Problems in practical management of essential hypertension

A study of 100 men with arterial hypertension showed that: 1) hypertension was predominantly moderate with 14% index of placebo reactivity; 2) only 3 patients had a surgically curable etiologic factor; 3) frequent associated findings were hereditary factors (60%), overweight and metabolic disorders (30 to 40%). Such results suggest that: a) hypertension could be treated, in the majority of patients, without preliminary etiologic investigations and, b) non invasive hemodynamics techniques are required to evaluate arterial and cardiac lesions which are the dominant factors in the prognosis.     

4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone series

4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ-1) was studied to determine its potential for clinical trail as a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone class. MAIQ-1 was shown to be among the most potent known inhibitors of the major target for the expression of antineoplastic activity by this class of agents, the enzyme ribonucleoside diphosphate reductase, requiring only 0.06 micronM for 50% inhibition. This potency at the enzymatic level was consistent with its antineoplastic activity against the murine neoplasms Sarcoma 180, Leukemia L1210, Leukemia P388, and the B16 melanoma. The acetylation of the 5-amino group of the model substrate 5-amino-1,4-dimethylisoquinoline was lower than that of 5-amino-1-methylisoquinoline when incubated with acetyl-coenzyme A and rat liver homogenate. This finding suggests that the presence of the 4-methyl function offers steric hinderance to enzymatic substitution of the adjacent 5-amino group. In vivo metabolism of MAIQ-1 in mice, studied with [3'-14C]MAIQ-1 showed that relatively slow excretion of this agent occurred, since the cumulative urinary excretion of radioactivity was only 35% in 48 HR. About 51% of excreted urinary radioactivity was present in chromatograms in an area corresponding to the iron chelate of MAIQ-1, and only a minor quantity of material migrating like acetylated MAIQ-1 was present in urine, a finding consistent with enzymatic data with liver homogenates. The results indicate that MAIQ-1 has the antineoplastic activity, enzyme inhibitory potency, and relative resistance to metabolic inactivation required of an agent of this class for clinical trials.     

C-21- and 6-hydroxylation of progesterone by rabbit liver subcellular fractions

In vitro C-21-hydroxylation of [3H]progesterone (P) has been demonstrated for the first time with rabbit liver microsomes and mitochondria. Deoxycorticosterone (DOC) was rigorously characterized as a metabolite of both mitochondrial and microsomal metabolism, whereas 6alpha-hydroxy DOC and 6alpha-hydroxy P were only identified as microsomal metabolites. 6beta-Hydroxy metabolites were also detected but were of less quantitative significance. Formation of 6alpha-hydroxy P and 6alpha-hydroxy DOC increased steadily between 5 and 120 min of incubation with the microsomal fraction, whereas DOC increased up to 30 min of incubation and then declined. Maximal yield of DOC was 25.9 and 22.5 pmol/mg protein with the mitochondrial and microsomal fractions, respectively.     

Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement

Zymosan particles, which are able to activate complement by the alternative pathway and to induce enzyme secretion from macrophages, were injected into knee joints of mice. After various time intervals, synovia were assessed histologically for various markers of inflammation. Within 7 days after intraarticular injection of zymosan, a chronic inflammatory arthritis with mononuclear cell infiltration, synovial hypertrophy and pannus formation was observed. Latex particles, which do not activate complement or macrophages, produced only mild, transient inflammatory reactions.     

The use of clomiphene citrate

Two hundred and fifty-five women received clomiphene citrate during a 10-year period. Fifty-six were treated diagnostically and one hundred and ninty-nine therapeutically for infertility. It is concluded that clomiphene may aid in confirming the diagnosis and establishing a prognosis in patients with primary or secondary amenorrhea. The success of clomiphene therapy in patients with anovulatory infertility is related to the etiologic factor responsible for the anovulation, but results can be improved by adjustment of the therapeutic regimen used. In the present series, 48% of the patients who ovulated became pregnant, and 25.3% of the pregnancies were miscarried. Those patients who ovulated spontaneously and became pregnant after having discontinued clomiphene therapy showed only a 10% abortion rate. A review of the results indicates that both the ovulation rate and the pregnancy rate can be improved if adjustments are made in therapy to ensure normal follicular maturation and corpus luteum function.     

A simplified polyacrylamide gel electrophoresis apparatus for simultaneous application of multiple buffer systems or detergent combinations

A previous design of an apparatus for the simultaneous fractionation by polyacrylamide gel electrophoresis in 10 different buffer systems (1) was replaced by a greatly simplified new design, employing small, cylindrical buffer partitions within the lower buffer reservoir and/or upper buffer reservoir of a conventional, temperature-regulated polyacrylamide gel electrophoresis apparatus for cylindrical gels. The apparatus was tested in application to the problem of simultaneous polyacrylamide gel electrophoresis in different buffer systems with the purpose of optimizing the operative pH for a particular fractionation problem. It was also applied to fractionations in a single buffer system to which various combinations of ionic and nonionic detergents were admixed.     

Folate status response to controlled folate intake in pregnant women

A metabolic study (84-d) was conducted to investigate the folate status response of pregnant subjects (n = 12) during their second trimester and nonpregnant controls (n = 12) to folate intakes approximating the current (400 microg/d) and former (800 microg/d) recommended dietary allowance (RDA). The overall goal of the study was to provide metabolic data to assist in the interpretation of the current RDA for folate. Subjects were fed a controlled diet containing 120 +/- 15 microg/d (mean +/- SD) folate and either 330 or 730 microg/d synthetic folic acid. Outcome variables between and within supplementation groups were compared at steady state. Serum folate was higher (P 0.05) were detected in serum folate between pregnant and nonpregnant women within the same supplementation group. Urinary 5-methyl-tetrahydrofolate excretion was greater (P 0.05) in 5-methyl-tetrahydrofolate excretion were detected between pregnant and nonpregnant women within supplementation groups. Differences (P 相似文献   

Identification of the amino terminus of neuronal Ca2+ channel alpha1 subunits alpha1B and alpha1E as an essential determinant of G-protein modulation

We have examined the basis for G-protein modulation of the neuronal voltage-dependent calcium channels (VDCCs) alpha1E and alpha1B. A novel PCR product of alpha1E was isolated from rat brain. This contained an extended 5' DNA sequence and was subcloned onto the previously cloned isoform rbEII, giving rise to alpha1Elong whose N terminus was extended by 50 amino acids. VDCC alpha1 subunit constructs were co-expressed with the accessory alpha2-delta and beta2a subunits in Xenopus oocytes and mammalian (COS-7) cells. The alpha1Elong showed biophysical properties similar to those of rbEII; however, when G-protein modulation of expressed alpha1 subunits was induced by activation of co-expressed dopamine (D2) receptors with quinpirole (100 nM) in oocytes, or by co-transfection of Gbeta1gamma2 subunits in COS-7 cells, alpha1Elong, unlike alpha1E(rbEII), was found to be G-protein-modulated, in terms of both a slowing of activation kinetics and a reduction in current amplitude. However, alpha1Elong showed less modulation than alpha1B, and substitution of the alpha1E1-50 with the corresponding region of alpha1B1-55 produced a chimera alpha1bEEEE, with G-protein modulation intermediate between alpha1Elong and alpha1B. Furthermore, deletion of the N-terminal 1-55 sequence from alpha1B produced alpha1BDeltaN1-55, which could not be modulated, thus identifying the N-terminal domain as essential for G-protein modulation. Taken together with previous studies, these results indicate that the intracellular N terminus of alpha1E1-50 and alpha1B1-55 is likely to contribute to a multicomponent site, together with the intracellular I-II loop and/or the C-terminal tail, which are involved in Gbetagamma binding and/or in subsequent modulation of channel gating.     

江西省地质灾害防治指挥中心空调系统设计方案分析

本文主要介绍了数码涡旋中央空调系统设计中应注意的事项,阐述了数码涡旋中央空调系统的特点。     

Engineering trimeric fibrous proteins based on bacteriophage T4 adhesins

The adsorption specificity of bacteriophage T4 is determined by genes 12and 37, encoding the short tail-fibers (STF) and the distal part of thelong tail-fibers (LTF), respectively. Both are trimeric proteins with roddomains made up of similar tandem quasi-repeats, approximately 40 aminoacids long. Their assembly requires the viral chaperones gp57A and gp38.Here we report that fusing fragments of gp12 and gp37 to another trimericT4 fibrous protein, fibritin, facilitates correct assembly, therebyby-passing the chaperone requirement. Fibritin is an alpha-helical coiledcoil protein whose C-terminal part (fibritin E, comprising the last 120residues) has recently been solved to atomic resolution. Gp12 fragments of109 and 70 amino acids, corresponding to three and two quasi-repeatsrespectively, were fused to the C-terminus of fibritin E. A similar chimerawas designed for the last 63 residues of gp37, which contain four copies ofthe pentapeptide Gly-X-His-X-His and assume a narrow rigid structure in theLTF distal tip. Expressed from plasmids, all three chimeras form solubletrimers that are resistant to dissociation by SDS and digestion by trypsin,indicative of correct folding and oligomerization.