Nocturnal blood glucose and IGFBP-1 changes in type 1 diabetes: Differences in the dawn phenomenon between insulin regimens.

OBJECTIVE: Insulin-like growth factor binding protein-1 (IGFBP-1) is known to regulate the bioavailability of insulin-like growth factor (IGF) and the levels of IGFBP-1 are increased in the morning in patients with type 1 diabetes mellitus. We investigated the nocturnal fluctuations of glucose, IGFBP-1, and free IGF-1 levels with three insulin regimens. RESEARCH DESIGN AND METHODS: Forty-eight type 1 diabetes patients were divided into three groups according to their basal insulin therapy (continuous subcutaneous insulin infusion [CSII], insulin glargine, NPH insulin). Blood samples were obtained every 2 h between 2 300 h and 0700 h to measure plasma glucose, IGFBP-1 and free IGF-1 levels. RESULTS: The dawn phenomenon was more frequent with NPH (62.1%) than with glargine (16.6%, p<0.05) and CSII (14.3%, p<0.05). In the NPH group, the serum IGFBP-1 levels were markedly increased from 21.0+/-3.6 ng/ml at 2 300 h to 200.3+/-21.8 ng/ml at 0700 h and free IGF-1 levels were inversely decreased; these changes were partially suppressed in the CSII and glargine groups. CONCLUSIONS: The use of insulin regimens that provide sufficient insulin levels in the early morning can suppress the dawn phenomenon, leading to improved glycemic control. The increase in circulating IGFBP-1 in the morning, as a result of waning of insulin action, lowers free IGF-1 levels and may cause insulin resistance.

Hyperbaric oxygenation therapy for simple adhesive postoperative intestinal obstruction in children: comparison of the use of a short tube versus a long tube.

We hypothesized that hyperbaric oxygenation (HBO) combined with a long tube (LT) [HBO + LT] would be more effective than HBO combined with a short tube (ST) [HBO + ST] for simple adhesive postoperative intestinal obstruction (APIO) in children, assuming that there is synergism between HBO and LT. The objective of this study was to determine retrospectively the effect of HBO + LT compared to HBO + ST for simple APIO in children. Seventy-three patients were diagnosed with simple APIO, and 51 of these patients were treated with HBO + LT during 104 HBO sessions, while 22 were treated with HBO + ST during 34 HBO sessions. HBO was performed at a pressure of 2 atmospheres for 60 minutes once daily. The recovery rates after HBO therapy were 87.5 % for the HBO + LT group and 82.4 % for the HBO + ST group (p = 0.4496). HBO was performed 5 +/- 3 (range 1 to 15) times for the HBO + LT group and 4 +/- 2 (range 1 to 8) times for the HBO + ST group (p = 0.9847) for ultimate recovery from simple APIO. The recovery rate after HBO therapy of up to 6 sessions was 78.2 % for HBO + LT and 92.1 % for HBO + ST (p = 0.0360) among the cases that recovered ultimately. The effect of HBO + LT did not significantly differ from that of HBO + ST, but the insertion of an LT is more intricate and the cost is higher than that of an ST. Therefore, we conclude that the use of an LT is not necessarily required for HBO therapy for simple APIO.

Multicystic dysplastic kidney detected by prenatal ultrasonography: natural history and conservative management.

Conservative management of multicystic dysplastic kidney (MCDK) without nephrectomy has recently been advocated. The purpose of this study was to determine the clinical course of conservatively managed unilateral MCDK detected prenatally. Between 1991 and 2001, ten children (three boys and seven girls) with unilateral MCDK detected by prenatal ultrasonography (US) were prospectively followed at our institution. At birth, US confirmed the prenatal findings in all cases. All patients underwent voiding cystourethrography, intravenous pyelography, and radionuclide scans. Postnatal follow-up US examinations were performed every 3 months until patients were 5 years old and annually from then forward. The mean age at diagnosis during the prenatal period was 29 weeks of gestation (range 21-38 weeks). Median follow-up time was 42 months (range 17-125 months). Follow-up US was performed in eight children; three (38%) showed partial resolution, three (38%) complete resolution, and two (24%) no change in cyst size. The mean age at complete resolution of the lesion was 23 months (range 9-33 months). No children developed hypertension or tumors, and all maintained normal growth. In the present study, the natural history of MCDK was benign, and serial US monitoring showed that the affected kidneys frequently showed resolution with time. The results of this study support the conclusion that a nonsurgical approach for patients with MCDK is advisable.

Degradation of microcystin by biofilm in practical treatment facility.

Potential for degradation of microcystin by biofilm was examined by some batch experiments using biofilm scraped from practical biological treatment facility combined with conventional treatment processes. The viable cells of Microcystis viridis, which produced microcystin LR, RR and YR were degraded at 6 to 10 days by the addition of biofilm. Biofilm collected in summer season had especially higher potential for degradation of Microcystis with complete degradation at 6 days. In all seasons, Monas spp. grew remarkably, accompanied with the higher decrease of the viable cells of Microcystis and the micro-animals were considered as a main predator for Microcystis cells. Intracellular microcystin LR, RR, YR were degraded simultaneously with high reduction of Microcystis cells. Dissolved microcystin LR of 1,000 microg l(-1) was effectively degraded by indigenous aquatic bacteria on biofilm during 5 days, the degradability became higher with the increase in the concentration of microcystin LR. From the results of our research, it was clarified that the aggregated microorganisms consisting of biofilm had high potential for degradation of intracellular and dissolved microcystin.

Ultrasonographic features of normalization of the pylorus after pyloromyotomy for hypertrophic pyloric stenosis.

PURPOSE: The purpose of this study was to describe the time course, early postoperative changes, and morphologic features of normalization of the pylorus after pyloromyotomy for hypertrophic pyloric stenosis. METHODS: The subjects were 17 infants (9 boys, 8 girls) who underwent umbilical incision Ramstedt pyloromyotomy. The pyloric muscle mass was measured immediately before the operation and then at intervals from 3 days to 6 months after the operation using a 7.5-MHz ultrasound probe. RESULTS: In longitudinal section, the dorsal part of the pyloric muscle thickened transiently and then thinned to normal values by 5 months after the operation. It was 5.1 +/- 0.8 mm (mean +/- SD) preoperatively, increased to 6.0 +/- 0.3 mm by day 3 after the operation (P <.05), and thinned to 2.8 +/- 0.2 mm by 5 months after the operation. Concomitantly, the length of the pylorus gradually decreased (from 20.1 +/- 2.9 mm preoperatively to 16.9 +/- 2.7 mm by 3 days postoperatively [P <.05] and to less than 15 mm, by 4 months). In transverse section, the muscle normalized as in the longitudinal section. At the site of the incision it was 4.3 +/- 0.4 mm thick preoperatively, thickened to 4.6 +/- 0.4 mm by 3 days after the operation (P <.05), thinned to 2.1 +/- 0.9 mm by 7 days (P <.05), and then increased slightly, but always was less than 3.0 mm. Morphologically, in transverse section, the incised area looked like a wedge by 3 days after the operation. CONCLUSIONS: After pyloromyotomy for hypertrophic pyloric stenosis, there is an early transient increase in muscle thickness within the first few postoperative days followed by a slow decrease that reaches normal thickness (<3 mm) by 5 months. This decrease in thickness is accompanied by a gradual decrease in length to 75% of the preoperative value by 5 months. The morphologic features in this normalization are first a wedge (day 3), then a flat tire (days 7 and 14), and finally an elongated ring (5 months). J Pediatr Surg 36:582-586.

Inhibition of the human chemokine receptor CXCR4 by antisense phosphorothioate oligodeoxyribonucleotides.

The CXC chemokine receptor CXCR4/fusion, a major coreceptor for the T-cell line T-tropic (X4) HIV-1 virus, plays a critical role in T-tropic virus fusion and entry into permissive cells. In the present study, we describe the effects of an antisense phosphorothioate oligodeoxyribonucleotide (anti-S-ODN) on the inhibition of CXCR4 gene expression in X4 HIV-1 infected HeLa-CD4 cells, to find more efficacious therapeutic possibilities for human immunodeficiency virus type 1 (HIV-1) infection. The naked antisense phosphorothioate oligodeoxyribonucleotide (anti-S-ODN-1), containing the AUG initiation codon at the center of the oligodeoxyribonucleotide, showed a slightly higher inhibitory effect on HIV-1 gag p24 production among all sequences tested. We also examined the concomitant use of a basic peptide transfection reagent, nucleosomal histone proteins (RNP), for the delivery of the anti-S-ODN-1. The anti-S-ODN-1 encapsulated with RNP had higher inhibitory effects on p24 products than the naked anti-S-ODN-1. When the anti-S-ODN-1 encapsulated with RNP was incubated with HeLa-CD4 cells, the surface levels of this chemokine receptor showed high suppression, indicating sequence-specific inhibition. The activities of unmodified oligodeoxyribonucleotide are effectively enhanced by using a basic peptide, RNP.

Characterization of whole-cell currents elicited by mechanical stimulation of Xenopus oocytes.

Whole-cell mechanosensitive current (I(ms)) in Xenopus oocytes was studied using the two-electrode voltage-clamp technique. I(ms) was evoked by mechanically pressing the oocyte surface with a glass micropipette. The current was found to depend on the amplitude of the stimulus, showed a time-dependent decay, and turned off immediately after the stimulus was removed. The current-voltage relationship for the peak current exhibited inward and outward rectification at negative and positive potentials, respectively, while that for the sustained current exhibited only inward rectification. I(ms) was significantly suppressed by 30 microM Gd3+. One millimolar amiloride also significantly suppressed the inward I(ms) at negative potentials, but not the outward one at positive potentials. Replacing extracellular Na+ with K+ did not change the current-voltage relationship, whereas replacing extracellular Na+ with choline+ or tetraethylammonium+ significantly decreased the inward I(ms). The outward rectifier at positive potentials was abolished by replacing extracellular Cl- with gluconate-, by intracellular injection of 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), by extracellular application of anthracene-9-carboxylic acid, and by replacing extracellular Ca2+ with Mg2+. These results suggest that mechanical stimulation activates stretch-activated cation channels and Ca2+-activated Cl- channels, the latter being secondarily activated by an increase in intracellular Ca2+ concentration by Ca2+ influx through stretch-activated cation channels.

Hemodynamic and thermal responses to a 30-minute constant-workload aerobic exercise in middle- or old-aged patients with cardiovascular diseases.

The aim of the present investigation was to compare the hemodynamic and thermal responses to a 30-min aerobic exercise between middle- or old-aged patients with normal left ventricular function and those with left ventricular dysfunction. Constant-load sitting ergometer exercise of approximately 90% of the subject's oxygen uptake (VO2) at the anaerobic threshold for 30 min was conducted in 21 patients with left ventricular dysfunction (61+/-10 years, left ventricular ejection fraction (LVEF) 35+/-7%) and 24 patients with normal left ventricular function (59+/-9 years, LVEF 71+/-7%). Heart rate (HR), blood pressure, deep temperatures in the forehead and thigh, and forearm skin blood flow (SkBF) were measured every minute, and cardiac output (CO) and stroke volume (SV) were determined every 10 min with the dye-dilution technique during the exercise. Patients of both groups exhibited a progressive elevation in each temperature and an increase in SkBF during the exercise. Although the VO2 and CO remained stable, almost the same magnitude of decrease in SV as increase in HR was seen after the 10th min of exercise in both groups. The magnitude of the decrease in SV was greater in old-aged than middle-aged patients with left ventricular dysfunction. Thus, the downward drift in SV during a 30-min constant-load aerobic exercise might not be influenced by left ventricular function, but intensified by aging in patients with left ventricular dysfunction.

Genes for phytochrome A in horseradish: isolation of cDNAs and analysis of expression during light-induced formation of adventitious shoots from hairy roots.

Three cDNAs for phytochrome A (phyA), designated ArPHYA1, ArPHYA2 and ArPHYA3, respectively, were isolated from a cDNA library prepared from proximal parts of the hairy roots of horseradish (Armoracia rusticana). The level of phyA was higher in those parts than in any other parts of hairy roots. The amino acid sequences deduced from the cDNAs were quite similar, with stronger homology to the product of PHYA of Arabidopsis thaliana than to products of genes for phytochromes of many other plant species. Levels of transcripts in roots and tubers were higher than those in leaves and petioles. The levels in hairy roots were highest at the proximal ends and increased with increased duration of culture in darkness. Furthermore, the levels in proximal parts decreased by 25-50% after light irradiation. The elevated levels of transcripts of PHYA genes at the proximal ends of hairy roots are discussed with reference to the light-induced formation of adventitious shoots.

[Study of transforming growth factor-alpha expression in duodenal ulcer].

Various growth factors were also reported to promote healing of peptic ulcer. We have used a monoclonal antibody in conjunction with a standard immunohistochemical technique to characterize the expression of transforming growth factor-alpha (TGF-alpha) in duodenal ulcer. TGF-alpha immunoreactivity is found in Brunner's gland, also in immature gland and in duodenal epitheliums, but not in gastric metaplasia of the duodenum. TGF-alpha expression of healing and scar stage was higher than that of active stage. The presence or absence of Helicobacter pylori infection did not affect the expression of TGF-alpha in duodenal ulcer.

Effects of okadaic acid on rat colon.

Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (Gt) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal Gt values were 54+/-6.2 and 36.2+/-4.2 mS/cm2, respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in Gt in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced Gt change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.

[The significance of 123I-BMIPP myocardial SPECT on the evaluation of angina pectoris].

Some patients of ischemic heart disease have low uptake in 123I-labeled beta methyl-iodophenyl penta-decanoic acid (BMIPP) SPECT in spite of normal uptake in thallium-201 (Tl) SPECT. To investigate their clinical significance, we performed both T1 and BMIPP myocardial SPECT in 26 cases with stable angina (n = 16) and unstable angina (n = 10), and compared with clinical backgrounds electrocardiogram (ECG) and left ventriculography (LVG). In 11 patients of them, the uptake of BMIPP was moderately reduced. We divided 26 cases into two groups according to uptake of BMIPP (normal/reduced). The two groups had no differences in length of angina attack and duration of disease, but they had a significant difference in the abnormality of either ECG or LVG. Three to six months after PTCA, we examined LVG in 18 cases, 12 of 16 cases with the abnormality of LVG showed the improvement of wall motion. We concluded the reduced uptake of BMIPP with normal uptake of Tl was related to more severe ischemia in cases with unstable angina.

Hypertrophic cardiomyopathy with apical left ventricular aneurysm.

We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level.

Arabidopsis thaliana ECP63 encoding a LEA protein is located in chromosome 4.

DCECP63 is a carrot embryogenic cell protein. To perform its genetic analysis, we isolated an Arabidopsis thaliana (At) ECP63 cDNA. The cDNA encoded a polypeptide of 449 amino acids (aa). Its deduced aa sequence showed extensive similarity with DCECP63, DCDC8 and BPBP8 which are embryonic proteins isolated from carrot and birch, respectively. The aa sequence contained eight well-conserved tyrosine phosphorylation sites and 16 repeats of 11 aa. Southern analysis showed that the AtECP63 gene might belong to a small multigene family. The AtECP63 transcripts accumulated specifically in mature seeds, and exogenous abscisic acid (ABA) induced its expression in immature siliques, but not in vegetative tissues. These results suggested that the AtECP63 gene encoding a putative phosphotyrosine protein belonging to late embryogenesis abundant (LEA) protein in group 3 might be involved in maturation and desiccation tolerance of seeds. Restriction fragment length polymorphism (RFLP) and cleaved amplified polymorphic sequence (CAPS) mapping showed that AtECP63 gene was present in the South part of chromosome 4.

Endoscopy in the diagnosis of small intestinal tumors.

The importance of endoscopy in the diagnosis of small intestinal tumors was evaluated in 15 patients with small intestinal tumors treated in our hospital. Two tumors were benign, and 13 were malignant (carcinoma in 5 patients, malignant lymphoma in 5 and leiomyosarcoma in 3). The presence of lesions could be determined by X-rays before surgery, but definitive diagnoses were difficult. When preoperative endoscopy of the small intestine was possible accurate preoperative diagnoses could be made based on the endoscopic findings and biopsies taken under direct vision. Endoscopy is therefore very important for the diagnosis of small intestinal tumors. It is necessary to develop small intestinal endoscopes that are easier to insert.

[A case of hemolytic uremic syndrome associated with circulating anticoagulant].

A previously well 66-year-old woman was admitted to our hospital because of severe abdominal pain, oliguria, jaundice and hemoglobinuria. At admission, the following values were obtained: red blood cell count 261 x 10(4)/mm3, serum creatinine 2.8mg/100ml, total bilirubin 8.0mg/ml, indirect bilirubin 5.7mg/100ml, LDH 13886 WU, negative direct and indirect Coomb's test and peripheral blood smear showing schistocytosis. She was diagnosed as hemolytic uremic syndrome and was successfully treated with plasma infusion, plasma exchange and hemodialysis. The results of the tests for verotoxin titer of E. coli O157: H7 and circulating anticoagulant were positive. The test result for anticoagulant eventually became negative during her clinical course. In this case, circulating anticoagulant might have contributed to the pathogenesis of hemolytic uremic syndrome.

Effects of L- and DL-carnitine on patients with impaired exercise tolerance.

We designed this study to determine whether orally administered L- and DL-carnitine can improve exercise tolerance in a group of patients with exercise intolerance. Nineteen patients with cardiac disease were randomly divided into 2 groups, an L-carnitine treatment group (n = 9) and a DL-carnitine treatment group (n = 10). Eight additional age-matched patients served as an untreated control group. Subjects in both carnitine treatment groups underwent cardiopulmonary exercise testing on a cycle ergometer in order to determine peak exercise time, peak oxygen uptake (VO2), lactate threshold (LT) and ventilatory threshold (VT) before and after the oral administration of 900 mg/day of L- or DL-carnitine for 2 weeks. Basal values of peak exercise time, peak VO2, LT and VT did not differ significantly among the 3 groups. Peak exercise time and peak VO2 tended to be increased in the L-carnitine treatment group, and tended to be decreased in the DL-carnitine treatment group. Both LT and VT (ml/kg/min) were significantly improved (LT: from 9.7 +/- 0.6 to 10.8 +/- 1.0, p < 0.05; VT: from 9.8 +/- 0.8 to 11.8 +/- 1.9, p < 0.02) by the administration of L-carnitine, while LT was significantly decreased (from 11.0 +/- 2.0 to 9.6 +/- 1.2, p < 0.05) and VT tended to be decreased by the administration of DL-carnitine (from 11.6 +/- 2.0 to 10.8 +/- 2.4). In the untreated control group, no significant changes were observed in the values of exercise tolerance between the 2 series of exercise testings. In neither group did carnitine modify hemodynamic parameters at rest or during exercise. In conclusion, this study demonstrated that L-carnitine increases and DL-carnitine decreases exercise tolerance in patients with impaired exercise tolerance.