Importance of fluorescein angiographic study in evaluating early retinal changes in Takayasu disease

PURPOSE: To determine the usefulness of fluorescein angiography in studying Takayasu disease. METHODS: We examined 31 eyes in 16 patients with Takayasu disease using indirect ophthalmoscopy, color photography, and fluorescein angiography. Ophthalmoscopic and fluorescein angiographic findings were compared. RESULTS: Fluorescein angiography revealed no additional retinal changes in 10 eyes that had no retinal vein dilatation as seen by indirect ophthalmoscopy. Seven (33%) of 21 eyes that had dilated retinal veins also had additional abnormal findings, such as microaneurysms, arteriovenous shunts, retinal neovascularization, and avascular areas. Some differences in grading the stages of retinopathy were noted with these newly found retinal changes, as compared with the classifications determined by ophthalmoscopy alone. CONCLUSIONS: In Takayasu disease, studying the fundus of patients with fluorescein angiography is particularly important in correctly classifying the stages of retinopathy when the retinal vein appears dilated in ophthalmoscopic observation.     

REP-1 gene mutations in Japanese patients with choroideremia

· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients. Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998     

Overview of pharmacological treatment of Kawasaki disease

Kawasaki disease has been researched for 32 years but its aetiology is still unknown. Conventional therapy for the disease includes corticosteroids and aspirin (acetylsalicylic acid) as anti-inflammatory and/or antithrombotic agents but they have not been proven to prevent coronary artery aneurysms. Although a high incidence of liver dysfunction in Japanese patients with Kawasaki disease receiving high dose aspirin (> or =80 mg/kg/day) suggests racial differences in salicylate sensitivity, the duration of fever in patients receiving high dose aspirin is shorter than that in patients receiving moderate dosages (30 to 50 mg/kg/day). Furthermore, most corticosteroid-resistant patients were found to develop coronary artery aneurysms, many of which were large. With the clarification of the pathogenesis and clinical features of Kawasaki disease, advances in its treatment have been achieved. The introduction of high-dose intravenous gamma-globulin (IVGG) was an epoch in this field and IVGG is now a standard therapy with the incidence of persistent coronary aneurysms 1.9% in children with the disease receiving IVGG. Today, research is mainly directed toward the treatment of IVGG-resistant patients. One to 3 days of pulsed doses of methylprednisolone (30 mg/kg/day) or readministration of IVGG 1 g/kg (once to several times) has been recommended for patients with IVGG-resistant Kawasaki disease.     

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and secretions of apolipoprotein B-containing lipoprotein and bile acids in HepG2

We studied the effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl) ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on intracellular cholesterol esterification and the secretion of apolipoprotein B100 (apoB)-containing lipoprotein and bile acids in the human hepatoma cell line HepG2. NTE-122 markably inhibited [3H]oleate incorporation into cholesteryl esters in HepG2 cells incubated with 5 microg/ml 25-hydroxycholesterol as a stimulus for ACAT (IC50=6.0 nM). On the other hand, NTE-122 did not affect [3H]oleate incorporation into triglycerides and phospholipids and [14C]acetate incorporation into cholesterol. The stimulation of ACAT by 25-hydroxycholesterol caused significant increases in the secretion of radiolabeled cholesteryl esters, radiolabeled triglycerides and apoB mass. NTE-122 pronouncedly inhibited the secretion of radiolabeled cholesteryl esters in proportion to the inhibition of cellular cholesterol esterification, and it significantly reduced the secretion of radiolabeled triglycerides and apoB mass in HepG2 cells incubated with 25-hydroxycholesterol. Furthermore, NTE-122 increased the secretion of bile acids synthesized from [14C]-cholesterol. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing both the cholesterol content and the amount of secreted very low-density lipoprotein and enhancing the excretion of bile acid from the liver.     

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and high-density lipoprotein-induced cholesterol efflux in macrophages

We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.     

Anaplastic large cell lymphoma associated with Sjögren's syndrome

We report a case of a 20-year-old Japanese female with recurrent anaplastic large cell lymphoma (ALCL) associated with Sj?gren's syndrome (SjS). She was first diagnosed to have ALCL presenting with axillary lymphadenopathy, which within a month underwent spontaneous remission, at the age of 12 years. Eight years later she developed left inguinal lymphadenopathy with clinical overt sicca symptoms associated with elevated serum IgG, interleukin (IL)-1beta and IL-6 levels. Lymph node biopsy was now diagnostic of ALCL characterized by large pleomorphic CD30+ blast cells with the specific chromosomal abnormality, t(2;5)(p23;q35). In contrast to this the salivary gland and renal biopsy revealed infiltration of small lymphocytes, morphologically and cytogenetically distinct from the ALCL cells. Interestingly, SjS symptomatology correlated with disease activity of ALCL and based on an association with elevated IgG and IL-6 levels, suggesting that the concurrence of these two diseases could be more than coincidental. To the best of our knowledge, this is the first reported case of ALCL presenting concurrently with SjS.     

Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent

Summary To determine whether E-643, a new -blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine--hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 151±28/89±14 mmHg), sitting (158±22/101±11 138±28/89±15 mmHg) and standing (153±32/103±21 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 69±10 beats/min), but was increased in the sitting (68±10 73±9 beats/min) and standing (73±10 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine--hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine--hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.     

A study on the psychological status of perioperative patients (II)]

In order to study the changes of the psychological status during perioperative period, we performed four different psychological tests, Spielberger's rating scale "The State-Trait Anxiety Inventory (STAI)", Self-rating Depression Scale (SDS), Maudsley Personality Inventory (MPI) and Baum test, in 63 patients who received simple total hysterectomy for myoma of uterus. The anxiety ratings showed a significant decrease postoperatively. On the contrary, the SDS index that expresses the level of depressive mood showed no significant change during perioperative period. Moreover the patients who had shown a tendency of nervousness in MPI kept the high level of the SDS index during perioperative period than the other patients who had not shown a tendency of nervousness in MPI. In Baum test, more than 75% of patients manifested psychologic fragility or lability. These results suggest that depressive mood affects strictly the psychological status in postoperative period more than anxiety. We presume that the depressive mood during perioperative period is responsible for the postoperative psychological disturbance.     

Effect on electroencephalogram of chewing flavored gum

The objective of the present study was to evaluate the effect on the electroencephalogram (EEG) of a chewing gum with and without our prepared new flavor. Electroencephalograms were obtained after the following three tests: chewing pure gumbase with sucrose (standard gumbase), chewing flavored standard gum and the inhalation of flavored aromatic oil. As the control, we used the pre-stimulus control EEG record without a stimulus. We examined the relationship between the pre-stimulus control record and the post-stimulus record using the changes of power in four bands. Chewing the standard gumbase led to an increase in the alpha wave and a decrease in the beta wave. Chewing the flavored standard gum and inhaling the flavored aromatic oil each increased the alpha and beta waves. In addition, chewing the flavored standard gum led to a change in the ratio of theta wave in the frontal area. The difference in the theta, alpha and beta bands in chewing gum with and without the added flavor suggested that the flavor as well as chewing could induce concentration with a harmonious high arousal state in brain function.