Tadao Miyahara

Lp(a) lipoprotein as a risk factor for coronary heart disease and cerebral infarction

Attempts were made to prepare antisera monospecific for Lp(a) lipoprotein and to investigate the distribution of subjects according to plasma levels of Lp(a) in Japanese controls and patients with coronary heart disease or cerebral infarction. Positive plasma reactions to the double diffusion test for Lp(a) (Ouchterlony) were observed in 32.3% of the healthy Japanese subjects, which is similar to results previously reported in western countries. The plasma threshold level of 17 mg/dl was considered an appropriate point for dividing subjects into positive and negative groups depending on reactions to the double diffusion test. When subjects were divided into two groups at 17 mg/dl, a significant association was found between a high plasma level of Lp(a) and either coronary heart disease or cerebral infarction in the distribution of the cortical artery. These results suggest that Lp(a) may play an important part as a risk factor for coronary heart disease and cerebral infarction.

Age-related variations in glycosylation of hydroxylysine in human and rat skin collagens

The extent of glycosylation of hydroxylysine in human skin collagen rapidly decreased during maturation and then gradually increased in proportion to the age. This decrease of glycosylation observed during maturation was also confirmed in whole, soluble and insoluble collagens from rat skin. These findings may contribute to the investigations on the functional role of glycosylation and also on the mechanism of maturational as well as senile processes.

Membrane potential changes associated with pinocytosis of serum lipoproteins in L cells

Abstract L cells exhibit spontaneous oscillations of membrane potential in accord with fluctuations of the cytoplasmic Ca 2+ concentration. Upon addition of low-density lipoprotein (LDL), L cells show a prolonged hyperpolarization which is followed by an increase in the frequency of membrane potential oscillations. These membrane potential changes induced by LDL were inhibited by Ca 2+ -channel blockers. LDL-induced membrane potential changes were accompanied by a vigorous pinocytosis which was coupled with the formation of ring-like ridge structures on the cell surface. These electrical and morphological changes were also induced by high-density lipoprotein (HDL) but not by very-low-density lipoprotein (VLDL). These results suggest that the application of LDL or HDL to the membrane surface elicits a rapid influx of Ca 2+ into the cytosol, resulting in membrane hyperpolarization. A rise in cytoplasmic Ca 2+ may be implicated in the primary factor for the pinocytic process.

Age-Related Change in the Reducible Cross-Link of Human Skin and Aorta Collagens

Age-related changes in the reducible cross-links of soluble and insoluble collagens from the human skin and aorta were evaluated. Histidinohydroxymerodemosine decreased with age up to the fifth decade and then remained constant in the insoluble skin collagen but could not be detected in the insoluble aorta collagen. Dihydroxylysinonorleucine could be observed, if in a small amount, in the insoluble aorta collagen but not in both the soluble and insoluble skin collagens. Hydroxylysinonorleucine seemed to be present in only a small amount, although coeluting unknown substances made it difficult to evaluate correctly. Two unknown components decreasing with age were found; the one in the insoluble skin collagen and the other in the insoluble aorta collagen. Difference in reducible cross-link was indicated between the skin and aorta collagens.

Lipoprotein abnormalities in survivors of cerebral infarction with a special reference to apolipoproteins and triglyceride-rich lipoproteins

Serum lipid and apolipoprotein concentrations were measured in 37 male survivors of cerebral infarction (CI) and in 30 healthy controls. Both groups had similar total cholesterol levels, but the HDL-cholesterol level was significantly lower and the serum triglyceride level was significantly higher in the CI patients than in the controls. The ApoB level was significantly higher in the CI patients but there was no significant difference between the 2 groups in the levels of the other apolipoproteins (ApoA-I, A-II, C-II, C-III, and E). The HDL-cholesterol/ApoA-I ratio was significantly lower in the CI patients. Both the VLDL-triglyceride and VLDL-cholesterol levels were higher in the CI patients but the VLDL-cholesterol especially its cholesterol ester level was conspicuously high. A population of VLDL particles that bound to heparin on heparin-Sepharose columns was increased in the CI patients. We suggest that cholesterol ester is excessively transferred from HDL to VLDL during the disturbed catabolism of VLDL in CI patients.

Five cases with familial hypercholesterolemia complicated by stroke.

家族性高コレステロール血症 (FH) は生下時より血清総コレステロール (TC) 値が異常に高く, 動脈硬化が早期より進展して高率に虚血性心疾患をおこすが, 脳卒中になることは非常に少ない.FHに脳卒中を合併する場合の特徴を明らかにするために, 自験5症例の脳卒中のタイプ, 各種の危険因子を検討した.2例は皮質枝梗塞であり, そのTC値は400mg/dl以上と高く, HDLコレステロール (HDL-C) 値は30mg/dl以下と低く, 動脈硬化指数は高かった。他の2例は穿通枝梗塞で残り1例は脳内出血であった.これら3例ではTC値が300mg/dl以下, HDL-C値は34~42mg/dlで, 動脈硬化指数は軽度上昇にとどまった.しかし5例に共通した危険因子は高血圧で, これが脳卒中をおこす最も重要な要因と考えられた。高血圧があってもTCとHDL-C値によって動脈病変が異なり, 皮質枝梗塞あるいは穿通枝梗塞になるのであろうと考えられた.

Significance of hypertension complicated by erythrocytosis as a risk factor for stroke

脳梗塞の成因解明のために, ヘマトクリット (Ht) 値が45%以上の高血圧患者の臨床的特徴を調べた.1,768名の外来患者のうち, この診断基準に合致する者は26名で, すべて中年以上の男性で, 赤ら顔の軽度肥満者が多かった.Htは平均48.9%, 白血球数と血小板数は正常範囲内にあった.1例に中等度の, 4例に軽度の脾腫大を認めた. 中等度の脾腫大の1例を除くと, 真性赤血球増加症の可能性はないと考えられた.血清総コレステロール値, トリグリセライド値, 尿酸値は高く, HDLコレステロール値は低かった.血漿レニン活性は正常であった.26例のうち16例もの多数に脳血管障害が認められた.従ってHt値が45%以上と比較的軽症の赤血球増加症を含めても, 高血圧を合併すると脳血管障害を発症しやすいと考えられる.それとともに高脂血症, 低HDL血症, 高尿酸血症など脳血管障害の危険因子を合併することが多い点にも注意する必要がある.

Abnormalities of glucose metabolism in patients with cerebral infarction

脳梗塞における耐糖能障害の役割を明らかにする目的で, 健常者17名と, 肥満のない慢性期脳梗塞患者129名 (皮質枝系梗塞70名, 穿通枝系梗塞59名) に50g経口糖負荷試験を行なった.脳梗塞患者では両群とも耐糖能の障害が高率に認められた.WHOの分類では耐糖能異常 (IGT) に含まれるものが多かった.遊離脂肪酸は高値であったが, 糖負荷に対する低下反応は正常であった.グルカゴンは低下反応の消失している例が多かった.インスリン (IRI) は両群とも反応の遅延がみられた.穿通枝系梗塞では30分値が健常者および皮質枝系梗塞に対して有意の低値を示し, インスリン指数やΣIRIも低値であったが, 皮質枝系梗塞ではΣIRIがむしろ高値を示した.この結果は, インスリン依存性の糖尿病が穿通枝系梗塞を発症しやすいのに対して, インスリン高値が皮質枝系梗塞のリスク要因となる可能性を示唆している.