An indicator quantitatively comparing two treatment effect sizes on responder and non-responder groups – exponential of estimated interaction parameter

 Sometimes a specific treatment is effective in one subgroup but not in another. An indicator allowing quantitative comparison of treatment effect in two subgroups would be useful in clinical medicine. We have developed such an indicator. It is obtained by calculations using Cox’s proportional hazard or logistic model with therapy, subgroup, and confounding explanatory variables. The parameter of the interaction between therapy and subgroup can be estimated and tested statistically. The exponential value of the interaction parameter is what we tentatively call the “hazard ratio ratio”, meaning the ratio between the treatment effects in two subgroups. The 95% confidence interval of the indicator can also be calculated. As a numerical example, the hazard ratio between the survival times of postoperative gastric cancer patients treated by adjuvant immunochemotherapy and patients without adjuvant immunochemotherapy in a subgroup with high serum glycosidically bound sialic acid (SA) level was lower than that in a low-SA subgroup using an estimate for hazard ratio ratio of less than 0.5 with statistical significance. We propose this indicator be used as a “responder/non-responder ratio” of therapy effect. Received: 11 April 1995 / Accepted: 5 September 1995     

Preliminary results in improving essential fatty acids enrichment of rotifer cultured in high density

High density cultured marine rotifer (Brachionusrotundiformis) fed on freshwater Chlorella wascultured secondarily with an emulsion of ethyl esters(65% DHA, 15% EPA) for EFA-enrichment, with orwithout freshwater Chlorella. Culture tanks (30 l, 20 lworking volume) set in a water bath (24 °C)were continuously supplied with air (2.50 lm^–1) or high-purity oxygen gas (1.25 lm^–1). Samples for fatty acid compositionanalysis were collected at 0, 6, 12, and 24 hoursafter the inoculation of rotifer, followed by themonitoring of rotifer density, DO, NH₄-N and pH.The n-3 HUFA content plateaued at 6 hours afterthe onset of the secondary culture and no significantdifferences were observed afterwards, regardless ofthe aeration methods. The HUFA content increased withdecreasing amounts of Chlorella added. Thehighest content (ca 3.5% on a dry basis) was notedin non-Chlorella feeding groups. When largeamounts of Chlorella were fed, the DO of culturewater drastically decreased and the NH₄-Nconcentration increased. The results from theexperiment indicate that the presence of Chlorella cells greatly affect the HUFA intake ofrotifers during the secondary culture process. Alsothe supply of high-purity oxygen gas was effective forpreventing a culture crash of rotifers during EFAenrichment.     

Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.

Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence.     

Studies on beige-nude mice with low natural killer cell activity. 1. Introduction of the bg gene into nude mice and the characteristics of beige-nude mice

To improve the take-rate of human tumours in nude mice, a nude mouse strain with the bg gene was established. The introduction of the bg gene was confirmed by examination of giant granules of blood neutrophils. The genetic profile of beige-nude mice was the same as that of the C57BL/6 strain according to genetic screening. The natural killer cell activity in the beige-nude mice was much lower than that in ordinary nude mice but slightly higher than that in beige mice. The reproductivity of beige-nude mice was as high as that of ordinary nude mice.     

Stimulatory Effect of Ascorbic Acid on Norepinephrine Biosynthesis in Digitonin-Permeabilized Adrenal Medullary Chromaffin Cells

The regulatory role of ascorbic acid in norepinephrine biosynthesis was studied using digitonin-permeabilized chromaffin cells. When permeabilized chromaffin cells were incubated with [3H]3,4-dihydroxyphenylethylamine ([3H]dopamine) in calcium-free medium, the amounts of radioactive dopamine and norepinephrine measured in the cell fraction were increased as a function of incubation time and dopamine concentration. Both the accumulation of dopamine and the formation of norepinephrine were shown to require the presence of Mg-ATP in the medium. These results indicate that the permeabilization of chromaffin cells by digitonin treatment does not disrupt the functions of chromaffin granules, including dopamine uptake, norepinephrine formation, and storage of these amines. Using this permeabilized cell system, the effect of ascorbic acid on the rates of dopamine uptake and hydroxylation was investigated. The formation of norepinephrine was stimulated by ascorbic acid at concentrations of 0.5-2 mM in the presence of Mg-ATP. By contrast, dopamine uptake was not affected by the presence or absence of ascorbic acid in the medium. These findings provide evidence that ascorbic acid may stimulate the conversion of dopamine to norepinephrine by increasing dopamine beta monooxygenase activity rather than by increasing the substrate supply of dopamine. These observations also suggest that the rate of norepinephrine biosynthesis in adrenal medullary cells may be regulated by the concentration of ascorbic acid within the cell cytoplasm.     

Competition between two similar plant varieties,green shrunk perilla and red shrunk perilla,in mixed cultures

Influences of plant density and time after seeding on the growth of two horticultural forms of perilla (Perilla frutescens var.crispa), green shrunk perilla (f.viridi-crispa) and red shrunk perilla (f.crispa), were examined in a mixed culture experiment. Relationships between mean individual plant weight and plant density in mixed populations were approximated by Ogawa's non-interaction type (NI-type) reciprocal equation. The density conversion factors in the equation for green and red perillas were always, respectively, smaller and larger than unity, suggesting that effects of a green perilla on the other individuals were always stronger than those of a red one in a mixed population. All coefficients in the NI-type reciprocal equation were expressed as functions of time after seeding. As a result, time trends of mean individual plant weights for both species in mixed populations could be reasonably estimated for different plant densities and mixed proportions. The results were also applied to Lotka-Volterra's equation. Time trends of Lotka-Volterra's competition coefficients for both plants could be calculated and were compared with those of density conversion factors.     

Density effects and self-thinning in even-aged pure stands ofEucalyptus camaldulensis Dehn

The competition density effect and changes of mean total tree weight (w) and stand density (ρ) during course of self-thinning were examined in even-aged pure stands ofEucalyptus camaldulensis Dehn. which were planted in the tropical monsoon region. The level of competition was controlled by changing the initial stand density from 625 trees ha⁻¹ to 40,000 trees ha⁻¹. Hozumi's model was used to describe thew-ρ trajectory with aging of each stand and thew-ρ relation between stands of different densities at each time. The higher density produced trees of smaller mean tree sizes. The higher the density, the sooner self-thinning began. The growth curve ofE. camaldulensis followed the logistic growth curve where both maximum size and intrinsic growth rate change with time. Mean intrinsic growth rate was maximized at initiation of growth after lag time and then gradually decreased as time progressed. Hozumi's model was considered to be the best model with wide applicability for describing and comparing the growth characteristics during the course of self-thinning among different species, especially in tropical forest plantations, in which many diverse species were used for reforestation.     

Alkaloid of Stephania japonica Miers On Protostephanine (12)

By the reduction of protostephanine methylmethine, two kinds of methines (α- and β-isomer) were isolated, and a stable nitrogen-free substance was successfully obtained by its Hofmann degradation. This in connection with other evidence, makes possible a complete assignement of structure for protostephanine.