Effect of Motilin on Endogenous Release of Insulin in Conscious Dogs in the Fed State

The aim was to investigate the insulin-releasing activity of motilin during and after feeding. A single intravenous bolus injection of motilin (0.01-0.3 microg/kg) dose-dependently stimulated endogenous release of insulin in the postprandial state. The insulin-releasing activity of motilin in the fed state was completely abolished by pretreatment with atropine or hexamethonium and was partly inhibited by ondansetron. Truncal vagotomy also greatly suppressed the motilin-induced insulin release. While phentolamine significantly enhanced insulin release in response to motilin, propranolol significantly inhibited this response in both states. The motilin-induced insulin release in the fed states was not accompanied by any changes in glucose concentrations. In conclusion, while the physiological significance remains unclear, these results indicate that physiological doses of motilin stimulate endogenous release of insulin via a vagally cholinergic muscarinic pathway, and that adrenergic and 5-hydroxytryptamine3 receptors are also involved in this response, in the dog.     

Serum interleukin-12 and interleukin-18 levels as a tumor marker in patients with esophageal carcinoma

Interleukin (IL)-12 and IL-18 participate in tumor immunology. Serum IL-12 and IL-18 levels were determined in patients with esophageal carcinoma, and the relationship between clinicopathologic factors and prognosis was investigated. Peripheral blood samples were obtained from 15 healthy volunteers and from 70 patients with esophageal carcinoma before curative surgery. IL-12 and IL-18 levels were determined in each serum sample by enzyme-linked immunosorbent assay. Mean serum IL-12 and IL-18 levels were significantly higher in patients with esophageal carcinoma compared with healthy volunteers (P < 0.05) and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels (P < 0.01). In patients with esophageal carcinoma, increasing serum IL-12 and IL-18 levels correlated with tumor growth and progression. The function of these two interleukin in the host immune response remains unclear. However, this part of the host immune response did not appear to contribute to the postoperative prognosis. Serum IL-12 and IL-18 levels might correlate with a certain depth of invasion and might be useful tumor markers in patients with esophageal carcinoma.     

Monoclonal anti-idiotype antibodies recognizing the variable region of a high-affinity antibody against 11-deoxycortisol. Production,characterization and application to a sensitive noncompetitive immunoassay

Anti-idiotype antibodies recognizing the variable regions of a particular anti-hapten antibody are valuable tools, which can be used in sensitive hapten immunoassays based on a noncompetitive format. Here, we describe the production and characterization of monoclonal anti-idiotype antibodies against idiotopes on the variable regions of an antibody showing high affinity and specificity to 11-deoxycortisol (11-DC). 11-DC is the biosynthetic precursor of cortisol and a diagnostic index for the assessment of pituitary-adrenal function. BALB/c or A/J mice were repeatedly immunized with the anti-11-DC antibody conjugated with keyhole limpet hemocyanin and their spleen cells were then fused with P3/NS1/1-Ag4-1 myeloma cells. Seven kinds of anti-idiotype antibodies were generated, one of which was a beta-type antibody recognizing the paratope and others which were alpha-type antibodies recognizing the framework region. A noncompetitive ELISA based on idiotype-anti-idiotype reactions was established using one of these alpha-type antibodies in combination with the beta-type antibody and with the anti-11-DC antibody. This noncompetitive assay system provided improved sensitivity (detection limit: 1.0 pg=2.9 fmol), which is approximately 10 times higher than the corresponding competitive enzyme immunoassay, and offered a practical specificity for clinical use. Appropriate serum 11-DC levels were obtained for normal subjects [0.16+/-0.09 (S.D.) microg/l (n=6), ranging from 0.086 to 0.316 microg/l] using the present assay system.     

Studies on the effects of initial injection doses of follicle stimulating hormone on the pregnancy and the ovarian hyperstimulation syndrome incidence in polycystic ovarian syndrome patients

Background:  Patients with polycystic ovarian syndrome (PCOS) are often resistant to clomiphene citrate, which causes the need for subsequent gonadotropin treatment. However, careful administration is required because of the potential side-effects, that is, ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy.
Methods:  Forty-three cycles in 22 patients with PCOS were enrolled in this study. Ovarian stimulation was initiated on day 7 of the menstrual cycle with 150 IU/day of follicle stimulating hormone (FSH; 150 IU course), 100 IU/day (100 IU course), and 75 IU/day (75 IU course), successively. If follicles over 12 mm in diameter did not develop after 1 week, the dose was increased. In each treatment course, the number of developed follicles, the serum estradiol level before ovulation, total FSH dosage and duration of administration, the incidence of OHSS, and pregnancy rate were examined.
Results and Conclusion:  The largest number of developed follicles and the highest serum estradiol level were found in the 150 IU course. In contrast, the total FSH dosage and duration of administration were highest and longest in the 75 IU course. The incidence of OHSS and pregnancy rate were highest in the 150 IU course and in the 75 IU course, respectively. The present study indicates that 100 IU or 75 IU of FSH is recommended as an initial injection dose for PCOS patients. (Reprod Med Biol 2003; 2 : 63–67)     

Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.     

Dissociable neural responses in the hippocampus to the retrieval of facial identity and emotion: an event-related fMRI study

In studies with brain-damaged patients and experimental animals, the medial temporal lobe, including the hippocampus and parahippocampal gyrus, has been found to play a critical role in establishing declarative or episodic memory. We measured the neural response in these structures, using event-related functional magnetic resonance imaging, while six healthy subjects performed the retrieval task for facial identity and emotion, respectively. Under the identity condition, the subjects participated in a yes/no recognition test for neutral faces learned before the scanning. Under the emotion condition, the subjects learned the faces with positive or negative expression and retrieved their expressions from neutral cue faces. The results showed that the left hippocampus is primarily involved in the identification of learned faces, and that the adjacent parahippocampal gyrus responds more to target than to distracter events. These results indicate a specific engagement of the left hippocampal regions in conscious recollection and identification of physiognomic facial features. The activity in the right hippocampus increased under both the identity and emotion conditions. The present results may relate with the functional model of face recognition in which the left hemisphere contributes to the processing of detailed features and the right hemisphere is efficient in the processing of global features.     

Usefulness of proviral load measurement for monitoring of disease activity in individual patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis

High human T-lymphotropic virus type I (HTLV-I) proviral load in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the proviral load has been reported to fluctuate in individual patients during the course of the disease. Clinical symptoms usually became stable after a prolonged period of symptom progression. However, the authors have experienced having some patients whose clinical manifestations suddenly became worse during the course of the disease. To clarify the role of high proviral load and its fluctuation in the pathogenesis of HAM/TSP, the authors measured the proviral load of serially taken PBMCs as well as of cerebrospinal fluid (CSF) cells from patients with HAM/TSP on long-term follow-up and compared these with their clinical manifestations. There was a wide distribution of proviral load, from 0.3 to 37.8 copies/100 PBMCs; however, the proviral load in individual patients was relatively stable during the course of the disease. Eighty-three percent of the patients with clinical worsening showed an increase in proviral load at the time point when clinical worsening was recorded, or at the preceding time point. The proviral loads in CSF cells were higher than those in PBMCs in individual patients. The ratio of proviral loads in CSF cells/in PBMCs, but not the absolute load, in either compartment, was significantly associated with clinically progressive disease and with recent onset of HAM/TSP. These findings indicate that clinical progression of HAM/TSP is associated with increased proliferation or immigration of HTLV-I-infected lymphocytes in the central nervous system.     

Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection

HYPOTHESIS: There have been few reports on the minimum surgical margins (SMs) required for successful liver resection in patients with colorectal metastases. This minimum requirement may be narrower than the previously recommended margin of 10 mm. OBJECTIVES: To identify the minimum margins by assessing the presence of micrometastases around the tumor using genetic and histological techniques, and to investigate whether SMs are associated with patterns of tumor recurrence or patient survival. DESIGN: Prospective and retrospective studies. SETTING: Tertiary referral cancer center. PATIENTS AND METHODS: Fifty-eight patients who underwent 62 liver resections for hepatic metastasis from colorectal cancer between December 1, 1996, and November 30, 2000, were included in the study. Tissue samples taken from the tumor, surrounding liver parenchyma, and Glisson pedicle near the tumor were tested for K-ras and p53 mutations using the mutant allele-specific amplification method. For the retrospective study on patient outcomes, 194 patients who had undergone liver resections between 1980 and 2000 were analyzed according to their SMs. RESULTS: Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and p53 gene mutations or both. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm of the tumor border. Micrometastases via Glisson pedicle were more common (14.3% [3/21]), but these were also confined to a short distance from the tumor edge (相似文献   

Clinical features of a form of Hirschsprung's disease caused by a novel genetic abnormality

Background/Purpose: The aim of this report is to describe the pattern of similarities among the patients, exemplifying a newly recognized form of Hirschsprung's disease (HSCR) caused by mutations of ZFHX1B encoding Smad interacting protein-1. Methods: Fluorescence in situ hybridization (FISH) using several cDNAs and RP11-BAC clones and mutation gene scanning using direct nucleotide sequencing analysis of polymerase chain reaction (PCR) were conducted. Personal records of the patients also were analyzed retrospectively to confirm the clinical features. Results: All the patients represented isolated cases without any familial tendency. Aganglionic segments were limited to the recto-sigmoid colon in 3 cases and the rectum in one. Chromosomal screening found normal karyotypes in all cases except one, in whom a translocation between chromosomes 2 and 13 was detected. In addition to HSCR, characteristic facial appearance (hypertelorism with strabismus and wide nasal bridge), microcephaly with epilepsy, and severe physical and mental disabilities were found in all the patients. FISH for the patient having the chromosomal abnormality showed that about a 5-Mb cytogenetic deletion flanked at the 2q22 translocation breakpoint. Among 3 genes mapping to this deleted region, 2 nonsense mutations and a 4-base pair deletion were detected in ZFHX1B.Conclusions: The clinical features of the patients have surprising resemblance and constitute a wide spectrum of neurocristopathies. These findings suggest that the ZFHX1B may be a very important gene for normal embryonic neural crest development. These also indicate that the HSCR can be regarded as a congenital malformation with a background of a multigenetic neurocristopathy. It is of great interest that mutations were located at the same spot (exon 8) of ZFHX1B in 3 of 4 cases, probably accounting for the unique clinical features of this newly recognized form of HSCR. J Pediatr Surg 37:1117-1122.