Epithelial cell proliferation during colonic chemical carcinogenesis in the rat

To define the significance of alterations in epithelial cell proliferation as a marker of high risk mucosa for colorectal cancer, we examined cell proliferative events in the colonic mucosa during chemical carcinogenesis using in vitro bromodeoxyuridine labelling and by analysing serial colonoscopic biopsy specimens from dimethylhydrazine (DMH)-treated rats. In both the rectum and flexure of the colon, an increased labelling index of colonic epithelial cells, an upward extension of the proliferating zone and an upward shift of the major area of DNA synthesis of epithelial cells were observed during DMH-induced colonic carcinogenesis in rats. These changes preceded the development of the colonic tumour and were observed in endoscopically normal rectal mucosa where the tumour was absent. We confirmed the altered cell proliferative events preceding the development of the tumour by examining serial colonoscopic biopsies. The results suggest that these alterations are features that identify premalignant colonic mucosa in DMH-treated rats.     

Effect of Helicobacter pylori infection on gastric mucosal phospholipid contents and their fatty acid composition

To investigate the effect of Helicobacter pylori infection on the 'gastric mucosal barrier', phospholipid contents and the fatty acid composition of endoscopic biopsy specimens of the gastric mucosa were analysed in healthy volunteers with and without H. pylori infection. The gastric corporeal phos-phatidylcholine (PC) content of H. pylori -positive healthy volunteers was less than that of H. pylori -negative healthy volunteers ( P < 0.05). Moreover, H. pylori -positive healthy volunteers had a decrease in linoleic acid composition ( P < 0.0001) and an increase in arachidonic acid composition ( P < 0.0001) and in the arachidonic acid/linoleic acid ratio ( P < 0.0001) of antral and corporeal PC compared with H. pylori-negative healthy volunteers. These findings suggest that H. pylori infection enhances production of various eicosanoids, resulting in changes in the gastric mucosal phospholipid contents and their fatty acid composition, that may consequently cause the gastric mucosal barrier to be weakened.     

Induction of autoimmune hepatitis and autoantibodies to liver antigens by neonatal thymectomy in mice

We examined development of autoimmune hepatitis in neonatally thymectomized C3H/HeN mice and tried to characterize the nature of liver antigens recognized by the autoantibodies at the molecular level. Autoantibodies to crude liver proteins detected by ELISA were found in 12 (67%) of 18 mice thymectomized 2 days after birth. However, autoantibodies were not detected in mice thymectomized 7 days after birth. The autoantibodies mainly consisted of IgG and reached the maximum level 8 weeks after birth. Hepatic inflammation, mononuclear cell infiltration in the portal area, was seen in 5 (28%) of 18 mice thymectomized 2 days after birth, but not in mice thymectomized 7 days after birth. Most infiltrating cells were Thy-1⁺ lymphocytes. The serum autoantibody level to crude liver proteins in mice with hepatitis was much higher than that in mice without hepatitis. We fractionated crude liver proteins by a Sepharose 6B column and examined the reactivity against the autoantibodies. The autoantibodies of three of five mice with hepatitis reacted with the ≈150 kD liver proteins other than liver-specific protein (LSP). By Western immunoblotting of SDS–PAGE using LSP and fractionated liver proteins, we found that the molecular weights of the target antigens were 52 kD in LSP and 150 kD (strong band), 138, 128, 120 and 110 kD (weak band) in fractionated liver proteins other than LSP. This 150-kD target molecule in crude liver proteins was found only in liver. These results indicate that hepatitis and autoantibodies to liver proteins are induced spontaneously by neonatal thymectomy in mice, and the candidates of autoantigen in this hepatitis model are 52-kD protein in LSP and 150-kD liver proteins different from LSP. Still more, we regard the 150-kD molecule as a new autoantigen related to hepatitis.     

Symbolic meanings of island in dreams

Abstract Six dreams reported from neurotic patients in the therapy of Jungian analysis are presented to illustrate the symbolic meanings of islands in dreams. The island in dreams symbolizes (i) the entrance point into Jungian analysis, (ii) a complex in which a dreamer has got involved and (iii) the beginning of the newly organized ego consciousness. The multiple meanings of islands are suggested to originate from several levels of the unconscious from which the identical symbol of island comes from.     

Relationship between Plasma Concentration and Antihypertensive Effect of the Dihydropyridine Calcium Antagonist,Benidipine, in Rats

Although benidipine hydrochloride, a hydrophobic and weakly cationic dihydropyridine calcium antagonist, has slow onset but long-lasting anti-hypertensive effect in experimental animals and man, after administration it rapidly disappears from the plasma. Correlation of the plasma concentration with reduction in blood pressure has been investigated in spontaneously hypertensive rats, and concentrations in the mesenteric artery were compared with those in plasma after oral and intravenous administration of benidipine to rats. After oral administration of benidipine to spontaneously hypertensive rats, the fall in blood pressure showed an anti-clock hysteresis phenomenon. Using concomitant analysis, plasma concentrations and anti-hypertensive activity could both be closely fitted to a one-compartment open model and the effect compartment for the pharmacological activity of benidipine could be described by a Hill equation. Concentrations in the mesenteric artery increased rapidly and then declined more slowly than in plasma. The mean residence time of benidipine in the mesenteric artery corresponded closely to the reciprocal of the rate constant for elimination of benidipine from the effect compartment. From these results it seems that benidipine is retained longer in the plasma membrane, an effective site, because of its physicochemical properties, and thus shows a more sustained anti-hypertensive effect than would be predicted from its disposition in plasma.     

Regulation of G1 cyclin-dependent kinases in liver regeneration

The liver serves as a suitable model for studying tissue regeneration. Although various growth factors have been implicated in the promotion of this process, their precise role in liver regeneration remains to be elucidated. Whatever the extracellular signals may be, they all converge on cell cycle regulators in the nucleus, where the sequential activation of cyclin-dependent kinases (Cdk) takes place. The activities of Cdk are regulated positively through their association with cognate cyclins, and negatively via interactions with Cdk inhibitors. In this review article, our recent data as well as results of previous reports on how these cell cycle regulators trigger and/or terminate the process of liver regeneration are summarized. The authors believe that ‘knockout’ mice, in which specific genes are deleted, will be useful for providing further insight into the positive and negative regulation of liver regeneration.     

Human herpesvirus-6-associated exanthema in a patient with acute lymphocytic leukaemia

We report the first case of human herpesvirus-6 (HHV-6) associated exanthema in a patient with acute lymphocytic leukaemia (ALL). We analysed DNA extracted from an exanthematous lesion using the polymerase chain reaction (PCR). DNA was positive for HHV-6 but negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus. Immunohistochemical staining of the skin with monoclonal antibody against HHV-6 confirmed the infection. The possibility of HHV-6 infection should be considered when an atypical skin rash is seen in patients with ALL.     

Use of Automatic Mode Change Between DDD and AAI to Facilitate Native Atrioventricular Conduction in Patients with Sick Sinus Syndrome or Transient Atrioventricular Block

The benefits of the automatic DDD (DDD/AMC) mode in the Chorus II pacemaker (Chorus 6234; Ela Medical Inc.), which automatically switches the modes between DDD and AAI to respect spontaneous AV conduction as much as possible in AAI while preserving safety pacing in DDD during paroxysmal AV block (AVB) only, remain unproven. This study examined the functions of the DDD/AMC mode in 12 patients with sick sinus syndrome (SSS; n = 10) or paroxysmal complete AVB (n = 2). A short-term (24 hours) comparative study between simple DDD mode and the DDD/AMC mode was performed in 8 of the 12 patients, and a medium-term (55.2 ± 54.6 days) follow-up of the DDD/AMC mode was completed in all 12 patients. A comparative pair of 24-hour surface Holter ECGs was obtained in 6 of the 8 patients in the short-term study. Telemetry and built-in Holter histograms were collected in the outpatient clinic in all 12 patients. Although the percentage atrial pacing of the telemetry increased from 59.2 ± 35.4 in DDD to 70.4 ± 31.8 in DDD/AMC (P < 0.009; n = 8), the percentage ventricular pacing decreased from 64.6 ± 37.7 in DDD to 36.2 ± 43.1 in DDD/AMC (P < 0.027) in the short-term study. In particular, the reduction of percentage ventricular pacing to < 10% was observed in four patients with SSS not associated with ± first-degree (1°) AVB on preoperative ECGs. Between the two modes a significant difference in arrhythmic events was not observed by the 24-hour surface Holter ECGS taken from the six patients in the short-term study. AAI-DDD switching associated with automatic modulation of AV delay and AV hysteresis occurred in all patients in the medium-term study. From the medium-term study, the total AV delay (AV delay plus AV hysteresis) exceeded 300 ms in 6 of the 12 patients in DDD/AMC, and usually became longest during nighttime. From the short- or medium-term study in the 12 patients, two patients preferred the DDD/AMC mode while one preferred the DDD mode. These results suggest that the DDD/AMC mode is useful, at least in SSS patients without ≥ 1° AVB, by reducing the percentage ventricular pacing.     

A Case of a Pseudomalfunction of a DDD Pacemaker

DDD pacemaker pseudomalfunction occurred in a 65-year-old man. This was due to premature ventricular contraction (PVC) response option and cross-talk detection window, which are designed to protect against pacemaker related tachycardia or cross-talk. Pseudomalfunction disappeared by eliminating PVC response option.