Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gene cluster for assembly of pilus colonization factor antigen III of enterotoxigenic Escherichia coli

The assembly of pilus colonization factor antigen III (CFA/III) of enterotoxigenic Escherichia coli (ETEC) requires the processing of CFA/III major pilin (CofA) by a prepilin peptidase (CofP), similar to other type IV pilus formation systems. CofA is produced initially as a 26.5-kDa preform pilin (prepilin) and then processed to a 20.5-kDa mature pilin by CofP which is predicted to be localized in the inner membrane. In the present experiment, we determined the nucleotide sequence of the whole region for CFA/III formation and identified a cluster of 14 genes, including cofA and cofP. Several proteins encoded by cof genes were similar to previously described proteins, such as the toxin-coregulated pili of Vibrio cholerae and the bundle-forming pili of enteropathogenic E. coli. The G+C content of the cof gene cluster was 37%, which was significantly lower than the average for the E. coli genome (50%). The introduction of a recombinant plasmid containing the cof gene cluster into the E. coli K-12 strain conferred CFA/III biogenesis and the ability of adhesion to the human colon carcinoma cell line Caco-2. This is the first report of a complete nucleotide sequence of the type IV pili found in human ETEC, and our results provide a useful model for studying the molecular mechanism of CFA/III biogenesis and the role of CFA/III in ETEC infection.     

Malignant fibrous histiocytoma of the pancreas

An extremely rare case of malignant fibrous histiocytoma In the pancreas Is reported. A 70-year-old man complained of upper abdominal discomfort. A tumor in the head of the pancreas was demonstrated by ultrasonography and computed tomography. The surgical specimen revealed a relatively well demarcated tumor, 9 × 7 × 6.5cm in size. Microscopically, fibroblastic, histiocytic, and muitinucleated giant tumor cells were observed in the myxoid area, but some tumor cells had proliferated in a storiform-pleomorphlc pattern. Immunohtstochemically, some tumor cells were positive for lysozyme, α-1-antitrypsin, α-1-antichymotrypsin, and vimentin. Electron microscopically, tumor cells showed a combination of fibroblastic and histiocytic features. The patient Is currently well with no evidence of recurrence or metastasis 22 months after operation.     

Polymorphous low-grade adenocarcinoma of submandibular gland origin

A case of polymorphous low-grade adenocarcinoma (PLGA) in the submandibular gland is reported. A 72 year old woman presented with a 5 year history of a gradually expanding tumor in the submandibular region. The surgical specimen revealed a relatively well demarcated tumor, 35 × 35 × 20 mm in size. Macroscopically, necrosis and hemorrhage were not seen in the solid tumor. Histologically, the tumor growth pattern was variable, composed of tubular, papillary, solid, trabecular and cribriform structures. Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA), S-100 protein, keratin, and carcino-embryonic antigen (CEA). Electron microscopically, prominent microvilli projected into the luminal spaces, and basal lamina and hemidesmosomes were seen in the tumor cells adjacent to the connective tissues. The submandibular gland is an extremely rare location for PLGA. To the authors' knowledge, this is the first case of its kind reported in the English literature.     

Hyperplastic foci in chronic liver disease: Their proliferative activity assessed by nucleolar organizing region

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count In the hyperplastic foci was significantly higher than that In the controls (P> 30.01). Small hyperplastic foci show Increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.     

Application of multiple methods to study the immunization programme in an urban area of Guinea

During 1988-89, studies were conducted to evaluate the immunization system in Conakry, Guinea. The first, a health facility survey, found that health staff screened the vaccination status of only 30% of children who presented for curative care. A sterile syringe and needle were used for less than half of the injections. In the second survey, key informant interviews with vaccinators and health centre chiefs showed that there were minimal lines of communication between health workers and the community, but that health workers did not perceive this to be a problem. Focus group discussions in the community revealed a high level of general knowledge about vaccine-preventable diseases. However, mothers did not know how many vaccinations their children should receive or by what age they should be completed. They complained of long waiting times in health centres, the high costs of vaccination, poor rapport with health workers, and the occurrence of abscesses after vaccination. The final study, a "knowledge, attitudes, and practice" community survey, showed that missed immunization opportunities and inappropriately timed vaccinations reduced potential vaccine coverage by almost 30% among children with vaccination cards. Higher socioeconomic status, delivery in hospital, and whether mothers perceived the vaccinations to be affordable affected whether the child began the immunization series. Once a child had entered the immunization system, completion of the series was determined by the mother's education level, employment status, and experience with vaccination services.     

Case study of paired cadaver renal allografts from the same donor: influence of local DIC kidney and concomitant acute rejection on early graft outcome

We report the clinical course of 2 recipients whose renal allografts were obtained from the same cadaver donor after cardiac arrest. The recipients showed different outcomes after transplantation. Graft biopsy after reperfusion revealed disseminated intravascular coagulation (so-called DIC kidney) and severe acute tubular necrosis (ATN) in both recipients. While one graft showed primary nonfunction, the other graft became functional after a post-operative anuric period. Serial graft biopsies performed during the oligo-anuric period revealed recovery of ATN and no intra-glomerular fibrin thrombi, but development of acute rejection was detected in both recipients. The left kidney graft showed more severe local DIC kidney than the right kidney, as well as more severe acute rejection in the oligo-anuric period. Despite aggressive anti-rejection therapy, the left kidney graft showed primary nonfunction. Therefore, severe acute rejection leading to primary nonfunction might have been related to more severe ischemic injury and more extensive local DIC kidney in the left kidney.     

Positron emission tomography-positive squalene-induced lipoid pneumonia confirmed by gas chromatography-mass spectrometry of bronchoalveolar lavage fluid

Squalene is a type of oil obtained from shark liver. We describe a 76-year-old man diagnosed with chronic exogenous lipoid pneumonia due to squalene. A chest CT scan revealed pulmonary consolidation with ground-glass opacities in the right upper lobe. Positron emission tomography (PET) revealed significant uptake of 2-deoxy-2-F-fluoro-d-glucose (FDG) and 3'-deoxy-3'-F-fluorothymidine (FLT). Bronchoalveolar lavage (BAL) fluid contained many lipid-laden macrophages, and a transbronchial lung biopsy specimen showed clusters of foamy macrophages in alveolar spaces and granulomatous lesions. In addition, the presence of squalene in the BAL fluid was confirmed by gas chromatography-mass spectrometry, leading to a diagnosis of squalene-induced lipoid pneumonia. To the best of our knowledge, this is the first report of squalene-induced lipoid pneumonia in which squalene itself was successfully detected. This case also suggests the possibility that lipoid pneumonia shows significant uptake in FDG-PET and FLT-PET.     

Detection of c-Ki- ras point mutation from pancreatic juice

Summary Cytological diagnosis of pancreatic carcinoma sometimes poses difficulties in distinguishing malignant from benign cells. Recent molecular study of pancreatic carcinoma has revealed a very high incidence of a point mutation of the c-Ki-ras oncogene at codon 12 in this neoplasm. To take advantage of this technique for the diagnosis of pancreatic carcinoma, we attempted to amplify the c-Ki-ras gene from endoscopically obtained pancreatic juice by isolation of DNA and polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). PCR was possible in approx 70% of the cases. A point mutation was nonradioisotopically detected in 4 of 6 pancreatic carcinomas and in one intraductal papillary neoplasm, whereas no mutation was detected in other cases. Thus, this method was thought to be useful for the diagnosis of pancreatic carcinoma.