Atomic-scale imaging of individual dopant atoms in a buried interface.

Determining the atomic structure of internal interfaces in materials and devices is critical to understanding their functional properties. Interfacial doping is one promising technique for controlling interfacial properties at the atomic scale, but it is still a major challenge to directly characterize individual dopant atoms within buried crystalline interfaces. Here, we demonstrate atomic-scale plan-view observation of a buried crystalline interface (an yttrium-doped alumina high-angle grain boundary) using aberration-corrected Z-contrast scanning transmission electron microscopy. The focused electron beam transmitted through the off-axis crystals clearly highlights the individual yttrium atoms located on the monoatomic layer interface plane. Not only is their unique two-dimensional ordered positioning directly revealed with atomic precision, but local disordering at the single-atom level, which has never been detected by the conventional approaches, is also uncovered. The ability to directly probe individual atoms within buried interface structures adds new dimensions to the atomic-scale characterization of internal interfaces and other defect structures in many advanced materials and devices.

Expression of cyclooxygenase-2, P-glycoprotein and multi-drug resistance-associated protein in canine transitional cell carcinoma.

Cyclooxygenase-2 (COX-2), P-glycoprotein (P-gp) and multi-drug resistance-associated protein (MRP) are considered important tumor-associated proteins in humans and dogs. In the present study, we immunohistochemically evaluated the expression of these proteins in canine patients with transitional cell carcinoma (TCC). Of 52 cases, 30 (57.7%) were positive for COX-2, 40 (76.9%) for P-gp, and only 10 (19.2%) for MRP. In addition, 27 samples (27/52, 51.9%) were positive for two markers, while 3 (5.7%) and 5 (9.6%) cases were positive and negative, respectively, for all three markers. No significant correlations were seen for COX-2 and P-gp on Fisher's exact test and Mann-Whitney's test, but a significance was seen on Spearman's rank correlation analysis using the IHC scoring system (P=0.043). These results suggest that P-gp expression is induced by overexpression of COX-2 in canine patients with TCC.

Increases in plasma atrial natriuretic peptide concentration antedate clinical evidence of preeclampsia.

Atrial natriuretic peptide (ANP) concentrations are typically elevated in hypervolemic states. However, ANP levels have been reported to be increased in the peripartum period in women with preeclampsia, a disorder characterized by central hypovolemia. We postulated that ANP levels are elevated in preeclamptic patients before clinically evident disease. ANP concentrations were determined in three groups: uncomplicated pregnancies, pregnancies complicated by preeclampsia, and non-pregnant reproductive-aged women. The former groups were matched for gestational age at plasma sampling and delivery. The plasma samples, obtained prospectively from each patient during the first, second, and third trimesters and within 72 h postpartum, were frozen before RIA. A significant gestational increase in ANP was noted in both groups of pregnant women, with third trimester levels exceeding first trimester levels (P less than 0.05). Consistent with previous reports, ANP levels were elevated in overtly preeclamptic patients vs. matched controls in the third trimester. The ANP concentration was also significantly increased during the second trimester in women destined to develop preeclampsia. Postpartum ANP values decreased in the preeclamptic group to approach the level in normal patients postpartum. Thus, it appears that the stimuli of ANP secretion differ in uncomplicated and preeclamptic patients. Moreover, an elevation of plasma ANP is detectable before the onset of clinical evidence of preeclampsia.

HNF-1 regulates the liver-specific transcription of the chipmunk HP-20 gene.

The chipmunk hibernation-specific protein HP-20 is a component of the 140 kDa complex that drastically decreases in the blood during hibernation, and its gene is expressed specifically in the liver. To reveal molecular mechanisms underlying the liver-specific transcription of the HP-20 gene, we isolated chipmunk HP-20 genomic clones. The HP-20 gene spans approximately 6 kb, and consists of three exons. The transcription start site, as determined by 5' RACE-PCR analysis, was found to be 160 bp upstream of the translation initiation codon. Transient transfection studies in HepG2 cells revealed that the 57 bp 5' flanking sequence was sufficient for the liver-specific promoter activity. A database search revealed that this region contains a potential binding site for hepatocyte nuclear factor-1 (HNF-1). In a gel retardation assay, in vitro-synthesized HNF-1 bound to the 5' flanking sequence from -52 to -26. A similar shifted band was also observed with HepG2 nuclear extracts, and this complex was super-shifted by an anti-(HNF-1) Ig. When transfected into COS-7 cells, HNF-1 transactivated transcription from the HP-20 gene promoter, and this activity was abolished by a mutation of the HNF-1 binding site, indicating that HNF-1 plays an important role in HP-20 gene expression.

Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5).

A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line. The sequence analysis revealed that the cDNA encoded a protein of 557 aa residues with a calculated molecular weight of 64,236. The encoded protein has typical structural characteristics shown in the TRAF family of proteins and binds to the cytoplasmic region of lymphotoxin-beta receptor more efficiently than to that of CD40 and CD30. The TRAF5 gene was mapped to the human chromosome 1q32.3-q41.1. Overexpression of human TRAF5 activates NF kappa B transcription factor in human 293T kidney cells. These results suggest that the human TRAF5 protein could be involved in the signal triggered by various members of the tumor necrosis factor receptor (TNFR) superfamily including CD40, CD30 and lymphotoxin-beta receptor.

Interleukin-4-dependent induction of preproenkephalin in antigen-specific T helper-type 2 (Th2) cells.

Naive Th cells obtained from OVA(323-339)-specific DO11.10 TCR-Tg mice did not express preproenkephalin (PPE) mRNA. However, culture of naive Th cells with OVA(323-339) peptide (OVA-pep) plus IL-2 under Th2-inducing conditions for 7 days resulted in an induction of PPE mRNA. The PPE mRNA was also induced by culturing with OVA-pep plus IL-2 (neutral condition). However, PPE mRNA induction under neutral conditions was totally abrogated by addition of anti-IL-4 mAb. The existence of methionine-enkephalin was also demonstrated in peptidase-digested peptides derived from Th2 cell lysate. These results demonstrate that IL-4 is a critical factor for the induction of PPE mRNA in freshly expanded antigen-specific Th2 cells.

Outcome of children prenatally exposed to cocaine and other drugs: a path analysis of three-year data.

OBJECTIVE: Cocaine and other drug use during pregnancy continues to be a major health concern. With increasing use of cocaine by women of childbearing age, large numbers of children have been exposed to this and other substances in utero. Currently, very little information regarding the long-term developmental implications of cocaine/polydrug exposure exists. The purpose of this study is to present 3-year cognitive and behavioral data on infants exposed to cocaine and other drugs during gestation. METHODS: The subjects and controls in this study are currently enrolled in a longitudinal, prospective evaluation. At 3 years of age, 92 children exposed to cocaine and other drugs, 25 children exposed to multiple drugs but no cocaine, and 45 drug-free controls were evaluated using the Stanford-Binet Intelligence Scale (fourth edition), the Child Behavioral Checklist, the Home Screening Questionnaire, and a Summative Perseverance Scale. The data were analyzed using an a priori model and path analytic procedures. RESULTS: The results indicate that prenatal drug exposure has significant direct and indirect effects on 3-year cognitive functioning as measured on the Stanford-Binet scale. The fit indices indicated that overall, the hypothesized model accurately reflected the actual data. CONCLUSIONS: The findings of the study provide specific evidence elucidating the nature of long-term developmental risk associated with intrauterine drug exposure. Drug exposure was found to have a direct effect on cognitive ability at 3 years of age. However, the effects of drug exposure are also mediated indirectly through head circumference, home environment, and level of perseverance at a task. Future explorations should continue to utilize path analysis techniques to further clarify the ramifications of drug exposure on the development of the growing child.

Chest compression-induced vertebral fractures.

Two cases with chest compression-induced thoracolumbar transvertebral fractures are discussed. This is a previously unreported complication of cardiopulmonary resuscitation. Dorsal kyphosis and osteopenia were present in both of these cases. There was no spinal cord injury documented, though the potential for injury and paraplegia exists. Care should be taken to avoid this complication, especially in the elderly with kyphosis; however, adequate compressions to insure support of circulation should be maintained.

C-fos expression in the rat brain after intraperitoneal injection of lithium chloride.

The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.

Three-year outcome of children exposed prenatally to drugs.

OBJECTIVE: To evaluate the 3-year behavioral and developmental outcome of children prenatally exposed to maternal substances of abuse. METHOD: Ninety-three children exposed prenatally to cocaine and other drugs taken by the mother during pregnancy (Group 1), 24 polydrug/noncocaine exposed children (Group 2), and 25 nonexposed children (Group 3) were evaluated at 3 years of age as part of a longitudinal prospective study of the impact of intrauterine substance exposure on long-term outcome. The Stanford-Binet Intelligence Scale: Fourth Edition(SBIS) was administered by examiners blinded to the exposure background of the children, and a pediatrician performed a complete medical evaluation on all the children. The children's primary caregiver completed the Achenbach Child Behavior Checklist. Stepwise multiple regression procedures were used to determine the factors that best predicted 3-year growth, intelligence, and behavior. RESULTS: Groups 1 and 2 differed from Group 3 on head circumference. Group 1 scored lower than Group 3 on SBIS Verbal Reasoning. Group 2 scored Slower than Group 3 on SBIS Abstract/Visual Reasoning. Cocaine exposure predicted poor verbal reasoning. Marijuana exposure predicted poor abstract/visual reasoning. Examiner rating predicted intellectual outcome and caregiver ratings. Caregivers rated exposed children as more aggressive than nonexposed. CONCLUSION: Contrary to information in the popular media, not all substance-exposed children suffer the same poor prognosis. In fact, generalizations about the fate of drug-exposed children must await additional research into the outcome of the broader population of drug-exposed children, examining the roles of maternal and environmental factors across a variety of geographic locations and socioeconomic levels.

State-dependent changes of extracellular glutamate in the medial preoptic area in freely behaving rats.

Microdialysis technique was applied to the medial preoptic area (mPOA) of the hypothalamus, a crucial site for the regulation of sleep, in order to analyze the interrelationship between the extracellular level of glutamate (Glu) and the vigilance states. Dialysates from the mPOA were sampled at 5-min intervals for 2-h diurnal period with a perfusion rate of 2.0 microliters/min in freely moving rats, whose sleep-waking behaviors were polysomnographically monitored. Extracellular Glu increased during wakefulness, exhibiting a peak at the transition period from wakefulness to non-rapid-eye-movement sleep (NREMS) (18.0% above the average), whereas it decreased during NREMS (9.2% below the average). It is likely that Glu in the mPOA is dynamically involved in the alterations of the vigilance states.

Gustatory reaction time under variable stimulus parameters in human adults.

Reaction times and perceived intensities for NaCl solutions were measured in sixteen human adults. Stimulus delivery was by means of a circular piece of solution-soaked filter paper held with forceps. The reaction time (T) decreased and the perceived intensity (S) increased with increasing the concentration (C) of NaCl solution applied to a fixed (78.5 mm2) tongue area. The comprehensive relations among T, S and C can be expressed by the following formula; T=a+b/log(C/Co), T=p+q/log(S/So), and logS=mlogC+logn, where a, b, p, q, m, n=constants, and So indicates the perceived intensity at the threshold concentration (Co). Meanwhile, the reaction time decreased and the perceived intensity increased with increasing the stimulated area (A) under a fixed (1.0 M) concentration of NaCl solution. The relations among T, S and A can also be expressed by the following equations; T=a'+b'/log(A/Ao), T=p'+q'/log(S/So), and logS=m'logA+logn', where a', b', p', q', m', n'=constants, and Ao indicates the threshold size of stimulated area.

Studies on the biosynthesis of carbapenem antibiotics. I. Biosynthetic significance of the OA-6129 group of carbapenem compounds as the direct precursors for PS-5, epithienamycins A and C and MM 17880.

Based on the working hypothesis that the OA-6129 group of carbapenem compounds might be the direct precursors for PS-5, epithienamycins A and C and MM 17880, Streptomyces fulvoviridis A933 17M9, a producer of PS-5, PS-6, PS-7, PS-8, epithienamycins A, B, C and D, MM 17880, MM 13902 and MM 4550, was subjected to NTG-mutation to provide a blocked mutant numbered 1501 which was found to produce OA-6129 A, OA-6129B1, OA-6129B2 and OA-6129C instead of PS-5, epithienamycins A and C and MM 17880, respectively. In a cell-free system, the parent strain demonstrated an ability to convert OA-6129A to NS-5, whereas the mutant did not. The L- and D-amino acid acylases were also shown to depantothenylate the OA-6129 group of carbapenems.

Cryopreservation of wild mouse spermatozoa.

Spermatozoa of wild mice from China, Czechoslovakia, Denmark, India, Japan and Switzerland were frozen and stored at -196 degrees C. After thawing, intact oocytes were inseminated in vitro with relatively high motility frozen-thawed mouse spermatozoa from Czechoslovakia, Denmark and India, while oocytes with a partially dissected zona were inseminated with low motility frozen-thawed spermatozoa from China, Japan and Switzerland. Embryos developing to the 2-cell stage from oocytes fertilized with frozen-thawed spermatozoa were transferred to the oviducts of female recipients on the first day of pseudopregnancy (day when a vaginal plug was confirmed). Successful embryo development to the 2-cell stage was 46 to 67%. Offspring resulted from 17 to 51% of these transferred 2-cell embryos.

Germ-line contribution of embryonic stem cells in chimeric mice: influence of karyotype and in vitro differentiation ability.

The effect of the karyotype and the ability to differentiate in vitro upon germ-line transmission by A3-1 embryonic stem (ES) cells in chimeric mice were examined. Germ-line transmission was confirmed in ES cells exhibiting 38% and more of the normal karyotype, but no chimeric mice and/or germ-line transmitters were observed regardless of the karyotype when the cystic embryoid body (CEB) was formed on day 8 and later in the suspension culture. Germ-line transmission of the ES cells was not significantly influenced by formation of the simple embryoid body (SEB). Germ-line transmitters were preferentially observed in chimeras when the ES cell contribution to coat color was markedly increased, but this contribution to coat color varied regardless of the karyotype or in vitro differentiation ability. These results suggest that A3-1 ES cells which exhibit CEB at 7 days after suspension culture and approximately 40% of normal karyotype are capable of germ-line transmission in chimeric mice.

Synthesis of oligodeoxyribonucleotide bearing 2'-S-alkyl residue and its effect on the duplex stability.

2'-Deoxy-2'-S-hexyluridine derivative was synthesized from 2,2'-anhydrouridine and 1-hexanethiol and incorporated into an oligodeoxyribonucleotide. The thermal stability of the duplexes formed by the 2'-S-hexyl modified ODN with either the complementary DNA or RNA strand was decreased compared to the unmodified counterparts.

[A case of craniopharyngioma with hyperprolactinemia in postoperative course (author's transl)].

Authors report a case of craniopharyngioma with hyperprolactinemia, which was never noticed before surgical operation and showed the amenorrhea-galactorrhea syndrome from 7 months after surgical procedure. The patient is a 44 years old housewife. By the medication of CB-154 (Bromocriptin), the high value of plasma prolactin came to normal range and the galactorrhea disappeared, but the amenorrhea persisted. Because author was able to except the possibility of combine of PRL releasing pituitary adenoma or ectopic malignant tumors from the various examination and laboratory findings, the mechanism of secretory disturbance of PRI inhibiting factor in hypothalamus was investigated. These are 1) compression or invasion to hypothalamus through the recurrence of residual tumor, 2) mechanical focal damage of hypothalamus due to surgical manipulation, 3) side effects in hypothalamus depended on postoperative radiation and 4) others. As first element is denied in findings of postoperative CT scan, author is considering that second and third element may be possible factor.

[A case of ruptured middle cerebral artery aneurysm with acute subdural hematoma after clipping of the aneurysm nine years previously].

It is known well that acute subdural hematoma develops most frequently after head injury, and secondly from pathological lesions such as intracranial ruptured aneurysm or AVM. A case of ruptured middle cerebral artery aneurysm which was clipped nine years before resulting in acute subdural hematoma is reported. At 6 pm on July 21, 1988, a 53-year-old woman with severe headache starting at 4:20 pm was transferred to our hospital. She suffered from herniated signs; Conscious disturbance; anisocoria; positive OCR; decerebrate posture. An emergency CT showed right acute subdural hematoma with severe midline shift. Following a decompressing craniotomy at 9 pm, the subdural clot was evacuated. It measured 90g in volume and the underlying cortex was normal. There was no evidence of SAH. Right carotid angiography three weeks after the first operation showed a middle cerebral artery aneurysm at the site of a clip which had been applied nine years ago. A second operation was performed on August 30, 1988. Via the right pterional route, the middle cerebral artery aneurysm was clipped successfully with a Sugita's clip replacing the first clip. We concluded that the regrowth and rebleeding of the middle cerebral artery aneurysm which had been clipped nine years before was most probable. She was discharged with slightly decreased consciousness and right motor weakness, on November 13, 1988.

[Treatment of the association of arteriovenous malformation and cerebral aneurysms].

The association of an arteriovenous malformation (AVM) and a cerebral aneurysm is not so rare. Many reports have analyzed its localized relationship and studied hemodynamically the development of the cerebral aneurysm. However its therapeutic measures have not been established so far. At this time, authors have experienced 9 cases of AVM associated with cerebral aneurysm, and have studied suitable therapeutic measures. All 9 cases developed with intracranial hemorrhage, and in 6 of 9 cases, cerebral aneurysm was recognized in the feeding arteries or feeding system of the AVM (Group I). In the other 3 cases, localization of cerebral aneurysm was hemodynamically considered to have less of a relationship with AVM (Group II). It was characteristic that cerebral aneurysm in Group I was multiple, and developed frequently in the peripheral regions of the cerebral artery, especially in feeding system of the AVM itself. An operation was carried out in all 9 cases, and in Group I, 2 of 6 cases were operated on in one stage. The other 4 cases because of difficulty of management in the same operative field, were divided into two stages. In cases with clearly hemorrhagic sources, operation was firstly performed on the hemorrhagic source, and its residual focus was operated on after several months. However, in cases with unknown hemorrhagic source, cerebral aneurysm existing on the proximal side was operated on firstly. On the other hand, in Group II, when the operation was performed at one or two stages, the hemorrhagic source was dealt with first.(ABSTRACT TRUNCATED AT 250 WORDS)