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PubMed1982

Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte.

In vivo primed T cells injected in the footpad of naive recipients elicit a typical delayed-type hypersensitivity (DTH) reaction in the presence of their specific antigen. The values of the footpad swelling obtained after these transfers show a clear distinction between negative and positive responses. Serial dilutions of primed T cell populations allow the establishment of titration curves by limiting dilution analysis according to Poisson distribution. The single hit titration curve indicates that a unique cell type underlies the DTH reaction. Furthermore, by using cloned T cells it can be demonstrated that the transfer of a single cell is able to initiate a DTH reaction. The revelation of T cell activity at unit level needs an optimal dose of antigen mixed with the sampled cells.

Animals↗
PubMed1978

Hereditary retinoblastoma: delayed mutation or host resistance?

Evidence is presented from the literature that there is little need to postulate delayed mutation for the retinoblastoma locus. Both penetrance and expressivity in the gene carrier can be defined as a variable determined by genetic and environmental factors, not by a Poisson distribution of tumors formed. Of individuals who received a new mutation from a healthy parent, approximately 13% do not manifest retinoblastoma, and the heritability of the host resistance is estimated at about 90%. The nonhereditary form of retinoblastoma may occur in the most susceptible group of the population.

Genes↗
PubMed1981

Descriptive statistics of swimming behavior of Schistosoma mansoni miracidia in artificial pond water.

Timed-exposure, dark-field photography was used to characterize the swimming behavior of Schistosoma mansoni miracidia in artificial pond water. Histograms and descriptive statistics were determined for helical swimming amplitude and wavelength, linear speed, turning frequency, and turning angle. Turning frequency could not be distinguished from a Poisson distribution so that turning appeared to occur randomly. Amplitude and wavelength showed no correlation. Faster miracidia exhibited less helical pattern while swimming. The effects of vertical movement of miracidia and of miracidial concentration were determined to be minimal.

Animals↗
PubMed1995

[Statistical study of workload at a birthing unit].

The work consists of a statistical study of the workload on a labour ward. This included a study of the admission/birth frequency and an investigation of the factors that influenced the process of admissions and the time spent on the ward. Also the relation between the number of midwives and women in labour present on the ward was investigated. It was found that the variation in the number of spontaneous admissions/births could be described reasonably well by a Poisson distribution. A simple statistical model was proposed to calculate the number of midwives necessary at any given birth frequency. For a specific choice of parameters the model fitted the actual distribution very well. The relative frequency of complications was highest for women with no previous births and smallest for women with one previous birth. The time spent on the labour ward depended significantly on the number of times the woman had given birth before and on whether the present delivery was complicated.

Delivery Rooms↗
PubMed1994

OmpA protein of Escherichia coli outer membrane occurs in open and closed channel forms.

OmpA protein of Escherichia coli outer membrane can produce diffusion channels when reconstituted into proteoliposomes (Sugawara, E., and Nikaido, H. (1992) J. Biol. Chem. 267, 2507-2511). The pore size is similar to that of the classical E. coli porins OmpF and OmpC, but the penetration rates of small solutes through the OmpA channel are about 50 times slower than that through the OmpF channel. Here we examined the possibility that only a small fraction of the OmpA molecules produces open channels. Unilamellar proteoliposomes were made so that each vesicle contained only a small number of OmpA molecules. These vesicles, containing 0.3 M urea within, were fractionated on a linear iso-osmolar density gradient made of urea and sucrose. This resulted in the clear separation of vesicles not containing any open channel, staying on top of the gradient, from those containing at least one open channel, sedimenting close to the bottom. Calculation using Poisson distribution indicated that only between 2 and 3% of the OmpA molecules contained open channel. The open form is estimated to allow the diffusion of L-arabinose at a rate comparable with that through the OmpF porin channel. The open and closed states were relatively stable properties of the protein. Denaturation of open form OmpA and its subsequent renaturation converted it into a nonfunctional or closed form, suggesting that the open and closed forms represent two alternative conformers of this protein.

Bacterial Outer Membrane Proteins↗
PubMed1995

Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma.

A major potential problem of autologous transplantation in the treatment of advanced malignancy is the infusion of tumor cells. A multi-institutional study of purified CD34-selected peripheral blood progenitor cell (PBPC) transplantation was conducted in 37 patients with advanced multiple myeloma receiving myeloablative chemotherapy. Fourteen days after intermediate-dose cyclophosphamide, prednisone, and granulocyte colony-stimulating factor (G-CSF), a median of 3 (range, 2 to 5) 10-L leukaphereses yielded 9.8 x 10(8)/kg (range, 3.7 to 28.3) mononuclear cells. The adsorbed (column-bound) fraction contained 5.9 x 10(6) cells/kg (range, 1.6 to 25.5) with 4.65 x 10(6) CD34 cells/kg (range, 1.2 to 23.3). Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity-determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg. After CD34 selection, residual tumor was detected in only three patients' products. Overall, a greater than 2.7- to 4.5-log reduction in contaminating multiple myeloma cells was achieved. CD34 PBPCs were infused 1 day after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg), and granulocyte-macrophage colony-stimulating factor was used until hematologic recovery. The median time to both neutrophil and platelet recovery was 12 days (range, 11 to 16 days and 9 to 52 days, respectively). The median number of erythrocyte and platelet transfusions was 7 (range, 2 to 37) and 3 (range, 0 to 85), respectively. Patients receiving fewer than 2 x 10(6) CD34 cells/kg had significantly prolonged neutropenia, thrombocytopenia, and an increased red blood cell and platelet transfusion requirement. Thus, CD34 selection of PBPCs markedly reduces tumor contamination in multiple myeloma and provides effective hematopoietic support for patients receiving myeloablative therapy.

Actuarial Analysis↗
PubMed1995

Correlation of therapeutic outcome in non-small cell lung cancer and DNA damage assayed by polymerase chain reaction in leukocytes damaged in vitro.

A pilot study was conducted in patients with advanced non-small cell lung cancer to examine whether the gene-specific damage in mononuclear cells (MNCs) incubated with cisplatin in vitro correlates with chemotherapeutic outcome in cisplatin-based chemotherapy. Twenty-one patients received cisplatin-based chemotherapy, consisting of cisplatin (80 mg/m2 i.v. on day 1), vindesine (3 mg/m2 i.v. on days 1 and 8), with or without mitomycin (8 mg/m2 i.v. on day 1). MNCs from peripheral blood were obtained from each patient before chemotherapy. The cells were incubated with cisplatin for 3 h in vitro and the 2.7-kb fragment of the hypoxanthine phosphoribosyltransferase gene was amplified by PCR for quantitation of DNA damage. There was a 4-fold interpatient variation in DNA damage in MNCs. Seven of 21 patients had a partial response to chemotherapy. When the dose of cisplatin required to reduce amplification of the hypoxanthine phosphoribosyltransferase sequence by 63% (D63 value) of MNCs was compared in each patient (defined by a Poisson distribution as the dose that produced an average of one lesion per single strand of the 2.7-kb fragment), the mean D63 value in patients showing a partial response (n = 7; 52 +/- 11 micrograms/ml) was significantly lower than that in patients showing no change (n = 10; 81 +/- 20 micrograms/ml; P = 0.0045) and in patients with disease progression (n = 4; 115 +/- 34 micrograms/ml; P = 0.0012). The mean D63 in patients with no change was also significantly lower than that in the patients with disease progression (P = 0.0386). Seven (70%) of 10 patients with a D63 value < 70 micrograms/ml were responders. No relationship was observed between the D63 values and hematological and nonhematological toxicities. It is suggested that DNA damage in MNCs incubated by cisplatin treatment in vitro in responders was greater than that in nonresponders. Gene-specific damage in MNCs from peripheral blood incubated with cisplatin in vitro assayed by PCR may predict the chemotherapeutic response in cisplatin-based chemotherapy for non-small cell lung cancer.

Adult↗
PubMed1995

Phenylketonuria in South Africa. A report on the status quo.

During the 1980s a pilot newborn screening programme for the early detection (and treatment) of amino acidopathies, especially phenylketonuria (PKU), was conducted by the Department of National Health and Population Development. The motivation for this pilot programme was the high priority accorded PKU screening in Europe and North America and the presumed similarly high incidence of this condition among South Africans of European origin. From a cohort of 59,600 newborns screened in the Pretoria area over a period of 8 consecutive years (1979-1986), only 1 case of PKU (and 1 of tyrosinaemia) was found. Statistically this result is compatible (Poisson distribution, 95% confidence interval) with a 'true' incidence of not more than 3/59,600 (or about 1/20,000) newborns. It is concluded from this result and other relevant information that newborn screening for PKU and other amino acidopathies is not cost-effective and justifiable, especially against the background of prevailing demographic conditions and more pressing health priorities in South Africa. This particular screening programme was discontinued in 1986. The results and conclusions are presented here for the record.

Cost-Benefit Analysis↗
PubMed1975

A measurement technique for cell adhesiveness.

Determination of the percentage of cells in clumps on a stained smear of human peripheral blood porvided a useful, accurate technique for measuring cell adhesiveness. Smears of human peripheral blood drawn with EDTA were prepared on a blood slide centrifuge, stained, and examined under a light microscope. Statistical analysis showed that the method resulted in a Poisson distribution of particles on the slide, where a particle was considered to be a simple cell, or two or more cells which appeared to be touching, Analysis of the distributions of erythrocytes and leukocytes showed that clumps were formed before the cells were deposited on the slide. When adhesiveness of erythrocytes or leukocytes was increased by incubation with antiserum to the corresponding cell type, the percentage of that cell type in clumps increased proportionately, Preliminary results using the method showed that normal human donors had similar to 1% of their erythrocytes and 1-5% of their leukocytes in clumps. In chronic myelocytic leukemia, as many as 60% of the leukocytes were in clumps.

Animals↗
PubMedDate not supplied

Action of dietary trypsin, pressed coffee oil, silymarin and iron salt on 1,2-dimethylhydrazine tumorigenesis by gavage.

Sprague-Dawley male rats, 24 days of age, were placed on diets based on a balanced ration as such and supplemented with Brazilian A rabica green coffee bean oil (0.10%), silymarin flavonolignans (0.10%), porcine trypsin (2429 mu/g ration) and ferrous sulfate (0.24% Fe) for a period of 32 weeks. A portion of the controls was switched to the iron salt diet at day 37 when 1,2-dimethylhydrazine was administered by gavage at a dosage of 20 mg/kg (base) and continued weekly for a total of 15 weeks. The colon and small intestinal adenocarcinoma numbers were determined for each group of rats surviving the carcinogen treatment and compared with the respective controls by a statistical design based on Poisson distribution. The results indicate that the adenocarcinoma frequencies of the colon, both total and occurrence in the proximal and distal portions were significantly decreased in the groups fed coffee oil, silymarin group and trypsin. The colon tumor numbers for the iron salt-fed were in the control range except for a decrement in the distal colon for rats on the diet from the start. Small intestinal adenocarcinoma scores with all supplemented diets did not differ significantly from the controls.

1,2-Dimethylhydrazine↗
PubMed1994

Consistency in nervous systems: trial-to-trial and animal-to-animal variations in the responses to repeated applications of a sensory stimulus in Aplysia.

What is the internal noise in a nervous system? We studied this question by determining the trial-to-trial consistency of the neuronal response in the abdominal ganglion of Aplysia californica. Because our voltage-sensitive dye recordings detected the spike activity from a large fraction of the neurons in the ganglion, these results provide a reasonably complete characterization of the consistency of the response to a sensory stimulus. The consistency of each neuron was evaluated by the number and timing of spikes in the response. The variability in the spike count was described using the coefficient of variation. The spike count variations follow a Poisson distribution, indicating that most of these variations were the result of a random process. For each neuron the reliability of the response to touch was measured in two ways; both measures indicated a broad distribution of reliabilities within the neuron population. The time of the maximum response also varied substantially in some animals. These timing variations were in part due to random processes and in part due to systematic effects (changes in activity of many neurons that were highly correlated). The time course of the activity of individual neurons was compared with the time course of the gill withdrawal. In some animals the activity of individual neurons was only poorly correlated with the behavior; in contrast, the summed activity of groups of neurons matched the behavior quite well. This implies that the behavioral output of the system may be a distributed combination of the activity of many neurons. The differences between animals were substantially larger than the trial-to-trial differences in one animal. The responses made by different preparations differed along many dimensions.

Action Potentials↗
PubMed1993

An index marker map of chromosome 9 provides strong evidence for positive interference.

An index marker map of chromosome 9 has been constructed using the Centre d'Etude du Polymorphisme Humain reference pedigrees. The map comprises 26 markers, with a maximum intermarker interval of 13.1 cM and only two intervals > 10 cM. Placement of all but one marker into the map was achieved with > 10,000:1 odds. The sex-equal length is 151 cM, with male length of 121 cM and female length of 185 cM. The map extends to within 2%-3% of physical length at the telomeres, and its coverage therefore is expected to be within 20-30 cM of full map length. The markers are all of the GT/CA repeat type and have average heterozygosity .77, with a range of .60-.89. The map shows both marked contraction of genetic distance relative to physical distance in the pericentromeric region and expansion in the telomeric regions. Genotypic data were carefully examined for errors by using the crossover routine of the program DATAMAN. Five new mutations were observed among 17,316 meiotic events examined. There were two double-crossover events occurring within an interval of 0-10 cM, and another eight were observed within an interval of 10-20 cM. Many of these could be due to additional mutational events in which one parental allele converted to the other by either gene conversion or random strand slippage. When there was no correction for these possible mutational events, the number of crossovers displayed by the maternal and paternal chromosomes was significantly different (P < .001) from that predicted by the Poisson distribution, which would be expected in the absence of interference. In addition, the observed crossover distribution for paternally derived chromosomes was similar to that predicted from cytogenetic chiasma frequency observations. In all, the data strongly support the occurrence of strong positive interference on human chromosome 9 and suggest that flanking markers at an interval of < or = 20 cM are generally sufficient for disease gene inheritance predictions in presymptomatic genetic counseling by linkage analysis.

Base Sequence↗
PubMed1993

Differential binding of acapsulate and encapsulated strains of Cryptococcus neoformans to human neutrophils.

Investigations into mechanisms of binding of encapsulated and acapsulate strains of Cryptococcus neoformans by human neutrophils were performed, using a monolayer assay. The two strains bound to neutrophils by different mechanisms although both had an absolute requirement for opsonization with complement components in normal human serum for binding to occur. Neutrophil binding of encapsulated yeasts required conformational changes in actin yet did not appear to lead to phagocytosis of the organism. A maximum of 12 acapsulate cells bound per neutrophil compared with only four encapsulated yeasts. Cytochalasin D treatment reduced the maximum numbers able to bind per neutrophil by 50%. The encapsulated cryptococci appeared to compete with each other for binding to neutrophils whereas the acapsulate yeast cells bound to neutrophils in an approximately Poisson distribution, suggesting independent binding. Binding of acapsulate cryptococci did not require actin filaments and appeared to trigger phagocytosis. Thus, the capsule of C. neoformans appeared to inhibit binding and internalization by neutrophils.

Actins↗
PubMed1995

Experimental evidence for the binemic structure of human chromosomes.

A binemic model of eukaryotyc chromosome was tested using PCR-amplification of some unique genes in individual sperm cells or in human DNA diluted to 1/2 of the DNA amount of a haploid cell. According to the model, all the hereditary information, including all the unique genes, is represented twice in the haploid genome. Backing up of information enhances reliability of the genome by several orders of magnitude. Hemoglobin G gene (HBG2) and parathyroid hormone gene (PTH) were studied. In the first experimental plot the DNA from one isolated spermatozoon was divided into 4 parts and G globin gene was attempted to be amplified in all 4 tubes. According to the binemic model the simultaneous positive reaction in a pair of tubes should occur in up to 75% of cases and the reaction in only one tube from the four should occur in the case of uninemy. In the second approach, human DNA was serially deluted to the 1/2 of the haploid genome per tube. After amplification, the number of tubes with positive signal were counted. According to the unineme model, 3.7 positive reactions from 10 were expected. According to the bineme model 6.3 positive reactions from 10 should be observed (as follows from Poisson distribution). The results obtained with both methods are in accordance with binemic model and are inconsistent with uninemy.

Base Sequence↗
PubMedDate not supplied

[Unusual attendance at Hospital Emergency Services for asthma and chronic obstructive pulmonary disease and SO2 air pollution in Cartagena (Spain)].

BACKGROUND: The objective of this investigation is to determine the influence of air pollution (SO2 and particulate matter) on the existence of days of unusual attendance at emergency services for asthma and chronic obstructive pulmonary lung disease (COPD). A registry of attendances for these diseases and the daily mean concentrations of SO2 and particles were used (1989-1991). RESULTS: Unusual attendance days are establish by the fortnightly movable mean of the period that has that day as central one, under the hypothesis of a Poisson distribution with equal mean as the calculated one. In the logistic regression model, Odds Ratio (OR) between an excess of attendance of cases for asthma and SO2 levels greater than 80.60 m/m3 was 3.6 (CI95%: 1.1-11.7). For COPD, SO levels ten days before were introduced, and OR for SO2 levels more than 56.5m/m was 4.7 (CI95%: 1.5-15.1). CONCLUSIONS: High SO2 levels are related with the appearances of days with an excessive use of emergencies for Asma and EPOC.

Air Pollution↗
PubMed1996

Dynamics of ethanol-induced transmitter packet release in the frog neuromuscular junction.

Intervals of spontaneous miniature endplate potentials (MEPPs) are usually thought to follow random kinetics because number vs. interval size plots can fit a Poisson distribution such that the largest number of intervals are found in the smallest interval bin. Even though several studies report that MEPPs have a tendency to clump together, an alternative dynamic has not gained acceptance. We found that spontaneous MEPP interval plots with commonly used bin sizes (10 ms or larger) from muscle fibers of diameters usually studied (20 microns) also skew to the smallest interval bin. In order to study very small junctions which do not generate enough intervals for a detailed analysis of high resolving power (small bin width) at normal frequencies of 0.05 MEPPs/s we increased MEPP frequencies with ethanol to obtain large samples. Ethanol accentuated the normal clustering of MEPPs and number vs. interval plots of 0.5 ms show periodic peaks at 400 Hz. A periodogram of power vs. frequency also showed a preferred frequency of 400 Hz. The first peak indicates a refractory period and the 400 Hz oscillation demonstrates that MEPPs are not independent. A release channel with a rhythmical nature is discussed as a possible molecular process which generates clusters of MEPPs.

Animals↗
PubMed1996

Validation of retroviral detection for rodent cell-derived products and gene therapy applications.

The availability of sensitive assays for detecting infectious murine retroviruses has become critical for the development and acceptance of a number of biopharmaceuticals, including monoclonal antibody-derived products and gene therapy vectors. Comparative studies demonstrated that the PG4 S+L- retrovirus infectivity test routinely yields higher titres than the mink cell test for xenotropic, amphotrophic and MCF murine retroviruses. A validation study for the PG4 S+L- assay demonstrated very good linearity (r2 of 0.95 to 0.99), reproducibility within a study (+/-0.35 log10 units), and precision between tests (+/-0.45 log10 units). Interference (or selectivity) in the presence of a non-specific antibody was insignificant (less than 0.2 log10 units). Sensitivity levels established from measurements as virus titres approach zero demonstrated a threshold value of 2-3 focus forming units (FFU)/ml. Two methods for increasing assay sensitivity were used including: (i) increased product samplings combined with a Poisson distribution analysis, and (ii) a 14-day co-cultivation with Mus dunni cells. Each of these methods was shown to increase sensitivity by at least one log10 unit. Murine retroviruses may also be detected by a less sensitive immunofluorescence assay (IFA) using specific monoclonal antibodies; this assay is essential for detecting certain recombinant ecotropic MuLVs. In summary, murine retroviral detection ranked by sensitivity is mink S+L- < IFA with monoclonal antibodies < PG4 S+L- < Mus dunni co-cultivation followed by PG4 S+L-.

Animals↗
PubMed1997

[Statistic tests concerning population mortality indicators].

The objective of this note is to present simple statistical tests applied to common comparison problems met in descriptive studies in the general population. These tests apply to classical mortality indicators: crude and specific death rates, standardized rates (direct and indirect methods). The tests are based on the convergence of the Poisson distribution towards the normal distribution. For each type of comparison, confidence intervals are also provided.

Adult↗