Compromised host

The number of immunocompromised host has been increasing recently. In this article, the defect of host-defence system, immune system and the way to prevent infections in these host were reviewed.     

Morphological investigation of H. pylori and its culture method

H. pylori plays important roles in the pathogenesis of active gastritis, peptic ulcer, and gastric cancer. Culture of H. pylori from suspicious materials is one of gold standard methods for the diagnosis of its infection. H. pylori has two types of morphological manifestation, spiral (mobile) and coccoid (immobile) forms. Morphological conversion from spiral to coccoid form and its reversion may be important role in its pathophysiology including bacterial properties, pathogenicity, and etiology. However, the mechanism and significance of such transformation of H. pylori have remained unknown. In this chapter, we introduce the conventional and new culture methods of H. pylori and review the current knowledge regarding both two types of morphological manifestation and pathophysiological significance of such transformation.     

Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese patients with autosomal recessive muscular dystrophy deficient in adhalin.

Dystrophin is associated with several novel sarcolemmal proteins, including a laminin-binding extracellular glycoprotein of 156 kD (alpha-dystroglycan) and a transmembrane glycoprotein of 50 kD (adhalin). Deficiency of adhalin characterizes a severe autosomal recessive muscular dystrophy prevalent in Arabs. Here we report for the first time two mongoloid (Japanese) patients with autosomal recessive muscular dystrophy deficient in adhalin. Interestingly, adhalin was not completely absent and was faintly detectable in a patchy distribution along the sarcolemma in our patients. Although the M and B2 subunits of laminin were preserved, the B1 subunit was greatly reduced in the basal lamina surrounding muscle fibers. Our results raise a possibility that the deficiency of adhalin may be associated with the disturbance of sarcolemma-extracellular matrix interaction leading to sarcolemmal instability.     

Effect of human epidermal growth factor on lung surfactant production in fetal rabbit

The effect of human epidermal growth factor (hEGF) on the maturation of fetal rabbit lung was studied. On the 25th day of gestation, 0.1 ml of saline solution containing 0.1 microgram of hEGF was injected intramuscularly through uterine wall into fetuses in one horn of the uterus (hEGF treated group) and the same amount of saline solution injected into fetuses in the other horn of the uterus (saline-control group). Sham operated group was also studied; saline was injected to fetuses in both horns. On the 27th day of gestation, fetuses were delivered by cesarean section. There were no significant differences in fatal body weight and fetal lung wet weight among three groups. Total phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) concentrations/g dry lung weight were high in order of hEGF treated group, saline injected group and sham operated group. There were no significant differences in PC concentrations among three groups. However, DSPC concentrations in both saline-control and hEGF treated group were significantly higher than that in sham operated group (p less than 0.01). The % composition of palmitic acid in PC molecule, which is the main component of saturated fatty acid of lung surfactant, was significantly higher in hEGF group than in sham operated group (p less than 0.05). Interestingly, there were no significant differences in DSPC level and the % composition of palmitic acid between saline-control and hEGF treated group. This phenomenon might be due to so called a "neighbor effect" that hEGF injected to fetuses in one side of the uterine horn influences the fetuses in the other side of the horn through placentas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fusogenic oncolytic vaccinia virus enhances systemic antitumor immune response by modulating the tumor microenvironment

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Neuropilin-1 on hematopoietic cells as a source of vascular development

Neuropilin-1 (NP-1) is a receptor for vascular endothelial growth factor-165 (VEGF165) and acts as a coreceptor that enhances the function of VEGF165 through VEGF receptor-2 (VEGFR-2). Studies using transgenic and knock-out mice of NP-1 indicated that this molecule is important for vascular development as well as neuronal development. We recently reported that clustered soluble NP-1 phosphorylates VEGFR-2 on endothelial cells with a low dose of VEGF165 and rescues the defective vascularity of the NP-1-/- embryo in vitro and in vivo. Here we show that NP-1 is expressed by CD45+ hematopoietic cells in the fetal liver, can bind VEGF165, and phosphorylates VEGFR-2 on endothelial cells. CD45+NP-1+ cells rescued the defective vasculogenesis and angiogenesis in the NP-1-/- P-Sp (para-aortic splanchnopleural mesodermal region) culture, although CD45+NP-1- cells did not. Moreover, CD45+NP-1+ cells together with VEGF165 induced angiogenesis in an in vivo Matrigel assay and cornea neovascularization assay. The extracellular domain of NP-1 consists of "a," "b," and "c" domains, and it is known that the "a" and "c" domains are necessary for dimerization of NP-1. We found that both the "a" and "c" domains are essential for such rescue of defective vascularities in the NP-1 mutant. These results suggest that NP-1 enhances vasculogenesis and angiogenesis exogenously and that dimerization of NP-1 is important for enhancing vascular development. In NP-1-/- embryos, vascular sprouting is impaired at the central nervous system (CNS) and pericardium where VEGF is not abundant, indicating that NP-1-expressing cells are required for normal vascular development.     

Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis

Myocyte diameter, fractional area of collagen, intensity of myocarditis and parasite persistence (explored by immunohistochemistry and PCR) were evaluated in serial sections of endomyocardial biopsies from 29 outpatients with chronic chagasic cardiopathy. The patients, 25 males and four females with a mean (S.D.) age of 43 (9) years, were subsequently followed up for 3-2861 days (median=369 days). During this follow-up, 16 (55%) of the patients died. The biopsies revealed myocarditis in 25 (86%) of the patients and high-grade myocarditis in 14 (56%). Although immunohistochemistry failed to demonstrate Trypanosoma cruzi antigens in any of the samples, five (33%) of the 15 biopsies successfully tested in the PCR-based assay for T. cruzi DNA were found positive, indicating parasite persistence. There was a significant positive association between myocardial parasite persistence and high-grade myocarditis (P=0.014); five (71%) of the seven endomyocardial biopsies with high-grade myocarditis that were successfully tested in the PCR assays showed persistent T. cruzi DNA. The survival time of the patients was not, however, found to be significantly associated with myocardial parasite persistence, any of the morphometric measurements taken, or the presence or intensity of myocarditis.     

Measurement of serum branched-chain amino acids to tyrosine ratio level is useful in a prediction of a change of serum albumin level in chronic liver disease.

Aim: In patients with hepatitis C virus (HCV)-associated chronic liver diseases, especially in those with liver cirrhosis, accurate evaluation of their protein nutrition status is very important to improve their quality of life. Whereas the serum albumin level is commonly used to evaluate patients' protein nutrition status, in the present study, the serum amino acid levels were measured, as they also provide valuable information. Methods: Serum albumin levels and branched-chain amino acids (BCAA) to tyrosine ratio (BTR) were determined in 447 patients with HCV-associated chronic liver diseases (313 with chronic hepatitis and 134 with liver cirrhosis). Results: Chronic hepatitis progressed to liver cirrhosis, serum albumin and serum BTR levels decreased significantlyas chronic hepatitis progressed to liver cirrhosis. Hypoalbuminemia was significantly more common in patients with liver cirrhosis than in those with chronic hepatitis; however, the incidence of an amino acid imbalance was significantly higher than that of hypoalbuminemia in patients with liver cirrhosis. The presence of an amino acid imbalance was associated with a reduction in the serum albumin level 1 year later. Conclusions: It is important to evaluate serum albumin levels and the BTR in patients with HCV-associated chronic liver diseases.     

An autopsy case of pulmonary and central nervous system metastatic osteosarcoma treated with thirty-six courses of chemotherapy over four years]

A 32-year-old man presented with cough, dyspnea and orthopnea ten years after amputation of the right humerus because of osteosarcoma. Chest radiographs and chest computed tomographs showed left pleural effusion, pericardial effusion and a giant intrathoracic mass, which was histologically diagnosed as a recurrence of the osteosarcoma. After 4 courses of chemotherapy combined with CDDP, the mass in the left upper lobe of the lung decreased in size, and it was then resected. Three months later, new metastatic lesions were detected in the thoracic area. Therefore, 29 additional courses of chemotherapy were administered (36 courses in total over 4 years; including regimens combined with CDDP, carboplatin, high-dose methotrexate, ifosfamide, dacarbazine, vindesine, etoposide, vincristine, taxotere and gemcitabine). In spite of the several courses of chemotherapy, brain and spinal cord metastases appeared, and the patient eventually died of cerebral hemorrhage. During the four years after the first recurrence he had good quality of life as a result of the chemotherapy.     

Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification

BACKGROUND: Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined. METHODS: By using all endoscopic records in the Katta General Hospital from April through to September 1999, we identified 392 patients. We examined the Los Angeles classification, peptic ulcer, gastric mucosal atrophy, hiatal hernia and other medical variable factors for their contribution to esophagitis in the patients. RESULTS: Patients (13.8%) were diagnosed as having reflux esophagitis with a mucosal break. In a multivariate analysis, reflux esophagitis was associated with hiatal hernia (odds ratio (OR) 2.276, 95% confidence interval (CI) 1.164-4.450), with patients over 65 years of age (OR 2.521, 95% CI 1.238-5.134) and the open type of gastric mucosal atrophy (OR 0.420, 95% CI 0.225-0.785). There was no significant difference between esophagitis and Helicobacter pylori infection and peptic ulcer. CONCLUSIONS: We observed that age, hiatal hernia and a lower rate of gastric mucosal atrophy were associated with the proportion of mucosal breaks accompanying esophagitis.