A Km mutant of arylsulfatase A

Semi-micro techniques are presented for the genotyping of galactokinase and galactose-1-phosphate uridyltransferase. Radioactive assays are used to quantitate the levels of enzyme activity, while agarose gel electrophoresis is used to type the variants of galactose-1-phosphate uridyltransferase. All three methods can be performed on 1 ml whole blood, making the procedures ideal for use in confirmation of galactosemia or galactokinase deficiency in newborn screening programs.     

Hepatitis A: A preventable threat

Hepatitis A is a major public health problem, particularly in the pediatric population. Although hepatitis A infection does not cause chronic liver disease, it is associated with significant morbidity. The virus is transmitted primarily by person-to-person contact via the fecal-oral route. The infection can be inapparent, subclinical, anicteric, or icteric. In general, the severity of the disease is inversely correlated with the age of the child. Occasionally, fulminant hepatitis, which is associated with a high mortality rate, may result. The diagnosis of acute hepatitis A is most commonly made through the detection of immunoglobulin M (IgM) anti-hepatitis A antibody. Treatment is generally supportive. General preventive measures include improved standards of hygiene and sanitation. Universal childhood vaccination is the most effective method for eradicating hepatitis A and preventing its transmission.     

RHD845A/1227A基因型个体家系调查分析

本研究对1例RHD845A/1227A基因型个体进行家系调查分析,并分析他们的遗传特性。通过盐水法和间接抗人球蛋白试验（IAT）检测RH（D）抗原,PCR—SSP法检测RHD1227A和RHD845A等位基因以及RHD合子型,基因测序方式分析RIHD基因编码区序列。研究结果表明：血清学检测发现1例RH（D）抗原盐水法检测阴性、IAT法检测阳性样本,经RHD基因编码序列分析发现,RHD第845位与第1227位均出现G／A碱基杂合现象,推测该个体基因型可能为RHD845A／1227A。家系调查显示,先证者父亲为RHD阴性,母亲为RHD阳性。PCR-SSP检测结果显示,父亲携带RHDl227A等位基因,基因型为RHD845A／RHD-;母亲携带RHD845A等位基因,基因型为RHD845A／RHD＋,证明先证者分别从父亲和母亲遗传RHD1227A和RHD845A等位基因,基因型为RHD845A／1227A。结论：经过家系调查分析发现了1例罕见的RHD845A／1227A基因型个体。根据家系调查证明,RHD845A和RHD1227A等位基因分别由遗传获得,而非由个体基因变异形成。     

Potential Therapeutic Applications of Adenosine A2A Receptor Ligands and Opportunities for A2A Receptor Imaging

Adenosine A_2A receptors (A_2ARs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A_2AR agonists may suppress transplant rejection and graft‐versus‐host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood–brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain. Increasing A_2AR signaling in adipose tissue is also a potential strategy to combat obesity. Several radioligands for positron emission tomography (PET) imaging of A_2ARs have been developed in recent years. This review article presents a critical overview of the potential therapeutic applications of A_2AR ligands, the use of A_2AR imaging in drug development, and opportunities and limitations of PET imaging in future research.     

A PHYSIOLOGICO-PATHOLOGICAL STUDY OF A CASE OF HEART-BLOCK OCCURRING IN A DOG AS A RESULT OF NATURAL CAUSES

What is believed to be the first known case of heart-block arising in a dog as a result of an ingenerate pathological lesion is here reported. The auriculo-ventricular dissociation was of that degree known as relatively complete block and became apparent on section of the right vagus nerve. Stimulation of the peripheral end of the cut vagus failed to inhibit the ventricles, although complete inhibition of the auricles occurred. The same results were obtained during the ventricular acceleration produced by strophanthin, so that the failure of the vagus to inhibit the ventricles is not due to the latter''s infrequent action, but more probably to a normal lack of direct chronotropic influence upon the ventricular muscle. These findings are similar to those obtained by Erlanger in experimental heart-block. To small repeated doses of strophanthin injected intravenously the heart reacted as follows: (a) irregular slowing of the auricles and conversion of the relatively complete into an absolutely complete a-v block; (b) a rise in the irritability of the cardiac muscle manifested by a rapidly progressing auricular and ventricular frequency, the ventricular frequency surpassing ultimately the auricular frequency; (c) complete arrest of the auricles, the ventricles continuing at their high rate; (d) sudden fibrillation of the ventricles and shortly afterwards arrest in diastole. There were found post mortem myxomatous-like thickenings at the free edge of the septal tricuspid leaflet and at the attached margin of the posterior aortic leaflet and along part of the right anterior aortic leaflet. There was also a grayish patch on the right side of the auricular septum above the auriculo-ventricular junction. The thickenings at the edge of the valves consisted of dense, circumscribed masses of what appeared to be new connective tissue. The same tissue was found pressing against the bundle along the greater part of the latter''s course. There was considerable fatty infiltration of the auricular musculature immediately above the bundle and, to a slight extent, of the bundle itself. The fibers of communication between the auricular muscle and the node of Tawara were relatively few as compared with those of the normal heart. A review of the pathology of heart-block is appended, showing the present status of the question, concerning the relationship existing between disease of the a-v conducting system and the various grades of heart-block.     

A_3亚型报告1例

1 病例简介 患者,男,55岁.2002年5月无明显原因出现乏力、面色苍白、走路活动时心跳加快等症状.2002年7月、12月先后在北京天坛医院和北医人民医院诊治,并确诊为骨髓增生异常综合征(MDS-RA).在此期间,患者接受中西医治疗,均未输血和化疗.2003年5月来本院急诊科就诊,血常规检查结果:RBC 2.02×1012/L,Hb 45g/L,Plt 62×109/L.接诊医生为患者申请悬浮红细胞2U,在交叉配血和血型复核时,发现ABO血型正、反定型不一致,正定型为"O"型,反定型为"A"型.遂将患者血液标本送至北京市红十字血液中心进一步鉴定,报告为A3亚型,建议患者输O型洗涤红细胞.至2004年6月,患者输入O型洗涤红细胞15U,无不良反应发生.     

A simple chromogenic assay for arylsulfatase A

Arylsulfatase A hydrolyzes the artificial chromogenic substrate 4-nitrocatechol-sulfate at 0 degree C at a rate of 24% of that at 37 degrees C whereas arylsulfatase B is almost inactive at 0 degree C. Based on this observation, a simple assay was developed which permits the accurate determination of low residual arylsulfatase A activities in cultured skin fibroblasts of infantile, juvenile and adult MLD patients and pseudodeficient individuals. In cultured skin fibroblasts, the following residual activities were found with this assay system: late-infantile patients, 0.0%, one juvenile patient, 1.0%, adult patients, 4.4-14% of normal average. healthy pseudodeficient probands ranged between 18% and 32%.     

Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice

The absolute frequencies of B cells-producing A5A idiotype have been determined in vitro by limiting dilution analysis in a culture system in which every LPS-reactive B cell grows into a clone of IgM-secreting cells. Spleen cells from normal A/J mice contain 1 A5A-idiotype-producing B-cell precursor in 2.5 X 10(3) LPS-reactive B cells. Approximately a 10-20-fold increase in frequencies of precursor cells from antigen priming with Strep A-CHO (1 in 2.8 X 10(2)) or from sensitization with IgG1 anti-A5A idiotype (1 in 1.3 X 10(2)). Injection of IgG2 anti-A5A idiotype which has been shown to suppress A5A idiotype in vivo results in only a marginal and maybe insignificant decrease in precursor frequencies (1 in 6.7 X 10(3)). On the other hand, priming does not result in a detectable qualitative difference in the specific precursor cells, since each clone of B cells secretes 30 ng of A5A-bearing Ig within 8 days of culture, regardless of being unprimed or primed. Nearly half of all A5A idiotype-producing clones, both from unprimed as well as from primed mice, show antigen specificity in binding A-CHO. Priming by antigen, therefore, also results in a 10-fold increase in the frequency of idiotype positive B cells without antigen specificity. This result is a prediction of the network hypothesis.     

A Cost-Benefit Analysis of A Community Free Clinic

Uninsured patients lacking access to primary and preventive care continues to be an issue. The purpose of this analysis is to describe operating costs surrounding a nurse-driven freestanding community clinic and to calculate quality of life benefits using clinically preventable burden scores. A retrospective records review of patients (n = 200) receiving care at a free clinic were used. Annual costs were $387,252. The benefit gained in quality-adjusted life years is estimated to be 57.47–203.94 yielding a return on investment ranging from $1,200,264-$8,948,184. Free clinics have sustained cost savings over time. Policies addressing this form of care are imperative.     

TRANSFORMATION OF A HISTOCOMPATIBILITY IMMUNOGEN INTO A TOLEROGEN

H-2 antigens on spleen cell membranes absorb antibody to H-2 antigens and induce both humoral and cellular responses. Liver cell membrane H-2 antigens by contrast also absorb antibody but do not influence cellular response and are tolerogenic for the humoral response. This paper demonstrates that syngeneic liver cells contain a substance which can transform the properties of allogeneic spleen cell membranes into those of allogeneic liver cell membranes, i.e., transform a humoral immunogen into a humoral tolerogen. The process appears to be accompanied by cleavage of an antigen component from the spleen membrane and hence to result in a structural change in the H-2 antigen.