Histologic and immunohistochemical characteristics of neoplastic and nonneoplastic subgroups of atypical squamous lesions of the uterine cervix

Atypical squamous lesion (ASL), a histologic diagnosis of unclear significance in the uterine cervix, can be divided into neoplastic and nonneoplastic groups. We aimed to determine the morphologic characteristics of these 2 groups. Histologic and immunohistochemical features were evaluated on the original biopsy specimen from 37 ASL cases, and the results were compared between neoplastic (19 cases) and nonneoplastic (18 cases) groups, which were determined based on the follow-up histopathologic findings. Mitosis, vertical nuclear growth pattern, no perinuclear halo, indistinct cytoplasmic border, primitive cells in the upper third of the squamous layer, p16+ cells in the upper two thirds of the squamous layer, and Ki-67+ cells in the upper two thirds of the squamous layer were significant indicators for neoplastic ASLs. Of the 19 neoplastic ASLs, 16 (84%) had 5 or more of these 7 indicators. The majority (16/18 [89%]) of the nonneoplastic ASLs had 2 or fewer indicators. Determination of the histologic and immunohistochemical characteristics is useful for distinguishing neoplastic and nonneoplastic ASLs.     

A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels

Multiple protein kinase C (PKC) isozymes are present in neurons, where they regulate a variety of cellular functions. Due to the lack of specific PKC isozyme inhibitors, it remains unknown how PKC acts on its selective target(s) and achieves its specific actions. Here we show that a PKC binding protein, enigma homolog (ENH), interacts specifically with both PKCepsilon and N-type Ca2+ channels, forming a PKCepsilon-ENH-Ca2+ channel macromolecular complex. Coexpression of ENH facilitated modulation of N-type Ca2+ channel activity by PKC. Disruption of the complex reduced the potentiation of the channel activity by PKC in neurons. Thus, ENH, by interacting specifically with both PKCepsilon and the N-type Ca2+ channel, targets a specific PKC to its substrate to form a functional signaling complex, which is the molecular mechanism for the specificity and efficiency of PKC signaling.     

A toxic substance from the sea urchinToxopneustes pileolus induces histamine release from rat peritoneal mast cells

A toxic substance (P-II fraction), fractionated from the pedicellariae of the sea urchinToxopneustes pileulus, dose-dependently caused the histamine release from rat peritoneal mast cells. The histamine release induced by P-II fraction increased with time, while compound 48/80 caused a more rapid histamine release. The dose-response curve for P-II fraction was studied with concentration 0.03–2.0 mg/ml. This reaction was dependent on Ca²⁺ and temperature. When glucose (5.5. mM) was omitted during the incubation step, the histamine release induced by P-II fraction was significantly reduced as compared to that of compound 48/80. Pyruvate reversed this reduction. On the other hand, the histamine release induced by P-II fraction was effectively potentiated by the addition of glucose (11.0 mM), but not that by compound 48/80. These results suggest that P-II fraction-induced histamine release differs from that of compound 48/80 disregards to the effects of glucose, because this histamine release appears to be more sensitive to the glycolytic pathway than compound 48/80-induced histamine release.     

Variation of the conserved neutralizing epitope in influenza B virus victoria group isolates in Japan

For almost 20 years, the neutralizing-epitope site specific for influenza B virus Victoria group isolates was conserved at the "tip" of the hemagglutinin molecule; however, it was not detected in half of the isolates from the 2002-2003 epidemic in Japan. Amino acid substitutions (D164E or N165K) were observed at the "tip", and the epitope was altered. The viral antigenicities were affected, and human antibodies did not substantially inhibit the hemagglutination in the hemagglutination inhibition tests. It is suspected that such variants will be important in future epidemics.     

Coping behaviors of severe diabetics

In order to study the relationship between personality and the development of diabetic retinopathy in patients with diabetes mellitus, diabetics with retinopathy (severe group) and sex-, age-, and duration-matched diabetics without complications were tested by psychological tests, and interviewed. The result of the Yatabe-Guilford personality test (Y-G) and Spielberger's State and Trait Anxiety Inventory revealed that subjects were emotionally and socially stable and well-adjusted types and less anxious in the severe group than in the mild group. The interview findings reveal that the severe group had neglected the medical treatment and the diet therapy for significantly longer periods of time and the incidence of a childhood parental separation was significantly higher in the severe group than in the mild group. Discussion focuses on the severe diabetics' coping behavior which is characterized by the neglect of medical treatment and diet therapy for extended periods of time, which in turn resulted in diabetic retinopathy and other complications. Such coping behavior is shown to be equivalent to that found in the alexithymic behavioral syndrome.     

Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 g/ml; 0.44 M) inhibited human neutrophil or T cell adhesion to tumor necrosis factor- (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.     

Separation of hemagglutination-inhibiting immunoglobulin M antibody to rubella virus in human serum by high-performance liquid chromatography.

High-performance liquid chromatography was successfully used to separate hemagglutination-inhibiting immunoglobulin M (IgM) rubella virus antibody from IgG rubella virus antibody in human serum. The fractionation by high-performance liquid chromatography was as effective as sucrose density gradient centrifugation in separating IgM antibody from IgG antibody.     

Plasma brain natriuretic peptide and the evaluation of volume overload in infants and children with congenital heart disease

This study was designed to explore whether it was possible to evaluate the severity of VSD, PDA, and ASD by measuring brain natriuretic peptide (BNP) levels. We also investigated normal BNP levels in children to provide a baseline for our study. We measured BNP levels in 253 normal children, including 11 normal neonates, and in 91 VSD patients, 29 PDA patients, and 34 ASD patients. BNP levels showed no age-related differences in normal children (the mean value: 5.3 +/- 3.8 pg/ml). In the healthy neonates, BNP levels rose from 10.4 +/- 11.9 pg/ml in cord blood to 118.8 +/- 83.2 pg/ml on day 0, then fell to 15.3 +/- 7.8 pg/ml by day 7. In VSD and PDA patients, BNP levels correlated significantly with Qp/Qs, LVEDV, and peak RVP/LVP. In ASD patients, BNP levels correlated with Qp/Qs and RVEDV. Especially, in VSD patients, as an index corresponding to 1.5-2.0 of the Qp/Qs ratio, BNP levels of 20-35 pg/ml were found to be best with regard to both sensitivity and specificity. In the healthy neonates, BNP levels changed rapidly after birth. In VSD, PDA, and ASD patients, BNP levels were well-correlated with the severity of the disease. Especially, in VSD patients, it that appears BNP levels may be useful in evaluating surgical indications, with 20-35 pg/ml levels being the appropriate cut-off value.     

Ascending and descending components of the medial forebrain bundle in the rat as demonstrated by the horseradish peroxidase-blue reaction

Summary The ascending and descending components of the medial forebrain bundle (MFB) were investigated by means of horseradish peroxidase (HRP) with a sensitive substrate. The HRP was injected iontophoretically into the MFB at various levels from the anterior commissure to the posterior hypothalamus. In order to prevent the diffusion of HRP to other brain areas, a double micropipette system was used. The descending components of the MFB are derived from (1) the anterior cingulate area, infra- or prelimbic area, and sulcal cortex, (2) the lateral septal nucleus and diagonal band, (3) the bed nucleus of the stria terminalis, (4) the paraventricular nucleus (5) the substantia innominata, (6) the amygdaloid complex (AM), (7) the ventromedial (VM) and dorsomedial (DM) hypothalamic nuclei, (8) the entopeduncular nucleus and (9) nucleus periventricularis stellatocellularis. The ascending components of the MFB originate in: (1) the medial preoptic nucleus, (2) the nucleus periventricularis stellatocellularis and rotundocellularis, (3) the posterior hypothalamic nucleus, (4) the parafascicular nucleus, (5) the ventral premammillary nucleus, (6) the substantia grisea periventricularis, (7) the lateral habenular nucleus, (8) the VM and DM, (9) the paratenial nucleus, (10) the AM and (11) the arcuate nucleus.Abbreviations used in Figures and Tables a nucleus accumbens - abl nucleus amygdaloideus basalis, pars lateralis - abm nucleus amygdaloideus basalis, pars medialis - ac nucleus amygdaloideus centralis - AC anterior cingulate area - al nucleus amygdaloideus lateralis - am nucleus amygdaloideus medialis - ar nucleus arcuatus - CC tractus corporis callosi - CSDV commissura supraoptica dorsalis, pars ventralis - DB diagonal band - DM nucleus dorsomedialis hypothalami - EP nucleus entopeduncularis - ha nucleus anterior hypothalami - hl nucleus lateralis hypothalami - hp nucleus posterior hypothalami - IL infralimbic area of frontal cortex - lh nucleus habenulae lateralis - LH₁ medial forebrain bundle (MFB) at the level of commissura anterior - LH₂ lateral preoptic area - LH₃ MFB at the level of the nucleus anterior hypothalami - LH₄ MFB at the level of the nucleus ventromedialis hypothalami - LH₅ MFB at the level of the nucleus posterior hypothalami - MFB medial forebrain bundle - pf nucleus parafascicularis - PL prelimbic area of frontal cortex - pol nucleus preopticus lateralis - pom nucleus preopticus medialis - posc nucleus preopticus, pars suprachiasmatica - pt nucleus parataenialis - pv nucleus premamillaris ventralis - PV nucleus paraventricularis - pvs nucleus periventricularis stellatocellularis - pvr nucleus periventricularis rotundocellularis - SC sulcal cortex - SGPV substantia grisea periventricularis - SI substantia innominata - SL lateral septal nucleus - ST bed nucleus of stria terminalis - sum nucleus supramamillaris - TO tractus opticus - tmm nucleus medialis thalami, pars medialis - VM nucleus ventromedialis hypothalami The nomenclature used in this paper is according to König and Klippel's Stereotaxic Atlas (1967).