The present study was conducted to compare the pharmacokinetics and pharmacodynamics (PD) of paclitaxel between Phase I trials of 3- and 24-h infusions and to determine the most informative ...pharmacokinetic parameter to describe the PD. Twenty-seven patients were treated in a Phase I study of paclitaxel by a 3-h infusion at one of six doses: 105, 135, 180, 210, 240, and 270 mg/m2. Pharmacokinetic data were obtained from all patients. Paclitaxel concentrations were measured in the plasma and urine using HPLC. The pharmacokinetics and PD were compared with those of a Phase I trial of paclitaxel by a 24-h schedule previously performed. The maximum tolerated dose of paclitaxel by a 3-h infusion was determined to be 240 mg/m2. The major toxicities were granulocytopenia, neuromuscular toxicities, and hypotension. Apparent differences in pharmacodynamic relationships for the change in granulocytes with dose, peak concentration, and areas under the concentration versus time curve were observed between the 3- and 24-h schedules. However, the relationship between the duration of plasma concentration above 0.05 microM and the change in granulocytes could be fitted to the same sigmoid maximum effect model in either schedule (P < 0.01). There were no clear relationships between peripheral neuropathy or hypotension and any pharmacokinetic parameters. The pharmacokinetics and PD of paclitaxel were schedule dependent. The duration of plasma concentration above 0.05 microM could be a common pharmacokinetic parameter predicting granulocytopenia for both schedules.
summary A case of ectodermal dysplasia in a Japanese boy is presented in this report. After prosthetic treatment was performed with partial dentures in both jaws, mandibular movement, dental casts, ...and lateral and frontal cephalograms were taken at an initial visit (age 7 years 8 months), and at follow‐up 1 year and 8 months later (age 9 years 3 months) to evaluate the developmental changes in masticatory movement, dental arch width, and craniofacial morphology. Stability of the jaw movements improved during the follow‐up period both with and without dentures. The facial skeleton grew between the initial visit and follow‐up. Mandibular length remained long compared with the average value for Japanese children. A possible genetic marker for mandibular growth (growth hormone receptor), which is considered to be an important factor in mandibular growth and development, was analysed for the gene variant and the result supported the characteristic mandibular growth in the reported case. These results indicate the characteristic craniofacial growth in this disease and emphasize the potential ability of functional development of jaw movements with oligodontia.
During the past 3 years, minimally invasive procedures have been adopted for the surgical treatment of primary hyperparathyroidism, and we have tried to perform endoscopic total parathyroidectomy for ...renal hyperparathyroidism.
Five 5-mm trocars were inserted through the skin of the anterior chest under a general anesthesia. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed.
Endoscopic procedure was successfully performed in five patients. The mean duration of total parathyroidectomies was 236 min. No evidence of injury to the recurrent laryngeal nerve was observed in any cases. At follow-up, the serum calcium and parathyroid hormone levels had returned to within the normal range in all patients. Postoperative cosmetic status was excellent.
We believe that endoscopic total parathyroidectomy by the anterior chest approach will find a role in the treatment of renal hyperparathyroidism.
This paper describes a three ring microphone array estimates the horizontal/vertical direction and distance of sound sources and separates multiple sound sources for mobile robot audition. ...Arrangement of microphones is simulated and an optimized pattern which has three rings is implemented with 32 microphones. Sound localization and separation are achieved by delay and sum beam forming (DSBF) and frequency band selection (FBS). From on-line experiments results of sound horizontal and vertical localization, we confirmed that one or two sounds sources could be localized with an error of about 5 degrees and 200 to 300 mm in the case of the distance of about lm. The off-line experiments of sound separation were evaluated by power spectrums in each frequency of separated sounds, and we confirmed that an appropriate frequency band could be selected by DSBF and FBS. The system can separate 3 different pressure speech sources without drowning out.
Nanoscale structural reorganization of a lipid bilayer membrane induced by a chemical recognition event has been imaged using in situ atomic force microscopy (AFM). Supported lipid bilayers, composed ...of distearylphosphatidylcholine (DSPC) and a synthetic lipid functionalized with a Cu
2+ receptor, phase-separate into nanoscale domains that are distinguishable by the 9
Å height difference between the two molecules. Upon binding of Cu
2+ the electrostatic nature of the receptor changes, causing a dispersion of the receptor molecules and subsequent shrinking of the structural features defined by the receptors in the membrane. Complete reversibility of the process was demonstrated through the removal of metal ions with EDTA.
A design concept of few-mode multicore fiber is presented. Cores with a step-index profile are designed to support two LP modes over the C band and the L band with a large effective area larger than ...110 μm 2 . The pitch of cores is determined regarding the inter-core crosstalk related to the LP 11 mode. The two LP modes multicore fibers with four cores and seven cores show a relative core multiplicity factor (RMCF) of 7.3 and 9.2, respectively. The RCMF of the proposed two LP modes multicore fiber is larger than that of previously reported single-mode multicore fibers.
To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the ...immunoglobulin heavy-chain variable region (VH) gene.
Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison.
The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%).
The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.
We examined the role of regulatory myosin light chain (MLC) phosphorylation of myosin II in cell migration of fibroblasts. Myosin light chain kinase (MLCK) inhibition blocked MLC phosphorylation at ...the cell periphery, but not in the center. MLCK-inhibited cells did not assemble zyxin-containing adhesions at the periphery, but maintained focal adhesions in the center. They generated membrane protrusions all around the cell, turned more frequently, and migrated less effectively. In contrast, Rho-associated kinase (ROCK) inhibition blocked MLC phosphorylation in the center, but not at the periphery. ROCK-inhibited cells assembled zyxin-containing adhesions at the periphery, but not focal adhesions in the center. They moved faster and more straight. On the other hand, inhibition of myosin phosphatase increased MLC phosphorylation and blocked peripheral membrane ruffling, as well as turnover of focal adhesions and cell migration. Our results suggest that myosin II activated by MLCK at the cell periphery controls membrane ruffling, and that the spatial regulation of MLC phosphorylation plays critical roles in controlling cell migration of fibroblasts.
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