二仙合剂的降压及其药理研究

二仙合剂可治疗妇女高血压,在腎型高血压狗也有降压效果。本文用5种高血压大白鼠(神經型、腎型、腎上腺燙伤型、睾丸切除型及卵巢切除型)来比較降压作用,并观察性周期、前庭时值及某些加压物质的升压反应。每天灌胃二仙合剂10克/公斤,共2周,神經型、腎型及睾丸切除型的降压面积%分别为-9,-11及-15%,与同型对照組比較,降压“显著”,腎上腺燙伤型及卵巢切除型的降压“不显著”。每天灌服二仙合剂10克/公斤,共7周,对未成熟大白鼠生长及性腺发育无影响。对神經型、腎型及腎上腺燙伤型雌鼠的性周期紊乱亦无糾正作用。二仙合剂能延长腎型高血压鼠的前庭时值,但在其他型则变化不显著。无明显对抗去甲腎上腺素及垂体后叶素的加压反应的作用。     

3A1 (CD7) expression precedes T beta gene rearrangements in precursor T (lymphoblastic) neoplasms

The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangements of the T cell receptor beta- chain (T beta) gene were found in most, but not all, cases (88%) of T cell lymphoblastic neoplasms. T beta gene rearrangement preceded surface expression of the T cell receptor-linked molecular complex T3. Of all monoclonal anti-T cell antibodies tested, only antibody 3A1 was capable of reacting with neoplastic cells from all cases irrespective of the occurrence of T cell receptor gene rearrangements. In contrast, markers T1 and T11, normally expressed by mature T cells, were absent from the neoplastic cells in many cases (73% and 60% positive cases, respectively). Thus, antibody 3A1 is a valuable probe for the identification of T lymphoblastic neoplasms since its target antigen is consistently expressed and does not require prior T beta gene rearrangement. Furthermore, expression of 3A1 prior to T beta gene rearrangement suggests that it may be a cell surface protein that participates in the triggering of T cell receptor gene rearrangement and expression. It is concluded that precursor T cell neoplasms display an early T cell development hierarchy that, in sequence, consists of 3A1 expression, T beta gene rearrangements, and surface T3 expression.     

A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22

Craniofrontonasal syndrome (CFNS, OMIM 304110) is a distinctive genetic disorder whose main clinical manifestations include coronal synostosis, widely spaced eyes, clefting of the nasal tip and various skeletal anomalies. CFNS originally was thought to be transmitted as an autosomal dominant trait, but recent studies suggest that it is X- linked dominant, whereby all daughters of males are affected, whereas none of their sons are affected. Here we report data confirming that CFNS is X-linked, mapping to a 13 cM interval in Xp22 with a maximum two-point lod score of 3.9 (theta = 0) at DXS8022 and a multipoint lod score of 5.08 at DXS1224. Detailed phenotypic analysis shows that females are more severely affected than males, a highly unusual characteristic for an X-linked disorder. CFNS represents the first multiple congenital anomaly syndrome with this unusual phenotypic pattern of X-linked inheritance.      

Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease

Glycogen storage disease type II (GSDII; Pompe disease), caused by inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder affecting heart and skeletal muscles. A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa mRNA and have a virtually complete acid alpha-glucosidase deficiency. Glycogen-containing lysosomes are detected soon after birth in liver, heart and skeletal muscle cells. By 13 weeks of age, large focal deposits of glycogen have formed. Vacuolar spaces stain positive for acid phosphatase as a sign of lysosomal pathology. Both male and female knockout mice are fertile and can be intercrossed to produce progeny. The first born knockout mice are at present 9 months old. Overt clinical symptoms are still absent, but the heart is typically enlarged and the electrocardiogram is abnormal. The mouse model will help greatly to understand the pathogenic mechanism of GSDII and is a valuable instrument to explore the efficacy of different therapeutic interventions.      

A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene

Several candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) map on chromosome 20, including the phosphoenolpyruvate carboxykinase gene (PCK1) and one of the maturity onset diabetes of the young genes (MODY1). Thus, we have investigated the entire long arm of chromosome 20. Linkage analyses were conducted in a total sample of 148 NIDDM families (301 NIDDM sib pairs) and in a subset of 42 early onset NIDDM families, where genetic components are likely to play a more important role (55 NIDDM sib pairs diagnosed at or before 45 years of age), using 10 highly polymorphic markers with an average map density of 7.5 cM. Using affected sib pair methods (two-point linkage and multipoint linkage analyses), significant results were obtained with the 20q13 region, in the vicinity of the PCK1 locus, only in the subset of 55 early onset NIDDM sib pairs (multipoint MLS = 2.74, P = 0.0004; MLS = 2.34, P = 0.0009 when using a conservative weighting procedure). Moreover, another region spanning the ribophorin II (RPNII, phospholipase C (PLC1) and adenosine deaminase (ADA) loci suggested linkage with NIDDM (multipoint MLS of 1.81 in all NIDDM sib pairs, P = 0.003; MLS = 1.31, P = 0.012 when using a conservative weighting procedure). Whereas our study suggests the location of a susceptibility locus for early onset NIDDM in the PCK1 gene region, further investigation in larger data sets is required to confirm these results and assess the role of other regions on chromosome 20q in human NIDDM.      

Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the hippocampus in vitro

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-5 microM) reversibly blocked the Schaffer collateral and mossy fibre excitatory postsynaptic potential (EPSP), while sparing the fast and slow gamma-aminobutyric acid (GABA)-mediated inhibition. Membrane potential, input resistance and spike accommodation were not altered. Inward currents induced by quisqualate were reduced to a greater extent by CNQX than those induced by kainate or N-methyl-D-aspartate. We suggest that CNQX may be a useful antagonist to study excitatory amino acid-mediated synaptic transmission.     

Two distinct calcium-activated potassium currents in larval muscle fibres ofDrosophila melanogaster

The non-synaptic membrane currents of muscle fibres have been studied in late embryogenesis ofDrosophila melanogaster using the voltage-clamp technique in wild-type andShaker mutant third instar larvae. Five currents were found in the wild type muscle membrane at this embryonic stage: one fast inward Ca current (I_Ca), two fast outward K currents (I_A and I_Acd) and two slow outward K currents (I_K and I_C). I_Acd and I_C are Ca-dependent.Several procedures were used to separate I_Acd from I_A: I_Acd is present inShaker mutants which are characterized by the absence of I_A (Salkoff and Wyman 1981); I_Acd, but not I_A, is suppressed by Co²⁺ (10 mM) or La³⁺ (1 mM); I_Acd shows steady-state inactivation at more positive potentials than I_A; I_Acd, unlike I_A, is 3,4-diaminopyridine (3,4-DAP) resistant. Furthermore, tetraethylammonium (TEA, 20 mM) which is known to be uneffective on I_A, blocks I_Acd. I_Acd could not be triggered by using strontium or barium as calcium substitutes. By partial substitution of Ca by Ba or Sr ions, it was found that Ba, but not Sr, blocks the I_Acd channel.A non-inactivating, TEA sensitive, Ca-dependent K current (I_C), which gave N-shaped I-V plots, could be separated from I_K by using Ca-channel blockers. I_C and I_K activate at membrane potentials of about –25 mV and –10 mV, respectively.The participation of I_Acd and I_C to membrane electrophysiology is discussed.