Novel interactions in platelet biology: CLEC-2/podoplanin and laminin/GPVI

Summary.  We have identified a novel platelet membrane protein, CLEC-2 as a receptor for rhodocytin, a platelet-activating snake venom. CLEC-2 is specifically expressed in platelets and megakaryocytes, and has an atypical ITAM, which undergoes tyrosine phosphorylation by Src kinases, resulting in downstream signaling including Syk, SLP-76 and PLCγ2. We found that CLEC-2 is the receptor for podoplanin, a sialoglycoprotein implicated in tumor-induced platelet aggregation and tumor metastasis. VWF bridges exposed collagen, at damaged vessels, to GPIb. Subsequently, GPVI binds to collagen, leading to integrin α2β1 activation. We found that platelets adhere to laminin, another major ECM component, through integrin α6β1, and are activated through GPVI. This is the first report on GPVI having a ligand, laminin, other than collagen. Laminin also interacts with VWF, leading to platelet adhesion via GPIb under sheer stress. The redundancy of platelet interactions with laminin and with collagen may serve to promote hemostasis at sites of damaged vessels.     

实验性变态反应性脑脊髓炎T淋巴细胞增殖和肿瘤坏死因子—α变化的意义

目的：探讨实验性变态反应性脑脊髓炎（EAE）T淋巴细胞增殖和肿瘤坏死因子（TNF）－α变化的意义。方法：观察Lewis大鼠主动免疫性EAE临床症状,T淋巴细胞增殖以及血清TNF－α水平,结果：EAE临床发病过程中,T淋巴细胞增殖活跃,血清TNF－α水平异常升高,并与临床症状呈正相关。结论：研究表明：EAE时,TI林巴细胞增殖旺盛和TNF－α生成增多。进而导致血脑屏障的破坏,炎细胞浸润,从而诱发EAE。     

Successfully Treated Isolated Posterior Spinal Artery Aneurysm Causing Intracranial Subarachnoid Hemorrhage: Case Report

There are very few published reports of rupture of an isolated posterior spinal artery (PSA) aneurysm, and consequently the optimal therapeutic strategy is debatable. An 84-year-old man presented with sudden onset of restlessness and disorientation. Neuroradiological imaging showed an intracranial subarachnoid hemorrhage (SAH) with no visible intracranial vascular lesion. Spinal magnetic resonance imaging (MRI) detected a localized subarachnoid hematoma at Th10–11. Both contrast-enhanced spinal computed tomography and enhanced MRI and magnetic resonance angiography revealed an area of enhancement within the hematoma. Superselective angiography of the left Th12 intercostal artery demonstrated a faintly enhanced spot in the venous phase. Thirteen days after the onset of symptoms, a small fusiform aneurysm situated on the radiculopial artery was resected. The patient''s postoperative course was uneventful and he was eventually discharged in an ambulatory condition. To our knowledge, this 84-year-old man is the oldest reported case of surgical management of a ruptured isolated PSA aneurysm. This case illustrates both the validity and efficacy of this therapeutic approach.     

Results of Prospective Cohort Study on Symptomatic Cerebrovascular Occlusive Disease Showing Mild Hemodynamic Compromise [Japanese Extracranial-Intracranial Bypass Trial (JET)-2 Study]

The purpose of this study is to determine the true threshold of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) for subsequent ischemic stroke without extracranial-intracranial (EC-IC) bypass surgery in patients with hemodynamic ischemia due to symptomatic major cerebral arterial occlusive diseases. Patients were categorized based on rest CBF and CVR into four subgroups as follows: Group A, 80% < CBF < 90% and CVR < 10%; Group B, CBF < 80% and 10% < CVR < 20%; Group C, 80% < CBF < 90% and 10% < CVR < 20%; and Group D, CBF < 90% and 20% < CVR < 30%. Patients were followed up for 2 years under best medical treatment by the stroke neurologists. Primary and secondary end points were defined as all adverse events and ipsilateral stroke recurrence respectively. A total of 132 patients were enrolled. All adverse events were observed in 9 patients (3.5%/year) and ipsilateral stroke recurrence was observed only in 2 patients (0.8%/year). There was no significant difference among the four subgroups in terms of the rate of both primary and secondary end points. Compared with the medical arm of the Japanese EC-IC bypass trial (JET) study including patients with CBF < 80% and CVR < 10% as a historical control, the incidence of ipsilateral stroke recurrence was significantly lower in the present study. Patients with symptomatic major cerebral arterial occlusive diseases and mild hemodynamic compromise have a good prognosis under medical treatment. EC-IC bypass surgery is unlikely to benefit patients with CBF > 80% or CVR > 10%.     

Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients

OBJECTIVES: In a variety of cancers, several polymorphisms of the tumor necrosis factor (TNF) genes have been reported to result in different clinical outcomes. We investigated whether a polymorphism of the TNF gene is associated with a susceptibility to bladder cancer and its disease status. METHODS: Polymorphisms in the TNF-alpha gene promoter (-308 bp) and the NcoI site in the first intron of the TNF-beta gene were analyzed in 141 Japanese patients with bladder cancer and 173 Japanese controls by polymerase chain reaction-restriction fragment length polymorphism. The correlations between the polymorphisms of the TNF genes and the clinicopathological features were analyzed. RESULTS: The number of cases and controls with TNF-alpha2 was too small to be assessable. In contrast, the TNF-beta1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold increased risk of bladder cancer compared to the TNF-beta2/2 genotype. In the bladder cancer group, patients with the TNF-beta1 allele had a significantly higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than those without the TNF-beta1 allele. Moreover, in the superficial bladder cancers, patients with the TNF-beta1 allele showed a significantly higher intravesical recurrence rate than those without the TNF-beta1 allele. CONCLUSION: This polymorphism in the TNF-beta gene appears to be associated with tumor occurrence and disease status, such as the tumor grade and the presence of CIS. Further study with an increased sample size is warranted.     

Plasmacytoma and follicular lymphoma in a case of Hashimoto''s thyroiditis

Monoclonal gammopathy (IgG, lambda) in a 37-year-old man with Hashimoto's thyroiditis, was markedly decreased after thyroidectomy. Histological examination of the thyroid showed large lymphoid follicles surrounded by a massive proliferation of plasma cells. Immunological studies revealed that interfollicular plasma cells stained monotypically for lambda chain, findings in keeping with a diagnosis of plasmacytoma of the thyroid. In addition, there was kappa monotypic staining of the lymphoid follicles and absence of tangible body macrophages, indicating the presence of a follicular lymphoma derived from a separate cell line from the plasmacytoma.     

Rupture of urachal diverticulum in radiation cystitis and neurogenic bladder dysfunction after radical hysterectomy

Abstract We experienced a rare case of the rupture of the urachal diverticulum in radiation cystitis and neurogenic bladder after radical hysterectomy. A 61‐year‐old woman presented with severe lower abdominal pain and urinary retention. Abdominal computed tomography revealed that the urachal remnant contained a large volume of urine that leaked to subcutaneous tissue. We excised the urachal diverticulum and bladder together and created a continent urinary diversion using transverse colon. Nine months after the operation, the patient could manage clean intermittent self‐catheterization 6 times a day through her umbilical stoma without any urinary complications.     

Effect of obstructive jaundice on neutrophil chemotactic activity: An in vivo assessment in zymosan-induced peritonitis model in rats

The effect of obstructive jaundice on local neutrophil accumulation in response to inflammatory stimulus was investigated in rats. Obstructive jaundice was produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid was measured to quantify neutrophil recruitment. Zymosan-induced neutrophil recruitment was significantly greater (more than two-fold) in bile duct-ligated rats than in sham-ligated or normal animals. Depletion of peritoneal cells significantly suppressed neutrophil recruitment after zymosan injection in all three groups, with no significant differences between the groups. In normal rats, replacement of their peritoneal cells by those from bile duct-ligated rats did not enhance zymosan-induced neutrophil recruitment. In contrast, bile duct-ligated rats treated with peritoneal cell replacement from normals showed significantly increased neutrophil recruitment after zymosan injection. In vitro neutrophil chemotaxis in response to formyl-Met-Leu-Phe was significantly enhanced in bile duct-ligated rats, compared with that in sham-ligated animals. The results suggest that local neutrophil recruitment in response to inflammation may be enhanced in obstructive jaundice and that increased neutrophil chemotactic activity, not macrophage activity, may play a prime role in the mechanism.     

Combination Therapy for Intestinal Amebiasis Using an Anti-amebic Drug and Total Parenteral Nutrition —Report of Two Cases—

Abstract: In this study we report on two cases of amebic colitis treated in our hospital. On admission both patients were in a severe state of malnutrition due to intermittent diarrhea which had continued for one month. Both patients suffered from amebic colitis presumably transmitted by homosexual intercourse. A definite diagnosis of amebic colitis was made from both fecal examination and colonoscopic biopsy. After the diagnosis was made, the patients were treated with metronidazole. This medication can eliminate Entamoeba histolytica, although it was insufficient for the treatment of the patients’malnutrition. Therefore we used total parenteral nutrition to treat their malnutrition. It was successful and resulted in their recovery and discharge. These two cases indicate that total parenteral nutrition therapy is useful for supporting the recovery of patients with amebiasis.