Smooth muscle distribution in the extrahepatic bile duct: histologic and immunohistochemical studies of 122 cases

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.     

Peroxiredoxins in breast carcinoma.

PURPOSE: Peroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency and some of them having also effects on cell differentiation and apoptosis. The mammalian Prx family has six distinct members located in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. EXPERIMENTAL DESIGN: We examined immunohistochemically a large set of samples from patients with breast carcinoma and investigated associations with parameters such as tumor-node-metastasis classification, hormone receptor status, and patient survival. Three biopsies of healthy breast tissue were used as controls. RESULTS: Expression of peroxiredoxins I, III, IV, and V was found in >or=80% of cases, whereas the expression of Prx II and VI was less frequent. Increased expression of Prx III was found to associate with the presence of progesterone (P = 0.02) and estrogen (P = 0.03) receptors, and Prxs IV (P = 0.009) and VI (P = 0.04) were overexpressed in progesterone receptor positive cases. Prx V was the only isoform that associated with items of tumor-node-metastasis classification, it was connected to a larger tumor size (P = 0.05) and positive lymph node status (P = 0.04). Prx V positivity was also connected with shorter survival (P = 0.04), whereas Prxs III (P = 0.002) and IV (P = 0.02) were related to better prognosis, probably resulting from their connection with a positive hormone receptor status. CONCLUSIONS: In conclusion, we found that expression of peroxiredoxins, especially III, IV and V, is increased in breast malignancy, suggesting the induction of Prxs as response to increased production of reactive oxygen species in carcinomatous tissue.     

一种新的细胞凋亡相关基因——高同型半胱氨酸诱导基因HCY-2的功能初探

目的　探讨高同型半胱氨酸 (HCY)血症引起心血管病和出生性缺陷的作用机制。方法　采用诱导筛选方法克隆高同型半胱氨酸诱导基因 HCY- 2 ,以 Northern印迹分析检测 HCY- 2基因在大鼠不同组织中的表达 ,以免疫组化方法验证 HCY- 2蛋白在大鼠不同组织中的表达。结果　以诱导筛选方法从大鼠血管平滑肌细胞内克隆到一个新的全长 c DNA,即高同型半胱氨酸诱导基因 HCY- 2 ,它编码 142个氨基酸。Northern印迹分析和免疫组化检测表明 ,HCY- 2基因可在大鼠心、肾、脑、肝、肺等组织中广泛表达。在体外 ,将重组 HCY- 2基因转移至内皮细胞中 ,能够引起细胞凋亡和 DNA损伤 ;在体内 ,将 HCY- 2基因转移至鸡胚内 ,则诱发鸡胚细胞凋亡 ,并引起畸形。结论　 HCY- 2基因可能是一种新的凋亡基因 ,高同型半胱氨酸血症可能通过 HCY- 2基因诱发心血管病和出生性畸形。     

Clinical study on the pattern of lymphnode metastasis in carcinoma of esophagus (an analysis of 200 cases)

Objective: To study the pattern of lymphnode metastasis in carcinoma of esophagus. Methods: 200 cases of resected esophageal cancer specimens were carefully examined pathologically. Lymphnode metastasis, its pathway and extent in relation to pathological changes were analyzed. Results: Lymphnode metastasis was mainly regional and extended vertically in both directions. Leaping-over metastasis was another feature. The deeper invasion by the tumor, the higher frequencies of metastasis development, and vice versa. However, leaping-over metastasis was more likely to occur where tumor invasion was less severe. Conclusion: Owing to the high frequency of lymphnode metastasis in the superior mediastinum and the widely spanned leaping-over metastasis, an operative approach by three incisions through right thoracotomy with excision of the whole segment of esophagus and anastomosis at cervical region was recommended, in order to dissect lymphnodes in the cervical, thoracic and abdominal regions and to leave less or no metastatic lymphnodes behind.     

Differential regulation of ciliary neurotrophic factor and its receptor in the rat hippocampus following transient global ischemia

To investigate a potential role of ciliary neurotrophic factor (CNTF) in transient global ischemia, we have studied the postischemic regulatory changes in the expression of CNTF and its receptor, the ligand-binding alpha-subunit (CNTFRalpha). Immunoblot analysis demonstrated CNTF levels were slightly upregulated already during the first day after ischemia and then increased markedly by more than 10-fold until 2 weeks postischemia. Immunoreactivity for CNTF became detectable 1 day after ischemia and was localized in reactive astrocytes. The intensity of the immunolabeling was maximal in CA1 during the phase of neuronal cell death (days 3-7 postischemia) and in the deafferented inner molecular layer of the dentate gyrus. Upregulation of CNTF expression was less pronounced in CA3 and absent in the stratum lacunosum moleculare and the outer molecular layer of the dentate gyrus and thus did not simply correlate with astroliosis as represented by upregulation of glial fibrillary acidic protein (GFAP). As shown by in situ hybridization, expression of CNTFRalpha mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Following ischemia, reactive astrocytes, identified by double labeling with antibodies to GFAP, transiently expressed CNTFRalpha mRNA with a maximum around postischemic day 3. This astrocytic response was most pronounced in CA1 and in the hilar part of CA3. These results show that CNTF and its receptor are differentially regulated in activated astrocytes of the postischemic hippocampus, indicating that they are involved in the regulation of astrocytic responses and the neuronal reorganizations occurring after an ischemic insult.     

Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD), and could initiate dopaminergic neuronal degeneration. Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.     

Interpretation of Wada memory test for lateralization of seizure focus by use of (99m)technetium-HMPAO SPECT

PURPOSE: Although the intracarotid amobarbital procedure (IAP) or Wada test is useful in lateralizing seizure focus in patients with temporal lobe epilepsy (TLE), the results of the IAP memory test are frequently nonlateralizing. An insufficient suppression of the medial temporal region contralateral to the seizure focus may contribute to the failure of lateralization. We tried to correlate IAP memory results with the functional changes in the contralateral medial temporal region as measured by single photon emission computed tomography (SPECT) during IAP. METHODS: We performed a (99m)technetium-(Tc) hexamethylene-propylene-amine-oxime (HMPAO) brain SPECT in 19 medial TLE patients during a contralateral IAP (sodium amobarbital injected contralateral to the seizure focus). Regional cerebral blood flow (rCBF) was measured in the contralateral medial temporal region. The amount of decrease in the rCBF was calculated by subtracting the previous measurement from the one obtained with the interictal SPECT. RESULTS: Ten (53%) patients passed and nine (47%) failed the contralateral IAP. The mean percentage decrease in rCBF was 5.3+/-5.3%. There was a significant negative correlation between a decrease in the rCBF and the IAP memory-retention score by Spearman correlation (p = -0.53: p<0.021). Patients with smaller decreases in rCBF (<5%) more frequently passed the contralateral IAP memory test than did those with larger decreases (80 vs. 22%; p<0.023). CONCLUSIONS: We suggest that an insufficient suppression of the contralateral medial temporal function is partly responsible for nonlateralizing IAP memory tests. An IAP-SPECT may be useful in interpreting IAP memory tests for the lateralization of seizure focus in TLE patients.     

The Marshall R. Urist Young Investigator Award. Orthopaedic applications of gene therapy. From concept to clinic

Gene therapy offers new possibilities for the clinical management of orthopaedic conditions that are difficult to treat by traditional surgical or medical means. To bring the potential of this novel technology into the clinic, a research program was initiated that aimed to identify orthopaedically useful genes and develop methods for delivering them to suitable sites under conditions in which gene expression remains at therapeutic levels for the appropriate periods of time; this program is now 10 years old. Rheumatoid arthritis was selected as the lead disease. Preclinical studies evaluating the local and systemic delivery of numerous different genes by in vivo and ex vivo methods in murine and lapin models led to the development of a human gene therapy protocol for arthritis. In this protocol, a gene encoding the human interleukin-1 receptor antagonist protein is transferred to the metacarpophalangeal joints of female patients with rheumatoid arthritis. The first patient was treated this way in July 1996. This is not only the first orthopaedic application of human gene therapy, but also the first use of gene therapy approved for a nonlethal disease. In addition to providing additional therapeutic options for the treatment of rheumatoid arthritis, the experimental data from this study suggest that gene transfer approaches may improve the treatment of osteoarthritis, the repair of cartilage, ligaments, tendons, menisci, intervertebral discs and bone, and the management of disorders such as osteoporosis and osteogenesis imperfecta. They also show promise as a means for developing novel and improved animal models of orthopaedic diseases. If the current rate of progress continues, wide clinical application of gene therapy in various orthopaedic indications should occur within the next 5 to 10 years.     

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.