A case report of a family with Peutz-Jeghers syndrome

A 58-year-old female was admitted because of colicky abdominal pain. Physical examination revealed firm abdominal wall, increased bowel sounds and multiple pigmented macules on the lips, oral mucosa, soles and volar aspects of the fingers and toes. Hyperventilation and tetanic rigidity of the extremities were also noted. The symptoms were successfully treated by intravenous injection of butropium bromide and diazepam. Roentgenological and fiberscopic examination revealed multiple polyps in the stomach, small intestine and colon ; the small intestine was most heavily loaded with polyps. Biopsy specimen revealed only inflammatory changes. The patient had undergone a resectien of the terminal ileum with polyps 15 years previously because of ileo-ileal intussusception. Histological re-evaluation of the polyp showed an actively proliferating papillary adenoma. The characteristic history and gastrointestinal findings lead us to the examination of the family, which revealed that her father, son and grandson had similar pigmentation of the skin and polyps in the gastrointestinal tract. These characteristic findings and family history permitted us to make a diagnosis of Peutz-Jeghers syndrome. The diagnosis had been missed supposedly because of unawareness of the skin lesions and the lack of hamartoma-like findings in the polyp. The tetanic rigidity of the extremities was probably hyperventilation syndrome induced by severe abdominal pain. The patient has been followed up for possible recurrence of symptoms and a potential malignant change

Morphologic change of Yoshida sarcoma cells and coelothelioma cells after exposing to the cell toxin from X-ray-irradiated animal

The unsaturated fatty acid fraction extracted from the liver of rabbit irradiated with X-rays exerts a strong cytotoxic effect on human coelothelioma cells and Yoshida sarcoma cells both in vitro and in vivo. The cell damage seems to initiate at the nucleus, finally leading to the complete cytolysis. The inhibiting effect of this substance on the mitosis of Yoshida sarcoma cells can be observed, especially marked from prophase up to metaphase giving almost the same results obtained after X-ray irradiation. From these results and the observations reported by several authors on the cell damage by X-ray irradiation, weshould call special attention to the fact that the essential mechanism of X-ray irradiation can be attributed to the cell toxin produced after the irradiation.</p

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout

AbstractBy using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic β cells. By contrast, hDTR was expressed in the pancreatic β cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic β cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34+ human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic β cells of these Tg mice is highly useful for diabetogenic research

Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse

<p>Abstract</p> <p>Background</p> <p>Several lines of evidence indicate that memory loss represents a synaptic failure caused by soluble amyloid β (Aβ) oligomers. However, the pathological relevance of Aβ oligomers (AβOs) as the trigger of synaptic or neuronal degeneration, and the possible mechanism underlying the neurotoxic action of endogenous AβOs remain to be determined.</p> <p>Results</p> <p>To specifically target toxic AβOs <it>in vivo</it>, monoclonal antibodies (1A9 and 2C3) specific to them were generated using a novel design method. 1A9 and 2C3 specifically recognize soluble AβOs larger than 35-mers and pentamers on Blue native polyacrylamide gel electrophoresis, respectively. Biophysical and structural analysis by atomic force microscopy (AFM) revealed that neurotoxic 1A9 and 2C3 oligomeric conformers displayed non-fibrilar, relatively spherical structure. Of note, such AβOs were taken up by neuroblastoma (SH-SY5Y) cell, resulted in neuronal death. In humans, immunohistochemical analysis employing 1A9 or 2C3 revealed that 1A9 and 2C3 stain intraneuronal granules accumulated in the perikaryon of pyramidal neurons and some diffuse plaques. Fluoro Jade-B binding assay also revealed 1A9- or 2C3-stained neurons, indicating their impending degeneration. In a long-term low-dose prophylactic trial using active 1A9 or 2C3 antibody, we found that passive immunization protected a mouse model of Alzheimer's disease (AD) from memory deficits, synaptic degeneration, promotion of intraneuronal AβOs, and neuronal degeneration. Because the primary antitoxic action of 1A9 and 2C3 occurs outside neurons, our results suggest that extracellular AβOs initiate the AD toxic process and intraneuronal AβOs may worsen neuronal degeneration and memory loss.</p> <p>Conclusion</p> <p>Now, we have evidence that HMW-AβOs are among the earliest manifestation of the AD toxic process in mice and humans. We are certain that our studies move us closer to our goal of finding a therapeutic target and/or confirming the relevance of our therapeutic strategy.</p