Production of transforming growth factor-beta 1 (TGF-beta1) by blood monocytes from patients with different clinical forms of leprosy

In the present study, the concentration of TGF-beta1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (PBMC) and either stimulated with PGL-1 or lipopolysaccharide (LPS) or left unstimulated was determined by ELISA. The cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. The adherent cells exhibited spontaneous release of TGF-beta1 in all clinical forms of leprosy and in healthy individuals; however, lepromatous leprosy/borderline leprosy (LL/BL) patients presenting erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-beta1 than either the other patients studied or the controls. These high TGF-beta1 levels were consistently observed when LL/BL ENL cells were stimulated with phenolic glycolipid (PGL-1) or LPS, and even in the absence of a stimulus (P < 0.01). The most significant differences in TGF-beta1 levels were observed when comparing the results in the presence of PGL-1 from ENL with, in order of significance: tuberculoid leprosy (TT) patients (P < 0.001), LL/BL patients without ENL (P < 0.01), healthy individuals (P < 0.01) and borderline-borderline/borderline-tuberculoid (BB/BT) patients with reversal reaction (RR) (P < 0.01). The BB/BT patients produced equivalent levels of TGF-beta1 compared with LL/BL patients without ENL, for all types of stimuli (P > 0.05). In contrast, TT patients produced the lowest levels of TGF-beta1 among all the subjects studied (both patients and healthy controls), especially following PGL-1 stimulation (P < 0.001, and P < 0.05, respectively). In conjunction with our previous data regarding TGF-beta1 expression in dermal lesions, it appears that TGF-beta1 probably plays different roles in leprosy: (i) to mediate a suppressive action locally, associated with the presence of PGL-1, and (ii) to induce proinflammatory effects when secreted systemically by monocytes, thereby acting as a modulatory cytokine in the acute inflammatory reactions of ENL and associated with the Th2 immune response in multibacillary forms of leprosy.     

Functional paraganglioma with tumor thrombus in the inferior vena cava,first case report

Pheochromocytoma (PHEO) is a rare neuroendocrine that tumor originated from the adrenal medulla that secrets catecholamines. Tumors from extra-adrenal chromaffin tissues are called extra-adrenal PHEO or paraganglioma (PGL). To our knowledge, adrenal PHEO and subclinical PGL with inferior vena cava (IVC) invasion had been sporadically reported, while functional PGL with IVC tumor thrombus has not been publicly reported yet. Perioperative management of those diseases is less well established because of their multidisciplinary nature and rarity. We herein present a case of primary malignant PGL with IVC invasion. A 16-year-old female patient with a history of severe paroxysmal hypertension was admitted to Peking Union Medical College Hospital on suspicion of retroperitoneal mass. In-house diagnostic work-up revealed a malignant PGL with IVC invasion, inferior mesenteric artery encasement and, aorta engagement. Multi-disciplinary discussions were held and careful preoperative preparation plans were made. After everything was ready, the functional PGL and tumor thrombus were completely resected, then a reconstruction of IVC was performed. The patient was discharged on postoperative day 14 and all her clinical symptoms disappeared afterward. No evidence of tumor residual or metastasis was found in the subsequent six months of follow-up. Gene tests were made for her and her family. Albeit its rarity, functional PGL with IVC invasion is not unresectable, a multi-disciplinary task force should be established to settle down every detail. We recommended 3-dimensional imaging reconstruction for gaining a better anatomic understanding. Literature reviews showed that complete resection is the premise of a good prognosis. In particular cases, complementary or alternative therapy like chemotherapy and ¹³¹I-metaiodobenzylguanidine might help, family hereditary genetic tests are advised as well.     

Genetic screening for pheochromocytoma: should SDHC gene analysis be included?

PGL3 syndrome is caused by mutations in the SDHC gene. At present, only a few families affected by SDHC mutations have been reported in the literature and in each of them the clinical presentation was characterised by paragangliomas located only in the head and neck regions. No evidence of thoracic or abdominal catecholamine-secreting chromaffin tumours has been reported to date. We report the case of a 15-year-old girl with hypertension and a norepinephrine-secreting abdominal paraganglioma who was found to harbour a novel nonsense SDHC mutation, demonstrating that the clinical presentation of PGL3 syndrome can be more diverse than expected.     

Hereditary Paraganglioma Due to the SDHD M1I Mutation in a Second Chinese Family: A Founder Effect?

OBJECTIVES/HYPOTHESIS: Hereditary paraganglioma is a rare condition that is inherited in an autosomal-dominant fashion. Four distinct loci have been associated with hereditary paraganglioma, including the SDHD, SDHC, and SDHB genes and a locus at 11q13. The SDHD, SDHC, and SDHB genes code for subunits of succinate dehydrogenase, which forms part of the mitochondrial respiratory chain. SDHD mutations are widely distributed along the gene with no apparent hot spots, although a founder effect has been described in the Dutch population. METHODS: Following a prior report of the SDHD M1I mutation in an Australian Chinese family, a second Chinese family with the same mutation is reported. The proband developed bilateral head and neck paragangliomas at age 34 years and a functioning adrenal pheochromocytoma and two extra-adrenal abdominal paragangliomas 7 years later. His brother had unilateral head and neck paraganglioma at age 39 years. Given the multicentricity of the proband's tumor and the familial clustering of paragangliomas, a clinical diagnosis of hereditary paraganglioma was made, and the proband was tested for a mutation in the SDHD gene. RESULTS: The proband was found to be heterozygous for the SDHD MII mutation that removes the start codon, and his brother subsequently tested positive for the same mutation. The family is not related to the Australian Chinese family. CONCLUSION: The finding suggests the possibility of a founder effect in the Chinese population and warrants further investigation.     

Projections from the diencephalon and mesencephalon to nucleus paragigantocellularis lateralis in the cat

The distribution of labelled cells in the diencephalon and mesencephalon has been mapped following injections of horseradish peroxidase into nucleus paragigantocellularis lateralis in the cat. Most of the labelled cells were found ipsilateral to the injection site. A group of small and medium-sized labelled perikarya (11-40 microns in diameter) was present in the caudal part of the periaqueductal grey matter (A3-P2) and in the adjacent tegmentum. Small, round or fusiform cells (8-25 microns were labelled in the tuberal region of the hypothalamus in the dorsomedial hypothalamus and in the lateral hypothalamic area. It is suggested that the cardiovascular responses which can be elicited by stimulation in these regions of the periaqueductal grey and hypothalamus are mediated via a relay on to spinally projecting neurones in nucleus paragigantocellularis lateralis which synapse on sympathetic preganglionic neurones in the intermediolateral cell column.     

免疫组织化学和PCR在早期麻风诊断中的应用

目的：探讨PCR、免疫组化应用于早期麻风诊断的价值。方法：采用PCR、免疫组化（PGL－1）和常规病理（HE、Fite抗酸染色）3种方法并用于临床诊断麻风病，用病理检查呈轻度非特异性炎症，查菌阴性的46例石蜡组织块，重新连续切片作对比观察。结果：3种检查结果比较，PCR阳性率（58．7％）＞PGL－1（36．9％）＞抗酸染色查菌AFB（15．2％），P＜0．05。结论：PCR、免疫组化两种检测技术，用于早期少菌型麻风的诊断比常规病理检查具有较高的敏感性和特异性。     

Genetic testing for pheochromocytoma-associated syndromes

Pheochromocytoma and paraganglioma are tumors of the autonomic nervous system. Various syndromes have been found to be associated with the development of pheochromocytomas and paragangliomas: multiple endocrine neoplasia type 2 (MEN 2, susceptibility gene: RET), von Hippel-Lindau disease (VHL, susceptibility gene: VHL), neurofibromatosis 1 (NF 1), and paraganglioma syndromes type 1, 3, and 4 (susceptibility genes: succinate dehydrogenase gene, SDH, subunits D, C and B, respectively). Prevalence and clinical features of pheochromocytomas and paragangliomas are different for each of these syndromes. Mutational analysis of the susceptibility genes of these syndromes in patients presenting with pheochromocytoma or paraganglioma may help to judge the risks of multifocality of the tumor as well as development of malignant pheochromocytoma or of other malignant tumors. Here we review the recent progress in clinical characterization and genetic testing for these syndromes. Based on tumor characteristics and prevalence data we give recommendations for an efficient genetic testing procedure in patients presenting with pheochromocytomas and paragangliomas.     

Intact pks15/1 in non-W-Beijing Mycobacterium tuberculosis isolates

To determine whether intact pks15/1 is unique to the W-Beijing family, we investigated 147 Mycobacterium tuberculosis strains with different IS6110 genotypes. Intact pks15/1 was found in 87.8% of cerebrospinal fluid and 84.9% of sputum isolates. It was found not only in W-Beijing strains (approximate, equals 97%) but also in other genotypes (38.5%-100%).     

PGL—1抗原和S—100蛋白检测在早期麻风病诊断中的意义

目的：为提高病理检查对早期麻风病的确诊率,从病原学,组织学及免疫学三方面了解麻风病早期皮损特征。方法：对45例临床诊断和疑似的麻风皮损,彩常规病理和免疫组化法进行了抗麻风菌特异性PGL－1单克隆抗体,S－100蛋白染色,结果：（1）连续切片的抗酸染色和PGL抗原检测可提高对早期皮损内抗酸菌（AFB）及PGL抗原的发现率。AFB及PGL抗原多分布在真皮浅层,神经内／或神经束膜及周围血管浸润的组织细胞中,（1）10例PGL抗原阳性的单个皮损麻风,7例AFB阳性,其中5例神经内有AFB,6例神经内有PGL抗原,4例神经内AFB及PGL抗原均阳性;（3）经S－100蛋白染色显示,未定类皮损组织学的非特异性炎性浸润,多是以淋巴细胞为主,有选择性的皮神经分支的炎性浸润,60％具有特异性神经病变;（4）除皮损数不清的3例外,单个皮损的确诊率为41．6％（10／24）。随着皮损数的增加,病理确诊率也增高,两块皮损和3块以上的确诊率分别为66．6％（6／9）和88．8％（8／9）。结论：PGL－1,S－100蛋白免疫染色,可提高早期麻风病的确诊率。