Isolated primary malignant lymphoma arising from the optic chiasm

Isolated primary malignant lymphoma rarely arises from the anterior visual pathway. A 59-year-old previously healthy man presented with progressive, painless, bilateral visual disturbance. Neurological imaging revealed an enhancing mass arising from the optic chiasm. Open biopsy was carried out under monitoring of visual evoked potentials and a histopathological diagnosis of diffuse large B-cell lymphoma was made. As systemic examination did not show any evidence of systemic lymphoma, we concluded that this patient had an isolated primary malignant lymphoma at the anterior visual pathway.     

Identification and structure–activity relationship of purine derivatives as novel MTH1 inhibitors

The human mutT homolog‐1 (MTH1) protein prevents the incorporation of oxidized nucleotides such as 2‐OH‐dATP and 8‐oxo‐dGTP during DNA replication by hydrolyzing them into their corresponding monophosphates. It was found previously that cancer cells could tolerate oxidative stress due to this enzymatic activity of MTH1 and its inhibition could be a promising approach to treat several types of cancer. This finding has been challenged recently with increasing line of evidence suggesting that the cancer cell‐killing effects of MTH1 inhibitors may be related to their engagement of off‐targets. We have previously reported a few purine‐based MTH1 inhibitors that enabled us to elucidate the dispensability of MTH1 in cancer cell survival. Here, we provide a detailed process of the identification of purine‐based MTH1 inhibitors. Several new compounds with potency in the submicromolar range are disclosed. Furthermore, the structure–activity relationship and associated binding mode prediction using molecular docking have provided insights for the development of highly potent MTH1 inhibitors.     

A nationwide analysis of renal and patient outcomes for adults with lupus nephritis in Japan

Clinical and Experimental Nephrology - The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This...     

Prevention of stroke and dementia by statin therapy: experimental and clinical evidence of their pleiotropic effects

Stroke and dementia are major causes of disability in most countries. Epidemiological studies have demonstrated that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are likely to reduce the risk for developing these formidable disorders. The favorable outcomes in statin users may be attributable to not only cholesterol-dependent actions, but also various cholesterol-independent actions called "pleiotropic effects." Several clinical trials have suggested that statins decrease the incidence of stroke, especially ischemic stroke. Statins improve endothelial function, inhibit platelet activation, reduce blood coagulability, and suppress inflammatory reactions, all of which may contribute to the beneficial effects of the therapy. Statins also reduce the risk of vasospasm caused by subarachnoid hemorrhage (SAH). In addition, statins might inhibit the development and progression of Alzheimer's disease (AD), the dominant type of dementia in most industrialized countries, upstream of the amyloid cascade. In vitro studies have shown that statins modulate the metabolism of the beta-amyloid precursor protein (APP) and reduce the extracellular level of its proteolytic product, amyloid-beta (Abeta). The aggregated Abeta is cytotoxic, leading to formation of neurofibrillary tangles and neuronal loss in the brain. Inflammatory processes are active in AD and may contribute significantly to AD pathology. We review the experimental background regarding the pleiotropic effects of statins and summarize clinical trials that examined the preventative effects of statin therapy on stroke and dementia. We include current trials in which statin therapy is initiated within 24 hr of onset of acute ischemic stroke.     

Prognosis following emergency surgery for ulcerative colitis in elderly patients

Purpose

Since 2000, the incidence of ulcerative colitis (UC) in patients over 60 years old has been rapidly increasing. We reviewed our surgical experience of elderly patients with UC treated at our hospital.

Methods

Patients aged 60 years or older at the time of surgery were defined as “elderly”. The medical records of all elderly patients who underwent surgery for UC during a 26-year period were retrospectively analyzed.

Results

The prognosis of elderly patients who underwent emergency surgery was extremely poor: 8 (26.7 %) of 30 such patients died within 30 postoperative days (PODs), whereas only 1 (0.88 %) of 114 who underwent elective surgery died within 30 PODs. Respiratory tract infection and sepsis resulting from methicillin-resistant Staphylococcus aureus or mycotic infection were the most common causes of death after emergency surgery.

Conclusion

The prognosis of elderly UC patients undergoing emergency surgery is very poor; thus, physicians and surgeons should collaborate to treat severe and fulminant disease, to optimize the timing of surgery. Early decisions about emergency surgery for UC will reduce postoperative mortality, especially in elderly patients.     

Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.     

Agglutination of Jelly Coat and Cortical Granule Components and the Block to Polyspermy in the Amphibian Xenopus laevis

A block to polyspermy in amphibians is established at fertilization by the conversion of the vitelline envelope to the fertilization envelope. In Xenopus laevis a major ultrastructural change in the envelope at fertilization is the appearance of an electron-dense layer, termed the F layer, between the envelope and the inner-most jelly coat layer, J(1). The F layer is derived, at least in part, from materials released from the cortical granules. Further definition of the origin and chemical nature of the F layer was sought by using isolated cortical granule (CG) exudate and jelly coat layer J(1). In double diffusion experiments, the isolated components interacted in an agglutination reaction producing a band of precipitation. The agglutination involved alpha-galactoside residues and metal ions (Ca(++)). Employing chemically modified jelly, we demonstrated that sulfhydryl-disulfide interchanges were not involved in the agglutination and, with (35)S-labeled jelly, that the agglutinating J(1) component possessed sulfate esters. Both the CG exudate and the J(1) components contained carbohydrate, as evidenced by their lectin reactivity. A number of ionic polymers, both natural and synthetic, were tested as chemical analogs of CG exudate and J(1); none gave an agglutination band. Dissolved jelly coat material from eggs of two different species of frogs agglutinated with CG exudate, while jelly from sea urchin eggs and hyaluronic acid from mammalian eggs did not. Thus, the agglutination reaction was chemically and phylogenetically specific. An electron-dense layer, similar to the F layer, formed on the outer of the vitelline envelope when jellied unfertilized eggs were immersed in CG exudate; such eggs were not fertilizable. We suggest that in Xenopus laevis, and perhaps other organisms as well, an agglutination type of reaction between cortical granule components and egg integuments is a participant in the structural and molecular events establishing a block to polyspermy.     

Basic studies on a labeled anti-mucin antibody detectable by infrared-fluorescence endoscopy

Background. We developed a fluorescent dye, indocyanine green (ICG)-sulfo-OSu, which was excited by infrared rays and conjugated to various antibodies. We attempted to clarify the staining patterns of anti-sulfomucin and anti-MUC1 antibodies in gastrointestinal cancer. We then evaluated the potential of the dye as a fluorescent label for antibodies specific to cancer, to be used as a diagnostic method for microcancer, with infrared fluorescence endoscopy. Methods. Paraffin sections of samples collected from 10 patients with esophageal cancer, 30 patients with gastric cancer, and 20 patients with colorectal cancer were immunohistologically stained using an anti-sulfomucin antibody and an anti-MUC1 antibody, and the staining patterns were examined. If a section had a high staining intensity, it was reacted with the ICG-suflo-OSu-labeled antibody and evaluated with infrared fluorescence imaging. Results. The staining patterns with the antibodies varied depending on the organs and the histological types and depth of the cancers, but the staining was generally good and the staining on the mucosal surface of cancer tissues was retained. Good images of cancer cells could be obtained by infrared fluorescence observation using the ICG-sulfo-OSu-labeled anti-MUC1 antibody. Conclusions. The anti-MUC1 antibody stained gastrointestinal cancer cells well, and nearly specific infrared fluorescence in cancer tissues was observed using the labeled anti-MUC1 antibody. The ICG-sulfo-OSu-labeled anti-MUC1 antibody has possible usefulness for the screening of cancer via infrared fluorescence endoscopy. Received: December 8, 2000 / Accepted: September 28, 2001