Development of hamster tracheal epithelium: III. Illustration of statistical methods for proportional data in biology

The data in the two companion papers (McDowell et al., 1985a,b) are of a commonly occurring type in which the dependent variable takes on one of a small number of distinct values; we wish to compare the relative proportions in which these values occur. Student's test is inapplicable. We explain here in detail the linear logistic model that is appropriate, using our data as an example. Several reasonable models must first be fit. We did this by the maximum likelihood method, using a computer. We then used a chi 2 test to decide statistically between models. This process amounts to deciding directly which of the independent variables are important in determining the outcome, and thus it is the center of physiologic interest. The outcome depends on the initial choice of parametrization of the model. Generalizations are required in more complicated, but still commonly occurring, types of data.     

A case of interstitial deletion of 10q25.2----q26.1.

A de novo interstitial deletion of chromosome 10, del(10)(pter----q25.2::q26.1----qter), was detected in a newborn female with facial anomalies, failure to thrive, and subsequent developmental delay. This case is compared with 10 previous reports of monosomy 10q within the q25----qter region.     

Poliomyelitis in intraspinally inoculated poliovirus receptor transgenic mice

Mice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice.     

Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina

1. Whole-cell recordings have been obtained from intact, photoactive retinal neurons using patch-clamp electrodes in the amphibian superfused retina eyecup preparation. 2. After removal of the vitreous humor from the surface of the retina, using a collagenase with low tryptic activity, high-resistance seals (1-10 G omega) could be formed between the patch pipette and the cell membrane by applying mild suction to the pipette. Additional suction broke the membrane patch and provided continuity between the low-resistance pipette and the interior of the neuron. 3. Measurements of input resistance and time constant were obtained from bipolar, amacrine, and ganglion cells. Assuming the membrane capacitance was 1 microF/cm2, time constant data were used to derive the specific membrane resistance. The average specific membrane resistance for the inner retinal neurons in our sample was 68,000 omega.cm2. 4. Analysis of the charging curve induced by a brief current pulse applied to the soma was used to analyze the average electrotonic length of dendrites. The charging curves of some ganglion cells were well represented by a single exponential, suggesting that they were essentially isopotential. 5. The voltage decay along an equivalent cylinder model of a ganglion cell was calculated, using the experimentally obtained values of membrane resistance to compute decay of steady-state voltages along the dendritic tree. The calculations indicate that with the high membrane resistance values implied by this study, the electrotonic length of dendritic cables were short, and there may be relatively little attenuation of the synaptic potentials irrespective of their location along the dendritic tree.     

A strain gauge device for measuring feeding or drinking in laboratory rats

The details of mechanical construction and electronic circuitry of a strain gauge system for continuously measuring food and water ingestion in laboratory rats are described. The system has been reliably tested over a number of years. It is eminently suitable for investigating daily rhythms in rat feeding and drinking behavior, where a large volume of data is collected over extended periods of time.     

The effect of ambient temperature cycles upon circadian running and drinking activity in male and female laboratory rats

The effect of a cycle of warm and cool ambient temperature (Ta) upon the free-running circadian running and drinking rhythms of male and female laboratory rats was investigated. Rats free-running in constant darkness and constant cool Ta (21 degrees C +/- 2 degrees C) were exposed to a 12:12 cycle of high (34 degrees C +/- 2 degrees C) and cool (21 degrees C +/- 2 degrees C) Ta. Three male rats and one female rat entrained to the Ta cycle. Ten of 12 male and 9 of 11 female rats exhibited post-Ta cycle phases not predictable from pre-Ta cycle phases. Most rats exhibited positive and negative masking of activity during the Ta cycle. Activity periods shortened for all rats during the Ta cycle, and male free-running periods lengthened upon cessation of the Ta cycle to values significantly greater than precycle periods. It was concluded that Ta acts as a weak zeitgeber in laboratory rats and has greater effects on males compared to females.     

Use of hybridot assay to screen for BK and JC polyomaviruses in non-immunosuppressed patients.

Urine samples from 50 patients attending a genitourinary outpatient clinic and from 13 renal allograft recipients were investigated for evidence of infection with human BK and JC polyomaviruses using cytology and a new DNA hybridot assay. Forty four per cent of samples from the renal allograft recipients were positive by cytology and 75% by DNA hybridisation, indicating that hybridot assay is more sensitive than cytological screening. BK and JC viral DNA was found in 20% of the patients attending the genitourinary clinic, showing infection with BK virus and JC virus in a group of patients with clinical conditions not normally associated with immunological deficiency-a finding that has not been reported before.     

Terminal-Phase Chronic Myelogenous Leukemia: Approaches to Treatment

The prognosis of patients with CML has improved little in the past 50 years. The relatively benign chronic phase invariably deteriorates to a refractory and rapidly fatal terminal phase. This terminal stage has been found to have two major subtypes as defined by morphologic, cytochemical, immunologic, and enzymatic criteria--myeloblastoid and lymphoblastoid. Aggressive combination chemotherapy has achieved minimal improvement in survival once the terminal phase has begun, perhaps because only Ph1-positive stem cells remain to repopulate the marrow at this stage. Bone marrow transplantation has also been unsuccessful as therapy for the terminal phase, possibly because the patients are too debilitated to tolerate transplantation once the terminal phase has begun. Combination chemotherapy has been applied in an effort to eliminate the Ph1 chromosome-containing clone during the chronic phase. This goal has not yet been consistently achieved. Chemotherapy has also not been able to delay the onset of the terminal phase nor to prolong survival. Even in those patients in whom the Ph1 chromosome-containing clone has been eliminated, relapse to the chronic phase with return of the Ph1 chromosome has generally occurred within a brief period of time. Bone marrow transplantation during the chronic phase may hold the promise of true cure for CML, with permanent elimination of the malignant clone. However, the chronic phase can be unpredictably long and patients in the chronic phase often have few, if any symptoms. Therefore, there has been a reluctance to employ drastic therapy during the chronic phase. Techniques to predict the transformation to the terminal phase prior to overt morphologic or clinical conversion are now being developed. It may be possible in the future to attempt HLA-matched sibling donor bone marrow transplantation at the earliest signs of transformation from the chronic to the terminal phase. In this manner, optimal survival might be achieved by allowing patients to be maintained in the chronic phase for as long as possible prior to the initiation of aggressive therapy. Until this is routinely possible, continued research designed to improve the therapy of the terminal phase must be pursued. These attempts are likely to include the development and evaluation of new chemotherapeutic agents, novel methods of administration of existing drugs to better exploit their pharmacokinetics (for example, continuous infusion), and the utilization of newly described treatment approaches (such as the use of "differentiating" agents in an attempt to prevent progression to blastic transformation).(ABSTRACT TRUNCATED AT 400 WORDS)