Effects of glycyrrhizin on immune-mediated cytotoxicity

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-α is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4⁺ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-α-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-α-induced cytotoxicity in the TNF-α-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.     

The influence of physical restraint or fasting on plaque-forming cell response in mice

Abstract This study was designed to investigate the effects of 1- and 3-day (16 h/day) physically restrained or fasting on immunological and endocrine responses in CBF1 mice. The influence of stressors on these responses was evaluated using anti-sheep red blood cell plaque-forming assay, and by examining T cell subsets, thymus weight and endocrine hormone levels. The results revealed that a significant elevation of the plaque-forming cells (PFC) was found in spleen cells in 1-day restrained mice, that the PFC were conversely suppressed following 3-day physically restrained stress, and that the PFC were not affected by 1- or 3-day fasting stress. Serum levels of norepinephrine were found to be significantly increased only in 1-day physically restrained mice. No change of T cell subsets and thymus weight was found in 1-day physically restrained mice. A significant increase in serum corticosterone levels was elicited in both 1- and 3-day physically restrained mice, and 3-day fasting mice, while increased Lyt2-positive T cells and thymic atrophy were found only in 3-day physically restrained mice. These findings suggest that immune function was differentially affected by the duration and types of stressors.     

A Small Gastric Cancer in Association with Menetrier Disease

Abstract: We studied a 57-year-old man who was diagnosed as having giant rugae at a mass-screening for gastric cancer. He was examined endoscopically for check-up purposes. In addition to giant rugal folds which occurred throughout the entire fundus and body of the stomach, a type IIc lesion was noted in the posterior lower wall of the gastric body. A biopsy revealed signet ring cell carcinoma. A total gastrectomy was performed. A resected specimen was serially sectioned and underwent histopathological examination; hypertrophy and cystic elongation of the gastric glands indicative of so-called giant hypertrophic gastritis was seen. The histological type of the type IIc lesion was undifferentiated adenocarcinoma with the signet ring cells being confined to the mucosal layer. This patient had a rare case of Menetrier's disease complicated by intramucosal carcinoma.     

The Specificity of the Penetrating and the Superficial Spreading Types of Early Gastric Cancer—Classification of Early Gastric Cancer Using the Interactive Image Analysis System—

Abstract: Specific types of early gastric cancer were investigated in accordance with the cancer surface area and the degree of penetration by means of quantitative measurements of the surface area of early gastric cancer using the interactive image analysis system. The results indicated a significant correlation between the surface area and the penetration depth in ordinary early gastric cancer. However these correlations were not observed in both well and poorly differentiated adenocarcinoma cases of the so-called PEN and SUPER types, which showed a significant specificity when compared with ordinary early gastric cancer. The PEN and SUPER types of early gastric cancer also exhibited various clinicopathological characteristics, and it was suggested that the poorly differentiated PEN type might be the initial lesion of a linitis plastica type gastric cancer. Examination of the conditions of the mucosa surrounding the cancer revealed a difference between the PEN and the SUPER types, and this suggested that the environment at the site of a cancer growth influences the type of growth and the spread of early gastric cancer.     

Longitudinal Dissociation in the His Bundle: A Possible Mechanism of Two Distinct Cycle Lengths in Atrioventricular Reentrant Tachycardia

Two wide QRS tachycardias with identical morphology but different cycle lengths (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left posterior accessory pathway (AP), which was successfully ablated by radiofrequency application. Neither dual AV nodal pathways nor other APs were documented. Splitting of the His-bundle electrogram was shown, and programmed stimulation induced sudden prolongation of intra-hisian conduction time. These results suggest longitudinal dissociation in the His bundle may be responsible for two distinct CLs in AVRT without dualAV nodal physiology.     

Successful Radiofrequency Current Catheter Ablation of Sustained Ventricular Tachycardia

We performed radiofrequency current catheter ablation in two patients with nonischemic sustained ventricular tachycardia (VT). In one patient, two morphologically distinct VTs were induced by electrical stimulation. One showed right bundle branch block pattern and the other left bundle branch block pattern. The earliest site of activation during each VT was determined at the septum of the right ventricle. However, these two sites were close to the His-bundle elecfrogram recording area. In the other patient, a VT with a left bundle branch block pattern occurred spontaneously after the administration of isoproterenol. The earliest site of activation during VT was determined at the outflow tract of the right ventricle. During tachycardia, radiofrequency current ablation (40 W ± 30 sec) was delivered to the earliest site of activation, A few seconds after fulguration, each VT was terminated and additional radio-frequency currents were given near these sites. After the ablation, VT could not be induced by the electrical stimulations, nor did it recur. No side effects were observed and the atrioventricular conduction remained intact. We feel that nonischemic VTs could possibly be treated by using radiofrequency current catheter ablation.     

Assessment of Angiographic Coronary Calcification and Plaque Composition in Virtual Histology Intravascular Ultrasound

Objectives

We assessed the relation between coronary plaque composition and angiographic calcification by using virtual histology intravascular ultrasound (VH‐IVUS).

Background

The plaque vulnerability according to angiographic calcification is unclear.

Methods

Subjects were 140 consecutive patients (145 lesions) undergoing VH‐IVUS before percutaneous coronary intervention. Subjects were divided into 4 groups: no calcification group (n = 27), spotty group (n = 65) that had calcium deposits under 90° in grayscale IVUS, intermediate group (n = 37) had calcium deposits with 90° or more and under 180°, and extensive group (n = 16) had calcium deposits with 180° or more.

Results

The number of VH thin‐cap fibroatheromas in spotty group was significantly larger than no calcification group, intermediate group, and extensive group (0.66 ± 0.71 vs 0.22 ± 0.42 [P < 0.01], 0.32 ± 0.48 [P < 0.05], 0.13 ± 0.34 [P < 0.01], respectively). Spotty group without angiographic calcification had significantly larger %necrotic core than with angiographic calcification (24.5 ± 6.7% vs 19.9 ± 7.2%, P < 0.05). Intermediate group without angiographic calcification had significantly larger necrotic core area than with angiographic calcification (2.5 ± 0.9 mm² vs 1.7 ± 0.9 mm², P < 0.05). Extensive group with angiographic calcification had significantly larger %dense calcium than without angiographic calcification (18.3 ± 4.0% vs 13.4 ± 4.4%, P < 0.05).

Conclusions

Lesions with spotty calcification was highly vulnerable in VH‐IVUS. Spotty or intermediate plaque calcification without angiographic calcification was more vulnerable than those with angiographic calcification. Extensive plaque calcification with angiographic calcification had more dense calcium than those without angiographic calcification.

     

Increased urinary excretion of human cytomegalovirus in children with malignancy: Detection by polymerase chain reaction

Human cytomegalovirus (HCMV) is one of the most important agents causing opportunistic infections in immunocompromised hosts. In this study, we examined the urinary excretion of HCMV in children with malignancy using polymerase chain reaction (PCR). Urine samples were collected from on-therapy, off-therapy patients with malignancy, and healthy controls. A simple DNA extraction method using glass powder was employed, and inhibitory effect of urine on PCR was prevented. For PCR, a pair of primers from the HCMV major immediate early gene sequence was used. Among patients who received intensive chemotherapy, 52.0% had urinary HCMV excretion after the chemotherapy course. In contrast, off-therapy patients and healthy controls showed a lower incidence of urinary HCMV excretion (20.4 and 8.7%, respectively). The incidence of HCMV urinary excretion in the on-therapy group was significantly higher than healthy controls (P < 0.05). In the on-therapy group, the total white blood cell count of the virus excreters was lower than that of non-excreters. The incidence of HCMV excretion was high in on-therapy patients. Most of the virus excreters were seropositive, so their viruria was thought to be caused by reactivation. Repeated monitoring of virus excretion by this rapid and simple method may be useful to detect HCMV infection early and to control it in such patients.     

Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) Elα gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.     

Functional and phenotypical activation of leucocytes in inflamed human colonic mucosa

Infiltrating leucocytes are activated to generate reactive oxygen species or to produce several molecules in inflamed colonic mucosa. To clarify the phenotypical and functional properties of activating cells in colitic mucosa, 23 patients with ulcerative colitis and 13 controls were studied using a combined method for determining in situ nitroblue tetrazolium reducing activity and immunohisto-chemical characterization. Antibodies 25F9 (anti-macrophage), EG2 (anti-eosinophil cationic protein), MAC387 (anti-calprotectin, expressed by activated myeloid-histiocytes lineage), and MAC-1 (anti-CD11b) were used. The proportion of EG2, calprotectin, and CD11b-positive cells were significantly increased in inflamed mucosa. The proportion of EG2, calprotectin, and CD11b-positive cells significantly correlated with the histological degree of inflammation. Proportion of EG2-positive cells but not calprotectin nor CD11b-positive cells was significantly correlated with nitroblue tetrazolium reducing activity. Aggregated cells reducing nitroblue tetrazolium seen in severely inflamed mucosa were found to be EG2 positive. Most of the calprotectin-positive cells were 25F9 negative. In addition to activation of neutrophils and macrophages, eosinophil activation has been shown to be involved in inflamed colonic mucosa.