Regulation of intracellular metabolism by biodegradable polyrotaxanes

Cellular response to our designed biodegradable polyrotaxanes was investigated in terms of changes in cytoplasmic calcium levels in platelets. The polyrotaxanes regulated thrombin-induced calcium increase in platelets although constituent molecules of the polyrotaxanes showed fewer effects on the intracellular metabolism. Further, an increase in membrane fluidity of red blood cell ghosts was significantly observed by the addition of the polyrotaxanes. Static light scattering study revealed that the polyrotaxanes formed a supramolecular association state in relation to the molecular weight of PEG: a loosely packed association with a specific molecular shape. From these characteristics, it is suggested that supramolecular level interactions between the polyrotaxanes and cell membranes regulate the intracellular metabolism. It is concluded that these biodegradable polyrotaxanes can be feasible as temporarily-controlled bioactivator.     

Conformation of tetragastrin in DMSO

A conformation analysis of tetrapeptide in DMSO was carried out by the Monte Carlo simulation including the solvent effect in the energy function. The lowest energy conformations in the zwitterionic and cationic states are a similar compact form, in which the two aromatic rings are close to each other. The distance distributions between the specified atoms in the molecule show that most conformations in the local energy minima are similar to this folded conformation, although there is another type of conformation of interest, which has an extended form with the two separate aromatic rings. Such results are consistent with the NMR and CD experiments, and suggest that the compact form of tetragastrin is essential as a biological active conformation. The folded structure is stabilized by the solute-solvent interaction. In particular, the non-bonding interactions between the solute and solvent molecules cause a folding effect on the molecular conformation in total. This study is a first case taking account of the solvent effect into the conformation analysis of tetragastrin.     

Classification of delusions in Alzheimer's disease and their neural correlates

Background: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data. Methods: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty‐five of the patients also had single‐photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. Results: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. Conclusions: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.     

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide

Background and Aim: Controversies remain over the need for antiulcer treatment following 1‐week eradication triple therapy for Helicobacter pylori‐positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. Methods: The study was conducted in 52 H. pylori‐positive patients with an endoscopically‐proven open gastric ulcer. All patients received 1‐week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7‐week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and ¹³C‐urea breath test. Results: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non‐eradicated patients. The overall gastrointestinal symptom‐free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. Conclusions: The results suggested that the combination therapy for open gastric ulcer was safe, well‐tolerated and effective. However, data from a double‐blind placebo‐controlled study is necessary to confirm these findings.     

Histological and immunological studies on eosinophilic granuloma of soft tissue, so-called Kimura's disease

Increase of serum IgE with frequent localization of IgE in the germinal centres, mast cell hyperplasia in lymph nodes and changes of specific granules in the infiltrated eosinophils, such as roughness of the matrix and appearance of tubular structures together with fusing and disappearance of the core, were demonstrated in eosinophilic granuloma of the soft tissue, so-called Kimura's disease, in association with increase of anti-Candida IgE antibody. It is suggested that this disease may be due to atopic allergy to Candida albicans.     

Cardiac rhabdomyoma of a neonate: An autopsy case report

A primigravida delivered a cyanosed female infant with a very low Apgar score. Cardiac anomaly of the fetus was detected at 32 weeks of gestation by ultrasonography. The baby died on the day of delivery. Autopsy revealed multiple tumor masses in the interventricular septum and ventricular walls. The tumor originating from the interventricular septum was the largest and measured 3.7 × 3 cm. Histologically, the tumor was composed of large polygonal glycogen-laden cells and ‘spider-cells’. Eosinophilic giant histiocytic cells were also observed in the spleen. Ultrastructural features of the tumor cells correlated with those of typical cardiac muscle cells.     

Studies on interrelations between eosinophilia, serum IgE and tissue mast cells

In an examination of a variety of diseases associated with a peripheral blood eosinophilia it is evident that the eosinophilia is not necessarily accompanied by increased amounts of serum IgE. Tissue eosinophilia occurring with mast cell hyperplasia and usually increased amounts of JgE, indicate atopic allergy. It is considered that the eosinophilic granuloma of soft tissue (Kimura's disease) is an atopic disease and quite different from histiocytosis X.     

Protein synthesis in the posterior cingulate cortex in Alzheimer's disease

Background: Neuroimaging studies using ¹⁸F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) and single photon emission computed tomography (SPECT) have shown that the posterior cingulate cortex (PCC) is the primary and most prominent area of cerebral metabolic and perfusional decrement in early Alzheimer's disease (AD). We carried out the present preliminary study to investigate whether a decline of cerebral blood flow (CBF) in the PCC in early to moderate AD was accompanied with that of cerebral protein synthesis (CPS). Methods: We carried out both N‐isopropyl‐p‐[123I] iodoamphetamine SPECT (IMP‐SPECT) and L‐[methyl‐11C] methionine positron emission tomography (MET‐PET) in eight AD patients with apolipoprotein E epsilon 4 allele in the early to moderate stage. We also carried out IMP‐SPECT in eight healthy controls (HC). We located 32 regions of interest (ROI), and values of regional MET or IMP uptakes were averaged in five regions; the frontal lobe (FL), the parietal lobe (PL), the medial temporal lobe (MTL), PCC and the occipital lobe. Furthermore, the values in the FL, PL, MTL and PCC were divided by values in the occipital areas, and normalized values of regional CBF (rCBF) and CPS (rCPS) were calculated. Then, the rCBF in the FL, PL, MTL and PCC were compared between AD and HC. In addition, the rCBF and rCPS were compared in the FL, PL, MTL and PCC of AD. Results: The rCBF in the PCC, but not in the other three regions, was significantly lower in AD than in HC. The rCBF was significantly lower than rCPS in the PCC, but rCBF and rCPS were comparable in the other three regions in AD. Conclusions: The CBF reduction in the PCC in AD was partly caused by neuronal loss in the PCC and partly supported the hypothesis that CBF reduction in the PCC was a result of functional deafferentation by neural degeneration in areas other than the PCC.     

Significance of different conjugate forms of bilirubin in the formation of pigment gallstones

The aim of the present study was to analyse bile samples from cases with gallstones by high performance liquid chromatography according to the type of stones present, with special reference to the glucoside and xyloside conjugates of bilirubin, and to investigate their deconjugation. The composition of bilirubin conjugates in bile was similar between cholesterol and black pigment stones except that the total bilirubin concentration was about 5 times higher in black pigment stone cases with haemolysis. Unconjugated bilirubin was higher in brown pigment stone cases than in cholesterol stone cases, although total bilirubin concentration was lower in the former. In addition, in brown pigment stone cases, bile contained statistically less bilirubin diglucuronide and more bilirubin diglucoside and monoglucoside than in bile with cholesterol stones (P less than 0.05). Glucoside and xyloside conjugates are also major components, regardless of the types of gallstones present, accounting for as much as 18 to 25%. Incubation experiment revealed that bilirubin diglucuronide was more readily deconjugated than bilirubin diglucoside or bilirubin monoglucoside monoxyloside. Therefore, glucuronide conjugates were likely to be the main source of unconjugated bilirubin in the formation of pigment gallstones.     

Minocycline-induced hemolytic anemia

A case of drug-induced immune hemolytic anemia is described. A 2 year old boy exhibited sudden anemia and hemoglobinuria after administration of minocycline (MINO). The specific immunoglobulin G antibody against MINO was demonstrated in the patient's serum by western blotting. This is a rare example where anti-minocycline immune complex-mediated hemolysis was responsible for an intravascular hemolytic process.