Phorbol ester synergizes with Ca2+ ionophore in activation of protein kinase C (PKC)alpha and PKC beta isoenzymes in human T cells and in induction of related cellular functions.

Studies described herein were designed to examine the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA), and a Ca2+ ionophore (ionomycin), singly or in combination, on the activation and expression of the Ca(2+)-dependent protein kinase C (PKC) isoenzymes (alpha, beta and gamma) at the protein and messenger RNA (mRNA) levels in T cells. These two agents induce the activation and proliferation of T lymphocytes by mimicking the action of inositol phospholipid-derived second messengers normally generated by triggering of the antigen-specific T-cell receptor (TcR)/CD3 complex. TPA-induced T-cell proliferation, expression of interleukin-2 receptor-alpha subunit (IL-2R alpha) and transferrin receptor, CD3 down-regulation and, lastly, the cytosol-to-membrane PKC translocation (determined by an enzymatic assay or by immunoblotting with a cross-reactive anti-PKC peptide antibody) were all facilitated by ionomycin. Immunoblots with isoenzyme-specific anti-PKC monoclonal antibodies demonstrated expression of immunoreactive PKC alpha, PKC beta and PKC gamma proteins that were translocated to the membrane upon TPA plus ionomycin stimulation. Resting T cells expressed abundant levels of mRNA for PKC alpha and PKC beta, but very low levels (relative to brain) of PKC gamma. TPA increased by two- to threefold the expression of PKC beta, but not of PKC alpha or PKC gamma, mRNA within 12 hr of stimulation. Ionomycin synergized with TPA in increasing the expression of PKC alpha and PKC beta mRNA. The two agents also synergized in inducing expression of additional activation/growth-associated genes, namely the c-myc protooncogene, ornithine decarboxylase (ODC) and IL-2R alpha. Ionomycin alone was inactive (or marginally active) in all of these assays. The translocation of distinct Ca(2+)-dependent PKC isoenzymes to the membrane and the up-regulation of PKC alpha and beta mRNA suggest that at least these two isoenzymes are involved in discrete steps of the pathway leading to T-cell activation and proliferation. Moreover, the combined effects of TPA and ionomycin on T-cell function and cell-surface antigen expression appear to be due, at least in part, to their synergistic activation of distinct PKC isoenzyme(s).     

Studies of neutrophil chemotactic factor of anaphylaxis in metabisulfite sensitivity

The mechanism(s) of adverse reactions to sulfites remains unclear. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed single-blind, placebo-controlled oral aqueous challenges with potassium metabisulfite in 13 patients with histories suggestive of sulfite sensitivity. Ten patients were also skin tested with potassium metabisulfite at 10 mg/mL and all had negative reactions. Serum samples were obtained from all the patients before the challenge and for 180 minutes after the challenge. The samples were tested for the presence of neutrophil chemotactic factor of anaphylaxis, using both a 51chromium microchamber chemotaxis assay and a leukocyte polarization technique. Six of 13 patients had positive challenges as defined by a fall equal to or greater than 20% in their forced expiratory volume in one second. No significant increase in neutrophil chemotactic factor activity was detected in the postchallenge serum samples from patients who experienced positive or negative challenges. We conclude that sensitivity to aqueous metabisulfite is not associated with mast cell degranulation in metabisulfite skin test-negative patients.     

Histamine modification of spontaneous rate and rhythm in infarcted canine ventricle

1. Histamine (10^?3 M) increased the spontaneous rate similarly in isolated preparations of normal left ventricular tissue from control, i.e. normal and sham-operated, dogs (control preparations) and in preparations consisting of normaland contiguous infarcted left ventricular tissue from dogs with subacute, i.e. 24 hours after left coronary artery ligation, myocardial infarction (infarcted preparations).
2. Histamine (10^?3 M) markedly enhanced the irregular rhythm of infarcted preparations.
3. The H₁-receptor antagonist, chlorpheniramine (10^?4 M), and the H₂-receptor antagonist, cimetidine (10^?3 M), antagonized the effects of histamine (10^?3 M) on the spontaneous rate of both control and infarcted preparations.
4. The H₁-receptor agonist, 2-pyridyl ethylamine (PEA, 10^?4 M), increased the spontaneous rate of control and infarcted preparations; these effects were antagonized by chlorpheniramine (10^?4 M). The H₂-receptor agonist, dimaprit, had no effect.
5. Similar to histamine (10^?3 M), PEA (10^?4 M) enhanced the irregular rhythm of infarcted preparations; dimaprit had no effect.
6. High local concentrations of histamine may occur in poorly perfused ischemic tissue. The enhancement of irregular rhythm produced by histamine, and the specific H₁-receptor agonist, PEA, leads us to suggest its involvement in arrhythmias associated with subacute myocardial infarction.

     

肝炎后高胆红素血症18例分析

0　引言　肝炎后高胆红素血症 ,极易与肝炎伴发高胆红素血症相混淆 .该病是肝炎后遗症之一 ,临床上并不少见 .患者常以间歇性黄疸或隐性黄疸前来就诊 ,但并无先天性黄疸、肝炎、肝硬化及肝内外胆管结石的临床证据 ,多数既往有肝炎病史 ,肝炎已达治愈标准 ,虽增加活动量亦无复发 ,临床预后良好 .现将我院 1995 - 10 / 1999- 0 9肝炎后高胆红素血症 18例作一小结 .1　临床资料　男 12例 ,女 6例 ,年龄 2 2～ 5 8(平均 40岁 ) .门诊 11例 ,住院 7例 .其中 11例曾患急性病毒性乙型肝炎 ,1例曾患中毒性肝炎 ,1例曾患药物性肝炎 ,5例无明确肝炎病…     

勃乐斯治疗肝硬化腹水30例

1　对象和方法1.1　对象　 2 0 0 0 - 0 3/ 2 0 0 0 - 0 96 0例肝硬化腹水住院患者 ,经B超、肝功能、胃镜、实验室检查证实为肝硬化引起的腹水患者 6 0 (男 48,女 12 )例 ,平均年龄 42 .5 (2 9～ 80 )岁 ;其中肝炎后肝硬化 47例 (78.3% ) ,乙醇性肝硬化 3例 (5 .0 % ) ,心源性肝硬化 3例 (5 .0 % ) ,原因不明者 7例 (11.7% ) ;随机分成治疗组和对照组各 30例 ,按 Child- pugh改良分级法 :治疗组肝功能 A级 2例 ,B级 11例 ,C级 17例 ;对照组肝功能 A级 2例 ,B级 12例 ,C级 16例 ,两组间无明显差异 (P>0 .0 5 ) ;6 0例患者自首次确诊肝硬…     

Historic Trials: Montreal Tramways v. Leveille (1933) 4 DLR 338

This trial concerned an injury in a newborn child which wasallegedly caused by an accident involving the mother duringher pregnancy. The trial is widely accepted as a turning-pointin law related to fetal injury, conferring the right of a childto claim compensation at birth for injuries inflicted duringpregnancy. This material is reproduced with the permission ofthe publisher, Canada Law Book Inc., 240 Edward Street, Aurora,Ontario L4G 3S9, Canada.     

Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review. Is it indicated?

PURPOSE: Neoadjuvant hormonal ablation therapy has been used to decrease the rate of positive surgical margins in patients treated with radical prostatectomy. We reviewed the available literature to determine whether this therapy is indicated and beneficial. MATERIALS AND METHODS: We performed a MEDLINE key word search and assessed randomized prospective articles. Data were analyzed for the rate of positive surgical margins, seminal vesicle invasion and lymph node metastasis as well as surgical characteristics, including operative time, blood loss, hospital stay, rate of complications and difficulty of surgical dissection. In addition, these data were evaluated for prostate specific antigen-free survival. RESULTS: Neoadjuvant hormonal therapy decreased the rate of positive margins in 6 of the 7 randomized prospective studies. In none of 4 randomized prospective series was there an improved rate of seminal vesicle invasion with neoadjuvant hormonal therapy. Of 4 studies 3 showed no improvement in the rate of lymph node metastasis after neoadjuvant hormonal therapy compared with that in controls. Similarly there was no improvement in prostate specific antigen-free survival and no significant difference in operative time, operative blood loss, transfusion or hospital stay in patients treated with neoadjuvant hormonal therapy and controls. In addition, in 2 of 3 studies there was no difference in the complication rate. CONCLUSIONS: Analysis of the available literature revealed no significant improvement in outcome to support the routine administration of neoadjuvant hormonal therapy before prostatectomy.     

Symptomatic hypertrophic pubic ramus nonunion treated with a retrograde medullary screw

Pubic ramus fracture nonunion is an unusual problem. Percutaneous retrograde superior pubic ramus medullary screw fixation was successfully used in two patients with prolonged symptomatic nonunions of the superior pubic ramus.