Chemical and pharmacological studies of Phyllanthus caroliniensis in mice

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.     

Vasoactive intestinal peptide induces both tyrosine hydroxylase activity and tetrahydrobiopterin biosynthesis in PC12 cells

Spike transmission probability between pyramidal cells and interneurons in the CA1 pyramidal layer was investigated in the behaving rat by the simultaneous recording of neuronal ensembles. Population synchrony was strongest during sharp wave (SPW) bursts. However, the increase was three times larger for pyramidal cells than for interneurons. The contribution of single pyramidal cells to the discharge of interneurons was often large (up to 0.6 probability), as assessed by the presence of significant (<3 ms) peaks in the cross-correlogram. Complex-spike bursts were more effective than single spikes. Single cell contribution was higher between SPW bursts than during SPWs or theta activity. Hence, single pyramidal cells can reliably discharge interneurons, and the probability of spike transmission is behavior dependent.     

The meaning of equivocal pancreatic cytology in patients thought to have pancreatic cancer

INTRODUCTION: Fine needle aspirations (FNAs) and endoscopic retrograde cholangiopancreatography (ERCP)-guided brushings (BRUSH) are useful tools in the differentiation between malignant and benign disease of the pancreas. Once the decision to obtain a cytologic confirmation of one's clinical suspicion is made, the interpretation of the findings, especially an equivocal or negative cytology finding, can be unclear. This study seeks to evaluate the utility of cytologic studies in the evaluation of a patient with suspected pancreatic malignancy. METHODS: A retrospective review of 224 cytologic reports, including 174 FNAs and 50 BRUSHs, from all pancreatic FNAs and BRUSHs performed between January 1989 and June 1995, was performed. Subsequent confirmation of the cytologic diagnosis was made either by histologic or strict clinical criteria. RESULTS: Forty-three percent of the cytologic reports were read as malignant, all others reported as suspicious, atypical, or negative. All cytology studies read as malignant and all FNAs reported as suspicious were histologically or clinically confirmed to be malignant. Of those reported as atypical or negative, 55% and 49% were confirmed to be malignant. Both FNA and BRUSH were 100% specific, 75% sensitive, and 80% accurate. CONCLUSIONS: We conclude that a cytological diagnosis of malignant or suspicious is reliable and useful for further therapy planning in the patient suspected to have a pancreatic malignancy. The reason for the cytologic tests was a strong clinical suspicion, therefore, a high incidence of cancer was found in the patients with atypical or negative readings. A diagnosis of atypical or negative is equivocal and requires further diagnostic maneuvers, frequently including surgery, to make the definitive diagnosis.     

Ab initio calculation of electronic coupling in the photosynthetic reaction center

We have carried out an ab initio electronic structure calculations of electron transfer couplings between chromophores in the bacterial photosynthetic reaction center. The couplings agree remarkably well with parameters obtained from recent quantum dynamical modeling of experimental data assuming an explicit intermediate mechanism. We also have computed couplings on the M-side of the reaction center and have found that the interaction of the primary donor to the M-side intermediate bacteriochlorophyll is quite small because of destructive interference of the two localized coupling matrix elements. This may explain the slow rate of electron transfer down the M-side of the reaction center.     

A 32-bp deletion within the CCR5 locus protects against transmission of parenterally acquired human immunodeficiency virus but does not affect progression to AIDS-defining illness

The beta-chemokine receptor CCR5 is required as a coreceptor by non-syncytium-inducing (NSI) strains of human immunodeficiency virus type 1 (HIV-1). NSI viruses predominate early during an infection and are thought to be important for the transmission of HIV-1. The importance of CCR5 during parenteral transmission of HIV-1 was investigated. The distribution of the homozygous deleted CCR5 genotype among 566 exposed persons with hemophilia and 97 exposed transfusion recipients indicated that the lack of CCR5 expression protected persons from infection. This suggests that the initial predominance of NSI viruses during an infection does not result from limited availability of CXCR4-expressing cells within the mucosa but rather implies a more fundamental requisite for CCR5-expressing cells early during an infection regardless of the route of transmission. In addition, no difference in the rate of progression to AIDS (CDC 1987 definition) of infected heterozygous compared with homozygous wild type subjects was observed.     

A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice

Cancer complicating pregnancy is uncommon, with an incidence of approximately 1 in 1000 pregnancies. The obstetrician attending 250 deliveries per year would need to accumulate 40 years of clinical experience to encounter two to three cases of PABC. The increases in the size, weight, vascularity, and density of the breasts associated with pregnancy make the detection of mass lesions difficult both clinically and mammographically. Most of the benign lesions seen in pregnancy are the same ones seen in the nongravid state. Most cases of PABC present as painless masses, and as many as 90% of these masses are detected by breast self-examination. Women with PABC generally have more advanced disease with larger tumors, a higher percentage of inoperable lesions, and a higher percentage of nodal involvement. Because most PABC presents with a palpable mass, the role of imaging modalities in the evaluation of these patients remains limited. Fine-needle aspiration cytology is the initial procedure of choice for evaluating breast masses during pregnancy and lactation. Therapeutic abortion does not improve survival. The general principle is to treat the cancer and to allow the pregnancy to proceed. No studies have shown an adverse effect of a subsequent pregnancy even in patients with positive axillary nodes and patients in whom pregnancy occurs earlier than 2 years after treatment.     

Membrane fusion promoted by increasing surface densities of the paramyxovirus F and HN proteins: comparison of fusion reactions mediated by simian virus 5 F, human parainfluenza virus type 3 F, and influenza virus HA

The membrane fusion reaction promoted by the paramyxovirus simian virus 5 (SV5) and human parainfluenza virus type 3 (HPIV-3) fusion (F) proteins and hemagglutinin-neuraminidase (HN) proteins was characterized when the surface densities of F and HN were varied. Using a quantitative content mixing assay, it was found that the extent of SV5 F-mediated fusion was dependent on the surface density of the SV5 F protein but independent of the density of SV5 HN protein, indicating that HN serves only a binding function in the reaction. However, the extent of HPIV-3 F protein promoted fusion reaction was found to be dependent on surface density of HPIV-3 HN protein, suggesting that the HPIV-3 HN protein is a direct participant in the fusion reaction. Analysis of the kinetics of lipid mixing demonstrated that both initial rates and final extents of fusion increased with rising SV5 F protein surface densities, suggesting that multiple fusion pores can be active during SV5 F protein-promoted membrane fusion. Initial rates and extent of lipid mixing were also found to increase with increasing influenza virus hemagglutinin protein surface density, suggesting parallels between the mechanism of fusion promoted by these two viral fusion proteins.     

Effect of surgical panel composition on patient outcome at a level I trauma center

OBJECTIVE: To compare the effect of staffing with general surgeons vs trauma specialists on patient outcome at a trauma center. DESIGN: The care of injured patients at a level I urban trauma center serving a population of 2.5 million was the responsibility of 12 surgeons (10 general surgeons and 2 trauma specialists) between January 1 and June 30, 1996 (group 1). Between July 1 and December 31, 1996 (group 2), trauma was the responsibility solely of 4 trauma specialists. An additional comparison was made with those patients in group 1 who were admitted to the general surgeons (group 1A). The outcomes and quality of care for these periods, as determined by the quality assurance screens, were retrospectively analyzed and compared. SETTING: Urban, tertiary care, level I trauma center. PARTICIPANTS: Each trauma and burn patient admitted during the study periods is included in this study. Upon the patient's discharge from the hospital, specially trained nurses completed a review of the patient's stay and entered it into the TraumaOne database (Lancet Technology Inc, Cambridge, Mass). There were 693 trauma patients in group 1 (472 in group 1A) and 734 patients in group 2. MAIN OUTCOME MEASURES: Mortality, length of stay, and 16 quality assurance screens were quantified and compared using chi(2) analyses and t tests. RESULTS: The age and sex of the 2 groups were similar. The mortality rate was 6.2% (43/693) in group 1, 6.1% (29/472) in group 1A, and 6.5% (48/734) in group 2 (P = .80 and P = .78, respectively). When stratified by injury severity score (ISS), lengths of stay were statistically similar, except for patients with an ISS of 0 to 7. Patients with an ISS of 0 to 7 in groups 1 and 1A stayed a mean of 2.6 days, compared with 3.2 days for group 2 (P = .01 and P = .02, respectively). The results of quality assurance screens (missed injury, wound infection, readmission, and 13 others) were similar in the 2 groups. CONCLUSIONS: Transitions in staffing afforded the opportunity to examine patient outcomes by surgeon specialization and frequency of call. In our sample, 12 well-trained surgeons taking call less frequently managed a trauma service as efficiently as a group of 4 trauma specialists, without any differences in morbidity and mortality.