表皮生长因子受体、血管内皮生长因子受体和BAD在非小细胞肺癌中的表达

背景与目的：表皮生长因子受体（epidermal growth factor receptor，EGFR）和血管内皮生长因子受体（vascular endothelial growth factor receptor，VEGFR）均属酪氨酸激酶受体（receptor tyrosine kinase，RTK），可调控细胞的增殖、分化与生存。BAD是Bcl-2家族中的促凋亡信号成分，在调控细胞凋亡特别是肿瘤细胞凋亡过程中发挥重要作用。但目前人们对上述这些重要蛋白在非小细胞肺癌（non—small—cell lung cancer，NSCLC）中的表达与肿瘤病理学的关系所知甚少。本研究探讨ECFR、VEGFR、BAD和磷酸化BAD在NSCLC中的表达情况以及与肿瘤病理的关系。方法：使用组织微阵列（tissue microarray，TMA）切片的免疫组织化学法，NSCLC患者51例（26例腺癌，16例鳞癌，8例大细胞癌，1例大细胞神经内分泌癌）。结果：51例患者中EGFR和VEGFR分别在10例（加％）和14例（27％）中出现过度表达。大细胞癌中未见VEGFR表达（0／8例），而鳞癌和腺癌患者中VEGFR表达分别为44％（7／16）和27％（7／26）。EGFR和VEGFR的表达与性别，肿瘤细胞分化及肿瘤浸润程度（包括胸膜浸润，血管浸润，淋巴结转移，肺内播散，脑转移情况）无关。51例患者中22例（43％）出现BAD蛋白表达缺失，且NSCLC的不同病理类型间差异有显著性。BAD蛋白表达缺失在16例鳞癌患者中10例（63％），8例大细胞癌患者中5例（63％），26例鳞癌患者中有7例（27％）（P=0．04）。51例患者中25例（49％）出现磷酸化BAD蛋白过度表达[其中26例腺癌患者中有13例（50％），16例鳞癌患者中有8例（50％），8例大细胞癌患者中有4例（50％）]。BAD蛋白的表达缺失与磷酸化BAD蛋白的过度表达经统计检验与上述肿瘤浸润程度无相关性。结论：肺鳞癌出现VEGFR表达增高的可能较大，而大细胞癌出现VEGFR表达增高的可能最小。在鳞癌和大细胞癌中可见BAD蛋白表达的显著缺失。NSCLC患者EGFR，VEGFR，磷酸化BAD蛋白的过度表达以及BAD蛋白表达的缺失与病理浸润程度无关。但这些受体酪氨酸激酶表达以及与NSCLC凋亡直接相关的媒介因子可能成为未来多靶向治疗中的候选靶标。     

Gliomatosis cerebri in a 10-year-old girl masquerading as diffuse encephalomyelitis and spinal cord tumour

Gliomatosis cerebri is the unifying term used when diffuse glial infiltration occurs throughout the cerebral hemispheres. The very few cases reported in children have presented with intractable epilepsy, corticospinal tract deficits, unilateral tremor, headaches, and developmental delay. Antemortem diagnosis is difficult because of the vagueness of the physical, radiological and pathological findings. Adult cases may simulate an acute diffuse encephalomyelitis and show postmortem evidence of a marked swelling of the spinal cord. Apparently benign intracranial hypertension with papilloedema has also been recorded. We report a 10-year-old girl who presented with a history and physical signs suggestive of benign intracranial hypertension. A diffuse encephalomyelopathy occurred, which was complicated by spinal cord swelling, followed by deterioration and death. Gliomatosis cerebri affecting the brain and spinal cord was found at postmortem examination.     

The genetic epidemiology of irrational fears and phobias in men

BACKGROUND: Much of our knowledge of the role of genetic factors in the etiology of phobias comes from one population-based sample of female twins. We examined the sources of individual differences in the risks for phobias and their associated irrational fears in male twins. METHODS: In personal interviews with both members of 1198 male-male twin pairs (707 monozygotic [MZ] and 491 dizygotic [DZ]) ascertained from a population-based registry, we assessed the lifetime history of agoraphobia and social, animal, situational, and blood/injury phobias as well as their associated irrational fears. Twin resemblance was assessed by means of probandwise concordance, odds ratios, tetrachoric correlations, and univariate and multivariate biometrical model fitting. RESULTS: The suggestive results obtained by analysis of phobias only were supported by analyzing both fears and phobias. All 5 phobia subtypes aggregate within twin-pairs. This aggregation is due largely or solely to genetic factors with heritability of liabilities ranging from 25% to 37%. Multivariate analysis revealed a common genetic factor, genetic factors specific to each subtype, and a common familial-environmental factor. CONCLUSIONS: In male subjects, genetic risk factors, which are partially common across all subtypes and partially subtype specific, play a moderate role in the etiology of phobias and their associated irrational fears. Family environment probably has an impact on risk for agoraphobia and social phobia. The genetic liability to blood/injury phobias is not distinct from those of the more typical phobias.     

Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events.

Previous studies of rhinovirus infection indicate that about one third of the persons with confirmed viral infection do not show evidence of cold symptoms. Factors that determine which infected individuals will develop colds are not known. Using a rhinovirus inoculation protocol, the authors explored the possible role of recent life events, current mood, and perceived stress in the development of symptoms in individuals known to be infected. As part of a larger study, 17 subjects were exposed to a rhinovirus and were individually isolated for 5 consecutive days; cold symptoms, mucus weights, and tissue use were monitored on a daily basis during this period. Although all 17 subjects had confirmed rhinovirus infection, only 12 subjects developed clinical colds, as indicated by self-reported symptoms and by objective symptom indices. The average number of reported major life events for the previous year was significantly higher for those who developed colds than for those who did not (p < .05). Measures of affect and perceived stress before the inoculation were not different for those who did and did not develop colds. Complementing recent research demonstrating psychosocial influences on experimental infection rates, these results provide evidence that the development of cold symptomatology in experimentally infected individuals is related to prior life events.     

Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis.

OBJECTIVE: To determine whether synovial macrophages and monocytes isolated from patients with rheumatoid arthritis patients are capable of differentiating into osteoclastic bone resorbing cells; and the cellular and humoral conditions required for this to occur. METHODS: Macrophages isolated from the synovium and monocytes from the peripheral blood of rheumatoid arthritis patients were cultured on bone slices and coverslips, in the presence and absence of UMR 106 rat osteoblast-like cells, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF), and assessed for cytochemical and functional evidence of osteoclast differentiation. RESULTS: Isolated calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), and vitronectin receptor (VNR) negative, CD11b and CD14 positive monocytes and macrophages differentiated into CTR, TRAP, and VNR positive multinucleated cells capable of extensive lacunar bone resorption when co-cultured for 14 d with UMR 106 cells in the presence 1,25(OH)2D3 and M-CSF. CONCLUSIONS: Mononuclear phagocytes (monocytes and macrophages) from rheumatoid arthritis patients are capable of differentiating into multinucleated cells showing all the cytochemical and functional criteria of mature osteoclasts. Synovial macrophage-osteoclast differentiation may represent an important cellular mechanism in the bone destruction associated with rheumatoid arthritis.     

Anti-Basement Membrane Antibodies in Immunologic Renal Disease

Abstract: Anti-basement membrane antibodies are now being associated with an increasing spectrum of disease, including Goodpasture's syndrome, rapidly progressive and occasionally milder forms of glomerulo-nephritis (GN), tubulointerstitial nephritis, pulmonary damage, and potentially other forms of tissue injury. We have developed a radioimmunoassay to detect circulating anti-glomerular basement membrane (GBM) antibodies. The antigens for this assay are derived from the noncollagenous portion of the GBM remaining after collagenase digestion. After immunoabsorptive purification, the major antigens precipitated by human anti-GBM antibodies can be characterized by polyacrylamide gel electrophoresis (PAGE) into an unresolved high molecular weight fraction and two antigenic peaks of 54,000 and 27,000 daltons. The noncollagenous nature of the antigenic material has been confirmed by amino acid analysis. The radiolabelled antigen has proven useful in detecting circulating anti-GBM antibodies in over 500 patients. The assay is of use in monitoring the activity of disease and judging the patient's response to therapy. It is also useful in determining the timing of renal transplantation, if required. Differences in antigenic content of glomerular and tubular basement membranes (TBM) have been noted between individuals. These antigenic differences. under certain circumstances, can lead to the induction of anti-basement membrane antibody responses after transplantation.     

Oliguria and its sequelae.

Fifty-nine patients were seen with oliguria in 1975. Forty had acute renal failure (ARF) and 19 rapidly reversible oliguria (RR). The causes of the oliguria were medical (64%), surgical (27%) and obstetrical (9%). The following were valuable in the assessment of patients with oliguria: urine sodium concentration (UNa) and osmolality, coagulation studies and high dose intravenous urography. Patients presenting with a high UNa or a coagulation abnormality were more likely to have ARF. Central venous pressure monitoring was helpful in the initial management but the administration of diuretics was not. Twenty patients with ARF were treated conservatively and the remainder by dialysis. Infection was both the commonest complication of ARF and the most frequent cause of death. Seventy percent of those with ARF died. Death was more common in the elderly or patients with a medical aetiology. The mortality of ARF remains high in spite of advances in the management of its metabolic and infective complications because of the acceptance of more high risk patients. An improved awareness of the preventable causes of oliguria is apparent.     

NAAG peptidase inhibitors and their potential for diagnosis and therapy

Modulation of N-acetyl-L-aspartyl-L-glutamate peptidase activity with small-molecule inhibitors holds promise for a wide variety of diseases that involve glutamatergic transmission, and has implications for the diagnosis and therapy of cancer. This new class of compounds, of which at least one has entered clinical trials and proven to be well tolerated, has demonstrated efficacy in experimental models of pain, schizophrenia, amyotrophic lateral sclerosis, traumatic brain injury and, when appropriately functionalized, can image prostate cancer. Further investigation of these promising drug candidates will be needed to bring them to the marketplace. The recent publication of the X-ray crystal structure for the enzymatic target of these compounds should facilitate the development of other new agents with enhanced activity that could improve both the diagnosis and treatment of neurological disorders.