Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.     

Liver units in three dimensions: I. organization of argyrophilic connective tissue skeleton in porcine Liver with particular reference to the “compound hepatic lobule”

Liver units were investigated in pig livers by means of histologic serial tracing, physical model building, and computer-aided three-dimensional imaging. Observations of the argyrophilic connective tissue skeleton were based mainly on the celloidin-embedded serial sections treated with silver impregnation. The parenchymal mass that clothed the initial segments of hepatic venous radicles was demarcated by fibrous septa which formed isolable units with two basic patterns: the simple hepatic lobule (SHL) and the compound hepatic lobule (CHL). Both lobule types presented regular limiting structures circumscribing each unit. Three-dimensional studies revealed that 25% of the lobules in a section belonged to the SHL type and 75% to the CHL type, the latter being predominant among the surface lobules. When considered in only two dimensions, however, the SHL-like lobules constituted the majority. Polygonal analysis disclosed that the pentagonal lobule was the most typical, instead of the “hexagonal” or “classic” lobule. The CHLs represented a multiaxial unit containing a system of venous tributaries in accordance with intralobular septation, whereas the SHLs were found with one axial vessel having a dendritic tendency at the incipient end; some SHLs were drained eccentrically by separate vessels into a sublobular vein. It was observed that, in dividing CHLs, whereas particular sinosoids were transformed into portal twigs, other sinusoids were changed into central venous tributaries. Fibrous deposition occurred along the septal-line sinusoids, bringing into view the septum-initiating plane. Fibroconnective tissue was supplied from the portal area and central (sublobular) adventitia, where portal triad structures and adventitial arterioles, respectively, were included. The findings of the present study facilitate the understanding of several characters of the lobules that have been reported previously, or occasionally postulated, such as the portal-central bridging tendency, the intralobular arterioles or ductules, the translobular artery or portal vein, the “portal-portal” or “portal-central” anastomoses, and the apposition of pericentral zone close to periportal zone. Based on differences in argyrophilia of sinusoidal reticulum, in proportion of lobule types, and in vasculature, the anatomic heterogeneity of liver unity was demonstrable in zonality, regionality, and locality. © 1991 WILEY-LISS, INC.     

An Analytic Model of Subminiature Auditory Sensation System for Sound Source Localization

It is reported that some types of insects have a remarkable ability to detect the direction of an incident sound even though its acoustic sensory organs are in very close proximity each other. Maybe the ears are jointed by a cuticular structure with which the separated motions can be coupled mechanically and thus be magnified. In this paper, a detailed model is setup to describe the principle of this type of localization using a mechanical coupled structure. The transfer functions and the responses of the model in terms of time and frequency are analyzed to describe the mechanism of its ability of directional hearing. This analytical model provides a method to design the experimental model for the predetermined incident sound pressure, and the analysis of this model shows that this structure have the ability to determine the direction of the incident stimulus.     

Hydatidiform mole: parental chromosome aberrations in partial and complete moles.

The relationship between parental constitutional chromosome abnormalities and the development of hydatidiform mole was evaluated in series from four institutions. Karyotype analysis was performed on blood samples from 237 patients with a pathological diagnosis of complete mole and 217 of their spouses. One patient was found to have a constitutional balanced translocation, t(11;18), while one spouse was found to have a balanced translocation, t(4;20). Among 125 patients with partial mole and 106 of their spouses, one male was found to be a translocation carrier, t(13;14). No significant increase in the frequency of translocations in the parents of complete moles was found in any of the series considered separately or together. Data from the combined series show no evidence of constitutional parental chromosome aberrations as an aetiological factor in the development of molar pregnancies.     

Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53‐ and p16/Rb‐dependent cell cycle regulator proteins

Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53‐ and p16/Rb‐dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P = 0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16‐Rb pathways are associated with SCC arising in MCT.     

Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients.

Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (Allo-HSCT); however, we have little information on the clinical features of CMV reactivation after cord blood transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed medical records of 140 patients who underwent RI-CBT at Toranomon Hospital between January 2002 and March 2005. All the patients were monitored for CMV-antigenemia weekly, and, if turned positive, received preemptive foscarnet or ganciclovir. Seventy-seven patients developed positive antigenemia at a median onset of day 35 (range, 4-92) after transplant. Median of the maximal number of CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease developed in 22 patients on a median of day 35 (range, 15-106); 21 had enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2 patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 14 patients. The other 8 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95% confidential interval 1.47-8.23). CMV reactivation and disease develop early after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.     

藏汉民族线粒体基因组全序列的比较研究

目的 以藏汉民族线粒体基因组全序列为基础,进行Haplogroup构建和系统发生分析,在全序列水平上比较核苷酸的变异,阐释可能的变异机制和蕴含的生物学意义.方法 采用Applied Biosystems 3730DNA自动测序仪分别对40名藏族和50名汉族的标本进行线粒体DNA序列测定,应用phredPhrap 16.0软件进行全序列拼接,并以rCRS(revised Cambridge Reference Sequence)为标准与测定序列进行比对分析;根据MTTO-MAP的标准,通过Network方法进行Haplogroup构建和系统发生的分析,并结合其它方法对产生的数据进行深入解读.结果 数据分析结果显示:在系统发生上,藏汉民族90个线粒体DNA序列归类到13个Haplogroups,除M9以外,其它各Haplogroup出现频率之间比较差异无统计学意义;通过两个民族的线粒体DNA全序列比对,发现21个分布频率有统计学意义的变异位点,其中的5个为新变异位点;另外,对D-Loop区的5个突变位点进行了单倍型构建,90个标本可分为2种Supertype,发现在藏汉民族之间Supertypel和Supertype 2的分布频率均有统计学意义.结论 藏汉民族在种族起源和系统发生上具有较近的母系遗传关系;在全序列有统计学意义的位点究竟是适应性或者中性选择,抑或是一种病理性突变尚需深入的探讨.     

Plasma B Vitamers: Population Epidemiology and Parent-Child Concordance in Children and Adults

Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent–child dyads are scarce. Profiling B vitamers in parent–child dyads enables an insightful determination of gene–environment contributions to their circulating concentrations. We aimed to characterise: (a) parent–child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28–71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia’s Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent–child pairs (10–31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.     

Evaluation of Job Strain of Family Physicians in COVID-19 Pandemic Period- An Example from Turkey

Journal of Community Health - The purpose of this study was to evaluate family physicians’ job strain during the Covid-19 pandemic and determine the effective factors. The study was carried...