CAMPATH-1H IN RHEUMATOID ARTHRITIS--AN INTRAVENOUS DOSE-RANGING STUDY

Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATHis a trademark of Glaxo-Wellcome group companies, registeredin the US Patent and Trademark Office) over 5 or 10 days inan open, uncontrolled study. Following therapy, patients weremonitored for adverse effects and disease activity for 6 months.Therapy was associated with prolonged peripheral blood lymphopeniain all dosing cohorts. During the month immediately followingtherapy, lymphopenia was most profound in the 400 mg cohorts.The first dose of monoclonal antibody (Mab) was associated witha ‘flu’-like syndrome, more pronounced at higherinitial doses. One patient developed haemolytic-uraemic syndrome.There were a number of dose-related infections during the earlypost-treatment period and one fatal opportunistic infectionwhich followed additional immunosuppressive therapy. Antiglobulinresponses developed in 9 of 31 patients tested. The majorityof patients showed symptomatic improvement following therapyand 20% of patients maintained a 50% Paulus response at 6 months,all of whom were in the 250 or 400 mg cohorts. CAMPATH- 1H appearsto be an effective treatment for RA. Allowing for the smallnumber of patients treated, infections were more common withhigher doses, although this was not true for adverse eventsoverall, and therapeutic responses were more sustained at higherdosing levels. The broad specificity of CAMPATH- 1H may be appropriatefor the immunotherapy of RA and future studies should aim todefine a dose with an optimal therapeutic ratio. KEY WORDS: CAMPATH-1H, Rheumatoid arthritis, Immunotherapy, Monoclonal antibody, Antiglobulin response     

多种血管新生指标在肝细胞肝癌中的表达及敏感性比较

目的　探讨血管新生指标CD34、CD31、vWF、Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌(HCC)中的表达及意义 ,同时比较上述几种血管新生因子与增殖细胞核抗原 (PCNA)、病理指标及预后的相关性 ,以便筛选出有效的临床预后指标。方法　采用免疫组化方法 ,对 5 3例肝细胞肝癌的标本进行CD31、CD34、vWF、Ⅳ型胶原纤维及层粘连蛋白的染色、计数 ,并用检测数据与患者的临床资料进行统计分析。结果　统计染色的血管面积后发现 ,CD34与多种临床病理指标无相关性 ;CD31与肝内门静脉浸润相关 ;vWF与肿瘤的TNM分期及肝内门静脉浸润呈正相关 ;CollⅣ与肝内门静脉浸润呈正相关、与术后生存期呈负相关 ;Lam与肝硬化及术中出血量呈负相关、与术后生存期呈正相关。PCNA与肿瘤TNM分期有关。结论　在HCC中 ,CollⅣ、vWF、及CD31为肝细胞肝癌的有效血管新生及预后指标 ;Lam则与肝硬化及术中出血相关 ;PCNA指数肿瘤分期有关 ;CD34不能用作血管新生或预后指标     

Interaction of Ia antigen-bearing polymorphonuclear leukocytes and murine splenocytes

Polymorphonuclear leukocytes (PMN) were induced in the peritoneum of a Balb/c mouse by ip injection of Fusobacterium nucleatum (FN) (greater than 95% PMN). A subpopulation of PMN harvested bore Ia surface antigens and stimulated a mixed lymphocyte reaction (MLR) when cultured with C57B1/6J splenocytes. The reaction was blocked by a short prior incubation of PMN with anti-Ia antibody or PMN cell depletion by the same antibody plus complement. The Ia antigen-bearing PMN were capable of antigenic modulation since incubation of PMN for 24 h rendered the cells incapable of stimulating an MLR. The Ia antigen-bearing PMN produced a soluble material that enhanced the phytohemagglutinin (PHA) response of murine splenocytes and the active material was a product of live cells since the supernatants contained no detectable lactate dehydrogenase activity. The data suggest that murine PMN subpopulations, defined by surface Ia antigen, can modulate mitogenic responses by production of an enhancing factor(s).     

The use of infrared thermography in the evaluation of oral lesions

We have attempted to quantify the degree of inflammation associated with oral lesions through the use of infrared thermography, since the increased vascularity associated with inflamed tissue might result in measurable increases in surface temperature. This would provide a better measure of the relief of pain and inflammation associated with cancer chemotherapy mucositis by an antiinflammatory drug such as benzydamine hydrochloride than the subjective pain scales now employed. One subject with normal oral mucosa and three subjects with oral lesions of varying aetiology were studied with a Hughes Series 4000 PROBEYE thermal video system utilizing an infrared imager and microprocessor. A 35-mm camera was used to obtain a colour photograph of each subject. Multiple thermograms were made in a temperature range of 30.0 degrees C to 34.2 degrees C at a sensitivity of 0.2 degrees C. Photographs were taken on different occasions to determine whether the temperature readings could be duplicated and to test the accuracy of each reading. The normal surface temperature of the control subject's mucosa was found to be significantly cooler than clinical areas of inflammation in patients with lesions induced by chemotherapy. The temperature of the areas of stomatitis was remarkably consistent (Subject C means 33.7 degrees C; Subject D means 33.9 degrees C). Interestingly, the necrotic center of a traumatic ulcer inhibited measurement of an underlying inflamed base and was thus equivalent in temperature to the normal control (Normal means 31.9 degrees C; Subject B necrotic lesion means 31.7 degrees C). These results suggest that infrared thermography may represent a means to assess quantitatively the degree of mucosal inflammation. Additional studies are in progress.     

Expression of a fibrinogen fusion peptide in Escherichia coli: a model thrombin substrate for structure/function analysis

The initial event in fibrin clot formation is the thrombin-catalyzed cleavage of the A alpha chain of human fibrinogen. Most of the information required for thrombin recognition and cleavage of the A alpha chain lies in the amino terminal 51 residue CNBr fragment. By selective modification of residues in this region, we probed the features that participate in thrombin interactions. We constructed a vector which expressed a tripartite protein (tribrid) consisting of amino acids 1 to 50 of the A alpha chain followed by 60 amino acids of chicken collagen and the beta-galactosidase protein from Escherichia coli. Cell lysates run on NaDodSO4-polyacrylamide gels contained the predicted band of molecular weight (mol wt) 125,000. The tribrid reacted with a monoclonal antibody, Mab-Y18, which recognizes the amino terminus of the A alpha chain. When cell lysates were incubated with thrombin, FPA was released. By including one heterogeneous oligonucleotide in the construction, we generated plasmids that encoded three specific amino acid substitutions. Surprisingly, changing Gly14 to Val did not alter thrombin cleavage, although recognition by Mab-Y18 was lost. Substitution of lie for Arg23 did not alter either thrombin cleavage or monoclonal recognition. Substitution of Leu for Arg 16 altered thrombin cleavage; unexpectedly, recognition by Mab-Y18 was not changed.     

Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities

Ninety-seven children who were diagnosed with acute lymphoblastic leukemia before 10 years of age and treated with chemotherapy alone, chemotherapy plus 1800-cGy cranial irradiation (RT), or chemotherapy plus 2400-cGy RT were evaluated for effects of therapy on dentofacial development. All patients were seen at least 5 years postdiagnosis. Dental abnormalities were determined from panoramic radiographs, and craniofacial evaluations were made from lateral cephalometric radiographs. Ninety-one (94%) of all patients and 41 (100%) of patients younger than 5 years of age at diagnosis had abnormal dental development. The severity of these abnormalities was greater in children who received treatment before 5 years of age and in those who received RT. Observed dental abnormalities included tooth agenesis, arrested root development, microdontia, and enamel dysplasias. Craniofacial abnormalities occurred in 18 of 20 (90%) of those patients who received chemotherapy plus 2400-cGy RT before 5 years of age. Mean cephalometric values of this group showed significant deficient mandibular development. The results of this study suggest that the severity of dentofacial-developmental abnormalities secondary to antileukemia therapy are related to the age of the patient at the initiation of treatment and the use of cranial RT.