A transient acidification linked to intracellular Ca2 in anti-μ-stimulated human B-lymphocytes

Mitogen-induced cellular proliferation is in many cell types preceded by rapid changes in intracellular pH and free Ca²⁺ concentration. We studied the patterns of pH and Ca²⁺ changes in normal resting human B-lymphocytes after exposure to and-μ antibodies and the monoclonal antibody 1F5, reactive with the CD20 antigen, both able to activate resting B-lymphocytes to enter the G₁ phase of the cell cycle. Monitoring intracellular pH with the pH-sensitive, fluorescent dye, 2',7'-bis(carboxyethyl)-5,6-carboxy-fluorescein, we demonstrated that poly- and monoclonal anti-μ antibodies induced a rapid (maximum change within 2 min) intracellular acidification of 0.06 pH units followed by a slower (10–15 min) alkalinization towards, or slightly above, the resting pH of 6.88. The acidification response was amiloride-resistant, whereas the return to baseline was sensitive. Intracellular free Ca²⁺ was measured by using the fluorescent Ca²⁺ dye, indo-i. Exposure of cells to anti-/i resulted in a rapid increase (maximum change within 2 min) in cytoplasmic Ca²⁺ of 340 nM and a slower decline in fluorescence back to baseline of about 180 nM. In contrast to anti-μ, 1F5 caused no change in cytoplasmic Ca²⁺ and pH. However, the Ca²⁺ ionophore ionomycin at low concentrations mimicked the Ca²⁺ response as well as the pH response to anti-μ. In Ca²⁺-free solutions the intracellular Ca²⁺ stores are usually rapidly depleted and, indeed, the Ca²⁺ and pH responses to anti-μ were reduced after 5 min and almost abolished after 35 min under such conditions. Our data therefore suggest that the anti-μ-induced rapid acidification is the result of increased intracellular Ca²⁺ and dependent on it.     

18F-FDG及11C-乙酸盐PET/CT诊断原发及转移性肝细胞癌:一项前瞻性研究的价值与不足分析

肝细胞癌是亚洲地区发病率最高的肿瘤之一,因此有众多的研究涉及肝细胞癌.然而,在研究中所用统计学方法和技术等不当易得出不正确的概念和结论.作者就已发表在美国<核医学杂志>上的<18F-FDG及11C-乙酸盐PET/CT诊断原发及转移性肝细胞癌的前瞻性研究>一文提出了一些不同观点,希望这方面的研究者能掌握正确的统计学方法、诊断标准及样本人选标准.     

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming

Background: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pre-treatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. Methods: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. Results: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. Conclusion: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.     

Gastric cytoprotection by amoxycillin in the rat

Abstract Amoxycillin in combination with anti-ulcer agents has been shown to prolong duodenal ulcer remission. While this effect can be related to the eradication of Helicobacter pylori , it is not known if amoxycillin might possess cytoprotective properties. Protection against ethanol-induced gastric mucosal damage by intragastric instillation of amoxycillin suspension (prepared from capsule form) and solution (from injection form, 100% pure amoxycillin), and by intraperitoneal injection of amoxycillin solution was studied using an ex vivo gastric chamber in the rat. Intragastric and intraperitoneal administration of amoxycillin dose-dependently protected the rat gastric mucosa from damage by absolute ethanol. This protection was lost when the rats were pretreated with indomethacin. Gastric mucosal blood flow as measured by laser Doppler flowmetry and gastric acid output were unaffected by amoxycillin. Amoxycillin imparts gastric cytoprotection, and one possible mechanism is by the release of prostaglandins.     

Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer

AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.     

Ureteral cancer associated with dermatomyositis

Dermatomyositis is a rare inflammatory myopathy that has characteristic cutaneous lesions. Although many malignancies are associated with dermatomyositis, urogenital malignancies have rarely been reported to be associated with dermatomyositis. We report here on the first case of ureteral cancer associated with dermatomyositis. A 42-year-old man presented to us with a skin rash. A clinical diagnosis of dermatomyositis was made due to the skin lesions, muscle weakness, arthralgia, the increased erythrocyte sedimentation rate and the increased creatine kinase level. The patient revealed microscopic hematuria and abnormal urine cytology during the investigation for the underlying malignancy. Retrograde pyelography demonstrated a suspicious lesion in the right mid-ureter, and the ureteroscopic biopsy revealed the urothelial carcinoma. Although an operation was recommended, the patient died of pneumonia associated with his interstitial lung disease, which is one of the poor prognostic indicators of dermatomyositis.     

PRIMARY HYPOTHYROIDISM AND ESSENTIAL HYPERNATREMIA IN A PATIENT WITH HISTIOCYTOSIS X

Abstract: :A 27 year old woman with histiocytosis X had an unusual initial presentation with features of primary hypothyroidism and a goitre. Diagnosis was made by lung and thyroid biopsies. Endocrine tests showed the presence of hypopituitarism and a discrete suprasellar mass, consistent with hypothalamic histiocytosis X, was demonstrated by computerised tomography. Radiotherapy and chemotherapy arrested the clinical progression of the disease.