Spontaneous age-associated amyloidosis in senescence-accelerated mouse (SAM)

Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R).Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%) Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm.The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.     

肺腺癌细胞微环境及转移与黏附分子表达的关系

目的研究肺腺癌细胞生长环境及转移性与黏附分子CD44v6和CD29的表达关系。方法将起源相同、转移性不同的两个肺腺癌细胞系AGZY和Anip分别用简便肿瘤多细胞球体(MTS)培养法培养，并设常规单层贴壁细胞培养对照。通过倒置显微镜、扫描及透射电镜观察MTS形成情况，并用免疫组化法分别对MTS及贴壁细胞上CD44v6和CD29表达进行检测。结果MTS培养成功，贴壁细胞与MTS在细胞结构及细胞连接结构上相似，两种MTS在形态及结构上差异无显著性。免疫组化结果显示，CD29在高转移性的Anip细胞及其MTS上呈阳性表达；在低转移性的AGZY细胞及其MTS上阴性表达。CD44v6在Anip和AGZY细胞及MTS上均呈阳性表达，差异无显著性。贴壁细胞与MTS上两种黏附分子表达均无差异。结论成功建立了一种简易制备MTS的方法。细胞生长方式(单层贴壁与MTS)可能不影响CD44v6和CD29的表达。CD29表达可能与肺腺痛转移性相关；CD44v6表达可能与肺腺癌转移无关。     

Reforming the coroner and death certification service

The intention of the Home Office is to introduce a new system that combines an independent check on all deaths and a professional oversight of death patterns, with, for the majority of cases, the minimum of bureaucracy. No public consultation is intended, so that reforms are not delayed. However as the proposals are developed in the coming months, the details, practicalities and costs will be discussed “with relevant professionals (not defined) and those with experience of the existing arrangements”. The imperfections of the present system are outlined. It is hoped the medical profession will have an input, since statements such as “ ‘hospital post mortems’, which are for medical research and public health protection purposes” need amendment. There should be a change in perception of the audit value of this procedure to BOTH the family and the treating doctor. Unfortunately it is proposed the new system in total should cost no more than at present. “Professionals” (not defined) will be involved in the financial detail.All deaths, after verification and certification of the medical cause of death (if known) would then be referred to the ‘medical examiner’ based in the coroner's office. He/she would be a qualified doctor employed by the new coroner service and independent of the Health Service. The medical examiner could provide supplementary advice on medical matters required by the coroner. “Retention of tissue should only take place where absolutely necessary and the coroner and his or her other staff should take account of the needs of families and friends carefully throughout the process.” “Coroners could take advice from their medical examiner to ascertain and prescribe the minimum level of invasiveness to establish the cause of death.” This issue is far from resolved, as signified by a recent call from the DoH giving a grant to study the value of MRI versus a full post mortem. No thought is given to systemic diseases, which may present in one organ system or another disease process, other than that causing death. Medical examiners will have to keep abreast of current developments in medicine BUT will be outside the NHS, which could cause problems. Medical examiners will be appointed (with an input from Regional Directors of Public Health) and managed from within the coroner service. They would work closely with the registrar of births and deaths.Deaths from unnatural causes or when the medical cause of death is unknown will result in judicial inquests. The medical examiner will have an input into causes of death and relevant investigations.Details of the proposed structure of the system are given, as well as the investigative and other roles of Coroner's officers.The establishment of medico-legal centres, as “examples of good practice” is advocated. The drawbacks of this system are stressed in this paper. There is at present an on-going review of forensic pathology services and it is hoped thought will be given to the increasing trend for sub-specialisation in medicine.     

Sequence and chromosomal localization of two PET genes required for cytochrome c oxidase assembly in Saccharomyces cerevisiae

Summary The nuclear genes PET117 and PET191 are required for the assembly of active cytochrome c oxidase in S. cerevisiae, yet their gene products are not subunits of the final assembled cytochrome c oxidase complex. Plasmids bearing PET117 or PET191 were isolated by their ability to complement the pet117-1 or pet191-1 mutations, respectively. By restriction mapping, subcloning, and deletion analysis of yeast DNA fragments that complement these mutations, the PET117 and PET191 genes were localized to smaller regions of DNA, which were then sequenced from both strands. The PET117 open reading frame is of 107 codons and the PET191 open reading frame is of 108 codons. Neither the PET191 nor PET117 DNA sequences have been reported previously, and the derived amino-acid sequences of the PET191 and PET117 open reading frames exhibit no significant primary amino-acid sequence similarity to other protein sequences available in the NBRF data base, or from translated Genbank sequences. By hybridization of PET117 or PET191 probes first to a chromosome blot and next to a library of physically mapped fragments of yeast genomic DNA, the map locations of the PET191 and PET117 genes were determined. PET117 is located on chromosome V near the HIS1 gene and PET191 is located on chromosome X near the CYC1 gene.     

Follow-up study in a patient with Setleis syndrome

We report on an 8-year-old Japanese boy with Setleis syndrome. The patient had a very characteristic “coarse” facial appearance, bitemporal “forceps marks,” skin aplasia, sparse hair, and skin hypo- and hy-perpigmentation. He also had previously undescribed manifestations, including an aberrant hair pattern of the forehead, linear skin lesions on the forehead, short palpebral fissures, a small skin tag on the right cheek, cone-shaped teeth, and pectus carinatum. Dermatoglyphic studies documented aberrant distal palmar creases (simian crease variant), 8 arches, and reduced total finger ridge count. When serial photographs were reviewed, his facial characteristics became more obvious with increasing age. © 1995 Wiley-Liss, Inc.     

Medullary locomotor strip and column in the cat

Responses of lateral medullary neurons to microstimulation of two points in the locomotor strip—rostral and caudal to the obex—were recorded intracellularly in mesencephalic decerebellated uncurarized cats. Excitatory and inhibitory postsynaptic potentials and orthodromic action potentials occurred up to 20 ms after a single stimulus. A number of cells responded to stimulation of a locomotor point by a repetitive discharge, and in some cells synaptic responses were evoked by contralateral stimulation. The responsive neurons were scattered among other cells in the lateral medullary tegmentum. At least one-third of neurons with synaptic responses to stimulation of the rostral locomotor point were antidromically invaded from the caudal one. The characteristic length of these descending axons was between 4 and 9 mm, although there were longer axons too.The lateral medullary cells which give synaptic responses to stimulation of the locomotor strip form the locomotor column located medial to the strip, and a portion of these cells send their axons to the strip. It is suggested that the activity is propagated polysynaptically along the column through axonal collaterals of its neurons. One can assume that when repetitive stimulation achieves a threshold for locomotion such a propagation occurs without decrement. As a result, spinal stepping generators are activated.     

T suppressor lymphocytes reverse ongoing acute allograft rejection

(LEW X BN)F1 cardiac allografts are rejected within 8 days in untreated LEW recipients. At the critical time point of 5 days after transplantation, the obviously rejecting grafts are enlarged and maximally infiltrated by host cells as shown by 111In-labeled lymphocyte tracer studies. However, when such hearts were retransplanted back to naive (LEW X BN)F1 secondary hosts, they survive indefinitely, showing that even late rejection is reversible in the absence of sustained host immunological drive. Attempts were then made to abrogate this advanced immune responsiveness using Cyclosporine (CsA). CsA therapy (15 mg/kg/day for 7 days) starting from day 5 produced indefinite graft survival, similar as if initiated at the time of operation. Addition of exogenous IL-2, which drives the proliferation of Tc, could not reverse this effect. Serial changes in phenotype of lymphocyte subpopulations infiltrating both acutely rejecting and indefinitely functioning cardiac allografts in unmodified and CsA treated hosts, respectively, were then studied. Ratio of Th:Tc/s cells in acutely rejecting grafts was 1.6 by day 3; it inverted abruptly to 0.7 by day 5-6, suggesting predominance of Tc/s during the later stages of allograft rejection. Similarly, treatment with CsA produced a transient depression of Th, with recovery of original Th:Tc/s ratio during the next 2-3 weeks. Adoptive transfer experiments were then performed to investigate the functional significance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)     

c-erbB-2、VEGF和组织蛋白酶D在胃癌中的表达及其相关性

目的：探讨癌基因c-erbB-2、血管内皮生长因子（VEGF）和组织蛋白酶D（Cath-D)在胃癌中的表达及其与胃癌生物学行为的关系。方法：采用免疫组织化学（S－P）法，检测了102例胃癌手术标本中c-erbB-2、VEGF及Cath-D的表达，同时观察了网状纤维分布与c-erbB-2、Cath-D之间的关系，并将检测结果与跟踪随访资料进行了综合分析。结果：102例胃癌组织中c-erbB-2表达阳性率为38.24%（39／102），与胃癌浸润深度（P＜0.05）、淋巴结转移（P＜0.05）密切相关；VEGF表达阳性率为50％（51／102），与胃癌浸润深度（P＜0.01）、生长方式（P＜0.01）、淋巴结转移（P＜0.01）密切相关；Cath-D表达阳性率为81.37%(83/102)，与胃癌浸润深度（P＜0.05）、生长方式（P＜0.05）、淋巴结转移（P＜0.05）及脉管内有无癌栓（P＜0.05）有关。对生存期分析显示：Cath-D、VEGF、c-erbB-2阳性患者预后差，5年生存率低于阴性表达患者。结论：c-erbB-2、VEGF及Cath-D与胃癌的生长、浸润、转移、预后有密切关系，可作为判断胃癌生物学行为和预后的重要指标。     

Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Rotavirus infection of cultured cells induces a progressive increase in plasma membrane permeability to Ca2+. The viral product responsible for this effect is not known. We have used tunicamycin and brefeldin A to prevent glycosylation and membrane traffic and study the involvement of viral glycoproteins, NSP4 and/or VP7, in rotavirus-infected HT29 and MA104 cells. In infected cells, we observed an increase of plasma membrane Ca2+ permeability and a progressive depletion of agonist-releasable ER pools measured with fura 2 and an enhancement of total Ca2+ content measured as 45Ca2+ uptake. Tunicamycin inhibited the increase in membrane Ca2+ permeability, induced a depletion of agonist-releasable and 45Ca2+-sequestered pools. Brefeldin A inhibited the increase of Ca2+ permeability and the increase in 45Ca2+ uptake induced by infection. We propose that the glycosylated viral product NSP4 (and/or VP7) travels to the plasma membrane to form a Ca2+ channel and hence elevate Ca2+ permeability.