Thymidine labeling index in breast tumors

The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in relation to menopausal status in 32 patients with malignant or benign breast disease. The thymidine labeling index (TLI) showed significantly higher median values in the cancer patients (3.48 per cent) than in the patients with benign diseases (1.02 per cent). TLI was not significantly affected by delayed incubation at room temperature for about 1 hour. In the breast cancer patients, TLI did not significantly correlate to tumor size, the presence of axillary lymph node metastasis or pathologic nuclear grading. The only significant difference was limited to the breast cancer patients without axillary lymph node metastasis in relation to menopausal status; the TLI in the premenopausal patients (5.10 per cent) was significantly higher (p<0.05) than that in the postmenopausal patients (2.28 per cent). These data thus suggest that among premenopausal patients without axillary lymph node metastasis, those with a high TLI could be potential candidates for adjuvant chemotherapy.     

Impaired Glucose Tolerance in Pregnancy - Is It of Consequence?

Summary: This study was done to determine if impaired glucose tolerance in pregnancy was associated with increased maternal and neonatal morbidity and if so, whether the increased morbidity was due to the confounding factors of increased maternal age and maternal obesity. It was a retrospective analysis to compare 944 women with impaired glucose tolerance (IGT) in pregnancy with 10,065 women without abnormal glucose tolerance. The incidence of impaired glucose tolerance in pregnancy was 8.6% in this study. Even when maternal age and obesity were excluded, the IGT group had significantly higher risks of labour induction (relative risk, RR, 1.15); Caesarean section (RR: overall 1.43, elective 1.72, emergency 1.31); Caesarean section for dystocia/no progress (RR 1.60); macrosomia (RR 1.69,1.76,1.61 for birth-weight =97th, 95th, 90th percentiles respectively) and shoulder dystocia (RR 2.84) when compared to the nondiabetics (NDM). The risks of hypertensive disease (RR 1.22) and Caesarean section for fetal distress/thick meconium-stained liquor (RR 1.53) were also higher in the IGT group but these increases were not statistically significant when maternal age and obesity were excluded. There was no significant difference in the rates of low Apgar scores at 1 and 5 minutes between the 2 groups.     

格林—巴利综合征患者血清和脑脊液中的抗硫脂抗体

探讨抗硫脂抗体与格林－巴利综合征（ＧＢＳ）的关系。方法采用固相酶联免疫吸附法对急性期ＧＢＳ患者血清和脑脊液（ＣＳＦ）中抗硫脂ＩｇＧ和ＩｇＭ抗体进行检测。结果ＧＢＳ患者血清和ＣＳＦ中抗硫脂ＩｇＧ及ＩｇＭ抗体的阳性率均明显高于正常对照组；血清中抗硫脂ＩｇＭ抗体滴度与标本收集时患者发病天数呈负相关（Ｐ＜０．０５），而血清中抗硫脂ＩｇＧ抗体滴度与临床分级（Ｐ＜０．０１）、ＣＳＦ中抗硫脂ＩｇＧ抗体滴度（Ｐ＜０．０１）呈正相关；血清中抗硫脂ＩｇＧ或ＩｇＭ阳性的ＧＢＳ患者，体检时有不同程度的感觉障碍患者为５６％，而血清中抗硫脂抗体阴性患者仅为１６％，两者之间差异有显著意义（Ｐ＜０．０５）。结论抗硫脂抗体可能在ＧＢＳ的病理过程中起重要作用     

Laparoscopic cholecystectomy

Laparoscopic cholecystectomy is a combined endoscopic-operative technique for removing the gallbladder. Patients with symptomatic gallstones are eligible for this procedure. Contraindications include pregnancy, acute cholangitis, advanced cholecystitis, acute pancreatitis, peritonitis, significant bleeding disorder, portal hypertension, and a prior major upper abdominal operation. The procedure does require experience and specialized training. It is guided by an endoscope, camera, and video monitor, and is performed through four cannulas. The gallbladder is dissected from the hepatic bed under observation on a monitor. The possible complications are bleeding, injury to the common bile duct, and technical problems, such as perforation of the gallbladder. The length of the hospital stay and the postoperative recovery time are markedly shortened compared with standard cholecystectomy. The procedure has an advantage over stone dissolution and biliary lithotripsy in that the gallbladder is removed, and additional or continued treatment is not necessary. This procedure offers sufficient advantages to the patient that it will likely become a standard for qualified abdominal surgeons.     

Anatomic and spiral computed tomographic study of the genial tubercles for genioglossus advancement.

OBJECTIVE: To measure and compare Chinese mandibular genial tubercles measured anatomically and with computed tomography (CT). STUDY DESIGN AND SETTING: Spiral CT scans were taken of 40 adult human skulls; the superior genial spines were measured using anatomic and CT methods. RESULTS: The height and width of the superior genial spines, mandible thickness, and distance from the menton to the inferior and superior margins of the superior genial spines were 5.82 +/- 0.71, 6.98 +/- 1.35, 11.95 +/- 1.59, 11.08 +/- 2.05, and 16.91 +/- 2.30 mm from anatomic measurements and 6.17 +/- 0.71, 7.01 +/- 1.13, 12.19 +/- 1.64, 10.41 +/- 1.55, and 15.73 +/- 2.12 mm using spiral CT, respectively. The anatomic and CT measurements were correlated. CONCLUSION: Spiral CT of the genial tubercles can help locate the osteotomy in genioglossus advancement. SIGNIFICANCE: This study acquired reference data on Chinese genial tubercles demonstrating that CT measurements of the genial tubercles reflect their anatomy, which should allow accurately locate the osteotomy.     

MUC4 expression increases progressively in pancreatic intraepithelial neoplasia

Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma.     

Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+.

The clinical and pathological features of carcinomas of the pancreas with DNA replication errors (RER+) have not been characterized. Eighty-two xenografted carcinomas of the pancreas were screened for DNA replication errors using polymerase chain reaction amplification of microsatellite markers. Cases with microsatellite instability in at least two markers of a minimum of five tested were considered RER+. RER status was correlated with histological appearance, karyotype of the carcinomas when available, K-ras mutational status, and patient outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas were poorly differentiated and had expanding borders and a prominent syncytial growth pattern. Neither a Crohn's-like lymphoid infiltrate nor extracellular mucin production were prominent. Ductal adenocarcinomas of the pancreas typically contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras. One of the three RER+ carcinomas was karyotyped and showed a near diploid pattern. All three of the RER+ tumors were removed via Whipple resection. One of the three patients is free of disease 16 months after pancreaticoduodenectomy, one is alive and free of tumor at 52 months but developed two colon carcinomas during this period, and the third died of pancreatic cancer at 4 months. None of the three patients had a family history of colorectal carcinoma. A review of the K-ras wild-type carcinomas in a previously characterized series of pancreatic carcinomas with known K-ras mutational status identified two additional cancers with poor differentiation, a syncytial growth pattern, and pushing borders. Both of the cancers were diploid and both patients were longterm survivors (over 5 years). The inclusion of such patients in previous prognostic studies of pancreas cancer may explain the failure of histological grade to be a predictor of prognosis. These data suggest that DNA replication errors occur in a small percentage of resected carcinomas of the pancreas and that wild-type K-ras gene status and a medullary phenotype characterized by poor differentiation, and expanding pattern of invasion, and syncytial growth should suggest the possibility of DNA replication errors in carcinomas of the pancreas.     

Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected holstein cattle

Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.     

Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms

Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist.