Targeting of "T" lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: role of different lymphocyte subsets.

In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCR alpha/beta+ and CD3+4-8-TCR gamma/delta+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4 + 8-TCR alpha/beta+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-alpha) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.     

维胺酯-β-环糊精包合物的研究

应用３因素８水平的均匀设计方法，优化出维胺酯－β－环糊精包合物最佳制备条件，所得包合物的包合率为９９．３％，其表观稳定常数为１３９４Ｍ－１．     

Point mutation in the parkin gene on patients with Parkinson’s disease

Summary To investigate the distribution of possible novel mutations from parkin gene in variant subset of patients with Parkinson’s disease (PD) in China and explore whether parkin gene plays an important role in the pathogenesis of PD, 70 patients were divided into early-onset group and late-onset group; 70 healthy subjects were included as controls. Genomic DNA from 70 normal controls and from those of PD patients were extracted from peripheral blood leukocytes by using standard procedures. Mutations of parkin gene (exon 1–12) in all the subjects were screened by PCR-single strand conformation polymorphism (SSCP), and further sequencing was performed in the samples with abnormal SSCP results, in order to confirm the mutation and its location. A new missense mutation Gly284Arg in a patient and 3 abnormal bands in SSCP electrophoresis from samples of another 3 patients were found. All the DNA variants were sourced from the samples of the patients with early-onset PD. It was concluded that Parkin point mutation also partially contributes to the development of early-onset Parkinson’s disease in Chinese. WANG Tao, male, born in 1961, Associate Professor This work was supported by grants from the key program of the special scientific project of Scientific & Technologic Agency of Hubei Province (Serial No. 2001AA308B01) and the Hygienic Research Project of Hygienic Agency of Hubei province (Serial No. WJ 01529).     

超声热疗临床应用的研究

目的：通过超声热疗配合常规放疗治疗晚期恶性肿瘤的临床研究，评价超声热疗的疗效及与疗效有关的加热参数。材料和方法： 对１７ 例晚期恶性肿瘤的１７ 个病灶用常规放疗加超声热疗。放疗用直线加速器外照射，每次２ Ｇｙ、周５ 次， 总剂量４０～７０ Ｇｙ。热疗在放疗后３０ ｍ ｉｎ 内进行，每周加热１～２ 次，每次加温时间 ６０ ｍ ｉｎ，６～８ 次一疗程。全例病人每次加温时实测肿瘤内温度。结果：在可评价的１３例中，ＣＲ ２３．１％ （３／１３）、ＰＲ ４６．２％ （６／１３）、ＮＣ ２３．１％ （３／１３）、ＰＤ ７．７％ （ １／１３） ， 有效率（ＣＲ＋ ＰＲ）为６９．３％ 。肿瘤中心部温度达到４２．５℃以上的累积时间和总加热次数是决定疗效的重要参数。在１７ 例患者的 ８９ 次加温中，副作用的发生率相对较低。结论：使用超声热疗配合放疗，只要实现满负荷加温，进一步提高肿瘤的局部控制率是完全可能的     

Glomus tumours of the hand and foot

Summary. Between 1982 and 1991 we treated 48 patients with a glomus tumour in the hand or foot. There were 42 women and 6 men, aged between 14 and 61 years. Forty-five tumours were in the subungual region and 41 were on the anterolateral aspect of a distal phalanx. The lesions presented with a classic triad of pain, tenderness and sensitivity to temperature, particularly cold. Excision of the tumour was curative.

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Resumé. Entre 1982 et 1991, 48 patients présentant une tumeur glomique de la main et du pied ont été traités dans notre département. Il y avait 42 femmes et 6 hommes, agés de 14 à 61 ans (moyenne 38 ans). 45 tumeurs étaient en situation sous-inguéale et 41 en situation latéro-palmaire de la phalange distale. 44 se situaient au niveau de la main et 4 au niveau du gros orteil. Ces lésions sont souvent non palpables fréquemment invisibles et habituellement indétectables à la radiographie. Cependant, le diagnostic est assez facile, lorsqu’existe la triade symptomatique: douleur, tumefaction molle et sensibilité au froid. L’excision complète après dissection soigneuse est le traitement adéquate. Le suivi des 48 malades a toujours montré une guérison complète.

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Accepted: 21 May 1996     

PLASMA PHOSPHOLIPASE A2 ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION

1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain.     

Hemodynamic study of external counterpulsation with left and right cardiac catheters in 15 cases]

The hemodynamic changes of 15 cases during external counterpulsation with left and right cardiac catheters were reported. The results showed that the diastolic pressure at the root of the aorta was remarkably increased, the peak value (countercurrent pressure) was 8.02 +/- 2.05 kPa higher than the diastolic pressure before counterpulsation; the aortic systolic pressure during counterpulsation was slightly decreased with a mean value of 0.81 kPa; there was no apparent change in the central venous pressure and pulmonary arterial pressure; pulmonary arterial wedge pressure was slightly reduced during counterpulsation. All the above data are useful in showing the improvement of cardiac and brain perfusion volume and clarifying its mechanism.     

Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

BACKGROUND: Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. OBJECTIVES: This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. RESULTS: While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. CONCLUSION: The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.