IDENTIFICATION AND CHARACTERIZATION OF THE HUMAN HEPATIC ANDROGEN RECEPTOR

Human liver contains components in both cytosol and nucleosol which bind the synthetic testosterone derivative, mibolerone, with a high affinity, moderate capacity and a high specificity for androgens. Gel filtration chromatography shows two binding components, a high molecular weight component (mol wt. 250 000) present in cytosol alone and a low molecular weight component (mol wt. 75 000) present in cytosol and nucleosol. Human liver contains the classical androgen receptor.     

REVERSE RELATIONSHIP BETWEEN MITOGEN ACTIVATED PROTEIN KINASE AND HUMAN PLATELET AGGREGATION

The role of MAPK in platelets was investigated. In human platelets maintained at 4°C for 2 hr, the MAPK activity increased (～ 2 fold) when compared to those maintained at 37°C. When aggregation was monitored under these conditions, the platelets maintained at 4°C or 15°C showed an 85% and 71% decrease respectively to thrombin (0.5 U/ml for 1 min) induced aggregation. When the platelet cytosol was maintained at 4°C and assayed for MAPK activity, the MAPK activity decreased significantly, indicating that the observed effects are seen in intact platelets only, and are not due to temperature effects on the assay. When platelets maintained at 4°C or 15°C (for 2 hrs) were transferred to 37°C, the MAPK activity decreased to levels observed in platelets maintained throughout at 37°C and was thus reversible. Therefore, it is concluded that a possible reverse relationship between MAPK and platelet aggregation plays a role in platelet responses.     

胃癌细胞凝集素受体变化与淋巴结转移的关系

本文采用ABC酶标技术，对63例胃癌组织及21例转移淋巴结进行菜豆凝集素（PHA）和花生凝集素（PNA）的亲和组化染色，观察胃癌原发灶与淋巴结转移灶的凝集素受体变化。结果示；（1）伴淋巴结转移的胃癌原发灶与PHA和PNA结合的阳性率(分别为90．3％和87．1％）高于以无淋巴结转移的胃癌原发灶（71．8％和65．6％）。（2）淋巴结转移组的PHA与PNA阳性强度以强阳性为主；无淋巴结转移组则以弱阳性和中等阳性为主。（3）淋巴结转移灶与胃癌原发灶的阳性强度基本一致，符合率为PHA57．1％，PNA71．4％。结果表明胃癌原发灶中凝集素受体的变化与淋巴结转移的状况密切相关，胃癌原发灶中带有PHA和（或）PNA受体的癌细胞具有转移的潜力。     

前列腺素E1和丹参对老年人血小板聚集率影响的比较

目的：观察比较前列腺素E1脂微球载体制剂（Lipo PGE1)和丹参对老年人血小板聚集率的影响。方法：将38例老年心、脑血管疾病患，在均衡原则下随机分成两组。一组予前列腺素E1脂微球载体制剂（Lipo PGE1)10μｇ／天，共１４天，另一组予丹针剂12ml/天，共14天，比较两对血小板聚集率的影响。结果：前列腺素E1组降低血小板聚集（P＜0．01），丹参组降低血小板聚集率（P＜0．05）。结论：前列腺素E1脂微球载体制剂（Lipo PGE1)和丹参都能抑制血小板聚集，而Lipo PGE1更有效，无一例发生静脉炎。但从效价比出发，丹参更适合国情。     

碘与甲状腺肿流行规律的调查研究

通过大面积流行病学调查和动物实验证实,碘与低碘或高碘甲状腺肿的流行都有密切的关系,这种关系表现为“U”形曲线形式。水碘含量(ln 10x)与甲状腺肿患病率所计算之方程式为:(?)=78.60-27.62x+2.33x~2。根据我国地方性甲状腺肿防治工作标准,水碘下限值为5μg/l,上限值为300μg/l。尿碘(ln5x)与甲状腺肿患病率计算之方程式为:(?)=214.26-62.84x+4.53x~2。其下限值为50μg/gCr,上限值为800μg/gCr。     

SOLUBILIZATION AND PARTIAL CHARACTERIZATION OF A PHYTOHEMAGGLUTININ RECEPTOR SITE FROM HUMAN ERYTHROCYTES

Trypsin treatment of human erythrocytes releases a soluble glycopeptide which binds to phytohemagglutinin and abolishes the erythroagglutinating and lymphocyte-stimulating properties of this molecule. The glycopeptide has been purified by alkaline borohydride treatment, proteolytic digestion, gel filtration, and DEAE-cellulose chromatography. The most highly purified glycopeptide has a molecular weight of about 2,000. The specificity for binding to phytohemagglutinin resides in the oligosaccharide portion of the molecule with the determinant sugar being a galactose residue which is penultimate to a N-acetylneuraminic acid in some chains and uncovered in others. The glycopeptide is about 3,000 times more potent than either N-acetylgalactosamine or galactose in inhibiting the mitogenic response of lymphocytes induced by phytohemagglutinin.     

尼群地平治疗高血压患者血药浓度与抗血小板聚集及降压作用的关系

２８例中年高血压患者分成两组，每组１４例，分别１次口服尼群地平０．５ｍｇ／ｋｇ及０．２５ｍｇ／ｋｇ，服药后定时测血药浓度、血小板聚集和血压。结果显示，血药浓度高峰和血压最低值在服药后２ｈ，血药浓度与血小板聚集及血压值呈负相关。两组药量对血小板聚集影响无明显差异，提示０．２５ｍｇ／ｋｇ即对高血压患者的血小板聚集有明显影响，但降压作用较差。作者认为高血压Ⅱ期患者口服尼群地平量以０．５ｍｇ／ｋｇ较为合适。     

ANALYSIS OF THE RELATION BETWEEN ALOPECIA AND RESISTANCE TO 1,25-DIHYDROXYVITAMIN D

Alopecia is a frequent feature in hereditary resistance to (1,25(OH)2D). We sought insight into this feature by analysing data from affected members of 30 kindreds. We assessed indices of mineral metabolism in one group with normal hair compared with a group with alopecia. Hereditary resistance to 1,25(OH)2D was diagnosed at an earlier age in alopecic patients (0.9 vs 3.3 years, P less than 0.05); this reflected late presentation of metabolic bone disease in some cases with normal hair and could not be attributed to early diagnosis resulting from the striking feature of alopecia. For untreated subjects, serum concentrations of calcium and 1,25(OH)2D were similar in both groups of patients. During calciferol therapy, however, the cases with alopecia showed lower serum calcium (1.9 vs 2.4 mmol/l, P less than 0.005), but higher serum 1,25(OH)2D (2900 v 340 pg/ml, P less than 0.005). Hair status did not predict the type of defect identified with cultured skin fibroblasts but did correlate with responsiveness of 25(OH)D 24-hydroxylase to 1,25(OH)2D3 in those cells. Cells from seven of eight kindreds with alopecia showed no 24-hydroxylase response to high doses of 1,25(OH)2D3 while cells from five of six kindreds with normal hair showed a 24-hydroxylase response to high doses of 1,25(OH)2D3. We conclude that in cases with hereditary resistance to 1,25(OH)2D alopecia reflects the more severe grades of this resistance based upon earlier age at time of diagnosis, lower potential for calcaemic response to calciferols, and lower potential for 24-hydroxylase response to 1,25(OH)2D3 by cultured skin fibroblasts.     

CHANGES IN CENTRAL OPIOID RECEPTOR BINDING IN RELATION TO INFLAMMATION AND PAIN IN PATIENTS WITH RHEUMATOID ARTHRITIS

A group of four patients with RA were examined to test the hypothesisthat there is a change in the endogenous opioid system in thebrain during inflammatory pain. Regional cerebral opioid receptorbinding was quantified using the opioid receptor antagonist[¹¹C] diprenorphine and positron emission tomography (PET).In the four patients studied in and out of pain, significantincreases in [¹¹C]diprenorphine binding were seen in associationwith a reduction in pain. Increases were seen in most of theareas of the brain that were sampled apart from the occipitalcortex. Significant region-specific increases over and abovethe more generalized changes were also seen in the frontal,cingulate and temporal cortices in addition to the straightgyrus. These findings are consistent with the hypothesis thatthere are substantial increases in occupancy by endogenous opioidpeptides during inflammatory pain. KEY WORDS: Rheumatoid arthritis, Pain, Inflammation, Positron emission tomograph, Opiate receptor, [¹¹C] diprenorphine, Brain     

抗人雌激素受体单抗的制备及鉴定

分别采用部份纯化的人乳腺癌雌激素受体（ｈＥＲ）及合成的与ｈＥＲ分子中ＤＮＡ结合区序列相同的多肽（ＡＴ３）作免疫原。经用Ｋｏｈｌｅｒ和Ｍｉｌｉｓｔｅｉｎ杂交瘤技术，制备出７株抗人雌激素受体单体（１Ｈ１２、２Ｄ７、ＡＴ３～２７等），并经ｓｅｐｈａｃｒｙｌ凝胶层析、免疫沉淀反应和间接免疫荧光标记法作特异性鉴定。其中一株高亲和力、高特异性的单抗（１Ｈ１２）在免疫沉淀反应中与人乳腺癌雌激素受体的特异性结合率达４６．２±２２．０％，并用该单抗成功地进行了人乳腺癌组织冰冻切片的ｈＥＲ间接免疫荧光标记。     

人甲状腺过氧化物酶单克隆抗体的制备与鉴定

以亲和纯化的人甲状腺过氧化物酶作免疫原,用经典的杂交瘤技术制备出29株抗人甲状腺过氧化物酶单克隆抗体（TPOmAb）,探讨了甲状腺微粒体抗体（TMAb）与TPObmAb之间的关系。发现TMAb对TPObmAb与~（125）I-hTPO的结合抑制性呈显著的量-效关系（r=0.982,P<0.001）;经间接免疫荧光技术证实原代培养的人甲状腺细胞膜表面存在hTPO,而FRTL-5细胞膜表面不存在hTPO,说明所制备的TPObmAb为hT-PO特异性单克隆抗体。     

THE CARDIOVASCULAR EFFECT OF VASOPRESSIN IN RELATION TO ITS PLASMA CONCENTRATION IN MAN AND ITS RELEVANCE TO HIGH BLOOD PRESSURE

The cardiovascular response and the changes of plasma arginine vasopressin (AVP) concentration following graded doses of AVP infused intravenously have been defined in six normal young men.The same measurements were also made during fluid deprivation in a patient with both nephrogenic diabetes insipidus and systemic hypertension. When, following AVP infusion, mean diastolic arterial pressure increased from 72·3 mmHg (SEM) to 78·2 mmHg (SEM) in the normal subject group, mean plasma AVP increased by 14·5 fmol/ml. When the patient was deprived of water, diastolic pressure increased, despite the fluid loss, from 90 to 105 mmHg, with a comparable increase of plasma AVP concentration of 15·3 fmol/ml. Further increases of plasma AVP concentration in either the normal subjects or in the patient were not associated with further increments of arterial pressure. We suggest that under pathophysiological circumstances in man plasma AVP concentrations may achieve levels which have a significant cardiovascular effect.     

IMPORTANCE OF HELICES A AND H IN OXYGEN BINDING DIFFERENCES BETWEEN BOVINE AND HUMAN HEMOGLOBINS*

Human and bovine hemoglobins (Hbs) exhibit several functional differences. They have a similar oxygen affinity in the presence of 2,3-diphosphoglycerate (2,3-DPG); however, bovine Hb has a greatly diminished 2,3-DPG effect, which itself is chloride dependent. The question is to determine whether these differences have a common structural origin, or whether they evolved in an independent fashion. The decreased 2,3-DPG effect can be partially reproduced by mutations at the effector binding sites, substituting the βNA1 valine–NA2 histidine present in human Hb with a methionine. While changes of human Hb at these sites could provoke the bovine characteristic of the lower 2,3-DPG effect, the oxygen affinities of these mutated Hbs were not as low as that of the bovine Hb. Modifications responsible for tertiary structural modifications of helix A in human Hb might help shift the N-terminal methionine position, thereby locking helix A in place. We replaced the residues proline β5(A2), arginine β104(G6), and tyrosine β130(H8) of human Hb by the residues present in bovine β-globin, namely alanine, lysine, and phenylalanine, respectively. These mutations did not allow us to obtain a low oxygen affinity recombinant Hb (rHb). This indicates that other factors also influence oxygen binding and the effects are only partially coupled.     

PROTEIN-A PURIFIED HUMAN IMMUNOGLOBULINS: A COMPARISON OF THYROID STIMULATING AND THYROTROPHIN RECEPTOR BINDING ACTIVITIES IN THYROTOXICOSIS

Protein-A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein-A Sepharose CL-4B from sera of euthyroid subjects had little effect in this system. The majority of Protein-A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in procine thyrocytes in a dose-dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4.35 (0.8 to 7.5, % stimulation over control) and 2.7 (-9.3 to 8.6, TBII index) for the bioassay and radioreceptor assay respectively. A value of greater than 10.0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83.6%) compared to 60 in the radioreceptor assay (82.2%). There was a positive correlation between the two assays (r = 0.821, P less than 0.001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine-131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P less than 0.05) in the iodine-131 group than in the patients treated with carbimazole. Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related.     

ANOMALOUS BINDING CHARACTERISTICS OF HUMAN THYROXINE BINDING GLOBULIN DUE TO A DILUTION-DEPENDENT SEPARATION ARTEFACT

Contrary to the accepted view, a recent study using Sephadex column separation suggested that thyroxine binding globulin (TBG) binds T4 and T3 with similar affinity, but with a much larger capacity for T4 than T3. We have evaluated this finding by comparing this separation method with equilibrium dialysis, taking account of the effect of serum dilution with each method. Estimates of free T4 fraction by equilibrium dialysis (with magnesium chloride precipitation) were valid over a wide range of serum dilutions. In contrast, Sephadex column separation gave a major overestimate of free hormone (underestimate of binding) in less diluted serum, indicating that this method cannot be used to establish a value for T4 affinity independent of serum dilution. Such a systematic error will result in a greater underestimate of affinity for the ligand with higher affinity when two ligands are compared at a single serum dilution. By equilibrium dialysis at 37 degrees C, the affinity of T4 for TBG was approximately 13-fold higher than that of T3, while the capacity of TBG for both T4 and T3 was close to the concentration of immunoreactive TBG. The previous report of similar T4 and T3 affinities appears to be due to a dilution-dependent underestimate of T4 affinity inherent in Sephadex column separation. Direct comparison of binding kinetics of various ligands requires a separation method that is valid over a wide range of binding protein concentrations.