Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

All-in-One Silk Fibroin Sponge as the Vitrification Cryodevice of Rat Pancreatic Islets and the VEGF-Embedded Scaffold for Subrenal Transplantation

Islet transplantation is a promising option for the clinical treatment of insulin-dependent diabetes, but a reliable islet cryopreservation/transplantation protocol should be established to overcome the donor shortage. The current study reports that a silk fibroin (SF) sponge disk can be used as a cryodevice for vitrification of large quantity pancreatic islets and the scaffold for subsequent subrenal transplantation in a rat model. The marginal islet mass (550 islet equivalents [IEQs]) on an SF sponge disk was vitrified-warmed and transplanted beneath the kidney capsule of a streptozotocin-induced diabetic rat with or without vascular endothelial growth factor (VEGF). Subrenal transplantation (no scaffold) of 550 IEQ fresh islets and post-warm islets vitrified on a nylon mesh device resulted in achieving euglycemia of recipient rats at 60% and 0%, respectively. Transplantation of 550 IEQ islets vitrified-warmed on an SF sponge disk failed to achieve euglycemia of recipient rats (0%), but the VEGF inclusion in the SF sponge disk contributed to acquiring the euglycemic recipients (33%). All cured recipient rats regained hyperglycemia after nephrectomy, and the histopathologic analysis exhibited a well-developing blood vessel network into the islet engrafts. Thus, an SF sponge disc was successively available as the cryodevice for islet vitrification, the transporter of the angiogenic VEGF, and the scaffold for subrenal transplantation in the rat model.     

Relationship between HLA-DR Antigen and HLA-DRB1 Alleles and Prostate Cancer in Japanese Men

Purpose: Human leukocyte antigens (HLA) are cell surface glyco-proteins playing a key role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumour cells may escape host immunity. We investigated the relationship between HLA, especially class II, molecules and prostate cancer in Japanese men using molecular techniques. Materials and methods: HLA class II typing was performed by the polymerase chain reaction-sequence specific primer (PCR-SSP) method of analysis and/or a commercial rapid assay based on the PCR followed by reverse dot-blot hybridization of the PCR products (Inno-LiPA assay). Allele frequencies were calculated. HLA allele frequencies reported in 1216 healthy Japanese individuals were used as the control data. Differences in allele frequency between subjects and the control group were analyzed by the chi-square test. The relationship between HLA antigens/alleles and prostate cancer is expressed in terms of relative risk (RR). Results: The frequencies of HLA-DR4 were significantly higher in Japanese men with prostate cancer than in the healthy control group (gene frequency 36.2% vs. 26.3% in control, p<0.05), although the relative risk of prostate cancer was less than 2. Furthermore, the frequencies of HLA-DRB1-0406, 0410 and 1405 allele were significantly higher in the prostate cancer group than in the control group (allele frequency was 7.3%, 4.5% and 5.4% vs. 3.03%, 1.79% and 2.22%, p<0.05, respectively). RR of those HLA-DRB1 allele for prostate cancer was 2.6 in each allele. Conclusions: HLA molecules may be useful for the early detection of prostate cancer as a risk factor, and also for recognizing cancer activity by using them as a marker helpful in the choice of appropriate treatment by predicting prognosis.     

Adolescent smoking behavior in Japan, 1996.

We conducted second nationwide survey on smoking behavior among Japanese high school students. The survey was a cross-sectional sampling survey. The survey's targets were junior and senior high schools throughout Japan. Sample schools were selected by stratified cluster sampling. Self-administered anonymous questionnaires were sent to sample schools for all students to fill out. 65.6% of the junior high schools and 67.0% of the senior high schools were responded to this survey. A total of 117,325 students responded and 115,814 questionnaires were subjected to analysis. 7.5% of boys and 3.8% of girls in the 1st grade of junior high school were classified as current smokers, compared with 36.9% of boys and 15.6% of girls in 3rd grade of senior high school. Less than 1% of boys and girls in the 1st grade of junior high school were classified as daily smokers, this figure increased markedly by the 3rd grade of senior high school to reach 25.4% of boys and 7.1% of girls. Of students in the 3rd grade of senior high school, 21.2% of boys and 9.9% of girls had tried smoking before 13 year of age. Cigarette consumption also increased with age, although the proportion of those smoking 20 or more cigarettes per day did not. The major source for cigarettes among current smokers was vending machines. This survey revealed that smoking prevalence among Japanese high school students has already reached quite high level. Comprehensive energetic measures for control minor smoking are necessary in Japan.     

pH,base deficit or lactate. Which is better for predicting neonatal morbidity?

Objective: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term.

Method: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH?≤?7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index.

Results: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH?≤?7.0 and lactate?≥?7.0?mmol/L presented similar validity to that of pH?≤?7.0 and BD?≥?12?mmol/L, but both were comparable to pH alone.

Conclusions: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes.     

Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34<Superscript>+</Superscript> cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.     

Reorganized small intestine from fetal mouse as an in vitro wound healing model

BACKGROUND: We developed a method for reorganizing the mouse small intestine. In the present study, we investigated whether the reorganized small intestine was morphologically and histochemically differentiated. We also evaluated the reorganized small intestine as an in vitro wound healing model. METHODS: Fetal mouse small intestines were dispersed into single cells, which were then cultured to a high density. Newly formed small intestine-like organs on a membrane filter were observed by light and electron microscopy. Alkaline phosphatase (ALPase) activity of the epithelium was analyzed. To evaluate the reorganized small intestine as an in vitro wound healing model, a scalpel was used to cut the reorganized intestine on a membrane, and the healing process was morphologically and immunohistochemically examined. RESULTS: After 6 days in culture, the surface was almost completely coveed with epithelial cells, and villus-like structures were observed. These epithelial cells formed microvilli, and in parallel with this development, ALPase activity of the microvilli increased (from day 4). Twenty-four hours after the cutting, the wound surface was almost completely covered with undifferentiated epithelial cells. The number of acetylated low-density lipoprotein labeled with 1,1,dioctadecyll,3,3,3,3, tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL)-positive macrophages increased after cutting. Platelet-derived growth factor (PDGF)-, basic fibroblast growth factor (bFGF)-, matrix metalloproteinase-1 (MMP-1)-positive cells were detected by immunohistochemical staining. CONCLUSIONS: The reorganized small intestine had a morphologically and histochemically differentiated organoid structure, and was useful as an in vitro model for investigating the process of wound healing.     

Blockade of menstrual cycle by thyroidectomy in Japanese monkeys (Macaca fuscata fuscata)

To examine the role of thyroid hormones in the seasonal breeding cycle in Japanese monkeys (Macaca fuscata fuscata), sexually mature females were thyroidectomized (n=6) in early December, during the midbreeding season, or they received sham operations (n=4). They were housed indoors individually, and blood samples were collected two to three times a week to monitor gonadotropin and gonadal steroid hormone secretions. Control monkeys exhibited ovulatory cycles during the breeding season. The mean dates of onset and end of the ovulatory cycles were October 22±13 d and February 25±14 d, respectively. These dates coincided well with those of our colonies under captivity. By contrast, three of the six thyroidectomized monkeys terminated ovulatory cycles immediately after operations; the remaining three monkeys ovulated only once or twice after thyroid removal. The mean dates of onset and end of the ovulatory cycles of thyroidectomized monkeys were October 18±4 d and December 31±4 d, respectively. This was a significantly earlier termination of the ovulatory cycles than in controls. Mean concentrations of plasma thyroxine of control monkeys were maintained throughout the experimental period, whereas plasma thyroxine concentrations of thyroidectomized monkeys decreased abruptly to undetectable levels. Thyroidectomized monkeys exhibited significantly higher levels of plasma prolactin (PRL) than controls. Moreover, even in control monkeys, plasma PRL increased during the transition out of the breeding season. These results suggest that thyroid hormones play an important role in the regulation of ovulatory cycles in Japanese monkeys, directory or indirectly, possibly by mediating the changes of PRL secretion.