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To explore changes in left ventricular (LV) function and the relationship of these changes with myocardial blood flow (MBF) evaluated byFifty-two consecutive patients with suspected CAD, who underwentMRI showed that the LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF) remained unchanged during vasodilator stress in all patients (n=52) as well as in the patients with CFR of2 (n=27), stress MBF of1.3 ml/g/min (n=28), abnormal myocardial perfusion (n=30), and more than one diseased vessel (n=46). In only four patients, the LVEF measured by MRI decreased by5% during vasodilator stress. In these four patients, CFR was lower (1.57 ± 0.12 versus 2.18 ± 0.86, p0.01) and the number of diseased vessels was higher (2.75 ± 0.50 versus 1.48 ± 0.92, p0.01) than in patients without post-stress LV dysfunction.The LV volume and systolic function evaluated by cardiac MRI remained unchanged during vasodilator stress; however, LV dysfunction during vasodilator stress may occur in patients with severe CAD.

A new class of heterotricyclic glutamate analogues recently was generated by incorporating structural elements of two excitotoxic marine compounds, kainic acid and neodysiherbaine A. Rather than acting as convulsants, several of these 'IKM' compounds markedly depressed CNS activity in mice. Here, we characterize the pharmacological profile of the series with a focus on the most potent of these molecules, IKM-159.The pharmacological activity and specificity of IKM compounds were characterized using whole-cell patch clamp recording from neurons and heterologous receptor expression systems, in combination with radioligand binding techniques.The majority of the IKM compounds tested reduced excitatory synaptic transmission in neuronal cultures, and IKM-159 inhibited synaptic currents from CA1 pyramidal neurons in hippocampal slices. IKM-159 inhibited glutamate-evoked whole-cell currents from recombinant GluA2- and GluA4-containing alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors most potently, whereas kainate and NMDA receptor currents were not reduced by IKM-159. Antagonism of steady-state currents was agonist concentration dependent, suggesting that its mechanism of action was competitive, although it paradoxically did not displace [(3)H]-AMPA from receptor binding sites. IKM-159 reduced spontaneous action potential firing in both cultured hippocampal neurons in control conditions and during hyperactive states in an in vitro model of status epilepticus.IKM-159 is an AMPA receptor-selective antagonist. IKM-159 and related nitrogen heterocycles represent structurally novel AMPA receptor antagonists with accessible synthetic pathways and potentially unique pharmacology, which could be of use in exploring the role of specific populations of receptors in neurophysiological and neuropathological processes.

A 17-year-old man in whom mucoepidermoid carcinoma of the left upper lobe bronchus was successfully treated by bronchoplasty. The patient has been suffered from relapsing respiratory infections over the past 2 years. Bronchoscopic examination revealed a tumor at the orifice of the left upper lobe bronchus. Thus, left upper sleeve lobectomy was carried out. The tumor was 18 x 15 x 14 mm in size and obstructed left upper bronchus with mucoid impaction peripherally. Hystological examination confirmed a diagnosis of low grade malignant mucoepidermoid carcinoma without lymph node metastasis. The patient has been well and free from recurrence for 4 years postoperatively.

We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.

We report a 31-year-old woman presenting flutter-like oscillation after acute infection. Ten days after low fever and diarrhea, she presented transient, horizontal and pendular ocular oscillation. This abnormal eye movement was diagnosed as flutter-like oscillation (FLO). Other neurological findings were normal. Cerebrospinal fluid was normal. Brain MRI revealed no particular abnormalities. Serum titers for anti-GD1a antibody were elevated. After treatment with steroid (1,000 mg/day methylprednisolone DIV), the FLO disappeared.

When quiescent endothelial cells (ECs) are exposed to angiogenic factor such as VEGF; ECs express proteases to degrade extracellular matrices, migrate, proliferate and form new vessels. However, the molecular mechanism of these events is not fully characterized yet. We are studying the signal transduction and transcriptional regulation of angiogenesis. We investigated the properties of two VEGF receptors, Flt-1 and KDR, by using two newly developed blocking monoclonal antibodies (mAbs), i.e., anti-human Flt-1 mAb and anti-human KDR mAb. VEGF elicited induction of transcription factor Ets-1 in human umbilical vein endothelial cells (HUVECs). This induction was mediated by the KDR/Flt-1 heterodimer and the KDR homodimer. The role of transcription factor Ets-1 in angiogenesis was further clarified. We established both high and low Ets-1 expressing EC lines, and compared angiogenic properties of these cell lines with a parental murine EC line, MSS31. The growth rate was almost identical among three cell lines. It appeared that gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) as well as integrin beta 3 were correlated with the level of Ets-1 expression. As a result, the invasiveness was enhanced in high Ets-1 expressing cells and reduced in low Ets-1 expressing cells compared with parental cells, and high Ets-1 expressing cells made more tube-like structures in type 1 collagen gel. These results indicate that Ets-1 is a principle transcription factor converting ECs to the angiogeneic phenotype.

It has been speculated that the veins of the gallbladder join the intrahepatic portal veins supplying the Couinaud's S4a-S5. This has been the theoretical ground for the resection of these 2 hepatic subsegments in advanced gallbladder carcinoma. However, no consensus has been reached on this concept.The current study describes the non-neoplastic perfusion defects in connection with the gallbladder bed in 100 consecutive hepatic CTAP (computed tomographies during arterial portography). The suitability of S4a and S5 subsegmentectomies of the liver for advanced gallbladder carcinoma was also investigated by examining CTAP images of the branches of the portal vein involved in the perfusion defect.Two types of gallbladder venous perfusion were observed: 1) sphenoid distribution from the gallbladder bed into the P4a (37%), P5 (52%) and P6 (3%), and 2) perfusion into the P4 (9%) or directly into the middle hepatic vein (9%) after communicating with the hepatic hilum at the dorsal side of S4.These results support liver resection at S4a and S5 as the surgical approach for cases of advanced gallbladder carcinoma.

Recently, the Japanese Classification on Cancer of the Biliary Tract was revised and adopted the new comprehensive staging that is similar to UICC's TNM classification. We should be paying close attention to the significance of newly defined extensive factors of carcinomas on the long-term prognosis.The surgical outcome for 99 patients who underwent resected middle (Bm) and lower (Bi) bile duct carcinomas was reviewed in order to evaluate the suitability of the surgical procedures employed for their treatment, namely, standard pancreatoduodenectomy for Bi carcinoma and bile duct resection with D2 lymph node dissection for Bm carcinoma.The overall 5-year cumulative survival rate (operative death excluded) of Bm and Bi carcinoma patients was 37.4% and the 5-year survival rate of the patients in whom surgical curability (curA) was accomplished was 51.6%. Recently, a new prognostic factor, "t-category", which indicates the degree of pericholedochal neoplastic invasion was proposed in the 4th edition of the Japanese General Rules for Surgical and Pathological Studies on Cancer of the Biliary Tract. The 10-year survival rates by t-category were 49.1% (t1), 19.7% (t2), and 0% (t3 and t4) respectively. For Bm carcinoma, the patients undergoing bile duct resection under the condition of curA showed excellent prognoses. For Bi carcinoma, the patients fulfilling particular histological criteria, i.e., those concerning the histological depth of neoplastic invasion (m, fm, panc1a), duodenal involvement (du0, du1), vascular invasion (pv0), pericholedochal neoplastic invasion (t1), lymph node metastasis (n0), and comprehensive stage I, had good postoperative outcomes. Taking into account the fact that the metastatic rate of paragastric lymph nodes was 1.3%, the cases of panc0,1 should be operated by pylorus-preserving pancreatoduodenectomy. The overall 5-year survival rates including far-advanced cases were 39.9% in Bm carcinoma patients and 36.9% in Bi carcinoma patients. However, these postoperative outcomes are far from satisfactory.Therefore, we concluded that pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy with extended D3 lymphadenectomy combined with systematic multimodal therapy are indicated in each and every case of Bm and Bi carcinoma.

Though SMANCS-Lipiodol suspension has advantages over tumor regression, its disadvantages should also be considered: (1) Anaphylactic reaction due to its high molecular weight. (2) Since it readily destroys the tissue, a smaller dose and repeated administration are required. (3) Due to its low viscosity, it easily enters the arterioles and causes damage even to the extrahepatic organs. When this drug is infused into the left hepatic artery in subsegmental fashion, it enters the neighboring gastric tissues through the communication of the left hepatic and left gastric arteries, and this ultimately causes intractable gastric ulcers. Considering the above facts, this drug should be used carefully.

We studied dyspnea and pulmonary function during treadmill exercise in 10 patients with pulmonary emphysema before and at least 3 months after thoracoscopic volume reduction. Dyspnea was significantly less after surgery. Ventilatory function, gas exchange, respiratory muscle function, and exercise performance also improved significantly. The degree of volume reduction, estimated by the decrease in FRC as measured by body plethysmography correlated with the degree to which dyspnea was relieved. Volume reduction may be appropriate as a treatment for dyspnea in patients with pulmonary emphysema.

Detection of gonadotropin releasing hormone (GnRH) mRNA in rat ovary was carried out, and cloning of LH, chorionic gonadotropin (CG) receptor in human ovary was attempted by use of polymerase chain reaction (PCR). Firstly, in an attempt to detect the expression of GnRH or related gene in rat ovaries at the RNA level, GnRH message was amplified. Total RNA from rat ovaries was converted to cDNA using reverse transcriptase and amplified in PCR using a pair of specific primers complementary to the rat GnRH cDNA. The DNA products were subcloned into plasmid vectors and their sequence determined. 1. In the rat ovary, a prominent PCR product of 462 bp was identified as a fragment of prothymosin alpha cDNA previously found in the spleen. 2. In contrast, RT-PCR amplification of hypothalamus and granulosa cell messages indicated the presence of a 244 bp product with identical sequence to GnRH. To confirm the presence of GnRH message, a second set of GnRH primers was used. PCR amplification of cDNA from hypothalamus, granulosa cells and whole ovary yielded a product identical with the authentic GnRH cDNA sequence. These data demonstrated the presence of mRNA for GmRH and prothymosin alpha in the rat ovary. Secondly, a part of the human LH, CG receptor was obtained from human granulosa cells by selective amplification with PCR of DNA segments presenting possible sequence similarity with genes for the porcine or rat LH, CG receptor. Total RNA from human granulosa cells was converted to cDNA and amplified in PCR using degenerate oligonucleotide primers corresponding to possible conserved regions in extracellular segments of the porcine or rat LH, CG receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of a 33-year-old man with anomalous origin of the left coronary artery from the pulmonary artery (ALCP) was reported with a referential consideration to the adult type of ALCP previously reported in Japan. The patient visited our hospital for further examination of cardiac murmur detected on a mass physical checkup. He was found to have a continuous murmur, the loudest in the left sternal border of 3rd intercostal space, and developed evidence of ischemia during the exercise stress test in the ECG leads of L2, L3, aVF, and V2 through V6. In addition, studies using echocardiography and color Doppler-echocardiography detected a hypertrophied intraventricular septum and a pattern of turbulent blood flow in the proximal pulmonary artery. Cardiac catheterization and aortography proved the existence of ALCP with a markedly developed collateral circulation from the right coronary artery to the left coronary artery. After surgical restoration by ligating the anomalous opening of the left coronary artery, and by bypass grafting to the left coronary artery, it was clear that dilation and kinking of the right coronary artery was lessened and hypoperfusion in the anterior left ventricular wall was improved. As far as we know, this case is the 35th of adult type ALCP reported in our country. Results from this case and others suggest that early detection and therapy for adult type ALCP is important from the point of view preventing ischemic progression, and indicate that restoration by ligation and bypass grafting may be one of the effective surgical procedures for ALCP.

We investigated changes in coronary venous oxygen saturation (CSO2-Sat) dynamics during intracoronary infusion of ergonovine (ERG) or acetylcholine (ACh) in patients with vasospastic angina. In 16 patients with suspected vasospasm in the left coronary artery, intracoronary ERG injection provoked vasospasm in 4 out of 6 patients, and intracoronary ACh in 6 out of 11 patients. A gradual decrease in CSO2-Sat, anteceding angina and ischemic ECG evidence, was characteristic in ERG-induced vasospastic patients, while no significant change of CSO2-Sat was observed in non ERG-induced patients. Intracoronary infusion of ACh was followed in all 11 patients by a transient increase in CSO2-Sat, suggesting decreased myocardial oxygen extraction due to increased coronary blood flow with ACh. However, earlier and sudden decreases in CSO2-Sat below the control levels were characteristic in 6 patients with ACh-induced vasospastic angina. These findings suggest that effects of ERG and ACh on coronary flow dynamics are essentially different although both drugs can provoke vasospasm.

K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G 125I]K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.

A case of acute myocardial infarction due to the lesion in the left main coronary artery was reported. A 50-year male was referred to our department for suspected acute myocardial infarction. Physical examination on admission revealed slight cyanosis with cold sweating due to severe chest pain. Pulse was irregular and heart rate was 78 beats/min. Blood pressure was 100/80 mmHg. A series of electrocardiograms (ECG) and laboratory data provided the diagnosis of wide-ranged anterolateral infarction in the left ventricle. Emergency coronary angiograms taken without delay showed a subtotal occlusion (99% stenosis) of the left main coronary trunk (LMT) before the initiation of intracoronary thrombolysis (PTCR). Following the intracoronary infusion of urokinase of 1,200,000 units, symptoms and ECG changes transiently improved but worsened later, and LMT stenotic lesion and delayed filling of myocardium were similar with before PTCR. Emergency coronary-aorto bypass graft (CABG) was undertaken without a significant delay to both the left anterior descending artery (LAD) and left circumflex coronary artery (LCX). With these treatments, the patient could survive despite the wide area of infarction due to LMT lesion. Coronary angiograms performed 37 days after the CABG showed that the graft to LAD was completely occluded and the LCX graft was patent with partial stenosis. Treadmill test at this time induced an anginal episode with ischemic ECG changes on moderate exercise, indicating the presence of significant area of ischemic myocardium. For salvage of the ischemic myocardium, percutaneous transluminal coronary angioplasty (PTCA) was successfully performed for the LMT stenosis, resulting in no episode of angina nor ischemic ECG changes during exercise loading.(ABSTRACT TRUNCATED AT 250 WORDS)

The exact mechanism(s) by which WR induces ovulation in women with PCOD is still uncertain. The aim of this study is to observe the change in sex steroids and pulsatile LH release (pul-LH-R) after WR. Before and either 7-8 days after the surgery (n = 8) or after 30 days of spironolactone treatment (n = 4), serum LH levels were measured every 15 min for 2-4 hours in PCOD women. Sex steroids were radioimmunoassayed before, and 3-4 and 7-8 days after WR. Testosterone (T) and androstenedione (A) in 7 women in whom spontaneous ovulation occurred after WR decreased significantly either 3-4 or 7-8 days after the surgery (p less than 0.001). Estrone decreased significantly (p less than 0.001) 7-8 days after the operation. The mean level of LH after WR in the 7 women decreased significantly (p less than 0.001). Furthermore, significant decreases both in the mean values of LH pulse amplitude (p less than 0.001) and frequency (p less than 0.01) were observed after WR. Ovulation occurred after 45 and 58 days of spironolactone administration in 2 PCOD women who showed changes in pul-LH-R and a drop in serum testosterone levels after 30 days of treatment. The data suggested that changes in pul-LH-R and decreased sex steroids after WR seemed to play key roles in the mechanism(s) by which WR induces ovulation.

To investigate a capsular swelling reaction of the strain K-9 of Klebsiella pneumoniae, possessor of large capsule, ultra-thin sections of the organisms were stained with uranyl acetate and lead citrate and were treated with rabbit antiserum. The ultra-thin sections of above stained organisms showed spike-like structure in outmost layer of the cell wall. When they were treated with rabbit antiserum, the outmost layers of the organisms was surrounded by a zone of oval to round polymorphous vesicular structure which covered the spike-like appendages. These findings were assumed being capsular swelling reaction of these organisms. However, when they were treated with rabbit antiserum which was previously absorbed with the polysaccharide surface antigen, polymorphous vesicular structures did not appear and sharp spiked structures issuing from the cell wall were exposed.

Basic and clinical studies in 37 patients with biliary tract disease on comparison between cefmenoxime (CMX) and cefotiam (CTM) were studied and the following results were obtained. In vitro antibacterial activities of CMX and CTM against 25 strains (15 organisms) isolated from bile of patients with biliary tract disease were stronger than that of cefazolin (CEZ). In cholecystectomized patients, CMX (2 g) or CTM (2 g) was injected intravenously, followed by determination of concentration in bile and gallbladder tissue about 2 hours after administration. In CMX administration, the mean concentration in gallbladder bile was 812.1 micrograms/ml, and the mean concentration in duct bile was 1,050.6 micrograms/ml, and the mean concentration in gallbladder tissue was 100.7 micrograms/g. In CTM administration, the mean values were, 1,092.5 micrograms/ml, 1,287.8 micrograms/ml, 28.5 micrograms/g, respectively. The concentration of CMX and CTM were almost similarly. The bile concentration of CMX (i.v.) was compared with CTM (i.v.) by cross-over method in cases of T-tube drainage. The peak bile concentrations of CMX and CTM were as high as 172.4 micrograms/ml and 182.2 micrograms/ml, respectively, 1 approximately 2 hours after 2 g intravenous administrations. Furthermore, the concentration of them were highly gained, 16.1 micrograms/ml of CMX and 33.8 micrograms/ml of CTM, even at 5 approximately 6 hours. In choledochostomized patients, CMX (4 g/day) was injected intravenously, followed by determination of concentration in intraperitoneal exudate. The mean concentration of CMX was 15.3 micrograms/ml on the first day after the operation, and 6.0 micrograms/ml even on the third day after the operation. Those results suggest that the high antibacterial activity of CMX against organism in bile and, the high penetration of CMX to bile, gallbladder tissue and intraperitoneal exudate will promise its important role in treatment of biliary tract infections.

Laboratory and clinical comparative investigations with cefotiam (CTM) and cefazolin (CEZ) were performed to confirm efficacy and safety in surgical, biliary tract infections. The following results were obtained. 1) The MICs of CTM against organisms, 20 strains, which were isolated from bile of patients with cholecystitis, were studied, especially those of CTM against E. coli and Klebsiella were 0.2 - greater than or equal to 100 micrograms/ml and 0.1--12.5 micrograms/ml, respectively, considerably lower than those of CEZ. And moreover against CEZ-resistant Proteus morganii and Serratia marcescens, CTM showed potent activities, that is, MIC values, 12.5--50 micrograms/ml and 0.78 microgram/ml, respectively. 2) In cholecystectomized patients, 2 grams of CTM was injected intravenously, followed by determination of bile concentration in gallbladder, common bile duct and concentration of gallbladder and liver tissue about 2 hours after administration. The mean bile concentrations of CTM in gallbladder and common bile duct were 1,213.2 micrograms/ml and 1,287.8 micrograms/ml, respectively. The peak concentration of CTM was 2,919.0 micrograms/ml. The mean concentrations of CTM in gallbladder and liver tissue were 28.5 micrograms/g and 45.7 micrograms/g, respectively. On the other hand, the mean bile concentrations of CEZ in gallbladder and common bile duct were 138.7 micrograms/ml and 128.8 micrograms/ml, respectively. 3) Bile concentrations of CTM was compared with those of CEZ by crossover method. The concentration of CTM was 37.7 micrograms/ml even at 5 or 6 hours after 2 grams intravenously administration. CTM showed extremely higher concentration than CEZ in bile. 4) The clinical effect was studied in 6 cases of surgical, biliary tract infections. The results were excellent in 2 cases, good in 3 cases and poor in 1 case, and the clinical efficacy was 83%. 5) CTM was administered to 6 patients who showed negative to intracutaneous reaction test. Nausea, itching, and eruption were observed in each 1 case after intravenously administration of CTM 2 g, however these adverse reactions disappeared within several hours. Throughout the course of treatment, any unusual laboratory findings related to CTM were not observed.

We present a technique used to avoid unnecessary embolization of the cystic artery in the treatment of hepatoma by transcatheter arterial embolization. A special long tapering catheter that is flexible and soft enough to be inserted into the distal small branches of the heptic artery is used. Embolic material ( Oxycel , absorbable cellulose) was mixed with Mitocin -C (mitomycin) and contrast material. This mixture will help to avoid reflux.