A case of gastric cancer with liver invasion responding to TS-1/low-dose CDDP chemotherapy

We report the case of a 79-year-old female with gastric cancer accompanied by liver invasion. She underwent simple subtotal gastrectomy in another hospital. Five months after surgery, combination chemotherapy with TS-1 (100 mg/body/day, 3 weeks) and CDDP (10 mg/body/day, day 1, 8, 15 drip infusion) in 1 course was performed, and complete response (CR) was noted. No severe adverse effects were observed during this combined therapy. TS-1 and low-dose CDDP therapy may prove effective for treating gastric cancer with liver invasion in advanced age.     

Sequence analysis of two ScFv genes of MAbs against Streptococcus mutans glucosyltransferase

Streptococcus mutans glucosyltransferases (GTFs) are considered to be the principal etiological agents of dental caries. Water-insoluble glucans (WIG) synthesized by those GTFs mediate sucrose-enhanced colonization for the bacterium on tooth surfaces and form dental plaque. GTFs have two functional domains, that is, an N-terminal catalytic sucrose-binding domain involved in sucrose hydrolysis and a C-terminal glucan-binding domain involved in the binding of the synthesized glucan polymer. Two hybridomas, each producing a monoclonal antibody (MAb) that inhibits the WIG synthesis by WIG synthesized GTF (GTF-I), were constructed. Those MAbs, P126 and P136, were shown to be able to recognize the different epitope domains in GTF; P126 recognized the N-terminal region, whereas P136 recognized the C-terminal region. We previously constructed two single chain fragments of immunoglobulin variable regions (ScFvs), which are capable of inhibiting GTF activity, from mice hybridomas producing P126 and P136. In the present study, we analyzed the nucleotide sequences of molecularly cloned ScFv genes (named ScFv/P126 and ScFv/P136), compared them in three complementarity- determining regions (CDRs), and also located their gene loci originate. Our results showed no particular relationship between the two ScFvs, and suggested the use of a certain type of VH or VL gene segment as well as possible evidence of the ability of these two MAbs to recognize different epitopes of GTF proteins.     

Molecular and cell biology of the sarcoglycan complex

The original sarcoglycan (SG) complex has four subunits and comprises a subcomplex of the dystrophin-dystrophin-associated protein complex. Each SG gene has been shown to be responsible for limb-girdle muscular dystrophy, called sarcoglycanopathy (SGP). In this review, we detail the characteristics of the SG subunits, and the mechanism of the formation of the SG complex and various molecules associated with this complex. We discuss the molecular mechanisms of SGP based on studies mostly using SGP animal models. In addition, we describe other SG molecules, epsilon- and zeta-SGs, with special reference to their expression and roles in vascular smooth muscle, which are currently in dispute. We further consider the maternally imprinted nature of the epsilon-SG gene. Finally, we stress that the SG complex cannot work by itself and works in a larger complex system, called the transverse fixation system, which forms an array of molecules responsible for various muscular dystrophies.     

The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.     

Electron spin resonance assay of ascorbyl radical generation in mouse hippocampal slices during and after kainate-induced seizures

As an index of oxidative status, we analyzed ascorbyl radical generation during and after kainate-induced seizures in mouse hippocampus, using an ESR spectrometer equipped with a special tissue-type quartz cell. A specific doublet ESR spectrum was observed after seizures, and the g value and the hyperfine coupling constant (hfcc) of the spectrum were identical with those of ascorbyl radical itself. Antiepileptic zonisamide inhibited the generation of ascorbyl radical accompanying the seizures.     

Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia

Hypothermia is the only neuroprotective therapy proven to be clinically effective. Identifying the molecules that play important roles in the efficacy of hypothermia, we developed a multi-channel computer-controlled system, in which the brain temperatures of freely moving rats were telemetrically monitored and maintained below 35 degrees C, and examined the time window necessary to exert its significant neuroprotective effects. Eight-week-old SD rats were subjected to a 2h middle cerebral artery occlusion (MCAO) with an intraluminal filament, and post-ischemic hypothermia was introduced at 0, 2, 4, or 6h after reperfusion until the rats were killed 2 days after MCAO. Since a significant protection was observed when hypothermia was started within 4h after reperfusion, it was concluded that the therapeutic time window of mild hypothermia lasts for 4h after reperfusion in our model. On the basis of the window, comprehensive gene expression analyses using oligonucleotide microarrays were conducted and identified potential genes related to the efficacy of hypothermia, which included inflammatory genes like osteopontin, early growth response-1, or macrophage inflammatory protein-3alpha. Therefore, the neuroprotective effects of post-ischemic mild hypothermia were strongly suggested to be mainly associated with the reduction of neuronal inflammation.     

Trial of vaginal breech delivery: current role

Breech presentation occurs at term in approximately 3% to 4% of singleton gestations. This presentation is associated with a variety of maternal and fetal conditions including preterm labor, abnormal amniotic fluid volume, hydrocephaly, anencephaly, mullerian anomalies, abnormal placentation, and multifetal gestation. Cesarean delivery has been associated with increased risk of subsequent accreta, placenta previa, hemorrhage, and hysterectomy. The Term Breech Trial initially suggested that planned vaginal breech delivery is associated with increased neonatal morbidity and mortality compared with planned cesarean delivery. Long-term follow-up of these vaginally delivered infants contradict the initial findings. Current debate surrounds the dilemma of whether the untoward complications of cesarean delivery are warranted given uncertain minimal increases in neonatal survival and improvement in neurologic outcome with planned cesarean.     

Improved peripheral blood stem cell collection following plasma exchange in a patient with elevated viscosity and coagulopathy

We report a case of improved CD34+ cell yields from peripheral blood stem cell (PBSC) collection following therapeutic plasma exchange (TPE) in a patient with elevated viscosity and coagulopathy. The patient was a 46-year-old male diagnosed with IgM lambda multiple myeloma that was largely unresponsive to standard chemotherapy. He had coagulopathy due to lymphoproliferative disease-associated acquired von Willebrand Factor (vWF) deficiency. The patient underwent two rounds of PBSC collections over 3 consecutive weeks (five total collections) prior to planned tandem transplant for multiple myeloma. Both rounds resulted in poor collections due to processing difficulties. It was decided to perform three TPEs daily immediately prior to attempting additional PBSC collections, to treat the patient's elevated viscosity and thereby potentially improve the efficiency of collections. Immediately following the three TPEs, two additional PBSC collections resulted in sufficient CD34+ cells to proceed to transplant. Lower IgM and/or viscosity levels present after the three TPEs likely permitted successful collection of stem cells.