Stimulation of apolipoprotein E secretion in human hepatoma Hep G2 cells by a cyclic acylpeptide, N-4909.
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Biomedical subjects
Publications and source records attributed to H Seto.
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The retinoblastoma protein (pRB) is inactivated in a wide variety of human cancers. In the course of our screening for antitumor antibiotics by using pRB-inactivated cells, an actinomycete identified as Streptomyces tanashiensis was found to produce four new active substances, leptofuranins A, B, C and D. The leptofuranins arrested the growth of normal cells and induced apoptotic cell death against tumor cells and cells transformed with the adenovirus E1A gene.
The structures of new antitumor antibiotics, leptofuranins A, B, C and D were elucidated to be as shown in Fig. 1 by NMR spectral analysis including a variety of two-dimensional techniques. The leptofuranins are novel leptomycin-related substances containing a tetrahydrofuran ring. Leptofuranins C and D were revealed to be in tautomeric isomerism and their relative stereochemistries were analyzed by NOESY experiments.
A complementary DNA encoding a mitogen-activated protein (MAP) kinase homolog has been isolated from tobacco plants. Transcripts of the corresponding gene were not observed in healthy tobacco leaves but began to accumulate 1 minute after mechanical wounding. In tobacco plants transformed with the cloned complementary DNA, trans inactivation of the endogenous homologous gene occurred, and both production of wound-induced jasmonic acid and accumulation of wound-inducible gene transcripts were inhibited. In contrast, the levels of salicylic acid and transcripts for pathogen-inducible, acidic pathogenesis-related proteins were increased upon wounding. These results indicate that this MAP kinase is part of the initial response of higher plants to mechanical wounding.
The biosynthetic pathway for production of the antibiotic fosfomycin by Streptomyces wedmorensis consists of four steps including the formation of a C-P bond and an epoxide. Fosfomycin production genes were cloned from genomic DNA using S. wedmorensis mutants blocked at different steps of the biosynthetic pathway. Four genes corresponding to each of the biosynthetic steps were found to be clustered in a DNA fragment of about 5 kb. Nucleotide sequencing of a large fragment revealed the presence of ten open reading frames, including the four biosynthetic genes and six genes with unknown functions.
We developed a rapid and sensitive method of identifying benzodiazepines and zopiclone in human serum using high-performance thin-layer chromatography (HPTLC). These drugs were developed and separated on plates within 8-11 min and detected by means of UV radiation and colour. Each drug was accurately identified by means of the values of RF x 100 and the spot colour in three systems. The detection limit of the benzodiazepines in serum was 0.1-0.4 micrograms/ml, except for cloxazolam and haloxazolam. The sensitivity was increased about ten-fold over the conventional method. These results suggested that the HPTLC system is useful for the initial detection and identification of these drugs in emergencies.
The nucleotide sequence of the Streptomyces hygroscopicus gene encoding P-methyltransferase, catalyzing the formation of a carbon-phosphorus bond, involved in bialaphos biosynthesis, has been determined. The amino-acid sequence deduced from the nt sequence, shows homology with those of magnesium-protoporphyrin IX monomethyl ester oxidative cyclase (Mg-ProtoMe cyclase) of Rhodobacter capsulatus and the enzyme catalyzing the methylation of the aldehyde carbon of phosphonoacetaldehyde in fosfomycin biosynthesis.
The nucleotide (nt) sequence of the Streptomyces hygroscopicus gene encoding carboxyphosphonoenolpyruvate (CPEP) synthase, that catalyzes a transesterification between phosphoenolpyruvate (PEP) and phosphonoformate (PF) in the bialaphos biosynthetic pathway, has been determined. The amino-acid sequence deduced from the nt sequence is similar to several eukaryotic 2-phospho-D-glycerate hydrolases (EC 4.2.1.11).
This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increased rCBF in bilateral anterior cingulates and decreased rCBF in bilateral middle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.
We report the case of a 58-year-old male with cholecystocolic fistula and hepatic abscess that were not diagnosed by routine radiologic examinations, but concurrently detected by hepatobiliary scintigraphy with 99mTc-PMT, and confirmed at operation. Hepatobiliary scintigraphy is noninvasive and useful in the detection of a biliary enteric fistula and lesions about related organs. Concurrent detection of cholecystocolic fistula and hepatic abscess on hepatobiliary series is of great clinical value in planning surgical intervention.
A patient with osteomalacia secondary to vitamin D deficiency after gastrectomy for gastric cancer is presented. Initial bone scintigrams showed both asymmetric and symmetric focal areas of intense uptake due to pseudofractures reminiscent of bone metastases. Radiographs only confirmed the presence of pseudofractures at some, but not all, of the abnormal sites demonstrated by bone scintigraphy. At first, metastatic bone disease was suspected. However, the appearance of repeated bone scintigram was normalized after treatment with vitamin D. A diagnosis of osteomalacia was established. The present case serves to illustrate that symmetric focal lesions are important features of pseudofractures secondary to osteomalacia, and comparison with radiographs and repeated bone scintigraphy are necessary in distinguishing between bone metastases and pseudofractures.
Wandering spleen is the term commonly applied to splenic hypermobility that results from laxity or maldevelopment of its suspensory ligaments. It comes to medical attention usually as an abdominal mass, or when the spleen undergoes torsion. Diagnosis on clinical grounds alone is rarely made, and ultrasonography, CT and MRI findings have no specific characteristics for this condition. 99mTc-labeled colloid taken up by the spleen may provide a specific diagnosis. We report a case of wandering spleen, in which the preoperative diagnosis was made on the basis of sequential liver-spleen scintigraphy with 99mTc-Sn-colloid and blood-pool scintigraphy with 99mTc-RBC. This is a rare case, in which hypermobility was assessed by sequential 99mTc-Sn-colloid scintigraphy, and to our knowledge, is the first case in which 99mTc-RBC scintigraphy provided useful information on splenic blood volume and its location.
To improve the early detectability of gastrointestinal (GI) bleeding, we have developed a new subtraction scintigraphic technique using in vivo labeled 99mTc red blood cells (RBC). Use of this new sequential subtraction method every 5 min makes it possible to detect early the bleeding site and calculate the bleeding rate. In phantom experiments, focal activity was detected on subtraction images at pump rates of more than 0.20 ml/min at any urethane thickness, but was negative on conventional scintigrams. The calculated pump rate by the subtraction method correlated well with the actual syringe pump rate (y = 1.07x - 0.02, r = 0.99, p < 0.01) in the case of an 8-cm urethane board as an abdominal wall. Twenty-four of 50 patients with suspected GI bleeding were confirmed to be positive within 24 hr. The subtraction method showed 15 true positive and 2 false positive cases within 60 min. On the other hand, the conventional scintigraphic method showed only 7 true positive and 1 false positive cases. Sensitivity of the subtraction method was 62.5%, which was significantly higher (p < 0.05) than that of the conventional scintigraphic method (29.2%). These results suggest that sequential subtraction scintigraphy with 99mTc-RBC is an effective method for the early detection of GI bleeding and shortening the examination time as compared with conventional scintigraphy.
A patient with neuro-Behcet disease is described. SPECT using Tc-99m HMPAO was performed to evaluate brain perfusion. The brain SPECT revealed decreased perfusion in the right frontal, parietal, temporal, and occipital lobes. MRI showed high intensity lesions in the white matter in the right periventricular centrum semiovale and frontal region on T2 weighted images. Gray matter abnormalities were evident on brain SPECT, but not on MRI. Brain SPECT using Tc-99m HMPAO may provide useful clinical information on regional cerebral cortical abnormalities associated with neuro-Behcet disease.
I-131 MIBG, a specific radiopharmaceutical agent for scintigraphic imaging and treatment of pheochromocytoma and neuroblastoma may be useful for detection of apudomas. Scintigraphy with I-123 radiolabeled MIBG was performed in a patient with metastatic carcinoid tumor from the rectum. I-123 MIBG scintigraphic findings showed multiple areas of abnormal tumor uptake of hepatic and bone metastases from the rectal carcinoid. Bone scintigraphy demonstrated multiple metastatic lesions. Computed tomography revealed multiple solid tumors of the liver. This report describes accumulation of I-123 MIBG in the liver and bone metastases from the rectal carcinoid. Radioiodine MIBG scintigraphy may be useful for detecting metastatic lesions, for evaluating postoperative recurrence, and also for the treatment of the carcinoid tumor.
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