Approximate case influence for the proportional hazards regression model with censored data.

A method is presented for approximating the influence of individual cases upon regression coefficient estimates obtained from the Cox proportional hazards model. Observations can thus be identified which may greatly influence statistical inferences regarding the effects of prognostic factors upon survival time. An example from a cancer clinical trial is given.

Response of mouse spermatogonial stem cells to X-ray induction of heritable reciprocal translocations.

Although heritable translocations are an important endpoint for the assessment of genetic risk from radiation, there has been a serious information gap with regard to their induction in spermatogonial stem cells, the most important cell stage in males for risk considerations. This led to uncertainty in estimating the magnitude of risk per unit exposure. Further, the relationship between the frequency of reciprocal exchanges scored by cytological analysis of the exposed male's meiocytes and the frequency of those transmitted to first-generation offspring needed to be re-examined.

Patient-oriented performance measures of diagnostic tests. 3. U-Factor.

When a clinician is faced with the problem of deciding whether to order a specific diagnostic test, the ideal information would be the utility of the "perform test" branch of the decision tree versus the utility of the "do not perform test" branch. This difference in utility is termed the Expected Utility of the Test ( EUT ). We propose a new performance measure of a test called the U-Factor (UF) which is related to EUT by a simple formula.

Patient-oriented performance measures of diagnostic tests. 2. Assignment potential and assignment strength.

Assignment Potential (AP) is a performance measure of a diagnostic test, characterizing the chance that, as a consequence of performing the test, the probability of disease will exceed a decision threshold, thereby permitting a management action to be taken. Another performance measure, Assignment Strength (AS) characterizes the average extent to which a decision threshold will be exceeded when the post-test probability of disease does exceed the threshold. Both AP and AS are functions of prior probability of disease and decision threshold, and can be represented as two-dimensional contour maps indicating their behavior throughout the entire probability and threshold space.

A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection.

The time course of hepatic zinc-isometallothionein synthesis was studied in the regenerating liver and compared with that produced after the parenteral injection of zinc (6 mg of Zn2+/kg). In the regenerating liver, zinc levels rose rapidly after partial hepatectomy and reached a maximum at approx. 14h before declining to approximately normal levels at 48h post-operation.

Patient-oriented performance measures of diagnostic tests. 1. Tools for prospective evaluation of test order decisions.

Prospective assessment of a test for possible use in evaluation of a patient ideally should be based on the test's ability to affect subsequent patient management beneficially, in relation to both the costs of the test itself and the costs of misclassification of disease status. This requires specification of the costs and benefits of subsequent actions and the cost of the test, estimation of the probability of disease, knowledge of the discriminatory properties of the test, and formal decision analysis. Often, however, the physician has less complete information with which to make a test order decision.

Analysis of survival by tumor response.

The common practice of comparing the survival of responders and nonresponders when reporting the results of cancer chemotherapy treatment is investigated. The usual method of comparing responders and nonresponders is biased in favor of responders, and these results are frequently misinterpreted as providing evidence that response prolongs survival, or that the treatment under study is effective. Two valid methods for comparing responders and nonresponders are discussed and recommendations are made concerning the analysis of survival by response.

Cadmium-metallothionein-induced nephropathy: a morphological and autoradiographic study of cadmium distribution, the development of tubular damage and subsequent cell regeneration.

A single intravenous dose of 0.8 mg thionein-bound cadmium (Cd) per kg body weight, as the isolated (Cd, Zn)-metallothionein (MT) from rat liver, in rats of the same strain is nephrotoxic, but not lethal. Apical vesiculation in epithelial cells of the renal proximal convoluted tubules is apparent within 1 h of dosing and, by 4 h, is extensive in some of these cells that surround the larger arteries in the cortex.

The identification and characterization of two separate carboxylesterases in guinea-pig serum.

The esterase activity of guinea-pig serum was investigated. A 3-fold purification was achieved by removing the serum albumin by Blue Sepharose CL-6B affinity chromatography. The partially purified enzyme preparation had carboxylesterase and cholinesterase activities of 1.

88MHz 113Cd-n.m.r. studies of native rat liver metallothioneins.

Well-resolved 113Cd-n.m.r.

Comparison of cadmium-metallothionein synthesis in parenchymal and non-parenchymal rat liver cells.

The time course of cadmium-metallothionein synthesis was studied in non-parenchymal and parenchymal cells, isolated by a cell-separation technique from the livers of rats after the simultaneous injection of CdCl2 (0.05 mg of Cd/kg) and a 10-fold molar excess of 2,3-dimercaptopropanol. Under these conditions of dosing, in contrast with the injection of CdCl2 alone, both cell types accumulate similar concentrations of Cd and synthesize equivalent concentrations of metallothionein.

Studies of cadmium-thionein induced nephropathy: time course of cadmium-thionein uptake and degradation.

The renal uptake and degradation of cadmium-thionein (Cd-Mt) were examined in relation to nephrotoxic effects. Studies with Cd-Mt labelled with [3H]cystine showed that both Cd2+ and tritium uptake in the kidneys were complete 4 h after injection. During this period, renal copper content doubles due to the replacement of thionein-bound Cd2+ with Cu2+.

Lack of association between induction of dominant-lethal mutations and induction of heritable translocations with benzo[a]pyrene in postmeiotic germ cells of male mice.

Benzo[a]pyrene was tested for induction of dominant-lethal mutations in germ cells of male mice. Clear-cut dominant-lethal effects were induced in middle and early spermatozoa. In contrast to the dominant-lethal observed the study showed no detectable increase in heritable translocations for these stages over the spontaneous level.

Difference in the ratio of dominant-lethal mutations to heritable translocations produced in mouse spermatids and fully mature sperm after treatment with triethylenemelamine (TEM).

The relative induction of dominant-lethal mutations and heritable translocations in triethylenemelamine-treated postmeiotic germ cells of mice was determined depending on the stage treated. Males were mated either 11.5-14.

Effects of thiol agents on the accumulation of cadmium by rat liver parenchymal and Kupffer cells.

The rate of Cd accumulation by adult rat liver parenchymal cells in serum free primary culture in the presence of 100 microM CdCl2 was 10 times greater than that by non-parenchymal Kupffer cells. Addition of the monothiol chelating agents, cysteine and penicillamine, decreased Cd uptake in both cell types, the effect becoming more pronounced as the monothiol concentration was increased from 0.1 to 1.

Comparison of two methods for detecting translocation heterozygotes in mice.

An accurate estimate of the error of misclassifying male translocation heterozygotes as normals is essential for the proper evaluation of results of the heritable translocation test in mice. The size of this error may vary from one laboratory to another depending, primarily, on the method or variation of the method used in screening for translocation heterozygotes. This report shows a way to estimate for misclassification errors involved in two methods, sequential and direct cytological analysis, of screening for translocation heterozygotes.

Heritable translocation and dominant-lethal mutation induction with ethylene oxide in mice.

Ethylene oxide was studied for induction of dominant-lethal mutations and heritable translocations in male mice. The chemical was prepared in water and injected intraperitoneally. The dominant-lethal study was conducted using a single injection of 150 mg/kg (maximum tolerated dose); in the heritable translocation study males were injected daily on weekdays for 5 weeks with 60 or 30 mg/kg dose per day.

Selective uptake of cadmium by the parenchyumal cells of liver.

The uptake of cadmium in vivo into parenchymal and non-parenchymal (sinusoidal) cells of the liver was studied by a cell-separation technique. Liver parenchymal cells accumulate cadmium more readily than do non-parenchymal cells and synthesize metallothionein. It is proposed that cadmium uptake and metabolism from injected CdCl2, is restricted almost exclusively to the liver parenchymal cells.

Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice.

There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment.