This article summarizes our recent finding that the nociceptin system is involved in the regulation of learning and memory. The nociceptin-knockout mice show greater learning ability in the water maze task, an enhanced latent learning in the water finding task, better memory in the passive avoidance task, and further, larger long-term potentiation in the hippocampal CA1 region than wild-type mice. Nociceptin itself induces an impairment of passive avoidance task in wild-type mice, which is reversed by naloxone benzoylhydrazone (NalBzoH). Thus, the nociceptin system seems to play negative roles in learning and memory, and NalBzoH may act as a potent antagonist for the nociceptin receptor.

Animals↗

PubMed2000

Differential expression and phosphorylation of particular fos family members by kainate in nuclear and cytosolic fractions of murine hippocampus.

An i.p. injection of kainate resulted in severe losses of neuronal cells stained by Cresyl Violet in the CA1 and CA3 pyramidal layers of the murine hippocampus within two weeks, without affecting those in the dentate granule layer up to six weeks. Immunohistochemical analysis revealed marked and predominant expression of Fos family members, including c-Fos, Fos-B and Fra-2 proteins, in the dentate granule layer of the hippocampus, but not in the pyramidal layers, 2-18h after administration. Immunoblotting experiments showed that kainate induced more potent expression of c-Fos protein in nuclear fractions obtained 2h after injection than those obtained 18h later, with similar expression between cytosolic fractions obtained 2 and 18h after administration. Both Fos-B and Fra-2 proteins were more potently expressed in nuclear and cytosolic fractions 18h after administration than 2h when determined on immunoblotting analysis. Two-dimensional electrophoresis revealed expression of several proteins immunoreactive to the anti-c-Fos antibody with different isoelectric points in response to kainate in nuclear and cytosolic fractions of the hippocampus for 2-18h after a single injection. Immunoprecipitation analysis using the anti-c-Fos antibody showed phosphorylation of c-Fos protein on serine residues in hippocampal nuclear fractions 2h after administration, with additional phosphorylation on tyrosine residues 18h later. Prior treatment of the protein synthesis inhibitor cycloheximide prevented the expression of immunoreactivities to the anti-c-Fos antibody detected on two-dimensional electrophoresis in hippocampal nuclear fractions obtained 2h after administration.These results suggest that in vivo kainate signals may lead to persistent expression of the transcription factor activator protein-1 that consists of different Fos family members, as well as of c-Fos protein phosphorylated on serine and/or tyrosine residues, at an early stage after administration. Such signal consolidation processes could play a role in mechanisms associated with neuronal survival after kainate in the dentate granular layer of murine hippocampus.

Animals↗

PubMed2000

Teratocarcinosarcoma of the nasal cavity. Report of a case showing favorable prognosis.

We report a very rare case of teratocarcinosarcoma of the nasal cavity showing a favorable prognosis. The patient was a 66-year-old man with a mass completely obstructing the right nasal cavity. Subsequently, extirpation of the mass and Denker-Watsuji operation were performed, and the patient was treated with a combination of radiation therapy and chemotherapy. Neither recurrence nor distant metastasis was observed during follow-up lasting 30 months. Histologic examination of the resected mass revealed several tissue elements including columnar and squamous epithelia with atypia, smooth muscle cells with rare mitotic activity, and neuroectodermal tissue. The glandular epithelium and smooth muscle cells were reminiscent of a primitive intestinal organoid structure, suggestive of teratomatous tumorigenesis. Our case and a review of the literature indicate that the absence of invasiveness to the stroma or surrounding tissue is closely related to a favorable prognosis.

Aged↗

PubMed2000

Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases.

We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions.

Apocrine Glands↗

PubMed2000

Genetic structure of Camellia japonica L. in an old-growth evergreen forest, Tsushima, Japan.

The spatial genetic structure of Camellia japonica was investigated, using microsatellite markers, in a 4-ha permanent plot within an old-growth forest. Spatial distribution of individuals was also assessed to obtain an insight into spatial relationships between individuals and alleles. Morisita's index of dispersion showed that 518 C. japonica individuals in the plot were clumped, and Moran's I spatial autocorrelation coefficient revealed weak genetic structure, indicating a low level of allele clustering. Average I correlograms showed that there was stronger genetic structure over short-distance classes. The clumped distribution of individuals and the positive autocorrelation over short-distance classes may result from the limited seed dispersal and microsite heterogeneity of the stand, while the genetic structure may be weakened by overlapping seed shadow and extensive pollen flow, mediated by animal vectors, and the high outcrossing rate found in C. japonica.

Ericales↗

PubMed2000

Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: a case report with an immunohistochemical study.

A rare example of malignant transformation in an ancient schwannoma arising in the right side of the neck of a 51-year-old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle-shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S-100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB-1 antibody was 30.5%. In contrast, S-100-positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. Immunohistochemistry would be useful as an ancillary technique in such a setting.

Biomarkers, Tumor↗

PubMed2000

Age dependency of neointima formation on vascular prostheses in dogs.

Neointima formed quickly on vascular prostheses implanted in young dogs but not in aged dogs. Previously, we found that impeding neointima formation on vascular prostheses occurred more frequently in aged animals. From these observations, we hypothesized that neointima formation was age-dependent in dogs. To test the hypothesis, 26 fabric Dacron vascular prostheses were analyzed. Half of them were retrieved from aged dogs (more than 13 years old) while the other half were from young ones (less than 1 year old). The grafts were harvested at 8 weeks and 3 months after implantation. The graft surfaces were photographed and analyzed by computer for the ratio of the areas with and without thrombus. Light and scanning electron microscopic observation revealed that most of the thrombus-free areas were lined with endothelial cells. Then the endothelialized areas were calculated. Using data obtained from macroscopic, light microscopic, and scanning electron microscopic observations, the arithmetic means were calculated as the degree of neointima formation. In young animals, the degrees at 8 weeks and at 3 months were 89.1 +/- 8.5% (mean +/- SD) and 95.7 +/- 3.3%, respectively. In old animals, they were 27.9 +/- 5.9% and 31.5 +/- 6. 8%, respectively. From these results, we concluded that neointima formation was age-dependent in dogs.

Aging↗

PubMed2000

Cyclic variation of integrated ultrasound backscatter in the left ventricle during the early neonatal period.

BACKGROUND: Significant changes in the contractility and histologic structure of the ventricular myocardium occur during the early neonatal period. Cyclic variation (CV) of ultrasonic integrated backscatter (IBS) reflects myocardial contractile performance. The aim of this study was to define normal values of and its serial changes in CV of IBS in the left ventricle of normal neonates. METHODS AND RESULTS: We recorded long-axis IBS images in 169 healthy neonates within 14 days after birth (mean 4.6 +/- 4.2 days) and in 84 infants and children (mean age 8.7 +/- 5.2 years). For each, we obtained CV of IBS in the interventricular septum (CV(IVS)) and the posterior wall (CV(PW)). In neonates, there was a significant linear correlation between CV and date after birth in measurements of both the interventricular septum and the posterior wall (r = 0.57 and 0. 60, respectively). In infants and children, there was no significant relation between age and CV(IVS) or CV(PW). In neonates >4 days after birth, the magnitude of CV(IVS) was not significantly different from that in infants or children. By contrast, the magnitude of CV(PW) was still significantly decreased in neonates >9 days after birth compared with that in infants and children (P <. 005). The ratio of CV(IVS) to CV(PW) (CV(IVS)/CV(PW)) was significantly higher in neonates than in infants and children (0.99 +/- 0.29 vs 0.80 +/- 0.22, P <.001). CONCLUSIONS: Both CV(IVS) and CV(PW) in neonates gradually increase after birth, indicating developmental maturation of the left ventricle. High values of CV(IVS)/CV(PW) might reflect the remnant of relatively high contractile performance in the right ventricle during fetal life.

Adolescent↗

PubMed2000

Left ventricular wall motion velocities in healthy children measured by pulsed wave Doppler tissue echocardiography: normal values and relation to age and heart rate.

Left ventricular wall motion velocities were measured by pulsed wave Doppler tissue (PWDT) echocardiography in 131 healthy children (mean age 7.5 +/- 5.5 years) at the interventricular septum and the posterior wall in the left ventricular short-axis view, and at the interventricular septum and the lateral wall in the 4-chamber view. The systolic wave (Sw) consisted of 2 components, and the difference between the 2 components was greater in the lateral wall than in the other walls. The peak early diastolic wave (Ew) velocity was also highest in the lateral wall. Most variables during systole correlated with age. The ratio of peak atrial systolic wave (Aw) velocity to peak Ew velocity (Aw/Ew) correlated with heart rate. The Aw/Ew in each wall correlated with the ratio of late (A) to early (E) peak mitral flow, although regression slopes differed among different wall segments. In younger children with increased heart rates, the Aw/Ew ratio increased because the Ew velocity decreased, although the A/E ratio increased because of an increased A velocity. Normal values for the PWDT variables change with heart rate and age in the pediatric population. The data reported in this study can be used as normal values for left ventricular function for PWDT echocardiography.

Adolescent↗

PubMed2000

Lobular endocervical glandular hyperplasia represents pyloric gland metaplasia?

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Adenocarcinoma↗

PubMed2000

A comparison of thinning and conventional free-flap transfers to the lower extremity.

This study compares the application of conventional free flaps and thinning flaps to the lower extremities. Thirty patients whose skin and soft tissue of the lower extremities had been reconstructed were divided into two groups: a conventional flap group, reconstructed using conventional free flaps (15 cases), and a thinning flap group, reconstructed using thinning flaps (15 cases). Postoperative complications, long-term results, and revisional surgery were studied in the two groups. Although survival after surgery was the same in both, in the conventional flap group, 11 patients required secondary revisional surgery, the excessive bulk of the flap resulting in poor aesthetics and difficulty in wearing shoes. The conventional flap group also required longer treatment. In the thinning flap group, only 5 of 15 patients received secondary revisional surgery. As a reconstruction material for the lower extremities, thinning flaps are both aesthetically and functionally superior to conventional bulky flaps.

Adolescent↗

PubMed2000

Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated cardiac hypertrophy.

We compared the role of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK)/p90(RSK) cascade in gp130-mediated cardiac hypertrophy with the contribution of the Janus kinase (JAK)/signal transduction and activation of transcription (STAT) and phosphatidylinositide 3-kinase (PI3-K) pathways. Primary cultured neonatal rat cardiomyocytes were stimulated with leukemia inhibitory factor (LIF). LIF sequentially activated Raf-1, MEK1/2, ERK1/2, and p90(RSK). We used PD-98059 (a specific MEK inhibitor), AG-490 (a JAK2 inhibitor), and wortmannin (a PI3-K inhibitor) to confirm that this cascade was independent of the JAK/STAT and PI3-K/p70 S6 kinase (S6K) pathways. PD-98059, AG-490, and wortmannin suppressed the LIF-induced increase in [(3)H]phenylalanine uptake by 54.7, 21.5, and 25.6%, respectively, and inhibited the increase in cell area by 61.2, 42.8, and 39.2%, respectively. Reorganization of myofilaments was predominantly suppressed by AG-490. LIF-induced expression of c-fos, brain natriuretic peptide, and skeletal alpha-actin mRNA was markedly suppressed by PD-98059 and moderately suppressed by wortmannin and AG-490. Atrial natriuretic peptide was significantly suppressed by AG-490. These findings indicate that this pathway is critically involved in protein synthesis, induction of c-fos, brain natriuretic peptide, and skeletal alpha-actin expression and is partially involved in myofilament reorganization and atrial natriuretic peptide induction in gp130-mediated cardiac hypertrophy.

Androstadienes↗

PubMed2000

A case of cigarette smoking-induced acute eosinophilic pneumonia showing tolerance.

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Bronchial Provocation Tests↗