Pregnancy: Oral misoprostol versus placebo for cervical dilatation before vacuum aspiration in first trimester pregnancy

Intravaginal misoprostol has been shown to be effective forcervical priming before a surgically induced abortion. The objectivewas to investigate the effectiveness of oral misoprostol incervical dilatation prior to vacuum aspiration between the 6thand 12th weeks of pregnancy. The results showed that in nulliparouspatients, the median cervical dilatation in the treatment group(7.8 mm) was significantly greater than that in the placebogroup (3.7 mm). In multiparous patients, the difference wasalso statistically significant (9.8 versus 6.0 mm). The easeof dilatation, assessed subjectively by the operating surgeons,was significantly improved in the treatment group. There wasalso a significant reduction in the duration of the operationand in the mean blood loss in the treatment group. The side-effectsencountered in the treatment group were mild and well acceptedby the women. Oral misoprostol is an effective and safe methodfor cervical dilatation prior to vacuum aspiration in firsttrimester pregnancy.     

Kupffer cell activation in the survival discrepancy between liver grafts from enterally and parenterally fed donors

Abstract This study was designed to investigate the effects of differences in the route of nutritional support of the donor on cold ischemia/reperfusion injury. Participation of Kupffer cells in these effects, based on the analysis of hepatic energy metabolism in early phases of reperfusion was also investigated. Orthotopic liver transplantation was performed between Large-White pigs weighing 20–30 kg after a 4-h cold preservation of the graft in Euro-Collins solution at 4°C. One group was fed orally with a standard laboratory diet (FED group, n = 5), a second group was fasted and given 20% glucose intravenously (12 kJ/kg per day) (PEF group, n = 5), and a third group was fed orally with a standard laboratory diet and given GdCI₃ (10 mg/kg) intravenously 24 h before operation (FEDGD group, n = 5). These treatments were given for 7 days prior to harvesting. The survival time was significantly longer in the PEF (34.8 ± 5.5 days) and FEDGD (28.0 ± 11.9 days) groups than in the FED (9.8 ± 2.0 days) group ( P < 0.05). The serum hyaluronic acid elimination rate determined from 1 to 2 h after reperfusion was significantly lower in the FED group than in the other two groups ( P < 0.001). The glycogen content of the livers 1 h after reperfusion in all three groups had been consumed rapidly, but the ATP content of the livers was significantly reduced in the FED group alone ( P < 0.01). Hepatic FFA clearance (C_FFA) was moderately increased in all three groups in the early phase after reperfusion, but it was higher in the FED group than in the other two groups, with significant differences 1 and 2 h after reperfusion ( P < 0.05). In conclusion, parenteral nutrition of the donors reduced cold ischemia/reperfusion injury which is related to Kupffer cell activation and, thus, was better than enteral nutrition for donor management.     

A case report of ultrasonic decalcification for calcified bicuspid aortic valve stenosis

Calcified stenotic aortic valve are usually replaced by the artificial valve. Recently, we are trying to decalcify the calcification of the aortic valve by ultrasonic energy. This case report reviewed a small physique, 47 year old female, who had the calcified stenotic bicuspid aortic valve and the narrow aortic valve ring (18 mm diameter). The ultrasonic decalcification was performed by the ultrasonic surgical instrument, SUS-201D (ALOKA), ultrasonic energy output range from 25% to 45%. After the ultrasonic decalcification, the movability of the aortic cusps were improved and the aortic opening was enlarged. The systolic pressure gradient across the aortic valve was improved from 100 mmHg to 20 mmHg. This method "ultrasonic decalcification" is very useful technique for the repair of the calcified aortic valve stenosis.     

Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease

Collapsin response mediating protein-2 (CRMP2) has been identified as an intracellular protein mediating Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling. In In vitro kinase assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3beta did not induce any phosphorylation of CRMP2. Phosphorylation by GSK3beta was exclusively observed in Cdk5-phosphorylated CRMP2, but barely in CRMP2T509A. These results indicate that Cdk5 primarily phosphorylates CRMP2 at Ser522 and GSK3beta secondarily phosphorylates at Thr509. The dual-phosphorylated CRMP2, but not non-phosphorylated or single-phosphorylated CRMP2, is recognized with the antibody 3F4, which is highly reactive with the neurofibrillary tangles of Alzheimer's disease. 3F4 recognized the CRMP2 in the wild-type but not cdk5-/- mouse embryonic brain lysates. The phosphorylation of CRMP2 at Ser522 caused reduction of its affinity to tubulin. In dorsal root ganglion neurones, Sema3A stimulation enhanced the levels of the phosphorylated form of CRMP2 detected by 3F4. Over-expression of CRMP2 mutant substituting either Ser522 or Thr509 to Ala attenuates Sema3A-induced growth cone collapse response. These results suggest that the sequential phosphorylation of CRMP is an important process of Sema3A signalling and the same mechanism may have some relevance to the pathological aggregation of the microtubule-associated proteins.     

A novel mutation in the FcgammaRIIIA gene (CD16) results in active natural killer cells lacking CD16

We report a novel mutation in FcgammaRIIIA (the transmembrane-form CD16) on natural killer (NK) cells in a patient with polyneuropathy. She had no history of recurrent infections. Her NK cells expressed no detectable CD16; however, her NK cytotoxic activity was normal, suggesting that CD16 expression and cytotoxic activity are independent of one another. Molecular analysis revealed a deletion of a single adenine base in exon 4 of CD16 at nucleotide 550. This deletion generates a STOP codon in an extra-cellular domain of the FcgammaRIIIA gene, thereby truncating the CD16 molecule. The patient's NK cells were not recognized by the anti-CD16 monoclonal antibodies 3G8 and Leu11c. Whether the development of her polyneuropathy is associated with this novel mutation is unclear.     

Cytogenetic characterization of ten cases of Ph1-positive acute myelogenous leukemia

Chromosome banding analyses were made on 10 cases of Ph1-positive AML (7 M1 and 3 M2). The standard type Ph1 translocation, t(9q +;22q -), was identified in all of them. Karyotypically normal cells were observed in 6-65% of bone marrow metaphases at the initial cytogenetic examination of 7 patients, whereas the remaining 3 patients had only Ph1-positive cells at diagnosis. Follow-up studies performed in 5 cases indicated that the frequency of karyotypically normal cells increased up to 81-100% when the patients were in remission, whereas it was much reduced in relapse. In 5 cases, there was observed a clone of cells in which the Ph1 translocation was the sole karyotypic abnormality. Various types of other chromosome abnormalities, in addition to the Ph1, were observed in all cases, among which-7 was the most frequent, being found in three cases as a stem line. Other additional changes encountered were + Ph1, del(5), i(17q), - 10, + 18, + X, and various numerical and structural changes including certain secondary translocations that occurred in the Ph1 (22q -) or its partner (9q +). The types and frequencies of these additional changes appeared to be different from those found in the acute phase of CML or in Ph1-positive ALL.     

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(–273)C (P=0.0074), C(–297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(–273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(–273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(–273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.     

Electrophysiologic studies on the pallido- and cerebellothalamic projections in squirrel monkeys (Saimiri sciureus)

Summary Thalamic projections of the pallidum and the deep cerebellar nuclei were studied by unitary recordings as well as field potential analysis in the thalamus of squirrel monkeys (Saimiri sciureus) under sodium pentobarbital anesthesia.Stimulation of the pallidum produced a positive field potential preceded by incoming afferent fiber volleys in the thalamus. Spontaneous discharges of thalamic neurons were suppressed during this positive potential, and intracellular recordings from the thalamic neurons revealed that the time course of this field potential corresponded to that of the hyperpolarizing potential. The hyperpolarization was presumed to be a monosynaptic inhibitory postsynaptic potential by the short synaptic delay (about 0.5–0.7 ms) and responsiveness to high frequency stimulation (over 150 Hz). The positive field potential on stimulation of the external pallidal segment was distributed in L.po (VA) and the reticular thalamic nucleus around L.po, whereas that on stimulation of the internal segment was in V.o.a (the anterior basal part of VL) and in Z.o (upper part of VL). The projection of the external segment appeared to be less dense than that of the internal segment.The projection of deep cerebellar nuclei was situated in V.o.a, V.o.p (posterior part of basal part of VL), V.o.i (VLm), the intralaminar nucleus (CL), and some part of V. im (the rostral part of VPLo). Projections of the interpositus and dentate nuclei were distributed in a more anterior part than those of the fastigial nucleus. A certain topographical arrangement of the projections of these three nuclei was found in V.o.p, V.o.i and V.im. No significant overlap was detected between projections of the pallidum and the deep cerebellar nuclei within the thalamus.     

Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.