(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release.

"Catecholaminergic and serotoninergic activity enhancer" effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP HCl], a compound with selective and potent "catecholaminergic and serotoninergic activity enhancer" effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (-)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3-10 mg/kg). (-)-BPAP HCl (1-3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (-)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390), suggesting that the effects of (-)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (-)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (-)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (-)-BPAP HCl significantly improved ptosis. These findings suggested that a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.

Optimization of tylosin feeding rate profile in production of acetyl-isovaleryl tylosin (AIV) from tylosin by Streptomyces thermotolerans YN554.

An optimal feed rate profile of a substrate (tylosin) for a novel antibiotic, acetyl-isovaleryl tylosin (AIV) production process was investigated. In the first step of optimization, a kinetic model for production of AIV from tylosin by Streptomyces thermotolerans was established properly using the least square method, followed by the confirmation that the proposed model could be used to predict the production process of AIV from tylosin. An objective function, state equations and an inequality constraint with respect to the tylosin feeding rate profile were applied to maximize the amount of AIV produced from tylosin in a fed-batch culture. The optimized tylosin feeding rate profile was determined using a direct iterative search algorithm based on the modified complex method. The simulation of AIV production at the optimal tylosin feeding profile indicates that the final amount of AIV is expected to be about 30% higher than that at the conventional constant tylosin feeding rate, which was also confirmed experimentally using a 30-l jar fermentor.

Preterm labor: placental pathology and clinical correlation.

OBJECTIVE: To determine the relevance of ischemia in the incidence of preterm labor. A second objective was to document perinatal outcomes for patients with preterm labor classified according to its clinical, functional, and pathologic characteristics (infectious, ischemic, mixed, or idiopathic). METHODS: Perinatal outcomes were evaluated for 145 consecutive patients with preterm labor, subdivided into etiologic categories according to clinical, functional (Doppler), and morphologic (placental pathology) characteristics. A group of 44 normal pregnancies delivered at term served as controls. RESULTS: Of the preterm labor group, 28.3% were classified as ischemic, compared with 4.5% of the control group (odds ratio and 95% confidence interval = 8.28 [1.8, 51.8]; P < .05). Compared with the control group, the preterm labor patients who delivered preterm had higher rates of ischemia (31.4% compared with 4.5%; P < .05) and infection (16.1% compared with 2.3%; P < .05). Among the preterm labor group, patients classified in the infectious or ischemic subgroups had a higher rate of preterm delivery (95.0% and 90.2% compared with 73.2%; P < .05), admission to the neonatal intensive care unit (75.0% and 61.0% compared with 40.0%; P < .05), and newborn weight under 1500 g (35.0% and 19.5% compared with 3.7%; P < .05) than the idiopathic subgroup. CONCLUSION: Preterm labor resulting from infection or ischemia is associated with a higher perinatal complication rate than idiopathic preterm labor.

Cloning, sequencing, and expression of cscA invertase from Escherichia coli B-62.

We have isolated a 2.5-kb DNA fragment from plasmid pST5R7 encoding a sucrose utilization system from Escherichia coli B-62 which confers a sucrose-fermenting phenotype to transformed E. coli K-12 strains. DNA-sequence determination revealed one full-length open reading frame 98% identical to cscA, the sucrose-hydrolase (invertase) gene of the csc regulon from E. coli EC3132. Functional characterization indicates that high-level expression and limited periplasmic release of invertase is responsible for the sucrose-fermenting capacity of transformed E. coli K-12 strains carrying cscA.

Cross axis vestibulo-ocular reflex induced by pursuit training in alert monkeys.

We examined the effect of conflicting vestibular and smooth pursuit information on the vestibulo-ocular reflex (VOR) in alert monkeys. Sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane. The monkeys were rewarded for tracking the spot and eye movements induced by rotation alone were examined every 15-30 min in complete darkness. Orthogonal eye movement responses to rotation were not observed before training but appeared after about 30 min of training. The gains (eye/chair) of the orthogonal component increased up to 0.2 after 1-2 h and were largest at the training frequency and approximately in phase with the stimulus; phase advanced at lower frequencies and lagged at higher frequencies. Amplitude tuning was also demonstrated when examined using different amplitudes at a constant frequency after training. Two hours of training to fixate an earth-stationary spot projected onto a patterned visual background that moved orthogonally to the rotation plane during rotation, did not induce a cross axis response. These results indicate that pursuit training during VOR is effective in inducing cross-axis eye movement responses that are tuned to the metrics of the training stimulus.

Direct fermentative production of acyltylosins by genetically-engineered strains of Streptomyces fradiae.

A tylosin-producer, Streptomyces fradiae, was transformed with plasmids carrying genes from Streptomyces thermotolerans that are involved in acyl modification of macrolide antibiotics. A transformant with pMAB3, in which macrolide 4"-O-acyltransferase gene (acyB1) and its regulatory gene (acyB2) are subcloned, produced several types of 4"-O-acyltylosins. A transformant with pAB11 delta EH containing macrolide 3-O-acyltransferase gene (acyA) in addition to the above two genes produced 3-O-acetyltylosin and 3-O-acetyl-4"-O-acyltylosins. Among the products of the latter transformant, 3-O-acetyl-4"-O-isovaleryltylosin (AIV) was detected as a minor component. When L-leucine, a precursor of isovaleryl-CoA, was added to the medium at the late stage of the fermentation, AIV content among the total macrolides increased ten-fold and AIV became a main product. This fact suggests that a high level of endogenous isovaleryl-CoA may be essential for the selective production of AIV by S. fradiae carrying pAB11 delta EH.

Nucleotide sequence analysis of the carbomycin biosynthetic genes including the 3-O-acyltransferase gene from Streptomyces thermotolerans.

A 3.2-kb DNA fragment of the carbomycin biosynthetic region including the 3-O-acyltransferase gene (acyA) from Streptomyces thermotolerans was sequenced, and four ORFs were found in the fragment. The second ORF, designated ORF-A, was transcribed in the opposite direction to the other three ORFs. The first ORF was identified as carA, a gene for carbomycin resistance. The amino acid sequence of ORF-A was homologous to proteins of the cytochrome P-450 family. Streptomyces lividans transformed with pCB20, in which ORF-A was subcloned, epoxidized carbomycin B at its C-12, 13 positions, thus producing carbomycin A. The third ORF, the amino acid sequence of which showed a homology to macrolide antibiotics O-acyltransferases was identified as acyA. The last ORF (ORF-B), which starts just 3 bp downstream from the TGA termination codon of acyA, was thought to be a carbomycin 4-O-methyltransferase gene, because the amino acid sequence deduced from ORF-B showed high homology to a putative midecamycin 4-O-methyltransferase encoded on mdmC.

Cloning of the macrolide antibiotic biosynthesis gene acyA, which encodes 3-O-acyltransferase, from Streptomyces thermotolerans and its use for direct fermentative production of a hybrid macrolide antibiotic.

A gene encoding the macrolide modification enzyme 3-O-acyltransferase (acyA) was cloned by chromosome walking onto the carbomycin biosynthetic region in Streptomyces thermotolerans TH475, with the 3' region of the gene encoding the macrolide modification enzyme 4"-O-acyltransferase (acyB1) as a probe. A shortened fragment (1.8 kb) containing acyA was subcloned with pIJ350. A high-level tylosin producer, Streptomyces fradiae MBBF, transformed with the plasmid could produce a hybrid macrolide, 3-O-acetyltylosin, most efficiently.

Cloning and nucleotide sequences of two genes involved in the 4''-O-acylation of macrolide antibiotics from Streptomyces thermotolerans.

A DNA fragment responsible for the 4''-O-acylation of macrolide antibiotics was cloned from a mutant strain of the carbomycin producer Streptomyces thermotolerans. The gene encoding the macrolide 4''-O-acyltransferase was within a 2.7-kb region of the cloned fragment (15-kb). Streptomyces lividans carrying the region converted exogenously added tylosin to 4''-O-acyltylosins. Nucleotide sequencing of the region showed two open reading frames (ORFs). Expression assay using deleted plasmids showed that both ORFs were essential for optimal expression of the acyltransferase activity. One of them (acyB1) was identical with carE reported previously as a gene encoding 4''-mycarosyl isovaleryl-CoA transferase. The other (acyB2) was assumed to encode a novel regulatory protein that could active acyB1 expression. acyB1 and acyB2 were highly conserved among streptomycetes with macrolide 4''-O-acyl transferase activity.

Acquisition of a sucrose utilization system in Escherichia coli K-12 derivatives and its application to industry.

An Escherichia coli strain, B-62, that was isolated from a clinical source and was epidemiologically unrelated to E. coli K-12 was the source of chromosomal DNA for a sucrose utilization system (Scr+) in the construction of a plasmid, pST621. The cloned insert of a gene encoding Scr+ in pST621 conferred a sucrose-positive phenotype onto transformed cells of E. coli K-12 derivatives. Sucrase activity of the transformants was as high as that which would correspond to a "gene dosage effect" of a vector plasmid pBR322, whereas the transformants' sucrose uptake activity was always lower than that of E. coli B-62. A region within an XhoI-SacI fragment (3.2 kb) of pBR322-glyA was replaced in the construction of another plasmid, pST5R7, by a fragment (about 2.6 kb) of pST622 containing the gene encoding Scr+. A genetically stable Scr+ derivative of E. coli K-12 was obtained by introducing the gene encoding Scr+ onto E. coli chromosome via homologous recombination between pST5R7 and the chromosome and subsequent plasmid segregation. The use of low-copy-number plasmid RP4 as a cloning vector was also effective for enhancing the stability of Scr+. Tryptophan producers E. coli SGIII1032S, in which the gene encoding Scr+ was cloned onto the chromosome, and E. coli SGIII1032, which carried Scr+ plasmid RP4.5R7, produced from 6% sucrose in shake flasks (33 degrees C, 96 h) 2.3 and 5.7 g of tryptophan per liter, respectively.

[The ultrasonographic characteristics of the endometrium during the spontaneous ovulatory menstrual cycle]. / Caracterización ultrasonográfica del endometrio durante el ciclo menstrual ovulatorio espontáneo.

Six hundred and four serial transvaginal sonograms were performed in 70 normal and healthy women throughout an ovulatory cycle. The endometrium was classified in 4 types (0, 1, 2 and 3) according to: the aspect of the myometria-endometrium and endometrium-endometrium interfaces, and the texture and thickness of the functional layer. Type 0 appears as a smooth, pencil line endometrium. Type 1 has a trilaminar structure with an iso or hypoechoic functional layer. Type 2 is also trilaminar, but myometria-endometrium interfaces are thicker than type 1. Type 3 appears as a thick and homogeneously echogenic image. The relative frequency of each type of endometrium was determined for every day of the menstrual cycle. Day 0 was defined sonographically as the day of follicle rupture. Type 0 was found during and immediately after menstruation. Type 1 was seen during mid-follicular phase and until day +2. Types 2 and 3 were observed post ovulatory in 100% of the cases. The endometrium increases in thickness more during preovulatory phase (mean: 5.5 mm), than in the luteal phase (mean: 2.6 mm). We conclude that this working classification of the endometrium is useful in clinical practice when associated to the ultrasonographic aspect of the ovaries and the moment of the menstrual cycle.

[Intravascular fetal transfusion in the management of perinatal hemolytic disease]. / Transfusión fetal intravascular en el manejo de la enfermedad hemolítica perinatal.

Five pregnancies with severe blood cell isoimmunization were managed with intrauterine intravascular transfusions. The procedures were performed percutaneously under direct ultrasound visualization. A total of 14 transfusions, of 16 attempted, were successfully performed. The 5 fetuses required more than one transfusion. Only one died before been born. The other four are alive and without sequelae. Technical aspects of the procedure as well as its indications, advantages, and historical drawbacks are discussed.

[Echo guided percutaneous needle biopsy for diagnosis of thoracic lesions].

Echo guided percutaneous needle biopsy was performed in 32 cases with thoracic lesions. A definitive diagnosis was made histopathologically in 11 (100%) of 11 malignancies, 4 (67%) of 6 benign tumors and 7 (47%) of 15 inflammatory lesions. Furthermore, using cytological specimens, definitive diagnosis was successfully made in 10 (91%) of 11 malignancies and 1 (17%) of 6 benign tumors. Such highly accurate diagnostic rates were due to 1) the accurate puncture of the lesions under real time sonographic guidance, 2) repeated biopsy in case in which sample was inadequate for cytological diagnosis, and 3) aggressive application of needle biopsy for histopathological diagnosis. Following this procedure, three patients suffered from a minor pneumothorax. To prevent pneumothorax, great care is necessary, especially in high risk cases, such as with a pneumatic pattern and thin lesion. One patient suffered from minor hemoptysis but recovered without any medication. No complications were noticed in cases of extrapulmonary lesions. We conclude that echo guided percutaneous needle biopsy is not only a complementary method for biopsy of mediastinal, peripheral pulmonary and chest wall lesions, but due to its simplicity and convenience, it should be a routine method for biopsy of thoracic lesions.

[Tuberculosis epidemic in a technical center].

A tuberculosis epidemic occurred in a class at a technical center in a large furniture company. An index case was a male student who had a severe family history of tuberculosis and his sputum smear was Guffky 3. PPD skin test and routine chest X-ray examination were immediately done on the forty-two classmates. As the result of these examinations, the distribution of maximum diameter of erythema in PPD skin test showed bimodal distribution, and tuberculosis was discovered in five patients by chest X-ray examination. During follow up for eighteen months another three new patients were found. In this company, routine chest X-ray examination had been carried out. The patient's delay and insufficient ventilation in the dormitory were considered to be the main causes of the tuberculosis epidemic.

[FEP and FAP combination chemotherapy in advanced gastric cancer. Research Group for Gastric Cancer].

Twenty-six patients with unresectable gastric cancer, divided into two groups, were treated with combination chemotherapy of FEP (14 patients) or FAP (12 patients). The FEP regimen performed every 4 weeks was as follows: UFT 400 mg/m2 (p.o.) everyday, etoposide 50 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. FAP regimen was performed every 4 weeks was: UFT 400 mg/m2 (p.o.) everyday, adriamycin 10 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. In FEP group, (7 males and 7 females) the average age was 64 (range 53 to 75). Two patients were in PS 1, 4 in PS 2 and 8 in PS 3. In FAP group (7 males and 5 females) the average age was 55 (range 30 to 74). One patient was in PS 1, 5 in PS 2 and 6 in PS 3. No one in either group had prior chemotherapy. Response rates in FEP and FAP groups were 28.5% (4/14) and 33.3% (4/12), respectively. The median survival periods were 4.5 months in FEP group and 6.5 months in FAP group. As for side effects, myelosuppression appeared most frequently, being followed by alopecia and nausea, although the degree of alopecia was milder in FEP than in FAP. We conclude that new combination chemotherapies of either FEP or FAP are useful for advanced gastric cancer.

Serologic study of febrile upper respiratory tract infections in adults.

We prospectively studied serum antiviral antibody response in adult patients with febrile upper respiratory tract infections. Paired sera were obtained in 158 patients from January 1982 to December 1983. Eighteen patients (11.4 percent) showed a significant antibody rise in the convalescent phase of the disease compared to the acute phase. Significant antibody rise was observed against all viruses examined: influenza viruses type A and B, adenovirus type 3, respiratory syncytial virus, and parainfluenza viruses type 1, 2 and 3. Two patients responded simultaneously to two viruses. Serum interferon was detected in acute phase of the disease in 4 of 8 patients examined in whom viral infections were proved. Detected interferon was alpha type.

[Adriamycin, cyclophosphamide, vincristine and methotrexate combination chemotherapy of small cell lung cancer].

Twenty-two patients who had not received previous chemotherapy for small cell lung cancer were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cyclophosphamide (500 mg/m2, i.v., on day 1, and 350 mg/m2, i.v., on day 8), vincristine (1 mg/m2, i.v., on day 1) and methotrexate (20 mg/m2, i.v., on days 1 and 8). This chemotherapy regimen was repeated at 3- or 4-week intervals. Among 20 evaluable patients, none showed complete response but 14 (70%) showed a partial response, with a median response duration of 8 weeks (range, 4-20 weeks). The median survival time for the 20 evaluable patients was 28 weeks. Toxicity included mild to moderate hematologic toxicity, alopecia and nausea and vomiting. This combination chemotherapy appears to be suboptimal for the treatment of small cell lung cancer, with no complete responses and a relatively short median survival time.

Laserthermia: a new computer-controlled contact Nd: YAG system for interstitial local hyperthermia.

Contact Nd:YAG laser surgery is assuming a greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A new contact probe allows a wider angle of irradiation and diffusion of low-power laser energy (less than 5 watts), using the interstitial technique for producing local hyperthermia. Temperature sensors that monitor continuously can be placed directly into the surrounding tissue or tumor. Using a computer program interfaced with the laser and sensors, a controlled and stable temperature (e.g., 42 degrees C) can be produced in a known volume of tissue over a prolonged period of time (e.g., 20-40 min). This new laserthermia system, using a single low-power Nd:YAG laser for interstitial local hyperthermia, may offer many new advantages in the experimental treatment and clinical management of carcinoma. A multiple system is now being developed.

Laserthermia: a computer-controlled contact Nd:YAG system for interstitial local hyperthermia.

Contact Nd:YAG laser surgery is assuming a role of greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A synthetic sapphire probe allows a wider angle of irradiation and diffusion of low power laser energy (less than 5 W) using an interstitial technique for producing local hyperthermia. Sensors placed directly into surrounding tissue or tumor continuously monitor temperature, and a pertinent computer program produces a controlled and stable temperature (e.g., 42 degrees C) over a period of time (e.g., 20-40 min). The Laserthermia system (Surgical Laser Technologies, Inc., Malvern, PA), using the Nd:YAG laser, offers many advantages in the experimental and clinical treatment of carcinoma by local interstitial hyperthermia.