Tomiko Nagayama

Lipoprotein(a) and ischemic cerebrovascular disease in young adults.

Background and Purpose Serum lipoprotein(a) level is genetically determined and remains almost constant throughout life. Based on this property, we investigated the serum lipoprotein(a) levels of ischemic stroke patients in the chronic stage (mean period after stroke, 27 months) and its relation to the types of ischemic stroke. Methods We measured serum lipoprotein(a) levels in 101 patients with chronic ischemic stroke and 37 normal control subjects, taking the clinical profiles into consideration. Results Lipoprotein(a) levels in patients with atherothrombotic stroke were 28.0±19.6 mg/dL (mean±SD), which were significantly (P < .01) higher than those in patients with lacunar stroke and in normal control subjects (16.4±13.5 and 11.7±10.5 mg/dL, respectively). The lipoprotein(a) levels in patients with atherothrombotic stroke were significantly higher in the subgroup who were a younger age at onset: onset before age 50 years, 35.3±20.5; onset at age 50 to 59, 35.4±21.7; onset at age 60 to 69, 17.0±12.8; and onset at age 70 or older, 16.3±6.8 mg/dL (P < .01 for onset before age 50 versus 60 to 69 years or 70 years or older; P < .01 for onset at 50 to 59 years versus 60 to 69 years or 70 years or older). Serum lipoprotein(a) was significantly increased (40.2 ±20.1 mg/dL) in young adults with atherothrombotic stroke (onset at younger than age 45 years) compared with that in patients older than 45 years (P < .01). Conclusions We conclude that lipoprotein(a) is a genetic, independent, and critical risk factor for ischemic stroke, especially in young adults.

Post-ischemic delayed expression of hepatocyte growth factor and c-Met in mouse brain following focal cerebral ischemia.

We investigated long-term changes in the expression of protein and mRNA of hepatocyte growth factor (HGF) and its receptor c-Met in mouse brain after permanent occlusion of the middle cerebral artery, by using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. HGF-immunopositive cells were observed in the periinfarct region from 4 days after occlusion, peaking at 14-28 days. The area containing HGF-immunopositive cells continued to expand until 28 days after occlusion. c-Met-immunopositive cells were observed exclusively at the periinfarct region at 7 and 14 days after occlusion. At 28 days after occlusion, there were many c-Met-immunopositive cells in the widespread periinfarct region. Triple immunohistochemical staining by using confocal laser scanning microscopy (CLSM) demonstrated that most of the HGF-immunopositive cells were localized to reactive astrocytes. The c-Met-immunopositive cells were also localized to reactive astrocytes. HGF mRNA was upregulated exclusively in the periinfarct region at 14 days. c-Met mRNA was upregulated in the periinfarct region from as late as 28 days after occlusion. Thus, HGF and c-Met show delayed expression in the periinfarct region at both protein and mRNA levels after induction of ischemia. Because HGF was recently shown to play critical roles in angiogenesis and neurotrophic activities, the temporal profiles of their expression may imply the involvement of HGF in the process of post-ischemic brain tissue repair.

Congenitally abnormal plasminogen in juvenile ischemic cerebrovascular disease.

Background and Purpose Congenitally abnormal plasminogen is characterized by markedly decreased fibrinolytic activity and has been reported mainly in association with venous occlusive disease. Case Description We found three young adult patients (34, 45, and 27 years old at onset) with ischemic cerebrovascular disease, all of whom had congenital plasminogen abnormalities but no other known risk factors. Hemostatic tests of all three patients revealed plasma plasminogen activities at almost one half of the normal level despite normal plasma plasminogen antigen levels. They were found to be heterozygotes with abnormal plasminogen (normal Ala-601[GCT] to abnormal Thr-601[ACT]) by DNA sequence analysis after polymerase chain reaction. Conclusions Congenital plasminogen abnormalities could be one of the risk factors of juvenile ischemic cerebrovascular disease of the arterial as well as venous type.

Persistent but reversible coma in encephalitis.

AbstractIntroduction: Nontraumatic coma in adults has a poor prognosis, and late recovery of consciousness is unlikely. Functional recovery is usually extremely poor. However, a few nontraumatic comatose patients have shown late recovery of both awareness and function. Methods: A retrospective survey was conducted by reviewing the medical records of all inpatients to our department during the 1990s. Patients with persistent but reversible nontraumatic coma were identified according to the following criteria: (a) deep coma with a Glasgow Coma Scale (GCS) score of 7 or less on admission; (b) nontraumatic cause; (c) persistence of unconsciousness for longer than 1 month; and (d) subsequent recovery of GCS (total) to normal. The clinical spectrum of patients meeting these criteria was evaluated. Results: Six patients (ages 16–75 years) met the criteria. Viral encephalitis was diagnosed in five (two with herpes simplex virus, two with cytomegalovirus, and one with Epstein-Barr virus or cytomegalovirus). Two young female patients with encephalitis manifested extremely protracted coma persisting for 3 and 18 months, respectively. Complications included nonconvulsive status epilepticus in two patients and relative overdose of clonazepam in one patient. Conclusion: Recognition of the clinical spectrum of persistent but reversible nontraumatic coma is important.

Detection of prothrombotic state in ischemic stroke by monitoring plasma molecular markers

The feasibility of using recently developed coagulation-fibrinolysis markers to detect hemostatic alteration in acute ischemic stroke was examined to see whether they may be employed as predictors of recurrence. We measured serially the plasma thrombin-antithrombin III complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC) and D-dimer in patients with ischemic stroke (53 acute, 102 chronic) and 37 normal control subjects. In the acute stage, TAT and D-dimer were significantly increased in both atherothrombotic and lacunar stroke. In cardioembolic stroke, TAT, PIC, and cross-linked D-dimer (D-dimer) were more significantly increased and reached a peak within 3 days (TAT) or at around the second week (PIC, D-dimer) poststroke. TAT, PIC, and D-dimer correlated with infarct size, but TAT and D-dimer were significantly increased even in patients with small infarcts. In the chronic stage, TAT was increased above the mean + 2 SD in 7 patients with cardioembolic stroke (n = 17), in 13 with atherothrombotic stroke (n = 37), and in 11 with lacunar stroke (n = 48). In those we had examined within 4 months before recurrence, TAT was increased above the mean + 2 SD in 7 patients (n = 8). We demonstrated TAT and D-dimer to be highly sensitive detectors of hemostatic alteration in small ischemic stroke, contrary to previous reports, and also showed that TAT can detect the prothrombotic state before recurrence.

Generation of high-density DNA markers from yeast artificial chromosome DNA by single unique primer-polymerase chain reaction

We have developed a method for the whole sequence amplification of yeast artificial chromosome (YAC) DNA excised from preparative pulsed-field gel electrophoresis using single unique primer-polymerase chain reaction procedures. We used seven contiguous YAC clones, which span 2 Mbp of the Huntington disease gene region on 4p16.3, to amplify the YAC DNAs. The average size of the amplified DNA was approximately 300 bp long, and 12 DNA markers located on the YAC clones positively hybridized with these amplified products, implying that the sequences of the YAC clones were comprehensively amplified by our procedures. These amplified YAC DNAs greatly facilitate the characterization of YAC clones, leading to the detailed analysis of the defined chromosomal region.

Expanded Spectrum of Coagulopathy in the Etiology of Cerebral Infarction in Younger Adults in Japan

To clarify the role of coagulopathy in cerebral infarction (CI) in adults with onset before age 45, we performed comprehensive and repeated hemostatic analyses in 77 consecutive young adult patients w

The Effect of BAY K-8644 on Cytotoxic Edema Induced by Total Ischemia of Rat Brain

The calcium channel activator BAY K-8644, a dihydropyridine (DHP) derivative, has been shown to possess neurochemical and behavioral activities, but its effect on ischemic brain damage has remained unknown. This report describes the effect of the drug on the progression of cytotoxic edema induced by total ischemia of the brain, evaluated by measuring the time constant, k, of elongation of the 1H-NMR relaxation time (T2) after brain biopsy. Twenty-six male Wistar rats were divided into four groups, (a) control (saline) group (n = 10), (b) BAY K-8644 vehicle group (n = 4), (c) BAY K-8644 0.03 mg/kg group (n = 6) and (d) BAY K-8644 0.3 mg/kg group (n = 6). The k value of group (d), 18.2 +/- 5.8 min (mean +/- SD), was significantly higher compared with those of groups (a) 10.3 +/- 1.6, (b) 11.8 +/- 1.5 and (c) 9.8 +/- 3.3 min (p < 0.01 by ANOVA). These results indicate that BAY K-8644 delayed the progression of cytotoxic edema induced by total ischemia of the rat brain.

DNA analysis of congenital abnormal plasminogen: Clinical significance.

線溶活性の低下を呈する先天性プラスミノーゲン異常症の患者13人とその家族5人において2つのPCR (polymerase chain reaction) 法を用いて遺伝子解析を行った.突然変異による高次構造の変化を電気泳動での移動度の差として検出するPCR-SSCP法 (single strandconformation polymorphisrn) は, 本症の遺伝子変異のスクリーニングに有用であった.その変異部位を明らかにするために行ったPCR直接塩基配列決定法により, プラスミノーゲンの601番目のAlanineをコードする塩基GCTがACT (Threonine) に点変異していることが示された.従来の等電点電気泳動法を改良し, 本症の異常を蛋白レベルでも明らかにした.また本症は若年発症の虚血性脳血管障害で有意に (P<0.05) 高頻度であり, その危険因子の一つとなりうるものと推定した.