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A mixed culture we had isolated, which degrades biphenyl/polychlorinated biphenyls, is composed of two strains, Pseudomonas fluorescens KKL101 and Pseudomonas sp. strain KKS102. KKS102 produces benzoic acid as a dead-end metabolite in the degradation of biphenyl. In this study we showed that KKL101 grew on benzoic acid as a sole source of carbon. This indicated a role of KKS102 in the growth of KKL101 and of KKL101 for the growth of KKS102 in the mixed culture.

This report describes a rare clinical course of a young Japanese woman with Takayasu's arteritis and a review of the literature. Her first symptom was angina pectoris due to isolated left coronary ostial stenosis, which was relieved by aortocoronary bypass grafting surgery using a saphenous vein graft. At that time, the C-reactive protein was negative and the histopathologic findings of the specimens of the aorta could not confirm aortitis. Although she was free from any cardiovascular symptoms for about fifteen years,. syncopal attacks occurred owing to severe stenosis of the major branches of the aortic arch revealed by intravenous digital subtraction arteriograms. Thus, Takayasu's arteritis could be a cause of coronary ostial stenosis in young women even if the inflammatory findings are negative and the major branches of the aortic arch are not involved at operation. In addition, revascularization using internal thoracic arteries might possess a potential risk of coronary insufficiency due to a later involvement of these proximal arteries.

The effects of cytokines and heavy metals on the expression and localization of metallothioneins (MTs) within U373MG astrocytoma cells were analyzed by using indirect immunofluorescence using a monoclonal anti-MT antibody (MT45). IL-1, CdCl2 (50 microM) or ZnCl2 (500 microM) remarkably augmented intracellular MT levels, whereas IL-6 or 10 microM of ZnCl2 showed no inducing activity. From 24 to 48 h after the addition of CdCl2 or IL-1, immunoreactive MTs were found in the cytoplasm and the nucleus. After 72 h, immunoreactive MTs accumulated in a granular form near the cell surfaces in the presence of CdCl2 (50 microM) or IL-1 plus ZnCl2 (10 microM). However, this accumulation was not observed when only IL-1 was added. Thus, Zn2+ facilitated the appearance of the granular form of immunoreactive MTs at a concentration where they do not induce MTs by themselves.

In order to determine the fine structure of the mammalian metallothionein (MT) epitope to a monoclonal anti-rat Zn-MT-II antibody (MT 189-14-7), N-terminal peptides of various lengths of mammalian metallothioneins (MTs) were synthesized by a conventional solution method using the newly developed beta-2-adamantylaspartate, and their immunological properties were examined. It was found that the N-terminal acetyl group was indispensable for the reaction with the monoclonal antibody and the N-terminally acetylated pentapeptide, Ac-Met-Asp-Pro-Asn-Cys-OH, was the smallest peptide which exhibited a significant reactivity with the antibody.

The objective of this study was to determine if endothelium-dependent vasodilation is preserved in the spastic segment of the epicardial coronary artery. Segmental responses of the coronary artery to substance P were examined by the use of a quantitative angiographic technique in 21 patients with variant angina. Coronary diameter at the basal state did not differ between the spastic and the nonspastic segments (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, p greater than 0.05). Changes in coronary diameter in response to substance P did not differ between segments with ergonovine-induced spasm and nonspastic segments. Maximal dilation averaged 27.1 +/- 9.5% in the spastic segment and 24.4 +/- 9.6% in the nonspastic segment (expressed as a percent increase over the value before drug administration). It appears that both the potential of the endothelium to release endothelium-dependent relaxing factor and the dilating response of the smooth muscle to endothelium-dependent relaxing factor are preserved, even in the spastic segment.

We report a case of lambda-AL amyloidosis which manifested prominent hepatic cholestasis. The patient was a 71-year-old Japanese male who was admitted to our hospital because of abdominal distension and jaundice. Laboratory examination revealed a marked deterioration of liver function with cholestasis. Gastric biopsy revealed amyloid deposition. Under a diagnosis of primary amyloidosis he was treated with corticosteroid and dimethylsulfoxide. However, jaundice progressed, renal function deteriorated rapidly, and he died two weeks after admission. Autopsy revealed a profound deposition of lambda-AL amyloid not only in the liver but also in the kidneys, spleen, lungs, heart and intestine.

Term rewriting systems have some excellent properties as a functional computation model. However, their programming is similar to logical programming rather than functional programming. This paper proposes the use of term rewriting systems as a mechanism of execution and verification, and the use of a functional programming language as syntax sugar which hides the underlying layer.

Ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the ligamentum flavum (OLF) in the thoracic spine can result in serious myelopathy, leading to circumferential compression of the spinal cord in advanced stages of the disease. The authors performed circumspinal decompression (circumferential decompression of the spinal cord) on these patients. This operation consists of two steps: posterior and lateral decompression of the spinal cord by removal of the OLF (first step) and anterior removal of the OPLL for anterior decompression (second step), followed by interbody fusion. In the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura to easily and safely remove the OPLL anteriorly at the second step. In the second step, the surgical approach varies according to the affected level; costotransversectomy in the upper thoracic spine and standard thoracotomy in the middle or lower thoracic spine. According to the authors, circumspinal decompression is not an easy procedure, but from their results in 10 patients, they identify it as a radical and promising surgical procedure.

Twelve Fusarium isolates were obtained from several agricultural commodities and soil collected in Japan, corn produced in New Guinea, and grapefruit from an unknown source. Their fumonisin-producing ability was tested on corn grits and 9 of the 12 isolates produced fumonisins. Since 3 isolates produced high levels of fumonisins, the extracts of their cultures were analyzed by LC/MS. The data including MS/MS analyses suggested that the isolate from unpolished domestic rice produced monomethyl ester of fumonisin B1. Furthermore, we detected novel fumonisin B1 analogues in the extract from the grapefruit, although we could not precisely determine their structures.

Subcostal 4-chamber view of transthoracic echocardiography revealed abnormal thickening of atrial septum (arrow) in a 43-year-old Japanese woman with frequent atrial premature beats (A). MRI was obtained by the ECG-gated spin-echo technique. T1-weighted image of the heart …

Using two-dimensional (2-D) echocardiography we evaluated the applicability of the left ventricular (LV) short axis view combined with manual scanning technique for the detection and evaluation of aneurysms of the membranous ventricular septum (AMS). In 12 patients with angiographically proven AMS, we recorded from the left sternal border the short axis view of the left ventricle continuously displayed from the aortic to the ventricular level by tilting the transducer manually along the LV long axis plane. We then compared the detectability of AMS by this method with that by other standard fixed 2-D echocardiographic views. This method proved to be best for the detection of AMS (12/12), followed by an apical four-chamber view (10/12), a parasternal LV long axis view (8/12) and an apical two-chamber (2/12) view. For the detection of AMS and for three-dimensional evaluation of the structure of the AMS and the original orifice of ventricular septal defect the method was shown to be clinically applicable.

Electrolytes in the smooth muscle tissue of the alimentary canal were measured and their behavior under various conditions were studied on the basis of values measured. The results are summarized as follows: 1. Organic changes due to edema and the like are more prominent in the region near the wound in cases of damaged intestine. Utmost care should therefore be exercised when surgical treatment including resection of the intestine is given. 2. Variations in electrolytes are slight in cases of mesenteric hematoma, and surgical treatment is not necessary. 3. Variations in electrolytes are rather prominent in cases of intestinal fistula, and full consideration should be given to the balance of electrolytes, particularly supplement of K. 4. In casees of intestinal anastomosis, the rate of variation is the highest near the site of anastomosis and on the third day after surgery. Therapeutically, therefore, attention should be given to prevention of complications such as incomplete suture. 5. In cases of intestinal obstruction, variations are more marked and rapid. It brings about a high degree of disequilibrium of intra-tissue electrolytes in the upper intestinal tract; hence the early and adequate treatments are needed.

The effects of chronic instrumentation on regional myocardial performance and regional myocardial blood flow were studied in 8 mongrel dogs. Regional segment lengths were measured by an ultrasonic dimension gauge technique at two areas of the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). Regional myocardial blood flow was measured by a tracer microsphere technique. These measurements were repeated while the animals were conscious on the 4th, 11th, 21st and 28th days after instrumentation. On the 4th day, the heart rate was rather high and regional shortening at both the LAD and LCX areas remained suppressed. After the 11th day, hemodynamic variables such as heart rate, left ventricular pressure and regional wall motion were fairly constant. Regional myocardial blood flow and its distribution were also constant throughout the experimental period. Fibrosis of the epicardium invariably induced by surgical procedures did not affect the distribution of regional blood flow as compared with that of the interventricular septum. Thus, a stable hemodynamic state was recorded after the 11th day following surgical manipulation and the implantation of sensors and catheters did not affect the level of regional myocardial blood flow or its distribution at rest. Such long term reproducible measurements of regional wall motion and regional myocardial blood flow may facilitate chronic studies of cardiovascular physiology.

The effects of oral diltiazem (90-180 mg/day for four weeks) on ventricular premature contractions (VPCs) were studied in 16 patients with frequent VPCs using 24-hour ambulatory ECG recordings. VPC frequency was evaluated as a function of underlying heart rate. Plots of VPC frequency vs. heart rate were made at 1-beat/min intervals for all heart rates recorded for at least five minutes during 24 hours. Patterns of correlation between VPC frequency and heart rate observed before diltiazem therapy included: 1) a relatively linear increase in VPCs with heart rate (positive correlation) in ten patients, 2) a linear decrease (negative correlation) in one patient, and 3) an increase at low heart rates and a decrease at high heart rates (bidirectional correlation) in five patients. Diltiazem significantly reduced the mean VPC frequency per 24 hours for patients with a positive correlation, but induced no significant change for patients with a negative or a bidirectional correlation. At the 65% level of VPC reduction, diltiazem was effective in eight of ten patients with a positive correlation but was not effective in the six patients with other correlations (p less than 0.01). These results suggest that an evaluation of VPC frequency as a function of heart rate predicts the response of VPCs to diltiazem.

This report describes a case with flail right and noncoronary cusps due to bacterial endocarditis, diagnosed with real-time two-dimensional echocardiography. Real-time two-dimensional phased array sector scanner demonstrated 2 cugdel-shaped lesions in the region of the left ventricular outflow tract through the aortic root, pendulating upward and downward floating along the blood stream. This study shows that the real-time two-dimensional echocardiography is a very useful noninvasive tool in the early diagnosis of flail aortic valve.

The extent of myocardial infarction related to the pre-occlusive perfusion are was quantitatively evaluated in a canine model. The perfusion area was determined preocclusively by selective injection of tracer microspheres into the coronary artery in question, then the main trunk and a small lateral branch of the left circumflex coronary artery was occluded in group 1 (10 dogs) and group 2 (10 dogs), respectively. Rapid freezing was used to prepare autoradiographic samples for determination of the perfusion are along with samples for dehydrogenase staining in order to delineate the extent of myocardial infarction. The relationship between perfusion area and infarct size was examined in 50 micrometers thick samples from base, middle and apex of the ventricle and a direct linear correlation between the perfused (P) and infarcted area (I) in the left ventricle (LV) was noted regardless of the perfusion size or the location in the ventricle. The linear relationship I = 0.93P - 4.9 (r = 0.95, P less than 0.001) was obtained in all 20 dogs. Transmural extent of necrosis was larger in the endocardium than in the epicardium, thereby representing a more salvageable myocardium in the epicardium. It is concluded that the preocclusive determination of perfusion are by high resolution autoradiography is a useful method of obtaining physiological perfusion not affected by ischaemia. Also the infarct size when standardized by the perfusion area is mainly influenced by transmural location but not by the spacial geometry or the size of the occluded area.

The effect of collateral circulation on regional myocardial flow and wall motion of left ventricle was studied on 5 anesthetized dogs with a surgically implanted constrictor on the left circumflex coronary artery (LC). The grade of LC stenosis and wall motion of left ventricle (LV) were determined by cineangiography of the coronary artery and LV at the period of acute and chronic occlusion. Regional myocardial flow was determined by tracer microspheres (TM), labeled with four different isotopes, Sr85, Cr51, Sc46, Ce141. The first TM1 was infused after LC stenosis, TM2 during a temporary complete LC occlusion at the period of acute occlusion; TM3 and TM4 in a similar way 3 to 4 weeks after the acute LC stenosis. Three to four weeks after LC stenosis, i.e. chronic period of occlusion, the degree of LC stenosis progressed from 70--80% to 100% occlusion, but collateral flow and collateral vessels to the ischemic LC area were increased together with an improvement of wall motion of the ischemic LC area. The results may support the idea that collaterals may be an effective compensatory mechanism for ischemia. In contrast to an increase of collateral flow to the ischemic LV free wall in all five dogs, an increase to the posterior papillary muscle was found only in two out of five dogs.

The interaction between the effects of an arterial stenosis and postocclusion hyperemia was studied in a model of the capillaron system. A capillaron is a module consisting of soft-walled permeable vessels (capillaries) in a compliant capsule. Stenosis reduced flow in accord with arterial cross-sectional area. Addition of a capillaron reduced flow to a basal level. In this basal state, autoregulation and postocclusion hyperemia could be studied. Basal flow and autoregulation give no indication of the severity of the stenosis. The magnitude of the postocclusion hyperemia varied with the arterial pressure and, inversely, with the stenotic orifice area. In the absence of arterial pressure changes, the magnitude of the postocclusion hyperemia indicates the severity of the stenosis.

The reliability of five equations in assessing stroke volume from pulmonary artery pressure curves were critically evaluated in six dogs and in six patients. To alter stroke volume, isoproterenol, dobutamine, pro-pranolol, lactate Ringer solution and artificial pacing were employed in the animal study and diltiazem (a calcium blocker) in the human study. A good correlation was found between the calculated and measured stroke volume (r = 0.80–0.86 in the animal study and r = 0.94–0.96 in the human study). The assessment of stroke volume from the pulmonary arterial pressure curves using equations was as good as that from the aortic pressure curves calculated simultaneously. These results suggest that the five equations may be clinically applicable for assessing stroke volume in critically ill patients. The employment of pulmonary arterial pressure curves in assessing stroke volume may be more useful clinically since its recording can be carried out more safety than recordings of aortic pressure curves.

Operations of intestine caused by abdominal injuries show a higher frequency of insufficiency of suture than the other operations in the past 10 years. Insufficiency is more often found in injuries of upper intestine than lower or large bowel.

A 28-year-old female was discovered to have mitral stenosis associated with ventricular septal defect, patent ductus arteriosus and tubular hypoplasia of the ascending aorta. The diagnosis of such complex anomalies was con firmed by an echocardiographic and cardiac catheterization study. Congenital mitral stenosis is a rare cardiac malformation and usually results in early death. This patient is a relatively long survival case in spite of many complications.

For the experimental studies on chronic coronary stenosis, an ameroid constrictor was modified to facilitate serial cineangiographic evaluation of the degree of arterial narrowing. A radiolucent plastic ring instead of a stainless frame was used to prevent outward swelling of the ameroid material. Coronary cineangiography was performed 10, 20 and 30 days after the implantation of the modified ameroid constrictor on the left circumflex coronary artery (LCX), which could prove the progressive coronary stenosis of 57, 78 and 88% on the respective days. Collateral channels from the anterior descending branch of the left coronary artery to the LCX were demonstrated angiographically in 5 out of the 6 dogs on the 30th day.

To determine the factors influencing the prognosis of variant angina, the clinical characteristics and long-term prognosis of 158 consecutive Japanese patients were examined and compared with those in previous major western studies (Pisa, Montreal, and Duke studies). The Japanese patients were characterized by relatively low prevalences of coronary risk factors, significant coronary stenoses and previous myocardial infarction. Survival and survival without myocardial infarction for the entire group or for the subpopulation with significant coronary artery disease were significantly better in the Japanese population than in the western populations; however, in the subpopulation without significant coronary artery disease, the prognosis was excellent in all four studies. If the prevalence of coronary artery disease was corrected for the Japanese population, there would be no difference in the prognosis between the Japanese and the western populations. It is concluded: (1) the overall prognosis of variant angina may be better in Japanese patients, and (2) coronary artery disease appears to be the strongest prognostic factor for assessing the differences in the prognosis between the Japanese and the western populations.

To elucidate possible genetic links in the pathogenesis of coronary artery spasm, we investigated the frequencies of human leucocyte antigen in 37 patients with variant angina and 236 unrelated healthy controls. We found no significant differences in human leucocyte antigen frequencies between the patients and the controls. These results may suggest that genetic factors in linkage disequilibrium with human leucocyte antigen may not be involved in the pathogenesis of coronary artery spasm.

The relationship between the hypercontractile response of the regional coronary artery to ergonovine and induced vascular change after endothelial denudation and a high-cholesterol diet was examined in dogs by arteriographic (in situ) and mechanographic (in vitro) methods. In 15 mongrel dogs, selective endothelial denudation of either the left circumflex coronary artery (LCX) or left anterior descending coronary artery (LAD) was repeated twice 1 month apart by means of coronary arterial catheterization. A high-cholesterol diet (20 g/day) was given thereafter for 3 (n = 15) and 6 (n = 8) months. Although there was no difference in the extent of coronary vasoconstriction between the LAD and LCX before or immediately after endothelial denudation, after intravenous administration of ergonovine a significant augmentation of coronary constriction along the denuded portion was noted arteriographically in the long-term phase (1 to 6 months). At the end of the study in vivo, isometric tension of the strips of the denuded and contralateral intact coronary arteries was measured during the cumulative addition of ergonovine, serotonin, or phenylephrine to the organ bath; agonist responses were standardized by the response to 35 mM KCl. Although the concentration-response relations for phenylephrine (10(-9) M to 10(-5) M) were not significantly different between intact and denuded arteries, responses of the denuded portion to cumulative addition of ergonovine (10(-10) M) or serotonin 10(-9) M to 10(-5) M) exhibited markedly depressed threshold concentrations along with a significantly lowered negative logarithm (pD2) of the dose producing 50% of the maximum effect. The tension developed in the denuded portion was also enhanced over that noted in the contralateral coronary artery during the cumulative addition of ergonovine but not during application of phenylephrine. Thus enhanced constriction documented arteriographically may be derived from the localized hypersensitivity to ergonovine. Microscopically, the endothelial denudation and a long-term high-cholesterol diet resulted in a regional intimal thickening with fibrous proliferation but little lipid deposition. Therefore smooth muscle in atherosclerotic arteries may be hypersensitive to specific agonists such as ergonovine and serotonin in a canine preparation. These results suggest that coronary spasm induced by ergonovine in humans is relevant to the presence of atherosclerotic changes in the vascular wall.

When a large left ventricular aneurysm or infarct is excised, a frequent complication is inability of the left ventricle to regain adequate performance. Reduction in ventricular volume and impairment of myocardial contractility, either of which can diminish cardiac output to levels incompatible with life, are probably the main factors that lead to left ventricular failure after such surgery. A prototype prosthetic myocardium, designed to mimic the actions of the left ventricular myocardium, offers a direct means of restoring both ventricular volume and contractility after excision of a large portion of the left ventricle. In dog experiments 17 ± 1.1 % (AV ± SE) of the left ventricle was infarcted and excised under cardiopulmonary bypass. The prosthetic myocardium was implanted and activated, and changes in hemodynamic parameters produced by the assist device were studied. "On" to "off" changes in 11 dogs in congestive failure averaged over the course of the experiment were as follows : m-AoP was increased 19 ± 1.7% (Mean ± SE) : LV Syst. Press. was increased 24 ± 1.7% ; SV was increased 34 ± 3.2%, LVEDP and m-LAP were reduced 43 ± 2.4% and 22 ± 1.4% respectively ; and LVSW increased 88 ± 8.8%. With these hemodynamic benefits this prototype represents an encouraging step toward the development of a device for orthotopic replacement of damaged myocardium.

Long-term prognosis of 90 patients with vasospastic angina without significant coronary artery disease (less than 50% reduction in luminal diameter) was examined for a mean follow-up period of 4 years. All patients had episodes of angina at rest and were treated with calcium antagonists. One patient developed myocardial infarction and 2 died suddenly during the follow-up period. In the patient with myocardial infarction, there was an abrupt worsening of angina prior to the infarction despite therapy with a calcium antagonist. One of the sudden death patients discontinued his calcium antagonist before his death. Of the sudden death patients, one had ventricular tachycardia and the other had a complete atrioventricular block during an anginal attack. The incidence of such serious arrhythmias was higher (p less than 0.01) in sudden death patients (2/2) than that in survivors (6/88). The treatment with calcium antagonists reduced the severity and frequency of angina in all patients. These results suggest that long-term prognosis of vasospastic angina without significant coronary artery disease is good as characterized by the low incidence of myocardial infarction and death and the favorable response to treatment with calcium antagonists.

The change in the left atrial dimension during diastole was examined in patients with mitral stenosis using echocardiography. The left atrial emptying fraction (LAEF), defined as the ratio of enddiastolic dimension to endsystolic dimension of the left atrium, was 0.65 +/- 0.03 (mean +/- SE) for normal subjects, 0.86 +/- 0.01 for low grade mitral stenosis, and 0.92 +/- 0.01 for high grade stenosis. The LAEF correlated well with mitral valve area index (r = -0.70), but the correlation between E-F slope of the anterior mitral leaflet and mitral valve area index was less significant (r = 0.48). In patients who received mitral valve replacement the LAEF and the left atrial dimension significantly improved. The left atrial emptying fraction is an easily obtainable and reliable index to estimate the severity of mitral stenosis, even in patients who have undergone mitral valvular surgery.

To determine the effects of diltiazem, a new calcium antagonist, on myocardial ischemia, two experiments were performed. The results showed 1) the intravenous bolus injection of large doses of diltiazem reduced ST segment elevation in open-chest dogs with acute coronary occlusion. The regional myocardial blood flow in the control area, as well as moderately and mildly ischemic areas increased significantly after diltiazem. However, the myocardial Mood flow of the severely ischemic area did not increase; 2) the continuous infusion of small doses of diltiazem after coronary occlusion for 24 hours caused a significant increase of myocardial blood flow to the circumscribed region at the ischemic center, and induced a tendency to a slight reduction in size of the myocardial infarction.

The effects of intravenous administration of nitroglycerin or dipyridamole on distribution of myocardial blood flow in the heart after coronary underperfusion were investigated. In 18 open chest, anesthetized dogs, flow of the tubing supplying the left circumflex coronary artery (LCA) was reduced and kept constant, and then the drug was given intravenously. Before and after an administration of saline, nitroglycerin (0.04 mg/kg) and dipyridamole (0.2 mg/kg), myocardial blood flow was measured by tracer microspheres (TM). The first and second carbonized 15 mu spheres (TM1 and TM2) were injected into the left atrium and the cannulated LCA perfusion system respectively before medication. Similarly, the third and fourth spheres were given after drug. Thus, by using four different TMs (141Ce, 51Cr, 85Sr, 46Sc) regional myocardial blood flow from the LCA perfusion route (TM2 and TM4) was measured separately from that of the other normally perfused coronary route (TM1 and TM3). The effect of drugs on flow distribution of these two independent routes was measured. The LCA underperfusion produced a significant diminution of regional flow and its end/epi ratio in the LCA territory. Nitroglycerin increased end/epi ratio in the ischemic myocardium in the LCA perfusion route, but dipyridamole increased the normally perfused coronary flow but caused a shift of flow from the ischemic left ventricle to the atria and right ventricle within the LCA territory.

1. (1) The cerebral arteries of 374 Japanese subjects were estimated for total lipids, free and ester cholesterol, lipid phosphorus, triglycerides and various types of glycosaminoglycans. The cerebral arteries were divided into normal and diseased. The samples were pooled for each decade, in an endeavour to dissociate age changes from those related to atherosclerosis. 2. (2) In general, lipid concentration increased with age and atherosclerosis. The ratio, ester/total cholesterol, in normal tissue was approximately 25–30%, in contrast with 45–50% in the lesions. Atherosclerotic lesions contained approximately 13 to 35 times as much esterified cholesterol as young normal tissue. The rise with age in total and esterified cholesterol in the Japanese cerebral arteries was much the same or just slightly steeper than that reported in South African and American Caucasians. 3. (3) Total glycosaminoglycans increased in both normal tissue and lesions. The proportion and concentration of heparan sulphate decreased in atherosclerosic lesions compared with grossly normal tissue; yet those of chondroitin-4- or -6-sulphate and dermatan sulphate increased. The relative proportions of glycosaminoglycans in normal tissues did not alter with age. 4. (4) Quantitative chemical analysis confirmed the low proportion of both hyaluronic acid and chondroitin sulphates in the total glycosaminoglycans of Japanese cerebral arteries.

SummaryIn zebrafish, endoderm induction occurs in marginal blastomeres and requires Casanova (Cas), the first endoderm-specific factor expressed in the embryo. Whereas the transcription factors Gata5 and Bon are necessary and sufficient for cas expression in marginal blastomeres, Bon and Gata5 are unable to induce cas in animal pole cells, suggesting that cas expression requires an additional, unidentified factor(s). Here, we show that cas expression depends upon the T box transcription factor Eomesodermin (Eomes), a maternal determinant that is localized to marginal blastomeres. Eomes synergizes potently with Bon and Gata5 to induce cas, even in animal pole blastomeres. We show that Eomes is required for endogenous endoderm induction, acting via an essential binding site in the cas promoter. Direct physical interactions between Eomes, Bon, and Gata5 suggest that Eomes promotes endoderm induction in marginal blastomeres by facilitating the assembly of a transcriptional activating complex on the cas promoter.