-myofibrillar, tropomyosin-like molecule is an important component of a cytoskeletal network necessary for cluster formation.

Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control.

Power spectrum analysis of heart rate fluctuations provides a quantitative noninvasive means of assessing the functioning of the short-term cardiovascular control systems. We show that sympathetic and parasympathetic nervous activity make frequency-specific contributions to the heart rate power spectrum, and that renin-angiotensin system activity strongly modulates the amplitude of the spectral peak located at 0.04 hertz. Our data therefore provide evidence that the renin-angiotensin system plays a significant role in short-term cardiovascular control in the time scale of seconds to minutes.

Ultrastructural localization and fluctuation in the level of the proliferating cell nuclear antigen and myc oncoproteins in synchronized neuroblastoma cells.

A method for rapid synchronization of neuroblastoma cells was developed using the thymidine block to arrest cells in the G1-S boundary. Following release from the thymidine block, cells traversed to G2-M in 7-8 h with 85% cell synchrony. Determination of the steady-state level of proliferating cell nuclear antigen (PCNA) mRNA and protein by Northern and Western blots revealed an accumulation of the PCNA messenger RNA transcripts and PCNA protein at G1-S and a rapid decrease when cells entered S phase. The level of both the messenger RNA transcripts and protein increased as the cells moved to late-S and G2-M. Similarly, the steady-state level of c-myc and N-myc messenger RNA transcripts and proteins increased during the G1-S block, decreased when the cells entered S, and increased as the cells moved through S phase to G2-M. However, immunofluorescence staining for PCNA and myc protein indicated a low level of staining for all three proteins at G1-S and a significant increase in staining intensity during S phase. Similarly, immunoelectron microscopy revealed low levels of N-myc and c-myc staining during G1-S and increased staining during mid-S and late S phase of the cell cycle. These results suggest differential cell cycle-dependent accessibility of myc protein and PCNA to staining in the intact cells compared to the whole cell extract. Furthermore, using immunofluorescence staining, confocal microscopy, and immunoelectron microscopy, we demonstrate for the first time that myc proteins are associated with the chromosomes during mitosis.

Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin.

A 36-year-old man being treated with cisplatinum, vinblastine, and bleomycin for testicular carcinoma developed a dense left homonymous hemianopsia, encephalopathy, and a partial nondominant parietal lobe syndrome. He subsequently had a resolution of all signs and symptoms, suggesting that these alarming events were a toxic but reversible side effect of the chemotherapy.

Avoidance response, house response, and wind responses of the sporangiophore of Phycomyces.

Avoidance response: An object placed 1 mm from the growing zone of a Phycomyces sporangiophore elicits a tropic response away from the object. The dependence of this response on the size of the object and its distance from the specimen is described, as well as measurements which exclude electric fields, electromagnetic radiation, temperature, and humidity as avoidance-mediating signals. This response is independent of the composition and surface properties of the object and of ambient light. House Response: A house of 0.5- to 10-cm diameter put over a sporangiophore elicits a transient growth response. Avoidance responses inside closed houses are slightly smaller than those in the open. Wind responses: A transverse wind elicits a tropic response into the wind, increasing with wind speed. A longitudinal wind, up or down, elicits a transient negative growth response to a step-up in wind speed, and vice versa. It is proposed that all of the effects listed involve wind sensing. This proposal is supported by measurements of aerodynamic effects of barriers and houses on random winds. The wind sensing is discussed in terms of the hypothesis that a gas is emitted by the growing zone (not water or any normal constituent of air), the concentration of which is modified by the winds and monitored by a chemical sensor. This model puts severe constraints on the physical properties of the gas.

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation.

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.

Beat to beat variability in cardiovascular variables: noise or music?

Cardiovascular variables such as heart rate, arterial blood pressure, stroke volume and the shape of electrocardiographic complexes all fluctuate on a beat to beat basis. These fluctuations have traditionally been ignored or, at best, treated as noise to be averaged out. The variability in cardiovascular signals reflects the homeodynamic interplay between perturbations to cardiovascular function and the dynamic response of the cardiovascular regulatory systems. Modern signal processing techniques provide a means of analyzing beat to beat fluctuations in cardiovascular signals, so as to permit a quantitative, noninvasive or minimally invasive method of assessing closed loop hemodynamic regulation and cardiac electrical stability. This method promises to provide a new approach to the clinical diagnosis and management of alterations in cardiovascular regulation and stability.

Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression.

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.

Mild hypovolemic stress alters autonomic modulation of heart rate.

In response to changes in central venous volume, changes in vagal efferent cardiac outflow have been demonstrated in animals but not in humans. In this study, frequency domains analysis was used to quantify modulation of heart rate by respiration and blood pressure in normal human adults undergoing mild central hypovolemic stress induced by blood donation and postural change. In supine subjects, blood donation caused no change in mean heart rate, pulse pressure, or in the variance of heart rate or blood pressure. There were small decreases in mean and systolic blood pressure. A significant decrease in vagal modulation of heart rate was seen in the 0.12-0.5-Hz frequency band, as measured by the change in the relation of lung volume to heart rate in this frequency band (-4.49 beats per minute [pbm] per liter [1], p < 0.001). Comparison of supine and tilt positions revealed marked changes in heart rate and blood pressure means and variances consistent with more pronounced decreases in intracardiac filling pressures and unloading of the arterial baroreceptors. A further progressive decrease in the vagal modulation of heart rate by lung volume was observed in the 0.12-0.5-Hz band, with a near-linear response of magnitude of respiratory sinus arrhythmia over a range of estimated central venous volume. Transfer function analysis can detect changes in autonomic response to mild degrees of central hypovolemia, which are insufficient to cause changes in mean heart rate or heart rate variance. This represents evidence for modulation of heart rate control by cardiopulmonary baroreceptors. A near-linear relation between magnitude of respiratory sinus arrhythmia and central venous volume suggests that this may have clinical relevance in patient monitoring.

Is dying being worked to death?

In recent years there has been a dramatic increase in the number of books and articles on death and dying. The ambivalence of some writers regarding the value of this proliferation of papers led the author to review and evaluate this literature; he found seven overlapping categories of death-related literature that were of both theoretical and practical value. He briefly explores possible reasons for the rise in this subject's popularity.

Race bias in the diagnosis and disposition of violent adolescents.

The authors compared psychiatric symptoms, violent behaviors, and medical histories of an entire one-year sample of adolescents from the same community who were sent either to the correctional school or the only state hospital adolescent psychiatric unit serving the area. The initial hypothesis that the incarcerated group would be equally disturbed but more violent than the hospitalized group was contradicted. Violence as well as severe psychiatric symptomatology was equally prominent in the two groups. The most powerful variables distinguishing the groups were race, accidents, and injuries (especially head injury), and sex. The medical and social implications of the findings are discussed.

Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive microenvironment.

The enteric system is formed by cells that migrate to the bowel from the neural crest. In order to gain insight into intraenteric factors that influence this migration, the colonization of the bowel of the ls/ls mouse was investigated. The terminal 2 mm of ls/ls intestine fails to become colonized by crest cells and thus remains aganglionic. The entire bowel of control mice and ls/ls mice was explanted before the appearance in situ of recognizable neurons and grown in organotypic tissue culture. Neurons, detected by the histochemical demonstration of acetylcholinesterase activity, developed throughout the length of the control gut, but, even in vitro, were excluded from the terminal segment of the ls/ls intestine. Co-culture experiments were done, in which primary and secondary sources of crest cells were combined with recipient segments of bowel, to test the ability of the recipient tissue to become colonized by neural precursors. The primary source was murine crest cells migrating away from an explant of the neuraxis. Secondary sources included avian and murine foregut (control and ls/ls) containing migratory crest cells as well as the quail ganglion of Remak. Recipient segments of bowel included control avian and murine hindgut, explanted before the tissue had become colonized by crest cells in situ, as well as the presumptive aganglionic bowel of ls/ls mice. Both primary and secondary sources of crest cells proved to be able to contribute neurons to the control segments of recipient hindgut. Species differences were no barrier to the colonization of the bowel in vitro. Moreover, the ls/ls foregut was as good a source of neural precursors for a normal recipient bowel, as was control avian or murine foregut. In contrast, none of the sources of crest cells that were utilized contributed neurons to the presumptive aganglionic gut of ls/ls mice. Both cells and processes of enteric neurons developing in vitro (detected by demonstrating neurofilament immunoreactivity) tended to be excluded from the presumptive aganglionic tissue. On the other hand, neurites, but not cell bodies, of dorsal root ganglia co-cultured with presumptive aganglionic ls/ls bowel did enter the abnormal zone. These data are consistent with the hypothesis that nonneuronal elements of the wall of the presumptive aganglionic region of the ls/ls gut are abnormal and prevent the colonization of this segment of the gut with viable neural precursors from the neural crest.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of age at introduction of complementary foods to breast-fed infants on duration of lactational amenorrhea in Honduran women.

Lactational amenorrhea (LA) is associated with postpartum infertility and is known to be related to breast-feeding frequency and duration, but the exact role of complementary feeding of the infant has not been clearly defined. Data on LA were collected during and after a 2-mo intervention trial in which low-income Honduran women who had breast-fed fully for 4 mo were randomly assigned to one of three groups: continued full breast-feeding until 6 mo (FBF, n = 50), introduction of complementary foods at 4 mo with ad libitum breast-feeding from 4 to 6 mo (SF, n = 47), or introduction of complementary foods at 4 mo with maintenance of baseline breast-feeding frequency from 4 to 6 mo (SF-M, n = 44). Women were followed up until the infant was 12 mo of age, or later if menses had not occurred by then. All but six of the women continued to breast-feed for > or = 12 mo. With the exclusion of those whose menses returned before 18 wk postpartum (which could not have been due to the intervention), the proportion of women who were amenorrheic at 6 mo was 64.5% in the SF group, 80.0% in the FBF group, and 85.7% in the SF-M group (chi-square test = 4.13, P = 0.02; one-tailed test with the latter two groups combined). The total duration of LA did not differ significantly among groups. The most significant determinant of LA was time spent breast-feeding (min/d), which was in turn negatively associated (P = 0.06) with the infant's energy intake from complementary foods in regression analyses. These results indicate that there is a significant effect of introducing foods at 4 mo on the likelihood of amenorrhea at 6 mo postpartum, but not thereafter, and that this effect is not seen in mothers who maintain breast-feeding frequency.

Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras.

BACKGROUND: The optimal age at which to introduce complementary foods is a topic of considerable debate. OBJECTIVE: This study was designed to evaluate this issue in a nutritionally vulnerable population in Honduras. DESIGN: Mothers of low-birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo, breast milk and total energy intake were measured for a nonrandom subsample (those who could stay overnight in a central unit: 32 EBF and 31 SF). RESULTS: At 4 mo, breast milk intake in the subsample was not significantly different between groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group (P < 0.005). Nonetheless, total energy intake (including solid foods) increased more from 4 to 6 mo in the SF than in the EBF group. However, there were no significant differences between groups in weight or length gain during the intervention or subsequently (6-12 mo). CONCLUSION: There was no growth advantage of complementary feeding of small-for-gestational-age, breast-fed infants between 4 and 6 mo of age.

Effects of age of introduction of complementary foods on iron status of breast-fed infants in Honduras.

To evaluate the effect of introducing complementary foods before 6 mo of age, we randomly assigned 164 infants who had been exclusively breast-fed for 4 mo to continue being exclusively breast-fed until 6 mo (EBF group) or to receive iron-fortified foods in addition to breast milk from 4 to 6 mo (BF+SF group). At 6 mo, the BF+SF group had higher mean iron intake (4 mg/d compared with 0.2 mg/d in EBF infants) and higher hemoglobin, hematocrit, and ferritin values than the EBF group (P < 0.05). The percentage with low hemoglobin (< 103 g/L) did not differ significantly between groups, but fewer infants in the BF+SF group had a low hematocrit (< 0.33; 21.4% compared with 32.0%, respectively; P < 0.05). The percentage of infants with ferritin concentrations < 12 microg/L at 6 mo was lower than the percentage with low hemoglobin or hematocrit, raising questions about the validity of the cutoffs at this age. Infants at greatest risk for anemia and low ferritin were those with birth weights < 2500 g; no infant with a birth weight > 3000 g had a low ferritin value at 6 mo. We conclude that the risk of iron deficiency is low among infants with birth weights > 3000 g who are exclusively breast-fed for 6 mo. Iron drops are recommended for low-birth-weight infants; for breast-fed infants with birth weights between 2500 and 3000 g, further research is needed to determine whether iron drops are more effective than complementary foods for preventing iron deficiency before 6 mo.

Maternal anthropometric status and lactation performance in a low-income Honduran population: evidence for the role of infants.

As part of a study on the optimal timing of complementary feeding in Honduras, we assessed breast milk volume and composition at 4, 5, and 6 mo in 141 low-income women who were randomly assigned to exclusively breast-feed for the first 6 mo or to complement breast milk with prepared solid foods beginning at 4 mo. Milk volume averaged 797 +/- 139 g/d at 4 mo. Maternal body mass index was positively associated with infant birth weight and milk energy density. In multivariate analyses in which group assignment was controlled for, milk volume was positively associated with birth weight but negatively associated with milk energy density. Infant breast milk energy intake was positively associated with birth weight and milk energy density. Maternal anthropometric status was not a significant predictor of milk volume or infant energy intake when birth weight and milk energy density were included in the models. These results indicate that infant characteristics, such as birth weight and the ability to self-regulate intake in response to milk energy density, mediate the relationship between maternal anthropometric status and lactation performance.

Precision, accuracy, and reliability of hemoglobin assessment with use of capillary blood.

BACKGROUND: Previous research has suggested that there may be significant within-subject variability, both site-to-site and over time, in hemoglobin concentrations in capillary blood. OBJECTIVE: This study examined the reliability of the portable hemoglobinometer (PHM) system with use of capillary blood and the implications of errors of the magnitude found for the classification of anemia status in individuals and population groups. The precision and accuracy of the method with use of venous blood were also tested. DESIGN: Three empirical data sets were used to measure reliability, precision, and accuracy of the PHM system [2 from Honduras (n = 87 and 141); 1 from Bangladesh (n = 73)]. Simulation data were used to assess the implications of errors for screening individuals for anemia and to estimate anemia prevalence. RESULTS: High within-subject variability (unreliability) was identified when capillary blood from the left hand was compared with that from the right hand (CV: 6.3%) and when measurements were taken on 4 consecutive days (CV: 7.0%). Reliability was only 69% and 50%, respectively. Precision and accuracy, however, were very high (concordance coefficients of 0.99 and 0.98 and CV < 1%). CONCLUSIONS: The simulation data showed that errors of the magnitude found due to unreliability can lead to misclassification of anemia status in individuals and small biases in anemia prevalence estimates. We recommend replicate sampling to reduce the influence of unreliability in the use of the PHM system with capillary blood.