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BACKGROUND Cytomegalovirus (CMV) infections in very-low-birthweight infants can lead to serious clinical consequences. When CMV-related symptoms occur after transfusion, CMV transmission is often attributed to the transfusion products rather than to breast milk. However, it is sometimes difficult to distinguish between transfusion-transmitted and breast milk–transmitted CMV infections. PATIENT AND METHODS A patient was born at 27 gestational weeks with a weight of 689 g. He was transfused with leukoreduced red blood cells (LR-RBCs), which were later found to be CMV seropositive and CMV DNA positive. He was also fed with CMV DNA–positive breast milk. Thereafter, he developed CMV disease with thrombocytopenia and jaundice. To determine the route of transmission, we analyzed the sequences of two variable CMV genes, UL139 and UL146, by direct sequence analysis. We also performed deep sequence analysis to determine whether there were polyclonal CMV strains in the LR-RBCs transfused. RESULTS CMV DNA sequence-matching rates for the LR-RBCs and the patient's blood were 64.6% for the UL139 gene and 68.6% for the UL146 gene. In contrast, the sequences of these genes in the patient's blood were 100% matched with those in the breast milk. Furthermore, by deep sequence analysis, the CMV strain found in the patient's blood was not detected in the LR-RBCs transfused. CONCLUSION The results indicate that the pathogenic CMV strain was transmitted through breast milk, which is consistent with the claims that transfusion-transmitted CMV infection due to leukoreduced blood products is uncommon.

Background and Purpose— Adrenomedullin (AM) induces angiogenesis and inhibits cell apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. Transplantation of mesenchymal stem cells (MSCs) has been shown to improve neurological deficits after stroke in rats. We investigated whether AM enhances the therapeutic potency of MSC transplantation. Methods— Male Lewis rats (n=100) were subjected to 2-hour middle cerebral artery occlusion. Immediately after reperfusion, rats were assigned randomly to receive intravenous transplantation of MSCs plus subcutaneous infusion of AM for 7 days (MSC+AM group), AM infusion alone (AM group), MSC transplantation alone (MSC group), or vehicle infusion (control group). Neurological and immunohistological assessments were performed to examine the effects of these treatments. Results— Some engrafted MSCs were positive for neuronal and endothelial cell markers, although the number of differentiated MSCs did not differ significantly between the MSC and MSC+AM groups. The neurological score significantly improved in the MSC, AM, and MSC+AM groups compared with the control group. Importantly, improvement in the MSC+AM group was significantly greater than that in the MSC and AM groups. There was marked induction of angiogenesis in the ischemic penumbra in the MSC+AM group, followed by the AM, MSC, and control groups. AM infusion significantly inhibited apoptosis of transplanted MSCs. As a result, the number of engrafted MSCs in the MSC+AM group was significantly higher than that in the MSC group. Conclusions— AM enhanced the therapeutic potency of MSCs, including neurological improvement, possibly through inhibition of MSC apoptosis and induction of angiogenesis.

Ghrelin, a novel growth hormone-releasing peptide, has been shown to cause a positive energy balance by reducing fat use and stimulating food intake. This study investigated whether plasma ghrelin is associated with clinical parameters in patients with chronic obstructive pulmonary disease. Plasma ghrelin was measured in 50 patients and 13 control subjects, together with anabolic and catabolic factors. Patients were divided into two groups based on body mass index: underweight patients (n = 26) or normal weight patients (n = 24). Plasma ghrelin was significantly higher in underweight patients than in normal weight patients and healthy control subjects. Circulating tumor necrosis factor-alpha, interleukin-6, and norepinephrine were significantly higher in underweight patients than in normal weight patients. Plasma ghrelin correlated negatively with body mass index and correlated positively with catabolic factors such as tumor necrosis factor-alpha and norepinephrine. In addition, plasma ghrelin correlated positively with percent predicted residual volume and residual volume-to-total lung capacity ratio. In conclusion, plasma ghrelin was elevated in underweight patients with chronic obstructive pulmonary disease, and the level was associated with a cachectic state and abnormality of pulmonary function.

Though Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis, its role in early atherogenesis has not been well elucidated. To clarify whether C. pneumoniae infection was related to early atherogenesis, we evaluated the association between serological detection of C. pneumoniae antibodies and aortic stiffness in 102 healthy young male volunteers (mean age 27.1+/-0.4 years). Serum C. pneumoniae IgA and IgG antibodies were measured by the enzyme-linked immunosorbent assay (ELISA). Aortic stiffness was estimated using the brachial-ankle pulse wave velocity (PWV). No significant differences were observed between IgA seropositive and seronegative groups with regard to conventional cardiovascular risk factors. However, the mean PWV value was significantly higher in the IgA seropositive group than the seronegative group. Analyses of subgroups according to C-reactive protein (CRP) level showed that those subjects with IgA seropositivity and a high CRP level (>0.17 mg/l) had the highest PWV values. Multivariate logistic regression analysis revealed that a combination of C. pneumoniae IgA seropositivity and a high CRP level was an independent predictor of high values of PWV. These results suggest that C. pneumoniae infection might contribute to early atherogenesis, which might be associated with chronic inflammation.

We examined the immunocytochemical features of after cataract tissue and cataractous lens epithelium prior to cataract surgery and at the time of surgery. Methods: This study included 23 cases. Antibodies against the following antigens were used: epidermal growth factor (EGF), EGF receptor (EGF-R), fibroblast growth factor (FGF), FGF receptor (FGF-R), transforming growth factor (TGF)-β, TGF-β receptor II (TGF-β -RII), insulin-like growth factor (IGF)II, platelet derived growth factor (PDGF)-AB, interleukin (IL)-6, IL-1 receptor II, tumor necrosis factor (TNF)-α, tissue plasminogen activator (TPA), prostaglandin (PG) E2, plasminogen activator inhibitor (PAI)-1, alpha smooth muscle actin (α-SMA), keratin, vimentin, myosin, fibronectin, laminin, types I, II, III, IV, V and VI collagen (Col), and lens epithelial cells (LECs). Results: The following substances were present in posterior and anterior capsular fibrosis of after cataract: EGF, EGF-R, FGF, FGF-R, TGF-β, TGF-β-RII, IGF-II, PDGF-AB, IL-6, IL-1RII, TNF-α, PGE2, PAI-1, α-SMA, keratin, fibronectin, laminin, Type I col, Type II to VI col and LECs. Elschnig's pearls of after cataract expressed FGF-R, TNF-α, laminin and LECs. Soemmering's ring of after cataract tissue expressed EGF, FGF, FGF-R, IL-1RII, TPA, PAl-1, keratin and LECs. The following substances were present in cataractous lensepithelium prior to cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-β-RII,IL-1-RII, TNF-α, PAI-1, keratin, laminin and LECs. The following substances were present in the lens epithelium of anterior capsules collected at the time of cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-β, TGF-β-RII, IGF-II, IL-6, IL-1-RII, TNF-α, PGE2, keratin, fibronectin, laminin, Type IV Col and LECs. Conclusions: These results prove that many kinds of signalling molecules and proteins exist in the process of after cataract formation.

Objectives. We sought to assess the clinical significance of peak negative myocardial velocity gradient (MVG) in early diastole as a noninvasive indicator of left ventricular (LV) diastolic function. Background. Peak systolic MVG has been shown useful for the quantitative assessment of regional wall motion abnormalities, but limited data exist regarding the diastolic MVG as an indicator of LV diastolic function. Methods. Peak negative MVG was obtained from M-mode tissue Doppler imaging (TDI) in 43 subjects with or without impairment of systolic and diastolic performance: 12 normal subjects, 12 patients with hypertensive heart disease (HHD) with normal systolic performance and 19 patients with dilated cardiomyopathy (DCM), and was compared with standard Doppler transmitral flow velocity indices. In a subgroup of 30 patients, effects of preload increase on these indices were assessed by performing passive leg lifting. In an additional 11 patients with congestive heart failure at the initial examination, the measurements were repeated after 26 ± 16 days of volume-reducing therapy. Results. Peak negative MVG was significantly depressed both in HHD (−3.9 ± 1.3/s, p Conclusions. Peak negative MVG derived from TDI may be a noninvasive indicator of LV diastolic function that is less affected by preload alterations than the transmitral flow velocity indices, and thereby could be used for the follow-up of patients with nonischemic LV dysfunction presenting congestive heart failure.

To test the hypothesis that a mucin ophthalmic solution could accelerate the healing of corneal epithelium, we conducted a study in rabbits using an ophthalmic solution containing mucin extracted from bovine submaxillary gland. The corneas of rabbits were abraded with a razor blade in the central portion over an area demarcated with a 7-mm trephine. Mucin-containing eye drops were instilled into the right eye 4 times a day for 3 days, and the vehicle was instilled into the left eye. After enucleation, the eyes were observed by scanning and transmission electron microscopy as well as light microscopy. Mucin-containing eye drops were shown to reduce the epithelial defect area more rapidly than the vehicle. Thus, the eye drops accelerated corneal epithelial wound healing.

Heme oxygenase-1 (HO-1) is a stress-inducible isoform of HO with potential cytoprotective effects. Monocyte activation/migration mediated by monocyte chemoattractant protein-1 (MCP-1) is one of the earliest and important events in the pathogenesis of atherosclerosis. We examined the effect of HO-1 on the production of lysophosphatidylcholine (Lyso-PC)-induced MCP-1 in the human promonocytic cell line U937. Increased HO-1 induction by hemin resulted in a significant decrease in the Lyso-PC-mediated induction of MCP-1 mRNA expression. SnPP (IX), the specific inhibitor of HO-1 enzymatic activity, prevented the hemin-mediated attenuation of MCP-1 mRNA expression. These results suggest that HO-1 may work as an anti-atherogenic agent through the attenuation of MCP-1 production. Keywords:: heme oxygenase-1, oxidized low-density lipoprotein, monocyte chemoattractant protein-1

Hepatocyte growth factor (HGF) is a potent angiogenic and antifibrotic factor. Cardioprotective effects of HGF for idiopathic dilated cardiomyopathy were examined in hamsters with electroporation of plasmid DNA into skeletal muscle. We used hamster skeletal muscle as a protein producer of HGF gene. A plasmid vector encoding HGF (HGF group, n=12) or empty plasmid (placebo group, n=12) was transferred with in vivo electroporation into tibialis anterior muscles of hamsters with inherited dilated cardiomyopathy (TO-2 strain). The HGF group had greater serum HGF levels (21.6±2.2 versus 0.11±0.07 ng/mL, P P P P P 2 , P P

Ghrelin is a novel growth hormone (GH)-releasing peptide which was isolated from the stomach. We have reported that ghrelin causes vasorelaxation in rats through GH-independent mechanisms. We investigated whether ghrelin improves endothelial dysfunction. Ghrelin was subcutaneously administered to GH-deficient rats for three weeks. After isolation of the thoracic aorta, aortic ring tension was measured to evaluate vasorelaxation. Acetylcholine-induced vasorelaxation was impaired in GH-deficient rats given placebo compared to that in normal rats given placebo. GH-deficient rats treated with ghrelin, however, showed a significant increase in the maximal relaxation as compared with those given placebo. This improvement by ghrelin was inhibited by N(G)-nitro-L-arginine methyl ester, a nonselective nitric oxide synthase (NOS) inhibitor. Western blot analysis demonstrated that treatment with ghrelin increased endothelial NOS (eNOS) expression in the aorta of GH-deficient rats. These results suggest that administration of ghrelin improves endothelial dysfunction and increases eNOS expression in rats through GH-independent mechanisms.

This study investigated whether treatment with beraprost sodium (BPS), an orally active prostacyclin analog, improves hemodynamics and survival in patients with peripheral-vessel chronic thromboembolic pulmonary hypertension (CTEPH), for which there is no surgical option.Oral administration of BPS has been shown to improve the hemodynamics and prognosis in patients with primary pulmonary hypertension; however, whether BPS has beneficial effects in CTEPH remains unknown.Forty-three patients with peripheral-vessel CTEPH were classified into two groups: patients treated with BPS (BPS group, n = 20) and those without BPS (conventional group, n = 23). Baseline demographic and hemodynamic data did not significantly differ between the two groups.BPS therapy improved New York Heart Association functional class in 10 patients (50%) and significantly decreased total pulmonary resistance from 18 +/- 6 to 15 +/- 8 Wood units (p0.05) [mean +/- SD]. Sixteen patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 58 +/- 45 months. In contrast, only three patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 44 +/- 30 months. The absence of BPS therapy, elevated total pulmonary resistance, heart rate, and age were independently related to the mortality by Cox proportional hazard analysis. The 1-year, 3-year, and 5-year survival rates for the BPS group were 100%, 85%, and 76%, respectively, compared to 87%, 60%, and 46% in the conventional group.This preliminary study suggests that oral administration of BPS may improve hemodynamics and survival in patients with peripheral-vessel CTEPH, for which there is no surgical option.

Complicating mitral regurgitation (MR) apparently enhances left ventricular ejection fraction, thereby leading to the underestimation of myocardial damage by routine echocardiography. We sought to assess the significance of myocardial velocity gradient (MVG) derived from Doppler tissue imaging as an indicator of the severity of myocardial damage in the presence or absence of MR. Peak systolic and diastolic MVG was obtained from 39 participants: 12 healthy participants, 10 patients with dilated cardiomyopathy complicating moderate to severe MR [MR (+) group], and 17 patients with dilated cardiomyopathy without significant MR [MR (-) group]. MVG was compared with standard echocardiographic and Doppler transmitral flow velocity indices. Plasma brain natriuretic peptide levels were measured in all patients. Left ventricular dimension and fractional shortening was similar between MR (+) and MR (-) groups. Plasma brain natriuretic peptide levels were significantly increased in MR (+) group (440 +/- 417 pg/mL) as compared with MR (-) group (122 +/- 107 pg/mL, P.05). Peak systolic MVG was significantly attenuated in dilated cardiomyopathy group with or without MR [MR (+) group = 1.3 +/- 0.5 seconds(-1), MR (-) group = 2.1 +/- 0.5 seconds(-1), where normal = 4.0 +/- 0.9 seconds(-1), P.01, respectively]. Peak systolic MVG was further attenuated in MR (+) group than in MR (-) group (P.01). Plasma brain natriuretic peptide levels were negatively correlated with peak systolic MVG (r = -0.66, P.0005). Peak diastolic MVG was attenuated in MR (+) and also in MR (-) groups [MR (+) group = -4.5 +/- 2.0 seconds(-1), MR (-) group = -4.4 +/- 1.1 seconds(-1), where normal = -8.7 +/- 2.4 seconds(-1), P.01, respectively], whereas transmitral flow indices failed to distinguish MR (+) group from normal as a result of pseudonormalization. MVG may reflect the severity of myocardial damage regardless of the presence or absence of complicating MR.

Ghrelin, a novel growth hormone-releasing peptide,has been shown to cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in cachexia associated with lung cancer.Plasma ghrelin level was measured in 43 patients with lung cancer and 21 control subjects. Patients with lung cancer were divided into two groups: patients with cachexia (n = 21) and those without cachexia (n = 22).Plasma ghrelin level did not significantly differ between all patients with lung cancer and controls (157 +/- 10 versus 132 +/- 8 fmol/ml, P = 0.1). However, plasma ghrelin level was significantly higher in patients with cachexia than in those without cachexia (180 +/- 17 versus 135 +/- 10 fmol/ml, P = 0.011). Furthermore, plasma ghrelin level increased significantly in patients with decreased food intake after chemotherapy (from 136 +/- 11 fmol/ml to 170 +/- 16 fmol/ml on day 8, 179 +/- 20 fmol/ml on day 21 after start of chemotherapy), although plasma ghrelin level did not significantly change in those without decreased food intake.Baseline plasma ghrelin level was elevated in cachectic patients with lung cancer, and follow-up plasma ghrelin level increased in patients with anorexia after chemotherapy. Considering the positive energy effects induced by ghrelin, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer.

Serum uric acid (UA) has been proposed as a marker for impaired oxidative metabolism and the present study investigated whether serum UA level increases in proportion to the severity of pulmonary thromboembolism (PTE) in 193 patients. Serum UA was repeatedly measured after treatment of PTE in 76 patients. Right heart catheterization was performed in a subgroup of patients (n=104). Serum UA on admission was significantly elevated in patients with acute PTE (6.2±2.3 mg/dl) and those with chronic PTE (7.0±2.1 mg/dl) compared with age-matched controls (4.5±0.9 mg/ml). In particular, serum UA was markedly higher in the 27 patients who died during hospitalization than in the remaining survivors (8.3 ±2.2 vs 6.5±2.2 mg/dl, p

The numbers of dry eye patients are steadily increasing at a remarkable rate. The pathogenesis of dry eye has multiple etiologies. One of these is an abnormal precorneal tear film that normally protects and lubricates the surface of the eye. The precorneal tear film is a three layered structure composed of the superficial oily layer, the middle fluid layer, and the deep mucus layer which binds loosely to the glycocalyx of the epithelial microvilli.3 It has been long understood that the thickness of precorneal tear film is 7 – 10 µm.1 However, in a recent study, Prydal and associates2 measured the film’s thickness by laser interferometry, and determined that it is actually much thicker, 34 to 45 µm.

老化と共に膵臓は形態的にも機能的にも変化を受ける. 事実, 老年者では耐糖能異常を示す症例は増大している. しかし, 正常型を示す例も残っており, これらが若年者と同様の膵内分泌 (インスリン分泌), 外分泌機能を保有しているか否か興味深い問題である. 著者らは, 100g GTT正常型の若年者, 老年者と内, 外分泌異常の考えられる慢性膵炎例を対象とした.方法: Ryan らにより最も強力な膵β細胞刺激試験として考えられている100g Glucose, 1mg Glucagon 0.5g Toblutamide 負荷試験 (Combined Stimulation Test と略) を行なった. また, 外分泌検査としてはPancreozymin-Secretin Test を行なった. (1)100g GTTでは血糖, IRI共若年者, 老年者間に有意差を認めなかった. 慢性膵炎では著明な高血糖とIRI分泌低下を認めた. (2) Combined Stimulation Test では老, 若年者間に有意差を認めた. すなわちIRIは Glucagon Tolbutamide 負荷後若年者では急上昇し, 35分値で頂値に達し, 以後減少し90分で負荷前値に復した. 老年者は負荷後のIRIの上昇は鈍く頂値も若年者に比し低く, 90分でも高値を示した. 慢性膵炎はさらに頂値は低く, 平担な曲線を描いた. 血糖は逆に老年者で負荷後, 急上昇し, 減少もゆるやかであった. 慢性膵炎は全経過, 高血糖を示した. 35分値のΔIRI/ΔBS (Insulinogenic Index) は若年者13.0, 老年者5.5, 慢性膵炎1.4と三者間に有意差を見た. P-S Test では液量, 最高重炭酸濃度, 総 amylase 排出量共に, 若年者に比し老年者やや低下, 慢性膵炎では明らかに低下した. IRI分泌と外分泌の関連性を検討すると, 若年者, 老年者, 慢性膵炎の三者を1つの Groupe として見た場合. Combined Stimulation Test の Maximal ΔIRIと総 amylase 排出量との間に有意の正の相関を認めた. 結論, 老年者においては, 一見耐糖能正常型を示す症例においても, 強度の膵内, 外分泌刺激を行なった場合, 明らかに若年健康人とは異なり, 分泌能の低下を認めた. この事は, 加齢と共に膵内, 外分泌予備能の低下, 膵組織の変化等を示唆するものであり, 老化に伴う本質的な現象と考えられる.

動脈硬化症を有する高脂血症患者および実験的高脂血性家兎を中心に, 血漿 Lecithin-Cholesterol Acyltransferase 活性を測定し, 血中脂質濃度との関係から, 高脂血症における本酵素の意義について検討した.本酵素活性は14C-free cholesterol を用いた赤沼らの方法に従って測定したが, 正脂血の動脈硬化症群では 健常群に比して本酵素活性は低下していたが, 高脂血症群では健常群と同様の活性値であった. 血中脂質濃度と本酵素活性との関係を検討したところ, 高脂血および正脂血の動脈硬化症症例では, 本酵素活性と中性脂肪,pre β リポ蛋白百分率および肥満度との間に有意の相関関係がみられた. ラノリン投与による高脂血性家兎でも, 対照家兎に比して, 本酵素活性は有意に亢進していた. 以上の成績から, 本酵素は血中脂質の濃度に適応して, 脂質の担送に重要な機能を果たしているものと考えられる.

The metabolism of orally administered maltitol was investigated and compared with clinical study, especially in two groups, one which exhibited diabetic type and the other non-diabetic type (contained intermediate type) in 50g glucose tolerance test.The following results were obtained. The variation curves of blood sugar, immunoreactive insulin, and non-esterified fatty acids levels effected by 50g maltitol tolerance test in both groups had been extremely lower than those effected by 50g glucose tolerance test.So, it was considered that maltitol per se had been hardly absorbable through intestinal wall, clinically as so with animal study. In the case of concurrent administration of 50g maltitol and 50g glucose, the absorption of glucose was inhibited, resulting in a lower increase of blood sugar level than in the case of an individual administration of 50g glucose.