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Biomedical subjects

S Yanai

Publications and source records attributed to S Yanai.

At least 19 recordsLinked to original sources
PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗
PubMed2003

Conservation of the syntenies between porcine chromosome 7 and human chromosomes 6, 14 and 15 demonstrated by radiation hybrid mapping and linkage analysis.

Comparative mapping studies facilitate the identification of genes located in quantitative trait locus (QTL) regions in domestic animals by utilizing information from the human genome. Radiation hybrid (RH) mapping is effective for this purpose because of its high resolution in ordered gene mapping on chromosomes. We constructed an RH map of pig chromosome 7, by adding 23 markers associated with genes. This RH map clearly demonstrated the mosaic of homology between pig chromosome 7 (SSC7) and human chromosomes 6, 14 and 15 at a 'gene' level, and was confirmed by linkage analysis. Clarification of the homology of SSC7 to human chromosomes will contribute to the elucidation of the gene(s) responsible for QTL detected on this chromosome.

Animals↗
PubMed2001

Interfacial behaviour and micelle formation of novel amphiphilic sequential lipid-lysine oligomers.

As part of work on the design and synthesis of new supramolecular carrier systems for drugs, a series of novel linear oligomers of alternating alpha-amino tetradecanoic acid and lysine having positively charged groups and lipid chains was synthesised. The smallest member of the series (n=2) is insoluble in water and diluted acid solutions, but the larger members are soluble in acid conditions and poorly soluble in alkaline conditions. Hence, in one series, one can conduct experiments both on the determination of micelle formation and spread monolayer behaviour. The surface pressure-area isotherms revealed limiting surface areas at the air/water interface ranged from 0.04 to 0.9 nm(2) according to the oligomer size, and a linear correlation between the observed area per molecule and that projected by computer-generated molecular models was demonstrated. The surface tension of the soluble members in dilute acid solution fell as the concentration of the oligomers was increased, indicating that all of these polymers were surface active with quite clearly defined critical micelle concentrations. The fluorescence intensity ratio of third to first band in the emission spectra of pyrene as a function of the polymer concentrations demonstrated that, even after normalising the data for the amount of lipid chains in the system, the (n=3) oligomer had fewer accessible hydrophobic sites for pyrene, and the forces of the repulsion between the charged head groups was crucial on the formation of micelles, especially in the case of the n=3 oligomer. Supramolecular fibre-like structures were observed in aqueous solution only when n=3 by transmission electron microscopy (TEM). Cryogenic TEM observation of the (n=3) solution also revealed that the micelles might elongate to form long cylindrical or fibrous structures. The diameter of these structures was estimated to be 6.0-13 nm, although their length varied.

Drug Carriers↗
PubMed2001

Iontophoretic pulsatile transdermal delivery of human parathyroid hormone (1-34).

Iontophoretic pulsatile transdermal delivery of hPTH(1-34) was examined in Sprague-Dawley (SD) rats, hairless rats and beagle dogs. Application for 60 min (200 microg; 0.1 mA cm(-2)) showed current-responsive increases in serum hPTH(1-34) levels in all the animals. In SD rats, the area under the curves of serum hPTH(1-34) levels (AUCs) were proportional to the doses (40, 120, 200, 400 and 1000 microg) and current densities (0.05, 0.1 and 0.15mA cm(-2)) applied. The absorption rates per 200-microg dose, calculated by a deconvolution method, were 6.7, 2.4 and 3.7 microg h(-1) for SD rats, hairless rats and beagle dogs, respectively. These values correlated well with the ratios of the skin porosity to the dermal thickness reported for these animals, which are believed to represent the reciprocal of the electrical resistance of the aqueous channels formed by the hair follicles. From this correlation, we suggested that absorption of hPTH(1-34) occurs mainly via the hair-follicle route, and that the absorption rate in man might be intermediate between those in hairless rats and beagle dogs. Three-fold repetitions of 30 min current with various rest intervals produced current-responsive triple pulses in serum hPTH(1-34) levels in SD rats. Seven-fold repetitions of current also produced similar current-responsive pulsatile serum hPTH(1-34) levels. However, peak serum hPTH(1-34) levels tended to decrease gradually after the fourth current application, possibly due to consumption of the electrodes, suggesting that three-fold repetitions of current might be optimal. These findings suggest that this iontophoretic administration system could create a repeated-pulsatile pattern of serum hPTH(1-34) levels without the necessity for frequent injections, and may be useful for the treatment of osteoporosis with hPTH(1-34).

Absorption↗
PubMed2001

Late occurrence of diffuse cerebral swelling after intracerebral hemorrhage in a patient with the HELLP syndrome--Case report.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-year-old female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome.

Adult↗
PubMed2000

Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein.

To elucidate the role of P-glycoprotein in human placenta, we examined its expression in placenta, and the transcellular transport and uptake of P-glycoprotein substrates in cultured human placental choriocarcinoma epithelial cells (BeWo cells). The uptake of [(3)H]vinblastine and [(3)H]vincristine into BeWo cells was increased in the presence of a metabolic inhibitor, sodium azide. The basolateral-to-apical transcellular transport of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin was greater than the apical-to-basolateral transcellular transport. In the presence of cyclosporin A, the basolateral-to-apical transcellular transport of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin was significantly increased, and the apical-to-basolateral transcellular transport was decreased. The uptake of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin into BeWo cells was significantly enhanced in the presence of several inhibitors, such as verapamil or mouse monoclonal antibody anti-P-glycoprotein MX-MDR (MRK16) as well as cyclosporin A. Although progesterone significantly enhanced the uptake of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin into BeWo cells, the uptake of [(3)H]progesterone was not affected by these inhibitors. Immunoblot analysis revealed that P-glycoprotein with a molecular weight of 172 kDa was expressed in BeWo cells and isolated trophoblast cells. Furthermore, P-glycoprotein was detected in human placental brush-border membrane vesicles, but not in human placental basolateral membrane vesicles. In conclusion, these data suggest that P-glycoprotein is expressed on the brush-border membrane (maternal side) of human placental trophoblast cells. P-Glycoprotein is considered to regulate the transfer of several substances including vinblastine, vincristine and digoxin from mother to fetus, and to protect the fetus from toxic substances.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Characteristics of monocarboxylates as energy substrates other than glucose in rat brain slices and the effect of selective glial poisoning - a 31P NMR study.

In rat brain slices we examined the differences in the levels of high-energy phosphates in the presence of various energy substrates by using 31P NMR with a time resolution of 4 min at 25 degrees C. In parallel experiments we recorded population excitatory postsynaptic potentials (EPSPs) from granule cells in rat hippocampal slices. During high K(+) stimulation (8 min) phosphocreatine (PCr) decreased to a low level and recovered to the control level in standard artificial cerebrospinal fluid (ACSF) in about 10 min. Population EPSPs disappeared following high-K(+) stimulation and recovered in standard ACSF. In iodoacetic acid (IAA)-pretreated slices, whereas glucose was unable to support energy metabolism, the PCr level, which decreased following high-K(+) stimulation, recovered in ACSF containing lactate or pyruvate. The half-time of recovery of PCr levels in ACSF containing lactate was longer than that containing glucose. Population EPSPs in standard ACSF were maintained for more than 1 h, but those in ACSF containing lactate decreased gradually by about half in 40 min. In IAA-pretreated slices, when further treated with fluorocitrate (100 microM) for 2 h, the recovery of the PCr level in ACSF containing lactate after high-K(+) stimulation was completely abolished, whereas the recovery of the PCr level in ACSF containing pyruvate was unaffected. These results indicate that neurons can utilize pyruvate as well as glucose, but not lactate, as exogenous energy substrates, and that lactate may be metabolized to pyruvate in glial cells and transported to neurons to be utilized as an energy substrate.

Animals↗
PubMed2000

Quantitative trait loci (QTL) analysis in a Meishan x Göttingen cross population.

In order to locate the genetic regions in the swine genome that are responsible for economically important traits, a resource population has been constructed by mating two female Meishan pigs with a male Göttingen miniature pig. In subsequent generations, 265 F2 offspring were produced from two F1 males and 19 F1 females. The F2 offspring were scored for eight traits including growth rate, teat number, vertebra number and backfat thickness, and genotyped for 318 genetic markers spanning the swine genome. Least-square analysis revealed quantitative trait loci (QTL) effects for vertebra number on chromosomes 1 and 2; for teat number on chromosomes 1 and 7; for birth weight on chromosome 1; for average daily gain between 4 and 13 weeks of age on chromosomes 9 and 10; for backfat thickness on chromosome 7; and for backskin thickness on chromosome 3.

Animals↗
PubMed2000

[Diagnosis using esophageal manometry and various loading tests].

Two approaches of infusion and microtransducer manipulation are available for esophageal manometry. If esophageal peristalsis and relaxation of the lower esophageal sphincter (LES) are diminished, the diagnosis of achalasia can be made. As compared with the infusion method, the microtransducer method requires no perfusion of water and has no limit on posture, allowing successful measurement in an empty esophagus. Thus this method, which allows measurement after feeding and continuous monitoring for 24 hours, seems to be more physiological than the infusion method. With this method, however, peristasis-like contractile waves and relaxation of the LES may be observed in addition to simultaneous contractile waves, even in cases of achalasia. Although methods to observe excessive reactions of the LES often involve a loading test with gastrin or mecolyl in some institutions, a loading test with cerulein is routinely used in our department. In healthy controls, administration of cerulein usually leads to decreased LES pressure, while increased LES pressure is observed in patients with achalasia (paradoxical response).

Ceruletide↗
PubMed1999

Fibroxanthoma arising from the cranial dura mater.

A primary xanthomatous tumor is very rare in the central nervous system (CNS). Here we report the case of a fibroxanthoma arising from the dura mater of the cerebrum that demonstrated no systemic disease or metabolic abnormalities. A 19-month-old, otherwise healthy boy was found to have an enlarged head. Magnetic resonance imaging demonstrated a left occipital dural mass lesion and an enlarged left cerebral hemisphere with ipsilateral ventricular enlargement. Subtotal removal of the tumor was performed through the left parieto-occipital craniotomy. The tumor was composed of a central fibrous portion, a peripheral xanthomatous area, and a boundary. The peripheral area of the tumor showed abundant uniform xanthomatous cells with a thin fibrous stroma and the mass was diagnosed as fibroxanthoma involving the dura. This may represent a distinct category of tumor, which is different from the previously reported cases of fibrous xanthoma and fibrous histiocytoma. Intracranial xanthomatous tumors may be heterogeneous in their origin and histological features. However, further studies are needed to elucidate their clinical features, biological behavior, and optimal treatment strategies.

Brain Neoplasms↗
PubMed1999

Treatment of infantile spasms with zonisamide.

We determined the efficacy of and tolerability to zonisamide (ZNS) in newly diagnosed patients with infantile spasms. ZNS, 4-20 mg/kg per day, was introduced as an add-on therapy or monotherapy in 27 children with infantile spasms (cryptogenic, 2; symptomatic, 25). The dosage was initially 2-4 mg/kg per day, and then was increased by 2-5 mg/kg every 2-4 days until the seizures disappeared. Nine (33.3%) out of the 27 patients who were administered ZNS exhibited the disappearance of seizures. ZNS was effective in all the cryptogenic cases and seven (28.0%) of the symptomatic cases. The effective daily doses were 5-12.5 mg/kg (mean, 7.8 mg/kg), and the daily dosages were 40-100 mg (mean, 61.1 mg). The steady-state plasma ZNS concentrations were almost within the therapeutic range. The mean time interval between the start of ZNS therapy and the seizure disappearance was 5.0 days. Six (75.0%) of eight effective cases, the exception being one for whom EEG was not performed after the therapy, showed the disappearance of hypsarrhythmia. The recurrence of seizures were observed in four of the nine cases. No adverse reaction to ZNS was noted in any patient. In conclusion, ZNS treatment is considered to be worthwhile trying, for early stage therapy for infantile spasms.

Anticonvulsants↗
PubMed1999

A linkage map of 243 DNA markers in an intercross of Göttingen miniature and Meishan pigs.

A resource family of pigs has been constructed by using a boar of Göttingen miniature pig and two sows of Meishan pig as parents. In the construction of the family, two F1 males and 18 F1 females were intercrossed to generate 143 F2 offspring. The members of the family were genotyped using 243 genetic markers including 26 markers developed in our laboratory in order to generate a linkage map of markers for use in detecting quantitative trait loci (QTLs) in the family. The markers consisted of 237 microsatellites, five PRE-1 markers, and one RFLP marker. The linkage map was revealed to cover all 18 autosomes and the X chromosome; and the total length of the sex-averaged linkage map was calculated to be 2561.9 CM. Four out of the 26 markers developed in our laboratory exended the current linkage map at the termini of chromosomes 1p, 5p, 11p, and Xq. The linkage maps of all the chromosomes except for chromosome 1 were found to be longer in females than in males. Concerning chromosome 1, the length of the linkage map showed no difference between females and males, which was attributed to low recombination rates between markers localized in the centromeric region in females. The average ratio of female-to-male recombination was calculated to be 1.55.

Animals↗
PubMed1998

Cerebellar control of the cardiovascular responses during postural changes in conscious rabbits.

In conscious control rabbits, tilting the head 30 degrees up from a position 30 degrees down induced initially an inhibition in the renal sympathetic nerve activity (RSNA), however this inhibition immediately released and became a transient increase. Following these responses in RSNA, blood pressure (BP) initially decreased but recovered to the control level within 3-5 s. After bilateral destruction of the lateral nodulus-uvula in the cerebellum, in contrast, the same tilting of the head caused an immediate large increase in RSNA without early inhibition, which was sustained at a high level. BP increased transiently, but then decreased and remained at a level lower than the control. These results indicate that the timing and duration of this transient increase in RSNA during tilting the head up are controlled by the lateral nodulus-uvula and may be important in the rapid adaptation of blood pressure. In addition, this suggests that the lateral nodulus-uvula may play an important role in the cardiovascular control under conditions of consciousness during changes in head position and body posture.

Animals↗
PubMed1998

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive.

Dandy-Walker Syndrome↗
PubMed1998

[Efficacy of continuous intravenous infusion of midazolam in the treatment of status epilepticus in children].

Midazolam infusion was tried as the treatment for 48 episodes of refractory status epilepticus or a cluster of seizures in 16 children. The mean age of patients was 3.5 years (range, 1 month to 18 years). Nine children had epilepsy, one purulent meningitis, one encephalitis, one acute cerebral infarction, and the remaining four had acute phase of hypoxic ischemic encephalopathy. The type of the seizure was a generalized tonic clonic seizure (including a partial seizure secondarily generalized) in 41 episodes, a tonic seizure in 3, an atypical absence in 1, and a complex partial seizure in 3, respectively. All patients received intravenous midazolam at 0.15 mg/kg as bolus, followed by a continuous infusion at 0.1-0.15 mg/kg/hr initially. The dose was increased gradually up to 0.3 mg/kg/hr until the complete control of seizures was achieved. Fourty-one of the 48 episodes of seizures were controlled within 30 minutes after the initiation of midazolam therapy. The mean infusion rate of midazolam required was 0.22 mg/kg/hr. The mean duration of the treatment was 4.1 days. None of the patients had serious changes in the blood pressure or respiratory status attributable to the use of midazolam. In conclusion, midazolam infusion is an effective and safe therapeutic approach for the management of childhood status epilepticus.

Anticonvulsants↗
PubMed1998

[A case of thoracic extradural spinal cord teratoma with neurological sequelae more than 10 years after surgery].

We describe a rare case of a 42-year-old man with extradural spinal cord teratoma who presented with left Brown-Séquard syndrome more than 10 years after surgery for a left posterior mediastinal tumor. When he was 29 years old, he underwent an operation for a posterior mediastinal tumor. Histological findings showed adenocarcinoma in teratoma. Ten years after the operation, the patient developed left leg weakness. Three years later, he developed superficial sensory disturbance in his right leg. MRI showed extradural tumor formation at the level of the Th 9 vertebra, which compressed the spinal cord from the left posterior side. At surgery, the tumor was well encapsulated and extended to the left posterior side of the spinal cord through the intervertebral foramen. The histological findings were almost identical to those from the mediastinal tumor. This dumbbell tumor apparently developed from the remainder of the posterior mediastinal tumor over a period of more than 10 years.

Adenocarcinoma↗
PubMed1997

Can twin fetuses be numerically clustered characterizing fetal cardiovascular system function?

To clarify whether twin fetuses could be clustered quantitatively observing in utero cardiovascular system function, 71 twin-paired fetuses between 24 and 40 weeks' gestation were subjected. Cluster analysis was performed using four variables; end-diastolic dimension and fractional shortening in the right ventricle (EDD, FS), resistance index in the umbilical artery (RIUA) and urine production rate (UPR). Three different groups were revealed. In Cluster 1 (C1), larger fetuses showed a significant increase in both EDD and UPR, and a significant decrease in FS, while smaller fetuses had a significant increase in RIUA and a decrease in UPR. In Cluster 2 (C2), smaller fetuses showed a significant increase in RIUA. Cluster 3 (C3) showed no significant deviations in any variable when referring to singleton pregnancies. C1 had a higher perinatal mortality rate than either C2 or C3, with the cause of death being cardiac failure in larger fetuses and renal failure in smaller fetuses. The frequencies of discordancy, hemoglobin difference above 5 g/dl and monochorionic placenta in C1 were also higher than fetuses in C3. C2 also showed higher frequencies of discordancy and small-for-gestational age than C3 fetuses. In C2 and C3, respiratory insufficiency was found to be the cause of neonatal death. The results revealed that C1 consists of twins with both larger and smaller fetuses displaying cardiac failure with an increase in renal perfusion and a decrease in renal and placental perfusion, respectively, and C2 consists of twins with smaller fetuses having both placental insufficiency and intrauterine growth retardation. C3 consists of twins with both lager and smaller fetuses having normal circulation, when compared to singleton pregnancy.

Birth Weight↗