Serum Creatinine-Cystatin C Based Screening of Sarcopenia in Community Dwelling Older Adults: A Cross-Sectional Analysis.

OBJECTIVES: To compare the discriminative capabilities for the manifestation of sarcopenia or physical frailty between serum creatinine- and cystatin C-derived indices among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Primary Care and Community. PARTICIPANTS: We utilized a subset of data from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, which was initiated in 2015 to gather comprehensive information on various health-related parameters among community-dwelling older individuals (age ≥65 years). MEASUREMENTS: Five serum creatinine-cystatin C based indices including the Sarcopenia Index, the serum creatinine/cystatin C ratio, the disparity between serum cystatin-C-based and creatinine-based estimated GFR, the total body muscle mass index (TBMM), and the prediction equation for skeletal muscle mass index (pSMI) were employed. Sarcopenia and physical frailty were identified based on the Asian Working Group for Sarcopenia criteria and the revised Japanese version of the Cardiovascular Health Study criteria, respectively. The receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the discriminative abilities of these tools. RESULTS: In the analysis of 954 participants, 52 (5.5%) were identified with sarcopenia and 35 (3.7%) with physical frailty. Regarding sarcopenia discrimination, TBMM and pSMI both exhibited area under the curve (AUC) values exceeding 0.8 for both men and women. Concerning the identification of physical frailty, AUC values ranged from 0.61 to 0.77 for males and 0.50 to 0.69 for females. In the multivariate logistic regression analyses, only TBMM and pSMI consistently displayed associations with sarcopenia, irrespective of sex (P<0.001, respectively). On the other hand, no consistent associations were observed between the indices and physical frailty. CONCLUSIONS: This study provides a robust association of a serum creatinine- and cystatin C-derived indices, especially TBMM and pSMI, with sarcopenia among community-dwelling older adults. Conversely, the application of these indices for the screening of physical frailty has its constraints, necessitating further investigation.

Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer.

BACKGROUND: Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue and previous reports have suggested the possibility of serum miRNAs as complementary tumour markers. The aim of the study was to investigate serum miRNAs and pepsinogen levels in individuals at high risk for gastric cancer both before and after H. pylori eradication. METHODS: Patients with recent history of endoscopic resection for early gastric cancer and the sex- and age-matched controls were enrolled. Serum was collected from subjects before or after eradication and total RNA was extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II levels were measured using enzyme-linked immunosorbent assay kits. RESULTS: Using miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before and after H. pylori eradication and miR-21 after eradication were significantly higher in the high-risk group than in the controls. H. pylori eradication significantly decreased miR-106b levels and increased let-7d only in the control group. After eradication, the combination MiR-106b with miR-21 was superior to serum pepsinogen and the most valuable biomarker for the differentiating high-risk group from controls. CONCLUSION: Serum miR-106b and miR-21 may provide a novel and stable marker of increased risk for early gastric cancer after H. pylori eradication.

Temporal association of serum progesterone concentrations and vaginal cytology in walruses (Odobenus rosmarus).

Concentrations of serum estradiol-17ß and progesterone were monitored in six female walruses using an enzyme immunoassay. Progesterone concentrations increased from March to May in females aged 6 y or older, and subsequently declined (October). No significant elevation of estradiol-17ß concentration was detected before an elevation of progesterone concentration. Vaginal smears from four females were examined with Papanicolaou staining. In all females, most epithelial cells were basophilic intermediate-superficial cells; no color change from basophilic to eosinophilic of the cells was detected. Meanwhile, the percentage of anucleate cells in vaginal smears reached its highest value before the elevation of progesterone concentration, followed by an increase in the percentage of leukocytes. We inferred that the change in populations of anucleate cells and leukocytes in vaginal smears reflected ovarian status and CL formation in female walruses.

Daily fecal sex steroid hormonal changes and mating success in captive female cheetahs (Acinonyx jubatus) in Japan.

Daily fecal estrogen and progestin concentrations were measured by enzyme immunoassay in five female cheetahs (Acinonyx jubatus) for 4-6 months. The animals were housed under different conditions: (1) a female always housed in a group including one or more males; (2) two females isolated individually for short or long periods; (3) the other two females housed together. These females were separately housed with males for mating around the time of the estrogen peaks. The hormone profiles were similar in all five females regardless of the housing conditions. However, only the female that had been isolated from other cheetahs for over a year mated and reproduce cubs successfully, whereas the remaining four did not (one was isolated for only 6 weeks, another was always housed with males and the other two were housed together). In all females, the estrogen peaks were obtained at regular intervals of approximately 8-15 days. Unlike estrogen, the progestin concentrations were always low in all females except during pregnancy and they did not increase following the estrogen surges. These results showed that female cheetahs are typically reflex ovulators and female receptiveness may not be reflected to her hormonal states. It was also suspected that individual housing and long-term separation are advantageous for breeding this wild cat in captivity, mimicking the ecological/behavioral patterns in the wild, though housing condition might have no effect on the estrous cycle.

Anti-parietal cell antibody and serum pepsinogen assessment in screening for gastric carcinoma.

BACKGROUND: Anti-parietal cell antibody is found in patients with Helicobacter pylori-positive gastritis and is related to atrophic gastritis and gastric carcinoma. AIM: To identify the characteristics of patients at high-risk for gastric carcinoma in terms of anti-parietal cell antibody and serum pepsinogen. PATIENTS AND METHODS: Subjects were 92 H. pylori-positive patients (54 men, 38 women; mean age, 57.9 years; range, 15-88 years). The serum concentrations of pepsinogen I and II were determined by radioimmunoassay, and the presence of anti-parietal cell antibody was assessed by enzyme-linked immunosorbent assay. Degrees of inflammation and atrophy in the corpus of the stomach were evaluated histologically. RESULTS: Patients were classified into four groups according to anti-parietal cell antibody status and pepsinogen I/II ratio. Anti-parietal cell antibody-negative/pepsinogen I/II-low patients had the highest risk for gastric carcinoma (prevalence of gastric carcinoma: 7/13=53.8%, odds ratio=7.6, 95% confidence interval, 1.2-48.0). Anti-parietal cell antibody titre was high when inflammation in the corpus was severe (p=0.06) and significantly low when atrophy in the corpus was severe (p=0.01). CONCLUSION: Our results showed that patients with a negative anti-parietal cell antibody titre and low pepsinogen I/II ratio are at high-risk for gastric carcinoma.

Effect of famotidine on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer.

AIM: We investigated the effect of acid suppression therapy on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer. METHODS: A total of 400 patients with bleeding peptic ulcer received either intravenous infusion of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years) or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean age 59.8 years) after successful endoscopic treatment. The fasting duration, hospital stay, volume of transfused blood, incidence of rebleeding and mortality were compared between the two groups. RESULTS: The incidence of rebleeding did not differ significantly between the famotidine group (9%) and the omeprazole group (8%). The mean hospital stay was significantly shorter in the omeprazole group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However, there was no statistically significant difference in fasting duration, volume of transfused blood or mortality. CONCLUSION: Our findings indicate that intravenous infusion of famotidine after successful endoscopic treatment is equivalent to drip infusion of omeprazole for prevention of recurrent bleeding.

Effect of long-term half-dose famotidine therapy on corpus gastritis in peptic ulcer disease.

BACKGROUND: Recent studies showed that acid-suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection. AIM: The aim of this study was to evaluate the effect of famotidine, a histamine receptor antagonist on corpus gastritis in patients with peptic ulcer disease. METHODS: We enrolled 287 patients, 173 with duodenal ulcer and 114 with gastric ulcer and 100 patients with H. pylori-positive gastritis as control subjects. Patients with peptic ulcer were classified according to whether or not they received famotidine-maintenance therapy (20 mg/day) after primary treatment. At the time of endoscopy, biopsy specimens were obtained from the antrum and the corpus. The degrees of neutrophil and lymphocyte infiltration, atrophy and intestinal metaplasia were scored according to the updated Sydney System. RESULTS: The degrees of neutrophil infiltration and atrophy in the corpus were significantly less in patients with gastric ulcer or duodenal ulcer than in patients with H. pylori-positive gastritis (P < 0.01). Differences in the degrees of neutrophil infiltration and atrophy in the corpus between the non-maintenance group and the maintenance group were not significant. CONCLUSION: Long-term therapy with famotidine does not appear to lead to an increase in the incidence of corpus gastritis or corpus atrophy in patients with peptic ulcer disease.

Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan.

BACKGROUND: Eradication of Helicobacter pylori is expected to prevent the development of gastric cancer. However, gastric cancer is sometimes discovered after successful eradication of H. pylori. AIM: To conduct a prospective study to determine the clinical features of patients who underwent successful eradication and were later diagnosed with gastric cancer. METHODS: A total of 1787 patients (1299 males and 488 females; mean age, 58.2 years; range: 15-84) who underwent successful eradication therapy between April 1994 and March 2001 were our study subjects. RESULTS: Gastric cancer occurred at a rate of 1.1% (20 of 1787) during the follow-up period. Gastric cancer comprises six of 105 (5.7%) with early gastric cancer after endoscopic resection, 12 of 575 (2.1%) with gastric ulcer and two of 453 (0.4%) with atrophic gastritis. Gastric cancer did not develop in any patient with duodenal ulcer. All patients with gastric cancer had baseline severe atrophic gastritis in the corpus. CONCLUSION: Careful endoscopic examination is necessary even after successful eradication of H. pylori in patients with early gastric cancer or gastric ulcer with severe mucosal atrophy in the corpus.

The long-term effect of Helicobacter pylori eradication therapy on symptoms in dyspeptic patients with fundic atrophic gastritis.

AIM: To investigate whether curing Helicobacter pylori infection improves symptoms over the long-term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis. METHODS: Ninety H. pylori-positive dyspeptic patients with fundic atrophic gastritis were enrolled in this study. We performed a randomized double-blind placebo-controlled trial comparing triple therapy (n=45) with that of placebo alone (n=45). Inflammation and mucosal atrophy were scored according to the Updated Sydney System. Symptoms were scored on a scale of 0 to 3 for six items. Fasting samples of gastric juice were taken before endoscopy, and gastric pH was determined. Serum gastrin and pepsinogen levels were measured, and body mass index was determined. These patients were followed up for 3 years, and all measures were evaluated both before and after therapy. RESULTS: Significant improvement in dyspeptic symptoms and gastritis scores, significant decrease in gastric pH, and significant increase in body mass index were found after 3 years eradication in nonulcer dyspepsia patients treated successfully for H. pylori infection. There were no significant changes in the placebo group. CONCLUSION: Our study shows that eradicating of H. pylori results in significant long-term reduction in symptoms of nonulcer dyspepsia with fundic atrophic gastritis.

[A child case of subarachnoid hemorrhage triggered by head injury: a case report].

We report a case of basal subarachnoid hemorrhage in a child. The etiology of this lesion was difficult to diagnose. The patient was a 9-year-old boy. He sustained minor head injury followed by loss of consciousness and cardiopulmonary arrest. He was brought to our emergency room by ambulance. On arrival, he presented with cardiopulmonary arrest and deep comatose state. Basal subarachnoid hemorrhage was revealed on CAT scan. 3D-CTA documented two bulging portions: one was at the junction between the left vertebral artery and the left posterior inferior cerebellar artery. The other one was shown at the basilar artery. He died on the 7th hospital day. The autopsy revealed a laceration of the left vertebral artery. Microscopically, the wall around the laceration showed a defect in the internal elastic membrane and a decrease of smooth muscle cells with moderate fibrosis in the tunica media. These findings were compatible with the structure of a congenital aneurysm. Hence, the patient was strongly suspected to have had a congenital aneurysm whose rupture was triggered by minor head injury.

Serum progesterone and estradiol-17beta concentrations, and lapaloscopic observations of the ovary in the cheetah (Acinonyxjubatus) with pregnant mare serum gonadotropin and human chorionic gonadotropin treatments.

In 3 adult female cheetahs, induced-superovulation treatment was conducted, by means of 200 IU of pregnant mare serum gonadotropin (PMSG) and 100 IU of human chorionic gonadotropin (hCG) 80 hr after PMSG. The administration of PMSG created a sharp increase in the estradiol-17beta concentration, resulting in 232 pg/ml 8 hr later in one specimen out of three. The hCG administration showed an increase in the progesterone concentration of 2.29 ng/ml 46 hr later. In addition, after direct observation of the ovary surface by laparoscopy, 5 follicles in the right ovary over 2 mm in diameter, and 7 corpora lutea (5 in the right ovary and 2 in the left) were found. It is assumed that ovulation can be induced with hCG after 80 hr on PMSG during a cheetah's diestrus or proestrus.

Evaluation of flash echo imaging of the canine gastrointestinal tract.

Although it is important to assess gastrointestinal blood flow, no generally useful, noninvasive assessment method has been established. Harmonic flash echo imaging, which is an intermittent second harmonic imaging technique, has recently become available to evaluate blood flow. We investigated the usefulness of harmonic flash echo imaging in the assessment of the gastrointestinal tract, and we used this technique to study the effect of nicotine on small bowel blood flow. Harmonic flash echo imaging was performed at the beginning of intravenous injection of a contrast agent. It was also performed on the small bowel immediately before and 10 min after nicotine administration to evaluate blood flow. Gastric and small bowel walls were clearly enhanced on the primary images. Small bowel enhancement, which is regarded as transmural blood flow, significantly decreased after nicotine administration. Harmonic flash echo imaging appears to be useful in the assessment of the transmural blood flow in the gastrointestinal wall.

Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

Formation of advanced glycation end products (AGEs) is accelerated in diabetic subjects along with hyperglycemia. Although several lines of evidence indicate that AGEs stimulate macrophages to secrete several cytokines and growth factors, little is known about the effect of AGEs on the primary function of macrophages, such as phagocytosis. On the other hand, impairment of the phagocytic function of monocytes/macrophages is suggested to contribute to the low resistance to infection in diabetic subjects. In the present study, we examined the effect of AGEs on the phagocytic function of macrophages. Using flow cytometric analysis of mouse resident peritoneal macrophages, we showed that AGEs suppress phagocytosis of fluorescent microspheres by cultured macrophages. In addition, experiments using streptozotocin-induced diabetic mice demonstrated a significant decrease in the phagocytic activity of resident peritoneal macrophages 12 weeks after induction of diabetes compared with age-matched control mice. The phagocytic activity of peritoneal macrophages correlated inversely with AGE content in the adjacent peritoneal tissue. Furthermore, reduced phagocytic activity of macrophages was associated with a reduction in intracellular ATP content. Because phagocytosis is an important component of the defense system, suppression of such activity by AGEs may explain, at least in part, the increased susceptibility of diabetic patients to infection.

Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus-evaluation of 24-h pH monitoring.

BACKGROUND: Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion which decreases to normal levels in patients with duodenal ulcer disease. The aim of this study was to evaluate the effect of eradication of H. pylori in a 24-h study of gastric acidity in patients with atrophic gastritis of the corpus. METHODS: Intragastric acidity was measured by continuous 24-h pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pylori-positive patients with histologically proven atrophic gastritis of the corpus (10 men, 4 women; mean age, 57 years) before and 1 year after anti-H. pylori therapy. RESULTS: H. pylori was absent in 13 of 14 patients 1 year after treatment. Both gastritis and atrophy scores were significantly lower after eradication therapy (P < 0.01). The 24-h median pH and the percentage of 24-h pH readings above 4.0 units were significantly decreased after eradication therapy (from 5.12 +/- 0.36 to 2.69 +/- 0.21, and from 65.5 +/- 6.6% to 28.2 +/- 6.1%, P < 0.01, respectively.) CONCLUSION: Eradication of H. pylori increases 24-h gastric acidity in patients with atrophic gastritis of the corpus. Improvement of the histology of the gastric antrum and corpus may lead to the normalization of gastric acidity.

[Medulloblastoma originating in the pons].

Medulloblastoma usually originates in the cerebellum. We report here a case of medulloblastoma originating in the pons. Pontine medulloblastoma is extremely rare, with only one report in the literature. An 11-year-old girl was admitted to our hospital with vertigo. Magnetic resonance imaging (MRI) revealed a tumor originating in the pons. On the 4th day after admission, the tumor bled. Because the patient's life was in danger from brain herniation, hematoma removal and tumor resection were carried out. The diagnosis was medulloblastoma. After surgery, the patient received radiation therapy and chemotherapy. Unlike tumors originating in the cerebellum, this tumor did not seem to be effectively reduced by these therapies. Radiation therapy and chemotherapy may not be effective for medulloblastoma originating in the pons. We considered it necessary to make a histological diagnosis even though the tumor originated in the pons and resection was difficult technically.

A new general method for the biosynthesis of stable isotope-enriched peptides using a decahistidine-tagged ubiquitin fusion system: an application to the production of mastoparan-X uniformly enriched with 15N and 15N/13C.

A new strategy is described for the production of peptides enriched with stable isotopes. Peptides of interest are expressed in Escherichia coli (E. coli) cells as recombinant fusion proteins with Saccharomyces cerevisiae ubiquitin. This method yields as much as 30-100 mg/l of isotope-enriched fusion proteins in minimal media. A decahistidine tag attached to the N-terminus of ubiquitin enables a one-step purification of the fusion protein via Ni(2+)-chelating affinity chromatography. The ubiquitin moiety is then easily and specifically cleaved off by a protease, yeast ubiquitin hydrolase. Since this enzyme is also expressed at a high level in E. coli cells and can be purified in one step, the presented strategy has an advantage in view of costs over others that use commercially available proteases. In addition, since ubiquitin fusion proteins easily refold, the fusion protein can be expressed either in a soluble form or as inclusion bodies. This flexibility enables us to prepare peptides that are unstable in a soluble state in E. coli cells. As an example, the expression and the uniform stable isotope enrichment with 15N and/or 13C are described for mastoparan-X, a tetradecapeptide known to activate GTP-binding regulatory proteins. An amide group at the C-terminus of this peptide can also be formed by our method. The presented system is considered powerful for the stable isotope enrichment of short peptides with proton resonances that are too severely overlapped to be analyzed solely by proton NMR.

G protein-bound conformation of mastoparan-X: heteronuclear multidimensional transferred nuclear overhauser effect analysis of peptide uniformly enriched with 13C and 15N.

Mastoparans, a family of tetradecapeptides from wasp venom, have been used as convenient low molecular weight models of receptors coupled to GTP-binding regulatory proteins (G proteins) for the understanding of the interaction between G proteins and receptors. Sukumar and Higashijima have analyzed the conformation of mastoparan-X (MP-X) bound to the G protein alpha-subunit using proton two-dimensional transferred nuclear Overhauser effect (TRNOE) spectroscopy [Sukumar, M., and Higashijima, T. (1992) J. Biol. Chem., 267, 21421-21424]. The resultant structure, however, was not well-defined due to severe overlap of peptide proton resonances. To determine the G protein-bound conformation of MP-X in detail, we have analyzed this interaction by heteronuclear multidimensional TRNOE experiments of MP-X uniformly enriched with 15N and/or 13C. By solving the overlap problem, we were able to determine the precise conformation of MP-X bound to Gi1alpha: the peptide adopts an amphiphilic alpha-helix from Trp3 to C-terminal Leu14, and the atomic root-mean-square deviation (rmsd) values in this portion about the averaged coordinates were 0.27 +/- 0.07 A for the backbone atoms (N, Calpha, C') and 0.84 +/- 0.16 A for all heavy atoms. These values are much smaller than the corresponding rmsd values of the structures obtained from the proton 2D TRNOE spectrum alone: 1.70 +/- 0.41 A for the backbone atoms (N, Calpha, C') and 2.84 +/- 0.51 A for all heavy atoms. Our results indicate that the heteronuclear multidimensional TRNOE experiments of peptides uniformly enriched with stable isotopes are a very powerful tool for analyzing the conformation of short peptides bound to large proteins. We will also discuss the structure-activity relationships of mastoparans in activating G proteins on the basis of the precise structure of MP-X bound to Gi1alpha.

Acute gastric anisakiasis: 28 cases during the last 10 years.

Anisakiasis is a disease which occurs following eating raw fish infected with anisakis larvae. Many cases have been reported from Japan and from other countries with increasing opportunities of eating raw fish such as "sushi" and "sashimi." We have reviewed 28 patients with acute gastric anisakiasis during the last 10 years from November 1984 to October 1994. This disease has rarely been detected in persons over 60 years of age and in patients with gastric surgery. Therefore it is postulated that gastric acid secretion influences the activities of anisakis larvae. An alkaline gastric pH could interfere with the toxicity of anisakis larvae.

Flow cytometric assay for cytotoxic activity of crude Clostridium perfringens enterotoxin using non-adherent cell FM3A.

The flow cytometric assay method was tested for the cytotoxic activity of Clostridium perfringens enterotoxin (CPE) in culture using mouse mammary carcinoma cell line FM3A stained with propidium iodide (PI). From the results obtained, FM3A cells proved to be susceptible to CPE. A reproducible dose-response curve with FM3A was obtained between crude CPE at 13.9-109 ng/ml and between purified CPE at 40-400 ng/ml, respectively. These findings indicate that non-adherent FM3A is preferable to determine the cytotoxic activity of CPE because it can be used without detachment procedures with trypsinin compared with adherent African monkey kidney cell line (Vero cells). Furthermore, the flow cytometry with non-adherent cell FM3A stained with PI only proved to be a useful method to determine the biological activity of CPE in culture isolates.

Intra-arterial alcoholization of advanced hepatocellular carcinoma.

For the purpose of achieving emergency hemostasis of a ruptured hepatocellular carcinoma (HCC) or prevention of such rupture, we applied a new method of transcatheter therapy: intra-arterial alcoholization. Five patients with a ruptured HCC and 42 with an impending rupture were treated by intra-arterial injection of absolute ethanol mixed with an equal volume of iodized oil, Lipiodol (EtOH-Lp). The tumor size ranged from 4 to 26 cm (mean 7.8 cm) in diameter. The catheter tip was placed in the segmental branch or a more distal position of the hepatic artery, and 2-40 (mean 10.6) ml of EtOH-Lp was infused under fluoroscopic guidance. Infiltration of ethanol into the HCC mass was recognized as a dense deposition of Lipiodol on plain abdominal X-rays and computed-tomography. In all five cases of ruptured HCC, hemostasis was achieved. In all 42 cases of impending rupture, tumor rupture was prevented, and all except 3 patients could be discharged. No significant complication of the gastrointestinal tract or biliary tract was seen. The incidence and severity of postembolization syndrome was markedly lower than those seen in cases treated with Gelfoam embolization.