Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1

BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.     

1 alpha(OH)D3 (ETALPHA) treatment and receptor studies in 16 patients with chronic and myeloproliferative disorders

10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily.     

Antibodies to interleukin-1 inhibit cytokine-induced proliferation of neonatal rat Schwann cells in vitro

Unfractionated cytokines have been shown to induce in vitro proliferation of neonatal rat Schwann cells but the nature of the mitogen(s) is not known. A mixture of rabbit antibodies specific for recombinant interleukin-1α (IL-1α) and interleukin-1β (IL-1β) inhibited Schwann cell proliferation induced by unfractionated human cytokines whereas antibodies to interleukin-2 (IL-2) and control IgG did not. However, purified human IL-1 and recombinant human IL-1α or β did not induce Schwann cell proliferation on their own.     

检测恶性淋巴瘤患者血清可溶性细胞间粘附分子—1的临床意义

目的　通过检测正常人、初治和治疗后完全缓解 ( CR)之恶性淋巴瘤患者血清可溶性细胞间粘附分子 - 1 ( s ICAM- 1 )水平 ,探讨其临床意义。方法　采用酶联免疫吸附法 ( ELISA)检测 2 5例正常人和 2 3例恶性淋巴瘤患者血清 s ICAM- 1含量。结果　初治恶性淋巴瘤患者血清 s ICAM- 1含量高于正常人 ( P <0 .0 1 )和 CR期恶性淋巴瘤患者 ( P <0 .0 5 ) ,而 CR期恶性淋巴瘤患者也高于正常人 ,但无显著性差异 ( P >0 .0 5 )。结论　检测血清 s ICAM- 1的含量对恶性淋巴瘤的诊断、病情观察及疗效判断可能有一定的临床意义。     

Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.     

Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy

We investigated the presence of anti-human T-lymphotropic virus type I (HTLV-I) IgM in sera and cerebrospinal fluid from patients with HTLV-I-associated myelopathy (HAM) by Western blot analysis. Analyses of 36 serum samples revealed that most patients (31/36; 86.1%) had anti-HTLV-I IgM, whereas only four of 23 (17.4%) HTLV-I carriers had it. In studies of cerebrospinal fluid, anti-HTLV-I IgM was detected in 24 of 36 (66.7%) HAM patients, whereas none was detected in nine HTLV-I carriers. The differences were statistically significant (p less than 0.01). These results suggest that persistent active replication of HTLV-I occurs in the central nervous system as well as in the peripheral blood of HAM patients, and may contribute to the development of HAM.     

Multidrug transport in human glioblastoma cells is inhibited by transforming growth factors type beta 1, beta 2, and beta 1.2

The transforming growth factors type beta 1, beta 2, and beta 1.2 suppress multidrug transport in human pat-1 glioblastoma cells and even in cells that strongly over-express mdr genes and are resistant to inhibition of multidrug transport by chemosensitizers. Thus, inhibition of multidrug transport by cytokines might be a new approach to increase cellular accumulation of chemotherapeutic agents in multidrug resistant glial tumor cells. Interestingly, a member of the more distantly related decapentaplegic subgroup of transforming growth factors, the bone morphogenetic protein BMP 2, did not inhibit multidrug transport.     

ABO血型与肝炎病毒感染关系的探讨

目的：探讨ABO血型与肝炎病毒感染的关系，方法：应用疾病关联分析方法对HBsAg和,抗－HCV阳性献血者与同期健康献血者的ABO血型资料进行比较分析。结果：ABO血型与HBsAg和抗－HCV阳性率之间无显著性相关关系（P＞0．05），结论：乙型肝炎和丙型肝炎病毒感染与ABO血型无显著性相关。     

蛇床子水提取液抑瘤作用的实验研究

目的 :研究蛇床子水提取液的体内抗肿瘤作用。方法 :通过 S180 肉瘤移植建立荷瘤小鼠模型 ,给予不同剂量蛇床子水提取液后观察 S180 荷瘤小鼠肿瘤生长曲线、血清唾液酸 (SA)、瘤重及小鼠生存天数的变化。结果 :蛇床子水提取液能明显抑制肿瘤生长 ,降低荷瘤小鼠血清 SA水平 ,0 .0 6mg/(g· d) ,0 .1 1 mg/(g· d)、0 .2 1 mg/(g· d)剂量组平均瘤重低于肿瘤对照组 (P<0 .0 5 ) ,抑瘤率依次为 2 3 .2 %、2 9.1 %和 2 4 .8%,且能延长荷瘤小鼠生存天数 (P<0 .0 1 ) ,动物生命延长率依次为 :2 6 .9%、3 4 .8%和 2 6 .6 %。结论 :蛇床子水提取液具有较强的抗肿瘤效应 ,有很好的利用前景 ,值得对其进行深入研究。