Bilateral submandibular sialadenitis following influenza A virus infection.

A 48-year-old male presented to our hospital with pyrexia and general fatigue. The patient was diagnosed with influenza A virus infection, and then given laninamivir octanoate hydrate. Eleven days after onset, he noticed bilateral swollen submandibular glands. He visited our hospital again, and underwent blood examination and cervical computed tomography (CT). CT indicated that bilateral submandibular glands were swelling. We believe that this is the first report of bilateral submandibular sialadenitis following influenza A virus infection, and thus we presented this patient.

Effect of plasma exchange on refractory hemophagocytic syndrome complicated with myelodysplastic syndrome.

A case of hemophagocytic syndrome (HPS) refractory to corticosteroid therapy was successfully treated by plasma exchange. The patient was a 56-year-old woman who had undergone regular hemodialysis for 10 years for complicated myelodysplastic syndrome (MDS) and then had had lung tuberculosis. After the onset of tuberculosis, she suffered from HPS and was treated by antituberculosis agents and high dose corticosteroid administration without any effect on the HPS. After adding a series of plasma exchanges, the HPS improved gradually, and her MDS began to respond to corticosteroid therapy. Plasma hypercytokinemia due to HPS was corrected by plasma exchange, and the correction of a high level of plasma inflammatory cytokine was considered to be one of the contributing factors for the improvement of HPS. These results suggest that therapeutic plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.

Estimation of glycogen levels in human colorectal cancer tissue: relationship with cell cycle and tumor outgrowth.

In this study, we quantitatively measured glycogen levels in tissue samples obtained from tumors, regions adjacent to tumor, and regions of normal colorectum to determine whether the levels were related to cell cycle and cancer growth. Glycogen levels were analyzed in relation to histopathological factors, (tumor size and stage of disease) and cell cycle progression. The glycogen level was found to be highest in the cancer tissue, lower in normal tissue, and lowest in the adjacent tissue. The difference in glycogen level between the cancer tissue and the other two regions was significant (P < 0.05). There was a negative correlation between glycogen level and tumor size, but it was not significant. The level of glycogen in cancer tissues decreased as the stage of the disease progressed, but a significant difference was not found between stages. There was a negative correlation between the glycogen level and the proliferation index. There was a positive correlation between the glycogen level and the proportion of cancer cells in G1 phase, while there was a negative correlation with S and G2M phases. Glycogen levels were highest in cancers with a high proportion of cells in G1, and decreased with progression to S phase. It may be that glycogen is utilized in the progression to S phase, and the cancer tissues are supplied with glycogen from the tumors themselves as well as their adjacent tissues. Cancer growth may be inhibited by artificial control of the glycogen level in the G1 phase of cancer cells.

Reactive oxygen species as a risk factor in verotoxin-1-exposed rats.

It has been suggested the the interaction of Escherichia coli O157-derived verotoxins (VTs) with the vascular endothelium plays a central role in the pathogenesis of the thrombotic microangiopathy and ischemic lesions characteristic of hemolytic uremic syndrome (HUS) and E. coli O157-associated hemorrhagic colitis. Intravenous administration of both E. coli O157-derived VT1 and lipopolysaccharide (LPS) in the rat induced a synergistic increase in thiobarbituric acid (TBA) values in those animal's plasma, as compared with that injected with VT1 or LPS alone. We then hypothesized that an increase in lipid peroxidation in the rat plasma was due to an enhanced production of endothelial cell-derived reactive oxidant. Based on determination of rat sera and cultured human aortic endothelial cells (HAECs), VT1 had little if any effect on LPS-stimulated increase of nitric oxide and the resultant peroxynitrite generations. Both RT-PCR and Western blot studies of reactive oxygen species-related enzymes showed that VT1 markedly decreased the expression of catalase mRNA and protein in HAECs, but caused less alteration in the levels of Cu, Zn-superoxide dismutase, and NADPH oxidase mRNA. Further studies by spin trapping analysis using 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) revealed a time-dependent increase in hydroxyl radicals by VT1 in HAECs. The accumulated data thus suggest that bacterial VT1 reduces mainly catalase levels in endothelial cells, which is synergistically potentiated by LPS, and that the resulting hydroxyl radical participates in endothelium injury through a marked enhancement of lipid peroxidation, leading to HUS.

[Changes in nitric oxide-related compounds in endotoxemic rats].

NO-related compounds in the blood of septic rats were examined by chemiluminescence method. Rats were treated with 5 mg/kg or 10 mg/kg lipopolysaccharides (LPS) and followed for 30 h. We have determined and evaluated the concentrations of the total NO-related compounds in whole blood (Total-NO), those in plasma (Plasma-NO) and membrane bound-NO (Membranous-NO) in erythrocytes from the LPS-challenged rats. 1) Levels of Plasma-NO after 3 h and Membranous-NO after 7 h in the rats were significantly increased, peaked at 14 h, and then restored to control levels at 30 h. 2) At 7 h in the rats, latter NO levels were exhibited within 10 nM/mg protein. 3) The existence of Membranous-NO can be confirmed by the in vitro experiments of rat erythrocytes incubating with different NO-donors, NOC-3 or SIN-1. 4) Taken together, the determination of Membranous-NO may be an additional marker for pathophysiological states of septic stress.

Plasma exchange for thrombocytopenia in antiphospholipid syndrome: a case report.

The remarkable effect of plasma exchange (PE) was observed on thrombocytopenia in a patient with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus. Three times PE led to recovery from severe thrombocytopenia refractory to treatment with corticosteroid, anticoagulant, and antiplatelet drugs accompanied by a decrease in the serum cardiolipin beta2 glycoprotein I antibody level. This result suggests that PE is a valuable therapeutic tool for refractory thrombocytopenia in APS.

[Clinical features of Japanese children infected with Cryptosporidium parvum during a massive outbreak caused by contaminated water supply].

A massive outbreak of cryptosporidiosis occurred at a local town of Saitama Prefecture, in 1996. During this outbreak, we investigated the clinical features of children seen at Saitama Medical School. Cryptosporidium parvum (C. parvum) was detected from 10 out of 28 (36%) children with diarrhea during June and August, 1996. The average ages of the children who were positive and negative for C. parvum were 6.5 and 5 year old, respectively. Among the children infected with C. parvum, colic pain was observed in 3 children and 4 children had vomiting. However, none of the children showed fever over 38.0 degrees C nor bloody stools. Family members of children infected with C. parvum also had diarrhea and/or vomiting (5/6). C. parvum was repeatedly detected from 2 out of 3 children. All infected children had an improvement of abdominal symptoms in 4 to 10 days. C. parvum should be included as a pathogen which causes enterocolitis in Japanese children.

An assay method for nitric oxide-related compounds in whole blood.

Recent evidence suggests that nitric oxide (NO) generated in vivo will be converted into the forms of nitrite/nitrate, nitrosyl hemoproteins, nitrosyl metal complexes, and S-nitroso-compounds in the circulation. Nitrosothiols have also been reported to be relatively stable metabolites with micromolar levels in plasma. We hypothesized, therefore, that the determinations of all the NO-related compounds in blood would be of diagnostic significance. The assay method described here consists of the thermolysis of all the NO-related compounds in whole blood and the detection of resulting nitrate by fluorometry or chemiluminescence after an enzymatic reduction. S-Nitroso-albumin and nitrosyl hemoglobin can be easily thermolysed to nitrate, and relatively stable S-nitroso-glutathione is also degraded to nitrate in the presence of blood constituents with high molecular mass (above 30 kDa). Concentrations of NO-related compounds in blood from healthy human as well as control or lipopolysaccharide-stimulated rats were determined. We found that membrane-bound NO which showed the augmented levels under the pathophysiological states could also be detected. Together with electron spin resonance spectra, our data indicate that the fraction of NO diffused and metabolized within red cells and the other NO-metabolites in plasma such as nitrite/nitrate and S-nitroso-compounds, both of which can reflect NO-production in vivo, would be recovered and detected quantitatively by this method.

Serum Soluble Interleukin-2 Receptor Levels in Patients with Breast Cancer.

Preoperative levels of serum soluble interleukin-2 receptor (1L-2R) were examined in 37 patients with breast cancer. We investigated the correlations of serum soluble IL-2R levels with various factors such as stage grouping, lymph node metastasis, distant metastasis, tumor size, histophthological type, estrogen receptor (ER), progesterone receptor (PgR) and CA 15-3. Serum soluble 1L-2R levels were measured with an enzyme-linked immunosorbent assay. Levels of serum soluble 1L-2R in the patients with stage III and IV breast cancer were significantly higher than those in the normal controls, and patients with stage I and II breast cancer. Preoperative levels of serum soluble IL-2R in patients with T3 and T4 were also significantly higher than those in patients with T1 and T2. Serum levels of IL-2R in patients with distant metastasis were also significantly higher than those in patients without distant metastasis. Moreover, serum levels of soluble IL-2R in patients with higher CA 15-3 were significantly higher than those in patients with normal CA 15-3 levels. We conclude that preoperative serum soluble IL-2R levels in patients with breast cancer may be a valuable parameter, especially in evaluating whether they have distant metastasis or not.

Tissue superoxide dismutase (SOD) activity and immunohistochemical staining in acute appendicitis: correlation with degree of inflammation.

The mechanism of progression of appendicitis has not been clarified. We examined tissue superoxide dismutase (SOD) activity, thiobarbituric acid reactive substance (TBARS), and the localization of Cu, Zn-SOD in 56 inflamed appendices in relation to histopathological classification. There was a significant difference in SOD activity between catarrhal appendix and phlegmonous and gangrenous appendix (2.3 +/- 0.1 vs 5.0 +/- 0.2 and 4.6 +/- 0.6 units/mg protein, respectively P < 0.05). TBARS value was highest in gangrenous appendix, being significantly different from the levels in the other two types (0.47 +/- 0.04 vs 0.19 +/- 0.01 n mol/mg protein, in catarrhal and 0.20 +/- 0.02, in phlegmonous appendix P < 0.05). Positive staining for Cu, Zn-SOD was demonstrated in 64% of catarrhal appendices, 96% of phlegmonous appendices, and 75% of gangrenous appendices, and intense positive staining was recognized in 9%, 28%, and 40% of these appendices, respectively. These results indicated that active oxygen influences the degree of inflammation in phlegmonous and gangrenous appendicitis. Gangrenous appendicitis and the other two types of appendicitis seemed to be different entities.

Serum soluble interleukin-2 receptor and immunohistochemical staining of IL-2R/Tac antigen in gastric cancer.

In the present study, we investigated the significance of serum soluble IL-2R as a tumor marker, and examined the existence and localization of positive cells for IL-2R/Tac antigen in gastric cancer tissues and its regional lymph nodes. Eighty-two patients with gastric cancer were included. Levels of serum soluble-IL-2R were measured by an enzyme-linked immunosorbent assay. In the tissues obtained from 19 cases, immunohistochemical staining was performed with the use of avidin-biotin-peroxidase complex technique, in which mouse anti-human interleukin-2 receptor antibody was used. The preoperative levels of serum soluble IL-2R in patients-with gastric cancer were significantly higher than those of normal controls (p<0.001). The levels of serum soluble IL-2R in cases with metastatic lymph nodes were also significantly higher than those without metastatic lymph nodes (p<0.05). Concerning the tumor markers, there were significant differences of serum soluble IL-2R levels between those who were positive and those negative for CA19-9, CEA, alpha-FTP, and IAP. In the immunohistochemical staining of IL-2R, 13 of 19 cases (68.4%) showed IL-2R positive cells in the gastric cancer tissues. In regard to the metastatic lymph nodes, 3 of 5 cases (60.0%) showed IL-2R positive cells. On the other hand, IL-2R positive cells were not recognized in normal gastric tissues and non-metastatic lymph nodes. These results may suggest that activated T-lymphocytes infiltrating into the cancer tissues play an antitumor role and release a large amount of alpha-chain of IL-2R, resulting in the high levels of serum soluble IL-2R in patients with gastric cancer.

Significance of superoxide dismutase (SOD) in human colorectal cancer tissue: correlation with malignant intensity.

The significance of superoxide dismutase (SOD) activity in colorectal cancer tissue was determined from the aspect of the antioxidant defense system. SOD activity and thiobarbituric acid reactive substance were measured in the tumor, in tissues adjacent to the tumor, and in regions that appeared normal, and the results were analyzed in terms of various histopathological factors (stage of disease, depth of invasion, venous invasion, etc.). DNA ploidy pattern and cell proliferation in cancer tissue were also measured, and the results analyzed in relation to SOD activity. SOD activity in cancer tissue was higher than in the other two regions. SOD activity in cancer tissue increased with the progression of stage, and changed with the depth of invasion. There was a significant difference in SOD activity between patients with venous invasion and those in whom this was absent. Stepwise regression analysis suggested that venous invasion was the most significant factor influencing SOD activity. The proliferation index was high in cancer tissue with low SOD activity. The incidence of aneuploidy was high in cancer with high SOD activity, whereas the incidence of diploidy was high in cancer with low SOD activity. These results suggest that elucidation of the antioxidant system in cancer tissue can provide us with a better strategy for cancer treatment.

Serum-soluble interleukin-2 receptor levels before and after surgical treatment for Graves' disease.

Serum-soluble interleukin-2 receptor (ssIL-2R) is released from its specific affinity membrane receptor on activated T lymphocytes and is detected as a form of the alpha-chain of IL-2R in the peripheral blood. We measured the ssIL-2R levels by enzyme-linked immunosorbent assay in 29 healthy subjects and 39 patients with Graves' disease who were given antithyroid drugs to prepare them for surgical treatment. The preoperative ssIL-2R levels in Graves' patients were significantly higher than those in the healthy controls (681 +/- 387 vs 369 +/- 149 U/ml); in particular, the preoperative levels in hyperthyroid patients were significantly higher than those in euthyroid patients. On the 5th day after thyroid resection, their ssIL-2R levels (560 +/- 296 U/ml) were significantly lower than the preoperative levels. There were no correlations between the preoperative ssIL-2R levels and the immunological parameters such as thyroglobulin antibody, microsomal antibody, and thyroid-stimulating hormone receptor antibody. Thus, we conclude that ssIL-2R levels can be decreased by surgical resection of goiter in Graves' patients whose hyperthyroid status does not respond to the administration of antithyroid drugs, and this may be a useful indicator of immunological status after surgical treatment of Graves' disease.

Significance of increased neutrophils in patients with advanced colorectal cancer.

We examined the ratio of neutrophils to lymphocytes (N/L ratio) in the peripheral blood in patients with colorectal cancer. The ability to produce active oxygen and phagocytosis of neutrophils, G-CSF, sIL-2R and IAP (immunosuppressive acidic protein) were also measured. The N/L ratios were significantly higher in the advanced stages of cancer than in normal controls. The ability to produce active oxygen in the terminal stage was 33% lower than in the control group. The G-CSF levels had no relationship with the neutrophil counts. IAP levels increased with cancer stage, and were inversely related to the ability to produce active oxygen. The IAP levels correlated well with the sIL-2R levels and the N/L ratio. These findings suggest that the ability to produce active oxygen, N/L ratio and IAP reflect anticancer mechanisms and that they may be useful when considering treatment or prognosis of patients with advanced stages of cancer.

Multiple endocrine neoplasia type 1 presenting as insulinoma, gastrinoma, and postbulbar duodenal ulcers: report of a case.

We report herein the unusual case of a 55-year-old man with multiple endocrine neoplasia type 1 presenting as hyperparathyroidism, hyperpituitarism, insulinoma, and gastrinoma with postbulbar duodenal ulcers. The patient was referred to our hospital for further investigations of nephrolithiasis, acromegaly, and hematemesis. Laboratory studies showed high serum levels of calcium, parathyroid hormone, growth hormone, insulin, gastrin, and prolactin. Computed tomography of the cranial cavity demonstrated an enlargement of the serra turcica and swelling of two parathyroid glands in the neck. Computed tomography and angiography of the abdomen also showed a mass in the head of the pancreas. Endoscopy demonstrated reflux esophagitis, erosive gastritis, and multiple postbulbar duodenal ulcers. We diagnosed this patient as having multiple endocrine neoplasia type 1, with concomitant lesions of the pituitary gland, parathyroid glands, and islet cells of the pancreas. Following excision of the two enlarged parathyroid glands, his serum calcium and parathyroid hormone levels fell to within the normal range. Thereafter, a total gastrectomy was performed to alleviate the frequent bleeding from the upper gastrointestinal tract. However, resection of the pancreatic mass could not be performed owing to severe inflammation around the duodenum, probably induced by the postbulbar duodenal ulcers.

Serum-soluble interleukin-2 receptor concentrations in patients with gastric cancer.

BACKGROUND: Serum concentrations of soluble interleukin-2 receptor (IL-2R) were found to be high in patients with autoimmune diseases, lung cancer, malignant lymphoma, tuberculosis, and other diseases. Serum-soluble IL-2R was evaluated as a tumor maker in patients with gastric cancer. METHODS: Preoperative concentrations of serum-soluble IL-2R were examined in 40 patients with gastric cancer. The authors investigated the correlations of serum-soluble IL-2R concentrations with various characteristics of this cancer (disease stage, gross appearance, depth of the tumor, lymph node metastasis, liver metastasis, peritoneal metastasis, histopathologic grade, serum carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-FTP), carbohydrate antigen 19-9 (CA19-9), and immunosuppressive acidic protein (IAP). Serum soluble IL-2R concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: Levels of serum-soluble IL-2R in patients with gastric cancer were significantly higher than those of normal control subjects. Serum concentrations of IL-2R in patients with lymph node metastasis were also significantly higher than those of patients without lymph node metastasis. There were no significant differences in histopathologic findings (grade, lymphatic invasion, venous invasion). Moreover, serum concentrations of soluble IL-2R in patients who were IAP positive were significantly higher than those who were IAP negative. CONCLUSIONS: Preoperative serum-soluble IL-2R concentrations in patients with gastric cancer reflect the occurrence of regional lymph node metastases. Preoperative evaluation of serum soluble IL-2R concentrations may be a valuable parameter of indicating the probability of lymph node metastasis preoperatively.

Diazotization reaction of nitric oxide trapped by hemoglobin.

The present study addresses to determine whether hemoglobin within red blood cells can be utilized as a spin-trap agent for nitric oxide. We demonstrate the diazotization method coupled with a gel filtration chromatography, which is simply due to the separation of nitrosylhemoglobin from nitrite, nitrate or other low molecular nitroso-compounds in biological systems and to the liberation of nitric oxide from nitrosyl heme-complexes in the acidic condition. The amount of nitric oxide can be estimated by the difference of absorbances at 542 nm between diazo-compounds formed by Griess reagent and hemichrome by phosphoric acid. Our results indicate that hemoglobin in red cells as a spin-trap agent would be useful for monitoring nitric oxide in the circulation under the several disease states.