Pb-Pb ages and initial Pb isotopic composition of lunar meteorites: NWA 773 clan, NWA 4734, and Dhofar 287.

Constraining the duration of magmatic activity on the Moon is essential to understand how the lunar mantle evolved chemically through time. Determining age and initial isotopic compositions of mafic lunar meteorites is a critical step in defining the periods of magmatic activity that occurred during the history of the Moon and to constrain the chemical characteristics of mantle components involved in the sources of the magmas. We have used the in situ Pb-Pb SIMS technique to investigate eight lunar gabbros and basalts, including six meteorites from the Northwest Africa (NWA) 773 clan (NWA 2727, NWA 2700, NWA 3333, NWA 2977, NWA 773, and NWA 3170), NWA 4734, and Dhofar 287A. These samples have been selected as there is no clear agreement on their age and they are all from the dominant low titanium chemical group. We have obtained ages of 2981 ± 12 Ma for NWA 4734 and 3208 ± 22 Ma for Dhofar 287. For the NWA 773 clan, four samples (the fine-grained basalt NWA 2727 and the three gabbros NWA 773, NWA 2977, NWA 3170) out of six yielded isochron-calculated ages that are identical within uncertainties and yielding an average age of 3086 ± 5 Ma. The age obtained for the fine-grained basalt NWA 2700 is not precise enough for comparison with the other samples. The gabbroic sample NWA 3333 yielded an age of 3038 ± 20 Ma suggesting that two distinct magmatic events may be recorded in the meteorites of the NWA 773 clan. The present study aims to identify and assess all potential issues that are associated with different ways to date lunar rocks using U-Pb-based methods. To achieve this, we have compared the new ages with the previously published data set. The entire age data set from lunar mafic meteorites was also screened to identify data showing analytical issues and evidence of resetting and terrestrial contamination. The data set combining the ages of mafic lunar meteorites and Apollo rocks suggests pulses of magmatic activity with two distinct phases between 3950 and 3575 Ma and between 3375 and 3075 Ma with the two phases separated by a gap of approximately 200 Ma. The evolution of the Pb initial ratios of the low-Ti mare basalts between approximately 3400 and 3100 Ma suggests that these rocks were progressively contaminated by a KREEP-like component.

CFD for wastewater treatment: an overview.

Computational fluid dynamics (CFD) is a rapidly emerging field in wastewater treatment (WWT), with application to almost all unit processes. This paper provides an overview of CFD applied to a wide range of unit processes in water and WWT from hydraulic elements like flow splitting to physical, chemical and biological processes like suspended growth nutrient removal and anaerobic digestion. The paper's focus is on articulating the state of practice and research and development needs. The level of CFD's capability varies between different process units, with a high frequency of application in the areas of final sedimentation, activated sludge basin modelling and disinfection, and greater needs in primary sedimentation and anaerobic digestion. While approaches are comprehensive, generally capable of incorporating non-Newtonian fluids, multiphase systems and biokinetics, they are not broad, and further work should be done to address the diversity of process designs. Many units have not been addressed to date. Further needs are identified throughout, but common requirements include improved particle aggregation and breakup (flocculation), and improved coupling of biology and hydraulics.

Effects of aerobic and resistance training on abdominal fat, apolipoproteins and high-sensitivity C-reactive protein in adolescents with obesity: the HEARTY randomized clinical trial.

OBJECTIVES: To investigate the effects of aerobic training, resistance training, or both on abdominal subcutaneous fat (subcutaneous adipose tissue (SAT)) (deep and superficial), visceral fat (visceral adipose tissue (VAT)), apolipoproteins A-1 and B (ApoA-1, ApoB), ApoB/ApoA-1 ratio and high-sensitivity C-reactive protein (HSCRP) in post-pubertal adolescents with obesity. PARTICIPANTS: After a 4-week supervised moderate-intensity exercise run-in period, 304 postpubertal adolescents with overweight (body mass index (BMI) ⩾85th percentile for age and sex+diabetes risk factor) or obesity (⩾95th BMI percentile) aged 14-18 years were randomized to four groups for 22 weeks (5 months): aerobic training, resistance training, combined training or a non-exercising control. METHODS: This study used a randomized controlled design. All groups received dietary counseling designed to promote healthy eating with a maximum daily energy deficit of 250 kcal. Abdominal fat (SAT and VAT) at the level of the fourth and fifth lumbar vertebrae (L4-L5) was measured by magnetic resonance imaging and ApoA-1, ApoB and HSCRP were measured after a 12-h fast at baseline and after 6 months. RESULTS: Changes in SAT at L4-L5 were -16.2 cm(2) in aerobic (P=0.04 vs control), -22.7 cm(2) in resistance (P=0.009 vs control) and -18.7 cm(2) in combined (P=0.02 vs control). Combined training reduced ApoB levels from 0.81±0.02 to 0.78±0.02 g l(-1) (P=0.04 vs control) and ApoB/ApoA-1 ratio from 0.67±0.02 to 0.64±0.02 (P=0.02 vs control and P=0.04 vs aerobic). There were no significant differences in VAT, ApoA-1 or HSCRP levels between groups. CONCLUSIONS: Aerobic and resistance training and their combination decreased abdominal SAT in adolescents with obesity. Combined training caused greater improvements in ApoB/ApoA-1 ratio compared with aerobic training alone.

Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.

Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.

Effectiveness of cold water immersion for treating exertional heat stress when immediate response is not possible.

Immediate treatment with cold water immersion (CWI) is the gold standard for exertional heatstroke. In the field, however, treatment is often delayed due to delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5 °C) delays of 5, 20, and 40 min on core cooling rates in eight exertionally heat-stressed (40.0 °C rectal temperature) individuals. We found that rectal temperature was elevated above baseline (P < 0.05) at the end of all delay periods (5 min: 40.08 ± 0.32; 20 min: 39.92 ± 0.40; 40 min: 39.57 ± 0.29 °C). Mean arterial pressure was reduced (P < 0.05) below baseline (92 ± 1.8 mm Hg) after all delay periods (5 min: 75 ± 2.6; 20 min: 74 ± 1.7; 40 min: 70 ± 2.1 mm Hg; P > 0.05). Rectal core cooling rates were similar among conditions (5 min: 0.20 ± 0.01; 20 min: 0.17 ± 0.02; 40 min: 0.17 ± 0.01 °C/min; P > 0.05). The rectal temperature afterdrop following CWI was similar across conditions (5 min: 35.95; 20 min: 35.61; 40 min: 35.87 °C; P > 0.05). We conclude that the effectiveness of 2 °C CWI as a treatment for exertional heat stress remains high even when applied with a delay of 40 min. Therefore, our results support that CWI is the most appropriate treatment for exertional heatstroke as it is capable of quickly reversing hyperthermia even when treatment is commenced with a significant delay.

Does type 1 diabetes alter post-exercise thermoregulatory and cardiovascular function in young adults?

Recent data demonstrated that individuals with type 1 diabetes mellitus (T1DM) exhibit impaired sweating and increased rectal temperature (i.e., heat storage) during exercise compared with healthy controls. Our purpose in this study was to investigate the consequences of T1DM on post-exercise thermal homeostasis. Sixteen participants (eight controls matched with eight T1DM) performed 90 min of cycling followed by 60 min of seated recovery. Esophageal and rectal temperatures, sweating (forearm, chest, and upper back), skin blood flow [forearm and upper back, presented as cutaneous vascular conductance (CVC)], and blood pressure [mean arterial pressure (MAP)] were measured at baseline and throughout recovery. Esophageal temperature was similar during baseline and recovery between groups (P = 0.88). However, rectal temperature was elevated in our T1DM group throughout recovery (P = 0.05). Sweating and CVC were similar between groups at all sites from 10-min post-exercise until the end of recovery (P ≥ 0.16). While absolute MAP was similar between groups (P = 0.43), the overall decrease in MAP post-exercise was greater in controls from 20 min (T1DM: - 8 ± 5 vs control: - 13 ± 6 mmHg, P = 0.03) until the end of recovery. We conclude that despite increased heat storage during exercise, individuals with T1DM exhibit a suppression in heat loss similar to their healthy counterparts during recovery.

The effect of propofol on patient reaction time and its relationship with loss of verbal contact before induction of anaesthesia.

Increasing the calculated plasma concentration of propofol has been shown to increase choice reaction time and visual and auditory response times. We studied the relationship of reaction to a vibrating handset as the effect-site target-controlled propofol concentration was incrementally increased in 20 patients during sedation, before induction of general anaesthesia. The reaction time increased, initially slowly and then more rapidly, as the calculated effect-site concentration of propofol increased, until the reaction to the vibrating handset was lost at a mean (SD) propofol effect-site concentration of 2.0 (0.6) µg.ml(-1) . The loss of response to verbal contact occurred at a propofol effect-site concentration of 2.4 (0.5) µg.ml(-1) . Reaction time may be of use clinically to warn of impending loss of verbal contact.

Patient-maintained propofol sedation using reaction time monitoring: a volunteer safety study.

Previous volunteer studies of an effect-site controlled, patient-maintained sedation system using propofol have demonstrated a risk of over-sedation. We have incorporated a reaction-time monitor into the handset of the patient-maintained sedation system to add an individualised patient-feedback mechanism. This study assessed if such reaction-time feedback modification would reduce the risk of over-sedation in 20 healthy volunteers deliberately attempting to over-administer themselves propofol. All the volunteers successfully sedated themselves without reaching any unsafe endpoints. All volunteers maintained verbal contact throughout, in accordance with the definition of conscious sedation. The mean (SD) lowest S(p) O(2) was 97 (1.7) % when breathing room air and no volunteer required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.7 (0.4) µg.ml(-1) . The present system was found to be safer than its predecessors, allowing conscious sedation, but preventing over-sedation.

Reaction time-monitored patient-maintained propofol sedation: a pilot study in oral surgery patients.

Previous volunteer studies of an effect-site controlled patient-maintained sedation system using propofol have demonstrated a risk of oversedation. We have incorporated a reaction time monitor into the handset to add an individualised patient-feedback mechanism. This pilot study assessed if the reaction time-feedback modification would prove safe and effective in 20 healthy patients receiving sedation while undergoing oral surgery. All patients successfully sedated themselves without reaching any unsafe endpoints. All 20 maintained verbal contact throughout. The mean (SD) lowest peripheral blood oxygen saturation was 98.0 (2.1)% breathing room air. No patient required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.6 (0.5) µg.ml(-1). The present system was found to be safe and effective, allowing oral surgery treatment under conscious sedation, but preventing oversedation.

A review of randomized controlled trials of aerobic exercise training on fitness and cardiometabolic risk factors in obese adolescents.

Aerobic training is the most prescribed exercise modality for the management of pediatric obesity. There is strong evidence that it decreases waist circumference, percent body fat and visceral fat, increases cardiorespiratory fitness, and decreases blood pressure in obese adolescents. However, the independent effects of aerobic exercise training on other cardiometabolic risk factors (ie, insulin resistance markers, plasma lipid levels, and inflammatory markers) are limited and yield inconsistent findings. Our article reviews randomized controlled trials evaluating the effects of aerobic exercise training on body composition, fitness, lipid levels, and insulin resistance in obese adolescents (aged 13-18 years) and outlines future research directions for this population.

Comparison of strength development with resistance training and combined exercise training in type 2 diabetes.

Resistance training has been shown to increase strength in type 2 diabetes; however, it is unclear if combining resistance and aerobic training (A + R) impedes strength development compared with resistance training only (R). The purpose of this study was to compare changes in strength with A + R vs R in individuals with type 2 diabetes. We evaluated monthly workload increments in participants from the Diabetes Aerobic and Resistance Exercise clinical trial. Muscular strength was assessed through training volumes and as the eight repetition maximum (8-RM) at 0, 3, and 6 months. Both groups increased their upper and lower body volumes monthly for 6 months. The relative increase in upper body workload in R was significantly greater than A + R at 4 months (161 ± 11% vs 127 ± 11%, P = 0.009) and at 6 months of training (177 ± 11% vs 132 ± 11%, P = 0.008). Both groups had improvements in 8-RM workloads at 3 and 6 months. The resistance training group had a significantly greater improvement in 8-RM on the leg press at 6 months compared with A + R (80 ± 11% vs 58 ± 8%, P = 0.045). Both R and A + R improved strength with a 6-month training program; however, increases in strength may be greater with resistance training alone compared with performing both aerobic and resistance training.

Mean arterial pressure following prolonged exercise in the heat: influence of training status and fluid replacement.

Prolonged exercise in the heat without fluid replacement represents a significant challenge to the regulation of mean arterial pressure (MAP). It is unknown, however, if MAP is equally challenged during the post-exercise period, and whether regular endurance exercise training can provide any benefit to its regulation. We examined MAP (Finometer) in eight trained (T) and eight untrained (UT) individuals prior to, and following, 120 min of cycling at 42 °C with (HYD) and without (DEHY) fluid replacement. Exercise during DEHY induced significant hyperthermia (T: 39.20 ± 0.52 °C vs UT: 38.70 ± 0.36 °C, P = 0.941) and body weight losses (T: 3.4 ± 1.2% vs UT: 2.7 ± 0.9%, P = 0.332), which did not differ between groups. Although MAP was equally reduced 5 min into the post-exercise period of DEHY (T: -20 ± 11 mmHg vs UT: -22 ± 13 mmHg, P = 0.800), its subsequent recovery was significantly different between groups (P = 0.037). While MAP returned to pre-exercise values in UT (-1 ± 3 mmHg), it remained reduced in T (-9 ± 3 mmHg, P = 0.028). No differences in MAP post-exercise were observed between groups during HYD. These data suggest that trained men exhibit a greater level of post-exercise hypotension following prolonged exercise in the heat without fluid replacement. Furthermore, fluid replacement reverses the sustained post-exercise hypotension observed in trained individuals.

Screening of anti-dengue activity in methanolic extracts of medicinal plants.

BACKGROUND: Dengue fever regardless of its serotypes has been the most prevalent arthropod-borne viral diseases among the world population. The development of a dengue vaccine is complicated by the antibody-dependent enhancement effect. Thus, the development of a plant-based antiviral preparation promises a more potential alternative in combating dengue disease. METHODS: Present studies investigated the antiviral effects of standardised methanolic extracts of Andrographis paniculata, Citrus limon, Cymbopogon citratus, Momordica charantia, Ocimum sanctum and Pelargonium citrosum on dengue virus serotype 1 (DENV-1). RESULTS: O. sanctum contained 88.6% of total flavonoids content, an amount that was the highest among all the six plants tested while the least was detected in M. charantia. In this study, the maximum non-toxic dose (MNTD) of the six medicinal plants was determined by testing the methanolic extracts against Vero E6 cells in vitro. Studies also determined that the MNTD of methanolic extract was in the decreasing order of M. charantia >C. limon >P. citrosum, O. sanctum >A. paniculata >C. citratus. Antiviral assay based on cytopathic effects (CPE) denoted by degree of inhibition upon treating DENV1-infected Vero E6 cells with MNTD of six medicinal plants showed that A. paniculata has the most antiviral inhibitory effects followed by M. charantia. These results were further verified with an in vitro inhibition assay using MTT, in which 113.0% and 98.0% of cell viability were recorded as opposed to 44.6% in DENV-1 infected cells. Although methanolic extracts of O. sanctum and C. citratus showed slight inhibition effect based on CPE, a significant inhibition was not reflected in MTT assay. Methanolic extracts of C. limon and P. citrosum did not prevent cytopathic effects or cell death from DENV-1. CONCLUSIONS: The methanol extracts of A. paniculata and M. charantia possess the ability of inhibiting the activity of DENV-1 in in vitro assays. Both of these plants are worth to be further investigated and might be advantageous as an alternative for dengue treatment.

Associations between physical fitness and HbA1(c) in type 2 diabetes mellitus.

AIM/HYPOTHESIS: In people with type 2 diabetes, exercise improves glucose control (as reflected in HbA1(c)) and physical fitness, but it is not clear to what extent these exercise-induced improvements are correlated with one another. We hypothesised that reductions in HbA1(c) would be related: (1) to increases in aerobic fitness and strength respectively in patients performing aerobic training or resistance training; and (2) to changes in strength and aerobic fitness in patients performing aerobic and resistance training. METHODS: We randomly allocated 251 type 2 diabetes patients to aerobic, resistance, or aerobic plus resistance training, or to a sedentary control group. Peak oxygen consumption VO2(peak), workload, treadmill time and ventilatory threshold measurements from maximal treadmill exercise testing were measured at baseline and 6 months. Muscular strength was measured as the maximum weight that could be lifted eight times on the leg press, bench press and seated row exercises. RESULTS: With aerobic training, significant associations were found between changes in both VO2(peak) (p = 0.040) and workload (p = 0.022), and changes in HbA1(c.) With combined training, improvements in VO2(peak) (p = 0.008), workload (p = 0.034) and ventilatory threshold (p = 0.003) were significantly associated with changes in HbA1(c.) Increases in strength on the seated row (p = 0.006) and in mid-thigh muscle cross-sectional area (p = 0.030) were significantly associated with changes in HbA1(c) after resistance exercise, whereas the association between increases in muscle cross-sectional area and HbA1(c) in participants doing aerobic plus resistance exercise (p = 0.059) was of borderline significance. CONCLUSIONS/INTERPRETATION: There appears to be a link between changes in fitness and HbA1(c). The improvements in cardiorespiratory fitness with aerobic training may be a better predictor of changes in HbA1(c) than improvements in strength.

Effects of aerobic exercise, resistance exercise or both, on patient-reported health status and well-being in type 2 diabetes mellitus: a randomised trial.

AIMS/HYPOTHESIS: The Diabetes Aerobic and Resistance Exercise (DARE) study showed that aerobic and resistance exercise training each improved glycaemic control and that a combination of both was superior to either type alone in patients with type 2 diabetes mellitus. Here we report effects on patient-reported health status and well-being in the DARE Trial. METHODS: We randomised 218 inactive participants with type 2 diabetes mellitus in parallel to 22 weeks of aerobic exercise (n = 51), resistance exercise (n = 58), combined aerobic and resistance exercise (n = 57) or no exercise (control; n = 52). Intervention allocation was managed by a central office. Outcomes included health status as assessed by the physical and mental component scores of the Medical Outcomes Trust Short-Form 36-item version (SF-36) and well-being as measured by the Well-Being Questionnaire 12-item version (WBQ-12); these were measured at the Ottawa Hospital. RESULTS: Using a p value of 0.0125 for statistical significance due to multiple comparisons, mixed model analyses indicated that resistance exercise led to clinically but not statistically significant improvements in the SF-36 physical component score compared with aerobic exercise (Delta = 2.7 points; p = 0.048) and control (i.e. no exercise; Delta = 3.3 points; p = 0.015). For mental component scores, there were clinically important improvements favouring no (control) compared with resistance (Delta = 7.6 points; p < 0.001) and combined (Delta = 7.2 points; p < 0.001) exercise. No effects on WBQ-12 scores were noted. Overall, 59/218 (27%) of participants included in this analysis sustained an adverse event during the course of the study, including 16 participants in the combined exercise group, 19 participants in the resistance exercise group, 16 participants in the aerobic exercise group, and eight participants in the control group. All participants were included in the intent-to-treat analyses. The trial is now closed to follow-up. CONCLUSIONS/INTERPRETATION: Resistance exercise was better than aerobic or no exercise for improving physical health status in these patients. No exercise was superior to resistance or combined exercise for improving mental health status. Well-being was unchanged by intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00195884 FUNDING: This study was funded by the Canadian Institutes of Health Research (grant MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant).

Edmonton Obesity Staging System for Pediatrics, quality of life and fitness in adolescents with obesity.

BACKGROUND: Body mass index (BMI) is often used to diagnose obesity in childhood and adolescence but has limitations as an index of obesity-related morbidity. The Edmonton Obesity Staging System for Pediatrics (EOSS-P) is a clinical staging system that uses weight-related comorbidities to determine health risk in paediatric populations. The purpose of this study was to investigate the associations of EOSS-P and BMI percentile with quality of life (QOL), cardiorespiratory fitness (CRF) and muscular strength in adolescents with obesity. METHODS: Participants were enrolled at baseline in the Healthy Eating, Aerobic and Resistance Training in Youth trial (BMI = 34.6 ± 4.5 kg m-2, age = 15.6 ± 1.4 years, N = 299). QOL, CRF (peak oxygen uptake, VO2peak) and muscular strength were assessed by the Pediatric QOL Inventory (PedsQL), indirect calorimetry during a maximal treadmill test and eight-repetition maximum bench and leg press tests, respectively. Participants were staged from 0 to 3 (absent to severe health risk) according to EOSS-P. Associations were assessed using age-adjusted and sex-adjusted general linear models. RESULTS: Quality of life decreased with increasing EOSS-P stages (p < 0.001). QOL was 75.7 ± 11.4 in stage 0/1, 69.1 ± 13.1 in stage 2 and 55.4 ± 13.0 in stage 3. BMI percentile was associated with VO2peak (ß = -0.044 mlO2 kg-1 min-1 per unit increase in BMI percentile, p < 0.001), bench press (ß = 0.832 kg per unit increase in BMI percentile, p = 0.029) and leg press (ß = 3.992 kg, p = 0.003). There were no significant differences in treadmill time or VO2peak between EOSS-P stages (p > 0.05). CONCLUSION: As EOSS-P stages increase, QOL decreases. BMI percentile was negatively associated with CRF and positively associated with muscular strength.

Understanding low adherence to an exercise program for adolescents with obesity: the HEARTY trial.

INTRODUCTION: Despite efforts to improve adherence to physical activity interventions in youth with obesity, low adherence and attrition remain areas of great concern. OBJECTIVE: The study was designed to determine which physiological and/or psychological factors predicted low adherence in adolescents with obesity enrolled in a 6-month exercise intervention study aimed to improve body composition. METHODS: Three hundred four adolescents with obesity aged 14-18 years who volunteered for the HEARTY (Healthy Eating Aerobic and Resistance Training in Youth) randomized controlled trial completed physiological (body mass index, waist circumference, per cent body fat, resting metabolic rate and aerobic fitness) and psychological (body image, mood, self-esteem and self-efficacy) measures. RESULTS: One hundred forty-one out of 228 (62%) randomized to exercise groups had low adherence (completed <70% of the prescribed four exercise sessions per week) to the intervention protocol. Logistic regression revealed that there were no baseline demographic or physiological variables that predicted low adherence in the participants. Appearance concern (a subscale of body image) (odds ratio [OR] 1.46, 95% confidence interval [CI]: 1.01, 2.1, P = 0.04), depressive mood (OR 1.12, 95% CI: 1.01, 1.23, P = 0.03) and confused mood (OR 1.16, 95% CI: 1.05, 1.27, P = 0.003) (two subscales of mood) were significant predictors of low adherence. CONCLUSIONS: Adolescents with obesity who had higher appearance concerns and depressive and confused moods were less likely to adhere to exercise. Body image and mood should be screened to identify adolescents who may be at high risk of poor adherence and who may need concurrent or treatment support to address these psychological issues to derive maximal health benefits from an exercise programme.

Identification of a tumor-associated antigen in cervical carcinoma by two dimensional (crossed) immunoelectrophoresis.

Two-dimensional immunoelectrophoresis was used to evaluate 8 cervical cancer speciments, 11 other gynecologic tumors, and 5 specimens of normal cervix. Antigens were water-soluble tissue extracts and antisera prepared in rabbits. When tested against antisera to cervical cancer, cancer antigens showed 14-17 precipitin lines whereas normal cervix showed 10-16. A single heavy heterogeneous precipitin line with an electrophoretic mobility of 0.58 relative to bovine albumin was observed in all cervical cancer specimens but not in normal cervical or other tumor specimens. Further evidence for the uniqueness of this antigen was sought by enhancement (addition of another antigen to the first phase of electrophoresis which increased the size of common peaks) and suppression (addition of another antiserum to the second phase, whereby the peak size of components to which both sera have antibody was decreased). The specific precipitin line was neither suppressed by the addition of antisera to normal tissue nor enhanced when normal tissue antigen was added to the tumor antigen preparation. More conclusively, adsorption of the tumor antiserum with normal tissue had no effect on the unique tumor-associated precipitin line, whereas all other precipitin lines were removed. This antigen was common to other cervical tumors because enhancement was demonstrated with three other cervical tumor specimens. The identification of a distinct and separate antigen associated with cervical carcinoma will permit further characterization and possible development of immunodiagnostic methods.

Dendritic cell-based immunotherapy of prostate cancer.

The immunotherapy of cancer, based on eliciting or enhancing the body's own capacity to mount an effective antitumor response, has produced encouraging early results in the areas of melanoma and renal-cell carcinoma. Such treatments utilizing dendritic cells (DC), immune cells that are excellent antigen presenters, are especially promising. We performed a phase I clinical trial assessing the administration of autologous DC pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) for the treatment of 51 men with hormone-refractory prostate cancer. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; group 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (group 4 and 5, respectively). No significant toxicity was observed. Immune reactivity against PSM-P2 was detected in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (group 4 and 5). An average decrease in PSA was observed only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. The excellent tolerance of this treatment approach, as well as the enhanced cellular responses, decreased PSA levels, and partial clinical responses in some patients suggests that it holds great potential in prostate cancer therapy.