Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM

Summary An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies – islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6 % IDDM and 16.1 % NIDDM patients had GADab, and 20.1 % and 4.8 %, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a sub-group of patients with latent or slow-onset IDDM. Half (53 %) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM. [Diabetologia (1997) 40: 1425–1430] Received: 11 March 1997 and in revised form: 13 May 1997     

Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.     

Levels of soluble HLA‐G in amniotic fluid are related to the sex of the offspring

Although HLA‐G is thought to play a modulatory role in the immune system, its function and expression require to be elucidated. We analysed soluble HLA‐G levels in mid‐trimester amniotic fluid (n = 64) from uncomplicated pregnancies. We found a decrease in soluble HLA‐G levels for female offspring as compared to male offspring (P < 0.007). This may be a consequence of the immuno‐modulatory capacity of HLA‐G.     

Caffeine and automaticity in encoding prelexical tasks: Theory and some data

The present study examined the integration of the automaticity theory and Yerkes-Dodson law using a three-factor design-Automaticity (automatic and nonautomatic behaviors), Drug (caffeine-high arousal and placebo-low arousal), and Task Difficulty (low and high levels of difficulty). A specific significant three-way interaction was predicted; that is, caffeine facilitates low difficity nonautomatic performance relative to placebo but decreases high difficulty nonautomatic performance relative to placebo, and caffeine does not affect automatic performance across levels of task difficulty relative to placebo. Three variations of the automatic/nonautomatic distinctions were used to examine its effects on the encoding and prelexical paradigm of information processing, thereby permitting a comparison of the predicted three-way interaction. The tasks were frequency monitoring (automatic)/free recall (nonautomatic) task in Experiment 1, and a variant (of task in Exp. 1) in Experiment 2 and an alternate task (vs tasks in Exps. 1 and 2) in Experiment 3. The results of Exp. 1 showed instances of the three-way interaction and thus, provides support for the proposed integration of the theory of automaticity and Yerkes-Dodson law. Overall, the results of the three experiments agreed with past findings. That, automatic performance is unaffected by empirical manipulation such as drugs and nonautomatic performance is affected by the manipulation of arousal (caffeine) in Exps. 1 and 2 and task demands (difficulty) in Exps. 2 and 3. Automatic performance, however, is not insensitive to all manipulations; Exps. 1 and 3 showed that task demands (difficulty) significantly affected it. So, there is more than one form of automaticity. In sum, the present study showed a method of comparing various forms of automaticity within a single experiment and using a pharmacological agent (drug) to test concepts of automaticity and other mechanisms of information processing.     

Isolation of endothelial cells from human first trimester decidua using immunomagnetic beads.

A technique was developed for the isolation of purified endothelial cells from first trimester decidual tissue, using QB End/40-coated magnetic polystyrene beads (Dynabeads). QB End/40 is an endothelial-specific monoclonal antibody which reacts with the coagulation cascade co-factor, thrombomodulin. Small endothelial cell aggregates were released from first trimester decidua by the sequential use of collagenase and trypsin. This dissociation method yielded 15-20% endothelial cells which were further purified to greater than 90% homogeneity by rosetting with QB End/40-Dynabeads. Cultures of purified decidual endothelial cells provide a useful tool for investigating cell-cell interaction in the first trimester placental bed.     

Management of advanced stage intermediate grade non-Hodgkin's lymphomas.

The treatment result of 271 cases of advanced stage intermediate grade lymphoma were reviewed. Ninety-four patients received CHOP chemotherapy, 45 BACOP and 17 m-BACOD. The clinical characteristics of the three groups of patients were comparable. Patients receiving CHOP had a complete response (CR) rate of 60 per cent, the disease-free survival of CR patients was 31 per cent at 5 years. The overall survival following CHOP chemotherapy was 38 per cent at 5 years. The use of the BACOP or m-BACOD regime did not appear to improve significantly the prognosis of these patients. Clinical staging, B symptoms, age and serum lactate dehydrogenase level were the most important independent prognostic factors.     

Long-term follow-up of patients receiving salvage chemotherapy for intermediate and high grade non-Hodgkin's lymphomas.

This is an analysis of the long-term follow-up data of 99 patients receiving HOAP-Bleo, IMVP-16 and PAC as salvage chemotherapy for refractory or relapsed intermediate or high grade non-Hodgkin's lymphomas. Most of the patients received HOAP-Bleo or PAC following failure of initial chemotherapy and IMVP-16 was used mainly for HOAP-Bleo failures. The longest follow-up time of the surviving patients was 108 months. Twenty-two and 29 per cent of the patients survived beyond 2 years following HOAP-Bleo and PAC respectively. The treatment outcome following IMVP-16 was worst with a 2-year survival of only 5 per cent, as it was used mainly following HOAP-Bleo failures. Although the prognosis of these refractory or relapsed cases are poor, salvage treatment is still worthwhile as a small proportion of these patients may have long-lasting remissions and occasional patients may be cured. Newer approaches such as autologous bone marrow transplantation should be compared with current salvage chemotherapy regimens.     

Evaluation of liver function and lipid metabolism following Norplant-2 rods removal

The effect of Norplant-2^R rods on liver function and lipid metabolism was evaluated in 100 Singaporean women. As with the Norplant six-capsule, the only change noted in liver function was that of a significantly elevated bilirubin, which was within the normal clinical range for the local population.As regards lipid metabolism, the mean values for total triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol seen at the end of five years of Norplant-2 rod use and six months postremoval were similar to the preinsertion mean. As a result, the HDL-cholesterol/total-cholesterol-HDL-chlesterol and LDL-cholesterol/HDL-cholesterol ratio remained fairly constant. This indicates that the use of Norplant-2 rods does not directly contribute to cardiovascular risk.

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Resumen El efecto de las barras Norplant^R-2 sobre la función hepátia y el metabolismo de los lípidos se evaluó en 100 mujeres de Singapur. Al igual que en el sistema Norplant^R de seis cápsulas, el único cambio observado en la función hepática fue un aumento significativo de la bilirrubina, que sin embargo continuaba comprendida en la gama clínica normal de la población local.En cuanto al metabolismo de los lípidos, los valores medios de los triglicéridos totales, colesterol, colesterol LDL y colesterol HDL observados al cabo de cinco años de utilización de barras Norplant-2 y seis meses después de ser éstas retiradas eran similares a los valores anteriores a la inserción. Estos resultados hacen pensar que la utilización de barras Norplant-2 no contribuye directamente al riesgo cardiovascular.

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Resumé L'effet des bâtonnets Norplant^R-2 sur la fonction hépatique et le métabolisme des lipides a été évalué chez 100 femmes à Singapour. Comme pour le système Norplant^R à six capsules, le seul changement constaté dans la fonction hépatique était une élévation significative de la bilirubine, qui restait néanmoins à un niveau clinique normal pour la population locale.En ce qui concerne le métabolisme des lipides, les valeurs moyennes des triglycérides totaux, du cholestérol, des cholestérol-LDL et cholestérol-HDL, examinés à la fin de cinq années d'utilisation des bâtonnets Norplant-2 et six mois après le retrait, étaient semblables aux niveaux d'avant l'insertion. En conséquence, les rapports cholestérol-HDL/cholestérol total-cholestérol-HDL et cholestérol-LDL/cholestérol-HDL étaient restés assez constants. Ces résultats laissent penser que l'utilisation des bâtonnets Norpant-2 ne contribue pas directement au risque cardiovasculaire.

     

ENDOTHELIAL DYSFUNCTION EXACERBATES THE IMPAIRMENT OF RELAXATION BY LYSOPHOSPHATIDYLCHOLINE IN PORCINE CORONARY ARTERY

1. Current evidence suggests that lysophosphatidylcholine (LPC), a component found in oxidized low-density lipoprotein (Ox-LDL), inhibits endothelium-dependent relaxation (EDR) mediated by endothelium-derived relaxing factor (EDRF) and endothelium-derived hyperpolarizing factor (EDHF). An objective of the present study was to characterize the roles of the different elements of EDR in LPC-induced impairment within the porcine coronary artery. Concomitantly, we sought to determine whether impairment of one component of EDR would increase the sensitivity of the endothelium to LPC. 2. Bradykini. (0.1 nmol/L-0.3 μmol/L) relaxed U46619 (30 nmol/L)-precontracted porcine coronary artery rings in a concentration-dependent manner. A reduction in the bradykinin-elicited response was observed in N^G-nitro-L-arginine methyl ester (L-NAME; 300 μmol/L)- and ouabain (50 μmol/L)-treated rings. Pretreatment with LPC (20 μmol/L), which on its own had no effect on normal endothelial relaxation, resulted in further inhibition of EDRF- and EDHF-induced relaxations. 3. Our results demonstrate that EDRF and EDHF are the primary mediators of EDR in the porcine coronary artery. Our data also show that while a low concentration of LPC (20 μmol/L) does not impair EDR, it can evoke vascular dysfunction following blockade of either the effects of EDRF or EDHF. Therefore, these data suggest that the partially damaged vascular endothelium could be more sensitive to threshold levels of this atherogenic phospholipid.     

c-myc protein in normal tissue. Effects of fixation on its apparent subcellular distribution.

The c-myc protein is thought to be a DNA-associated nuclear protein. However, immunohistochemical studies on normal or tumor tissues have shown conflicting findings on its subcellular distribution. By using various fixation procedures on cytospin preparations of HL60 cells, the authors found the subcellular distribution of the c-myc protein to be dependent on the method of fixation. When studying mouse tissues in frozen sections using a biotinylated monoclonal antibody against the c-myc protein, they found the protein to be widely distributed in various normal adult mouse tissues, in most cases localized to the nucleus. However, when these tissues were studied after formalin fixation and paraffin embedding, a loss of nuclear staining was observed concurrent with the appearance of c-myc protein immunoreactivity in the cytoplasm. It is concluded that immunohistochemical studies on the expression of this oncogene should take into consideration the effects of fixation when its subcellular distribution is being examined.