Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.     

Evaluation of increasing digital blood flow during early period of air-cooled cold test

The present study was performed to elucidate peripheral hemodynamic changes, especially, digital blood flow, caused by an air-cooled cold test. Experiments were carried out by placing the subject's left hand in a box that was kept at a temperature of about 18 degrees C by air-cooling. At the same time, the digital blood flow, digital blood pressure, compliances of the peripheral resistance and capacitance vessels were measured. These parameters were measured on the left forefinger of the cooled side, and also on the opposite side according to Kato's method at 3 points, 1) at normal condition (before cooling stated). 2) 30 seconds after the cooling began and 3) 10 minutes after the cooling began. The following results were obtained; 1) The systemic blood pressure, digital blood pressure and heart rate showed no statistically significant differences in measurements taken at the above three stages. 2) The mean value of the digital blood flow was found to have increased after 30 seconds, and to have decreased after 10 minutes of cooling. Statistically, significant differences were noted at the above three stages. 3) The mean value of the peripheral vascular resistance was found to have increased after 30 seconds, and to have decreased after 10 minutes. 4) Compliances of the peripheral resistance vessel and capacitance vessel showed no significant changes on either side except between normal condition and after 10 minutes of cooling.     

An effect of aluminum on hemesynthesis--special reference to erythrocyte uroporphyrinogen--1--Synthetase and protoporphyrin

In order to evaluate an inhibitory effect of Al on haem synthesis, erythrocyte uroporphyrinogen-1-synthetase (RBC-Uro-S) activity and erythrocyte level of protoporphyrin (RBC-protoporph) were measured and compared with RBC-Al in 22 patients on maintenance hemodialysis. RBC-Uro-S activity was varied from 38 to 83 nM/ml RBC/hr 37 degrees C (54.18 +/- 12.42 nM/ml RBC/hr 37 degrees C) and a slight elevation could be found no more than in two cases. On the other hand, RBC-protoporph levels showed to be significantly elevated in many cases such as 8 cases out of 22 (36.4%). (normal subjects: 63.25 +/- 27.61 micrograms/dl RBC, HD patients: 90.0 +/- 28.35 micrograms/dl RBC). This study failed to confirm a significant negative correlation between RBC-Al and RBC-Uro-S activity, but a positive significant correlation could be found between RBC-Al and protoporphyrin levels. However we could confirm a negative correlation neither between RBC-Al and Hb values nor between RBC-Uro-S activity and Hb values. Therefore we concluded that Al-intoxication in the patients on long term hemodialysis had a definite inhibitory effect on heme synthesis, but it was by no means a major factor in pathogenesis of anemia associated with chronic dialysis.     

Kinetics of sequential metabolism from D-leucine to L-leucine via alpha-ketoisocaproic acid in rat.

D-Leucine is considered to be converted into the L-enantiomer by two steps: oxidative deamination to form alpha-ketoisocaproic acid (KIC) and subsequent stereospecific reamination of KIC. We investigated the pharmacokinetics of leucine enantiomers and KIC in rats to evaluate how deamination of D-leucine, reamination of KIC, and decarboxylation of KIC were affected to the overall extent that converted D-leucine into the L-enantiomer. After intravenous administrations of D-[(2)H(7)]leucine, L-[(2)H(7)]leucine, or [(2)H(7)]KIC, their plasma concentrations together with endogenous L-leucine and KIC were determined by gas chromatography-mass spectrometry. The rapid appearances of [(2)H(7)]KIC and L-[(2)H(7)]leucine were observed after administration of D-[(2)H(7)]leucine, whereas no detectable amount of D-[(2)H(7)]leucine was found after administrations of [(2)H(7)]KIC or L-[(2)H(7)]leucine. The fraction of conversion from D-[(2)H(7)]leucine into [(2)H(7)]KIC (F(D-->KIC)) was estimated by using the area under the curve (AUC) of [(2)H(7)]KIC on the D-[(2)H(7)]leucine administration [AUC(KIC(D))] and that of [(2)H(7)]KIC on the [(2)H(7)]KIC administration (AUC(KIC)) to yield 70.1%. The fraction of conversion from [(2)H(7)]KIC to L-[(2)H(7)]leucine (F(KIC-->L)) was 40.2%. The fraction of conversion from D-leucine to the L-enantiomer (F(D-->L)) was considered to be the product of F(D-->KIC) and F(KIC-->L), indicating that 28.2% of D-[(2)H(7)]leucine was metabolized to L-[(2)H(7)]leucine via [(2)H(7)]KIC. These results suggested that the relatively low conversion of D-leucine into the L-enantiomer might depend on irreversible decarboxylation of KIC. Regardless of [(2)H(7)]KIC, F(D-->L) was also calculated directly using AUC(L(D)) and AUC(L) to yield 27.5%. There were no differences between the two F(D-->L) values, suggesting that almost all of the formation of L-[(2)H(7)]leucine from D-[(2)H(7)]leucine occurred via [(2)H(7)]KIC as an intermediate.     

Endoscopy in the diagnosis of small intestinal tumors

The importance of endoscopy in the diagnosis of small intestinal tumors was evaluated in 15 patients with small intestinal tumors treated in our hospital. Two tumors were benign, and 13 were malignant (carcinoma in 5 patients, malignant lymphoma in 5 and leiomyosarcoma in 3). The presence of lesions could be determined by X-rays before surgery, but definitive diagnoses were difficult. When preoperative endoscopy of the small intestine was possible accurate preoperative diagnoses could be made based on the endoscopic findings and biopsies taken under direct vision. Endoscopy is therefore very important for the diagnosis of small intestinal tumors. It is necessary to develop small intestinal endoscopes that are easier to insert.     

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

Background

Intestinal stricture lesions in Crohn’s disease are characterized as submucosal fibromuscular accumulation. There has been a controversy about whether the fibrogenic cells in stricture lesions in Crohn’s disease originate from a smooth muscle cell or a fibroblast lineage. In the present study, we aimed to elucidate: (1) the origin of the fibrogenic cells in stricture lesions; and (2) the roles of the local angiotensin II system, including mast cell chymase, in stricture formation.

Methods

Methanol-Carnoy’s-fixed colonic tissues, obtained from the stricture sites of 18 patients with Crohn’s disease, were analyzed by immunostaining for vimentin, smooth muscle actin (1A4 and CGA7), angiotensin II type-1 receptor, angiotensin II-converting enzyme, and mast cell tryptase and chymase. As controls, unaffected (normal) portions of 11 colonic tumor specimens were also investigated.

Results

Submucosal fibromuscular accumulation was seen in every stricture lesion. The majority of mesenchymal cells accumulated in the stricture lesions were moderately differentiated intestinal smooth muscle cells [vimentin(+), 1A4(+), and CGA7(+)]. Moreover, occasional intestinal smooth muscle cells in the muscular layers, adjacent to the site of the submucosal fibromuscular response, showed distinct positivity for vimentin, indicating phenotypic modulation toward an immature, or dedifferentiated state. These smooth muscle cells accumulated in the stricture lesions were positive for angiotensin II type-1 receptor. Abundant chymase-positive mast cells were distributed in these lesions.

Conclusions

These results suggest that the proliferation and migration of moderately differentiated intestinal smooth muscle cells from the muscular layers are the major pathologicalmechanisms in stricture formation in Crohn’s disease, and the angiotensin II system is involved in this process.     

Factor VIII contributes to platelet-fibrin thrombus formation via thrombin generation under low shear conditions

Introduction

Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism.

Objective

To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions.

Methods

The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG₁. Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion.

Results

Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s.

Conclusions

These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.     

An 8-year-old boy with vertebral artery dissection with cerebellar ataxia featuring suspected vertebral artery hypoplasia

We report an 8-year-old boy with left vertebral artery dissection featuring cerebellar ataxia in which congenital vertebral artery hypoplasia was suspected as a predisposing factor in the dissection. The patient suddenly suffered from vertigo and vomiting while swimming, and he was brought to our department. The initial brain Computed Tomography (CT) demonstrated no abnormalities, and his symptoms disappeared the next morning. However, one month after onset, brain Magnetic Resonance Imaging (MRI) revealed ischemic changes (infarction) in the left cerebellum. Transfemoral angiography showed complete occlusion at the C2 portion of the left vertebral artery, suggesting dissection and diffuse narrowing of the proximal segment of the occlusion site. Three-dimensional CT angiography also revealed diffuse narrowing of the left vertebral artery from the bifurcation of the subclavian artery. He has since been living daily life without any difficulties. The detailed etiology of cerebral artery dissection remains unknown, but arterial anomalies should be considered as a predisposing factor.