Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

Evaluation of the clinical pathway for laparoscopic cholecystectomy and simulation of short-term hospitalization.

The effectiveness of the clinical pathway for laparoscopic cholecystectomy was evaluated, and the efficiency of medical care was analyzed. The duration of hospitalization and the number of National Health Insurance (NHI) points for medical service fees were compared between 86 patients treated after introduction of the clinical pathway (pathway group) and 56 patients treated before introduction of the clinical pathway (pre-pathway group). In the pathway group, variance from the pathway occurred in 24 patients (27.9%) due to postponement of discharge in 7 patients, to earlier discharge in 5 patients, and to insertion of a bile duct catheter in 5 patients. Total and postoperative hospitalization times were significantly shorter in the pathway group than in the pre-pathway group (8.0 +/- 1.6 vs 13.7 +/- 9.0 days, p<0.0001, 5.4 +/- 1.1 vs 6.5 +/- 2.2 days, p<0.0001, respectively). In the pathway group, the total number of NHI points was lower and the number of points per day was higher. By simulation, the total number of NHI points for the 5-day pathway (discharge on postoperative day 3 or earlier) was significantly lower than that for the current 7-day pathway. Moreover, the weekly profit per bed with the 3-day pathway (discharge on postoperative day 1) was more than twice that with the current pathway. The results suggest that the clinical pathway for laparoscopic cholecystectomy is beneficial for patients and useful for the introduction of diagnosis procedure combination in our hospital.     

Cellular niches controlling B lymphocyte behavior within bone marrow during development

In bone marrow, hematopoiesis is thought to depend on special microenvironments known as niches that maintain blood cells. However, the identity of niches and interaction of blood cells with niches remain poorly understood. Here we identify stage-specific cellular niches for B lymphopoiesis. The earliest precursors, pre-pro-B cells and end-stage B cells, plasma cells require CXC chemokine ligand (CXCL)12. CXCL12-expressing cells are a small population of stromal cells, scattered throughout bone marrow and located some distance from the cells expressing interleukin (IL)-7. Multipotent hematopoietic progenitors are attached to the processes of CXCL12-expressing cells and pre-pro-B cells adjoin their cell bodies. Maturer pro-B cells that require IL-7 have moved away and adjoin the IL-7-expressing cells. Plasma cells again seed CXCL12-expressing cells. We demonstrate the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggest that CXCL12 maintains the cells in the niche.     

Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Diversity of Hepatitis G Virus within a Single Infected Individual

The extent of population diversity among GB virus C (GBV-C)/hepatitis G virus (HGV) within a persistently infected individual (Iw) was investigated by sequence analysis of multiple clones generated from polymerase chain reaction (PCR)-amplified products of cDNA analogous to fragments of 5 non-coding region (5NC), envelope region 1/2 (E1/E2) and non-structural region 3 (NS3) of viral genome. Although nucleotide substitutions were more common in coding regions than in the 5NC region, there was no region corresponding to the hypervariable region of hepatitis C virus in the E1/E2 region. Transition substitution exceeded transversion by 7 to 12-fold, and 79.4% of substitutions were synonymous. This bias against substitutions producing amino acid replacements and the use of Pfu DNA polymerase with an error rate 10 times lower than the observed frequency of substitution, suggests that most substitutions were not artefactual. This data suggests that individual genomes of HGV within an infected individual may differ from each other at 0.23–0.84% nucleotide position and at 0.42–0.61% amino acid position.     

HLA-DR Antigens in Pemphigus among Japanese

The frequency of HLA-DR4 was significantly increased at P < 0.02 in 37 unrelated pemphigus patients (62.2%), when compared with unrelated 73 healthy controls (30.1%). This antigen was more frequently found in pemphigus foliaceus (70.6%) than pemphigus vulgaris (55.8%).     

Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane.

The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane.     

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.     

Review: extracellular matrix regulates tooth morphogenesis

Mineralized tissues are unique in that they use proteins to attract and organize calcium and phosphate ions into a structured mineral phase, thus precise knowledge of the expression and extracellular distribution of matrix proteins is very important to understand their function. Tooth development is regulated by sequential and reciprocal interactions between neural crest-derived mesenchymal cells and the oral environment. However, the precise molecular mechanisms that mediate interactions between epithelium and mesenchymal cells are not clear, although basement membrane (BM) components have been shown to play important roles in these regulatory events. In addition, the extracellular matrix layer, whose main components are laminin, collagen IV, nidogen, and sulfated proteoglycan, and the BM layer are both considered to be involved with cell proliferation and differentiation. During tooth morphogenesis, extracellular matrices are dramatically changed. Further, the BM components, laminin and collagen IV support dental epithelium; however, in the late stage, they begin the processes of enamel matrix secretion and calcification, after which the BM structure between the dental epithelium and mesenchyme disappears. In addition, tooth abnormalities associated with several kinds of human diseases that cause mutations in the extracellular matrix, as well as the molecular mechanisms of the basement membrane and enamel matrix during tooth morphogenesis, are not clearly understood. In our review, we discuss the role of the extracellular matrix, with focus on the BM and enamel matrix during tooth morphogenesis.