Three-field dissection or two-field dissection?--A proposal of new algorithm for lymphadenectomy

BACKGROUND/AIMS: There are no systematic criteria for cervical lymphadenectomy in esophageal carcinoma. We provide a new algorithm for deciding whether to use three-field dissection or two-field dissection. METHODOLOGY: Ninety-eight patients underwent curative esophagectomies with three-field lymph node dissections for squamous cell carcinoma of the thoracic esophagus. We examined the outcomes and predictors for survival of these patients. Therefore, we devised a new decision tree for deciding whether to use three-field dissection or two-field dissection. RESULTS: The overall 5-year survival rate for the 98 patients was 41.3%. The number of positive nodes was the only significant predictor for survival in the multivariate Cox proportional hazard model. The outcomes of patients with positive supraclavicular/internal jugular nodes were poor. On the other hand, positive cervical paraesophageal nodes do not worsen prognosis. We provided a new algorithm for selecting procedure of lymphadenectomy based on the presence of lymph node metastases. This algorithm is decided by the number of positive nodes, the presence of cervical node metastasis and recurrent nerve node metastasis. According to this decision tree, there were a few patients who needed absolutely three-field dissections. CONCLUSIONS: The new algorithm may be helpful for deciding three-field dissection or two-field dissection for thoracic esophageal carcinoma.     

A case of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy) with Notch 3 (Arg169Cys) mutation and typical granular osmiophilic materials in peripheral small arteries]

We report a 64-year-old Japanese woman with recurrent ischemic strokes and progressive dementia without any cardiovascular risk factors. Her first stroke was at 45 years old, and she has a family history of ischemic strokes compatible with an autosomal dominant trait. Marked leukoaraiosis and multiple lacunar infarcts were shown on brain MR images, and no atherosclerotic changes were observed in her extra- and intra-cranial arteries by cervical arterial echography and intracranial MR angiography. Excluded other inherited or metabolic diseases causing leukodystrophy by examination of her blood samples, her disease was diagnosed as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy). We demonstrated granular osmiophilic materials (GOM) on the wall of small arteries from a biopsied peripheral nerve tissue specimen and detected a mutation Arg169Cys of Notch 3 gene. Many CADASIL patients have been reported and over 28 kinds of mutations of the Notch 3 were identified in western countries, while few CADASIL patients have been reported in Japanese people. Among them, eleven CADASIL families have been reported and only five mutations (Arg133Cys, Cys174Phe, Arg213Lys, Arg90Cys and Arg141Cys) have been determined so far. The mutation of Notch 3 in our patient was determined as Arg169Cys, and this is the first report on a Japanese patient with CADASIL due to this mutation.     

Studies of experimental allergic encephalomyelitis in old mice

In old BALB/c mice susceptibility to experimental allergic encephalomyelitis (EAE) with bovine proteolipid apoprotein (PLP) is reduced significantly. Eleven of 21 8-week BALB/c mice developed clinical signs of EAE following injection of PLP but only two of 18 12-month BALB/c mice and one of 19 24-month BALB/c mice showed clinical signs of EAE. Susceptibility to EAE induced by either PLP or bovine myelin basic protein (MBP) also was reduced in old SJL mice. However, the aging process had no effect on the clinical signs of EAE in both strains, if EAE appeared. Some old BALB/c mice developed histologic EAE with significant demyelination without clinical signs. Lymphocyte proliferative response to mitogens and antigens, and interleukin-2 (IL-2) production, also were depressed in the aged mice (24-month BALB/c and 18-month SJL) probably due to the functional defect of T cells, since the function of macrophages as antigen-presenting cells was not affected in the old mice. PLP-sensitized spleen cells (SPC) from 8-week mice were able to adoptively transfer EAE to young and aged recipients. PLP-sensitized T cells from 8-week mice, reconstituted with young or old monocytes, also were able to transfer EAE into young mice. In contrast, spleen cells from aged mice did not induce EAE, so the reduction of EAE susceptibility was mainly explained by the failure of T cell activity. This T cell defect was not restored by exogenous IL-2.     

脂蛋白对实验变态反应性脑脊髓炎的阻断研究

腹腔注射脂蛋白（ＰＬＰ）进行免疫耐受诱导，可保护小鼠既不发生ＰＬＰ引起的主动性实验变态反应性脑脊髓炎（ＥＡＥ）又不发生ＰＬＰ特异性淋巴细胞引起的被动性ＥＡＥ。提示在ＥＡＥ发病过程中，ＰＬＰ较髓鞘硷性蛋白（ＭＢＰ）更具作用。免疫耐受的机理可能为非胸腺依赖性且与非特异性免疫有一定关系。     

Developmental and aging changes in the expression patterns of beta-amyloid in the brains of normal and Down syndrome cases

Immunohistochemical staining with polyclonal antibodies to synthetic amyloid (residues 1-28 of A4) was performed on normal and Down syndrome brains from fetuses to adults. Positive staining appeared in the cytoplasmic processes of astrocytes in the subpial layer and white matter of developing brains, and reappeared in astrocytic fibers of the subpial layer as well as in cerebrovascular and plaque core amyloid in elderly brains. The reappearance of positively stained astrocytes and amyloid occurred earlier in adult Down syndrome patients. The results indicate that the A4 protein is a developmental protein, and its reappearance in Alzheimer and adult Down syndrome brains may be related to the regeneration process.     

HLA-DPβ and susceptibility to multiple sclerosis: An analysis of caucasoid and Japanese patient populations

Nonradioactive sequence-specific oligonucleotide (SSO) probes specific for the HLA-DPβ locus have been used in a simple dot-blot assay to DPβ-type samples amplified by the polymerase chain reaction (pcr) from Caucasoid (n = 24) and Japanese (n = 23) patients with multiple sclerosis (ms) as well as ethnically matched controls. In contrast to previous reports, no DPβ allele was found to be increased in either patient population. However, the results do show a dramatic difference in the allele frequencies between the two control populations, further emphasizing the need for ethnically matched controls in studies of HLA and disease.     

Elevated levels of anti-CD9 antibodies in the cerebrospinal fluid of patients with subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive and highly lethal disease of the central nervous system. Although the primary cause of SSPE is believed to be persistent infection of neuron and glial cells by a measles virus, the precise mechanism of the progression of this disease has not yet been elucidated. CD9, a member of the tetraspanin family, is expressed in myelin and other nervous tissues. This study detected significant amounts of anti-CD9 antibodies in the cerebrospinal fluid (CSF) of all patients with SSPE included in the study. Anti-CD9 antibodies were also detected in the CSF of some patients with other neurologic disorders, but those patients had lower levels of anti-CD9 antibodies than did the patients with SSPE. The level of anti-CD9 antibodies was elevated and reached a peak that coincided with the appearance of brain atrophy. These findings shed light on a new aspect of the causes and progression of SSPE.     

Modulation of experimental allergicencephalomyelitis (EAE): Suppression of active reinduction of eae in rats recovered from passively transferred disease

Lewis rats that have recovered from EAE induced by the passive transfer of in vitro activated lymphocytes sensitized to myelin basic protein showed suppression upon subsequent active reinduction of EAE. This suppression was manifested during the early convalescent stage (up to 30 days after the primary cell transfer) and seemed to be acquired partly idiotype-specifically and partly idiotype-nonspecifically. The convalescent rats were fully susceptible to the transfer of sufficient numbers of effector cells, and they could induce pre-effector cells in response to the encephalitogen in vivo as effectively as in naive rats. This suppression was not transferred to naive rats by lymphoid cells from the convalescent rats. The mechanism of this suppression was thought to be a defect in expansion and/or differentiation of pre-effector cells to effector cells in the convalescent rats.     

Antibodies to proteolipid apoprotein in chronic relapsing experimental allergic encephalomyelitis

Titers of serum antibodies to proteolipid apoprotein (PLP) were determined in chronic relapsing experimental allergic encephalomyelitis (EAE) of strain 13 guinea pigs sensitized with whole central nervous system tissue. Levels of the antibodies were slightly higher in the animals with relapse than those without relapse during the early chronic stage (days 40-99 postinoculation). The titers were significantly higher in the relapsed animals during the chronic stage (days 100-199). Although the clinical course was polyphasic, the humoral response to PLP was monophasic. Since PLP alone causes chronic EAE with widespread demyelination in guinea pigs (Yoshimura et al. 1985), the high titers of anti-PLP antibodies seem to have something to do with the immunologic mechanisms of chronic relapsing EAE.