Comparative study of population pharmacokinetics upon switching of cyclosporine formulation from Sandimmune to Neoral in stable renal transplant patients.
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Publications and source records attributed to T Endo.
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The critical micelle concentrations of 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[monomethoxy poly(ethylene glycol) (5000)] (PEG-DPPE) and its distearoyl analogue (PEG-DSPE) were 70 and 9 microM, respectively, in buffer solutions ([Tris] = 20 mM, [NaCl] = 140 mM, pH 7.4) at 37 degrees C. When these PEG-lipid micelle dispersions were mixed with the dispersions of phospholipid vesicles comprised of a C16 membrane, of which the carbon number is 16, or a C18 membrane, the PEG-lipid micelles were dissociated into monomers and then spontaneously incorporated into the surface of the preformed vesicles. The incorporation rates and the enthalpy changes during incorporation were measured with an isothermal titration microcalorimeter. The incorporation rate of PEG-DPPE was faster than that of PEG-DSPE, because the dissociation rate of the PEG-DPPE micelles was faster than that of PEG-DSPE micelles. The incorporation equilibrium constant of PEG-DSPE was larger than that of PEG-DPPE due to its slow dissociation rate from the membrane, caused by the stronger hydrophobic interaction. The combination of PEG-DSPE and the C18 membrane was the most thermodynamically stabilized pair. Furthermore, the dispersion stability of the surface-modified vesicles prepared by this spontaneous incorporation was analyzed by using the critical molecular weight of the polymer for the aggregation of vesicles. The aggregation of the vesicles was successfully supressed with an increase in the molecular weight of the PEG in the PEG-lipid and its incorporation ratio.
A fundamental process in limb bud development is the formation of position-dependent cartilage pattern. Cells of the distal mesenchyme maintain positional values as the expression pattern of transcription factors, for example, hox genes, which induce position-related cell differentiation and cell surface differences. Cultured, dissociated limb bud mesenchymal cells segregate from each other, and eventually form cartilage nodules. This sorting out is position-dependent, not cell-type dependent, suggesting that the positional values may be involved. Positional valves were found to be retained in limb bud recombinants. In the chick system, the expression of HoxA13 and HoxD12 was present in the distal half of stage 20 recombinants, whereas these markers were expressed throughout the stages 25 recombinants. In the Xenopus system, multiple digit formation was introduced in limb recombinants, and a position-related relationship between regeneration potency and the multiple digit formation could be established. This determination of multiple digit formation with different stages of limb mesenchyme may be useful in understanding mechanisms of the loss of vertebrate limb regeneration potency.
OBJECTIVE: To clarify the CT characteristics of groove pancreatitis, which is a segmental form of chronic pancreatitis. MATERIALS AND METHODS: The CT findings in four patients with proved groove pancreatitis were reviewed retrospectively. The examinations consisted of plain CT, dynamic CT, and high dose enhancement CT in each patient. Correlation between the CT findings and the resected specimens was performed in three patients. RESULTS: In every patient a mass was detected in the head of the pancreas that involved the duodenum. Dynamic CT demonstrated a poorly enhancing lesion extending between the pancreatic head and the duodenum. Cysts in the duodenal wall and/or the groove and duodenal stenosis due to wall thickening were seen in four and three patients, respectively. These CT findings reflect the histological characteristics of this disease. CONCLUSION: Computed tomography, including dynamic study, can demonstrate the characteristic findings of groove pancreatitis and suggest the diagnosis.
Eight isolates, identified as either Acanthamoeba castellanii or A. polyphaga from human eye infections, contact lens containers, and soil in Japan, were characterized by restriction fragment length polymorphisms (RFLP) of mitochondrial DNA (mtDNA). Mitochondrial DNA was digested with either Bgl II, EcoR I, Hind III, Hpa I, Sca I or Xba I, electrophoresed in agarose gels, and stained with ethidium bromide. Four distinct RFLP phenotypes that refer to the collection of six fragment size patterns obtained for a single strain with six enzymes, were discovered among the eight strains used in this study. Three strains morphologically classified as A. polyphaga share a single RFLP phenotype with the Ma strain of A. castellanii. The interspecific sequence differences of 7.06-12.74% in DNA nucleotide were estimated from the proportion of DNA fragments shared by each pair of mtDNA.
Toxoplasma gondii tachyzoites were quiescent in mouse peritoneal fluid or in K2SO4 buffer at pH 8.2. They became consistently motile when K+ was replaced by other monovalent or divalent cations at a constant pH (pH = 8.2). They also became motile when Cl- was substituted for SO4(2-). Nitrate or SCN-, can also be substituted for Cl- to a certain extent. Tachyzoites showed independent movement for more than 15 min in KCl, and for about 5 min in the other buffers at pH 8.2 after which they were exhausted and stopped. These tachyzoites could not then be further stimulated to motility by renewal of the suspension buffer. Infection of monolayer cells was demonstrated only with parasites which were motile during inoculation. The highest infectivity was thus obtained either with freshly collected tachyzoites or with those preincubated in K2SO4 buffer for 30 min at 37 degrees C at alkaline pH and thus not yet exhausted for motility. Approximately 34 to 38% of these latter organisms were seen to enter cells when they were inoculated into cultures immediately after being resuspended in MEM for 30 min at 37 degrees C. Conversely, those whose motility had been exhausted by the preincubation in buffers other than K2SO4, pH 8.2 could not enter monolayer cells. Additionally, parasites were unable to enter cells when inoculated into cultures in K2SO4 buffer at alkaline pH; instead they remained quiescent on the surface of the monolayer cells, suggesting that Toxoplasma enters the host cells by active invasion.
The clinical features of familial gastric cancer are still unknown. To approach this question, we investigated the clinicopathological characteristics of 16 cases of familial gastric cancer. In this study the criteria used to define familial gastric cancer was the existence of three or more family members with gastric cancer in at least two successive generations. The clinicopathological characteristics of cases who fulfilled this criteria were studied. This study contained 16 familial gastric cancer probands. Seven cases (44%) of gastric cancer had developed at the cardiac region of the stomach. This frequency was significantly higher than for gastric cancer in the general population in Japan (15.4%, p < 0.01). Undifferentiated types were dominant in familial gastric cancer (69%, p < 0.05). Furthermore, the frequency of disseminated peritoneal (40%) and liver metastases (20%) in familial gastric cancer was also significantly higher than for gastric cancer in the general population in Japan (10.9%, p < 0.01, and 4.4%, p < 0.05, respectively). Familial gastric cancers were frequently located at the cardiac region and appeared to be more aggressive than sporadic gastric cancers. The unique characteristics of familial gastric cancer suggest a genetic background in their etiology.
Plasma melatonin rhythm in humans was investigated: its stability, relationship to the sleep-wake rhythm, and response to light. The so-called day-to-day variation of reference phases of plasma melatonin rhythm was within 1.4 h when blood was sampled at 1-hour intervals. Therefore, a change in phase beyond this value is regarded as a phase shift of melatonin rhythm in individuals. Plasma melatonin rhythm was spontaneously desynchronized from the sleep-wake rhythm and probably regulated by the common circadian pacemaker which drives the rhythm in rectal temperature. When a bright-light pulse was applied, the melatonin rhythm produced a phase shift, but the amount of phase shift seems to be different for the ascending and descending phases of nocturnal melatonin rise. Finally, a partial entrainment was observed in a subject who developed a non-24-hour sleep-wake syndrome later, in which the plasma melatonin rhythm was free-running whereas the sleep-wake rhythm was apparently entrained by a 24-hour day-night alternation. It is concluded that the plasma melatonin rhythm is the best marker of the human circadian pacemaker so far available.
The influence of an oil contrast medium on fertilization in rabbit oviducts was investigated. The oil contrast medium (Lipiodol-UF) was injected into the catheterized oviducts of anaesthetized animals, and they were mated 1, 3, 5 or 7 days later. When mating took place 1 day after injection, none of the ova that were subsequently recovered were fertilized; the fertilization rates when mating occurred 3, 5 or 7 days after injection of the medium were 78.9, 90 and 100%. Fertilization within the oviduct was, thus, impaired by the injection of oil contrast medium, but appeared to be fully recovered 7 days later.
It has been suggested that the mechanical interference involved in inserting a tube into the oviduct before ovulation, during tubal insemination, may impair the capacity of the tubal fimbriae to pick up ovulated eggs. When fresh sperm cells are used, the semen has to be injected into the oviduct before ovulation to allow time for sperm capacitation. In the present study in rabbits, sperm cells capacitated by pre-incubation in vitro were injected into the oviducts through the tubal fimbriae after ovulation. Two of the six rabbits inseminated became pregnant and gave birth to one and three offspring, respectively. Injecting capacitated sperm cells after ovulation may avoid the potential problems posed by mechanical damage of the tubal fimbriae.
The dose-response relationship for the inhibitory effect of indomethacin on implantation and continuance of pregnancy was examined in four groups of rabbits administered with indomethacin (2.5, 5.0, 7.5 and 10.0 mg/kg) during the implantation period and compared with a control group. Implanted fetuses and corpora lutea were counted by laparotomy, and the number of offspring born was noted. The inhibitory effect of indomethacin on implantation was found to be dose-dependent, and the birth rate decreased in the indomethacin groups compared with the control group. As a result, even where implantation had been achieved, death of the implanted fetuses occurred at a high rate in rabbits administered with indomethacin during the implantation period.
The proportions of unfertilized eggs in the oviducts, showing abnormal cleavage, were examined in hamsters given single or repeated doses of 30 i.u. human gonadotrophic hormone for the induction of ovulation. In control animals (n = 7), 1.7% of the total ovulated eggs were morphologically abnormal unfertilized eggs showing cleavage. The proportions of unfertilized eggs that were abnormal in the groups of seven hamsters treated with one, two or three doses of the gonadotrophin were 20.4%, 19.4%, and 30.4%, respectively. The proportion of unfertilized eggs showing abnormal cleavage thus appeared to increase with repeated administrations of gonadotrophin.
The involvement of the immune system in changes in luteal function was evaluated in rabbits. Pseudopregnancy was induced in 10 females and the spleens (considered to be the source of macrophages) of five were excised on day 7 of pseudopregnancy, while the five controls had sham splenectomies. Subsequent changes in serum progesterone concentrations were measured as an indicator of luteal function and luteolysis. A second pseudopregnancy was induced 31 days after splenectomy. The first pseudopregnancy was prolonged and during the second pseudopregnancy the serum progesterone concentrations on days 3 and 7 were much lower in the splenectomy group than in the control group. On day 14 of the second pseudopregnancy, the serum progesterone concentration markedly decreased in the control group while it remained almost at the level of day 7 in the splenectomy group. These results suggest that splenectomy suppresses the expression of luteal function and delays luteolysis in rabbits.
Macrophage activity as indicated by phagocytosis in the corpus luteum at the luteolysis stage was examined in rabbits during pseudopregnancy. The day of induction of pseudopregnancy was regarded as day 0, and the phagocytotic activity of macrophages obtained from luteal tissues was examined on days 7 and 16. When sheep red blood cells (SRBCs) were used to assess phagocytotic activity there was no difference in phagocytosis between days 7 and 16 but, when sensitized SRBCs were used to assess phagocytotic activity, the activity of macrophages on day 16 was more than double that on day 7 (P < 0.05). These results indicate that immunomediated phagocytosis of luteal macrophages is enhanced at the luteolysis stage (day 16). This phenomenon may contribute to the process of luteolysis.
The minimum dose of human chorionic gonadotrophin needed to induce ovulation was determined in hamsters, in which the luteinizing hormone surge was blocked by administration of phenobarbitone. Doses of 1.0, 2.5, 5.0 and 10.0 IU human chorionic gonadotrophin were injected subcutaneously, and 5.0 IU was found to be the minimum dose needed to induce ovulation in all of a group of seven hamsters. When this minimum dose was used to induce ovulation repeatedly, one, two or three times, in groups of seven hamsters the percentages of abnormal eggs seen were 5.3%, 5.6% and 6.4%, respectively. These results indicate that the marked increases in the proportions of abnormal eggs produced when ovulation is repeatedly induced, which have been observed in previous studies, can be prevented by using the minimum effective dose of human chorionic gonadotrophin.
HMW-NCA is involved in the pathogenesis of nasal hypersensitivity reactions in humans. We, however, have little evidence about the role of neutrophils which migrate to the site of allergic reactions by HMW-NCA and other chemotactic mediators. This role of neutrophils in nasal hypersensitivity still remains to be clarified.
OBJECTIVE: Growth during continuous ambulatory peritoneal dialysis (CAPD) and after renal transplantation (Tx) was assessed in children under the age of 12 years. DESIGN: Growth was assessed by calculating the standard deviation score for height of normal children of the same age and gender. PATIENTS: Twenty-one patients undergoing CAPD and 13 patients who had received renal Tx at Kitasato University Hospital. RESULTS: Overall growth in those children undergoing CAPD and after renal Tx was not good, but growth during CAPD seemed to be slightly better than after renal Tx using conventional immunosuppressive drugs. Only young children who had started CAPD or received renal Tx before the age of 5 years with functioning graft showed catch-up growth, but the final height of these children may still be smaller than normal. CONCLUSION: Growth in children with end-stage renal disease is poor but growth during CAPD seems to be slightly better than after renal Tx using conventional immunosuppressive drugs.