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Biomedical subjects

K Fukushima

Publications and source records attributed to K Fukushima.

At least 127 records · Page 7Linked to original sources

Bone marrow changes mimicking myelodysplasia in patients with hemophagocytic lymphohistiocytosis.

In hemophagocytic lymphohistiocytosis (HLH), cytokine-induced pancytopenia is a common finding and is associated with hypoplastic and hypocellular bone marrow and abundant hemophagocytosis. To date, neutrophil nuclear segmentation abnormalities have not been clarified in HLH patients. We report a study of bone marrow from 6 cases of HLH that showed abnormal granulocytes, dyserythropoietic changes, and micromegakaryocytes mimicking the findings in myelodysplasia at the onset of disease. Pelger-Huët anomalies were particularly noted in all cases. The increased levels of cytokines in these cases may have caused cellular damage leading to the morphological changes in the bone marrow of these HLH patients. The impact of these findings on pathophysiology and prognosis in HLH patients remains to be determined.

Adolescent↗

Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance.

Crohn's disease (CD) is a condition characterized by excessive numbers of activated T cells in the mucosa. We investigated whether a defect in apoptosis could prolong T cell survival and contribute to their accumulation in the mucosa. Apoptotic, Bcl-2+, and Bax+ cells in tissue sections were detected by the TUNEL method and immunohistochemistry. T cell apoptosis was induced by IL-2 deprivation, Fas Ag ligation, and exposure to TNF-alpha and nitric oxide. TUNEL+ leukocytes were few in control, CD, and ulcerative colitis (UC) mucosa, with occasional CD68+ and myeloperoxidase+, but no CD45RO+, apoptotic cells. Compared with control and UC, CD T cells grew remarkably more in response to IL-2 and were significantly more resistant to IL-2 deprivation-induced apoptosis. CD T cells were also more resistant to Fas- and nitric oxide-mediated apoptosis, whereas TNF-alpha failed to induce cell death in all groups. Compared with control, CD mucosa contained similar numbers of Bcl-2+, but fewer Bax+, cells, while UC mucosa contained fewer Bcl-2+, but more Bax+, cells. Hence, the Bcl-2/Bax ratio was significantly higher in CD and lower in UC. These results indicate that CD may represent a disorder where the rate of T cell proliferation exceeds that of cell death. Insufficient T cell apoptosis may interfere with clonal deletion and maintenance of tolerance, and result in inappropriate T cell accumulation contributing to chronic inflammation.

Abatacept↗

Ultrasensitive determination of NE-100, a novel sigma ligand, in human plasma by liquid chromatography and electrospray ionization tandem mass spectrometry combined with a column-switching technique.

For the highly sensitive and selective determination of NE-100, a novel sigma ligand, at levels of low picogram per milliliter of human plasma, a method with excellent reliability employing liquid chromatography (LC)-electrospray ionization (ESI) tandem mass spectrometry (MS-MS) combined with a column-switching technique has been developed. The method involves the use of a stable isotope labeled compound as the internal standard (I.S.), liquid-solid extraction of a plasma specimen with a C8 cartridge, automated on-line clean-up on a short trapping column, subsequent separation on a micro-bore C18 column and detection with ESI-MS-MS using m/z 356 ([M+H]+) as a precursor ion and m/z 105 as a product ion in a selected reaction monitoring mode. The detection and the quantification limits of NE-100 in plasma were 0.5 pg/ml with a signal-to-noise ratio (S/N) of 3 and 2.3 pg/ml, respectively, with an S/N of 21. The good linearity of the calibration graph was obtained in the range of 2.3 to approximately 907.0 pg/ml with excellent reliability. The developed method was applied to the determination of NE-100 in plasma obtained from the clinical trail.

Anisoles↗

Inhibitory effect of a self-derived peptide on glucosyltransferase of Streptococcus mutans. Possible novel anticaries measures.

Glucosyltransferase (GTF) plays an important role in the development of dental caries. We examined the possible presence of self-inhibitory segments within the enzyme molecule for the purpose of developing anticaries measures through GTF inhibition. Twenty-two synthetic peptides derived from various regions presumably responsible for insoluble-glucan synthesis were studied with respect to their effects on catalytic activity. One of them, which is identical in amino acid sequence to residues 1176-1194, significantly and specifically inhibited both sucrose hydrolysis and glucosyl transfer to glucan by GTF-I. Double-reciprocal analysis revealed that the inhibition is noncompetitive. Scramble peptides, composed of the identical amino acids in randomized sequence, had no effect on GTF-I activity. Furthermore, the peptide is tightly bound to the enzyme once complexed, even in the presence of sodium dodecyl sulfate (SDS). Kinetic analysis using an optical evanescent resonant mirror cuvette system demonstrated that the enzyme-peptide interaction was biphasic. These results indicate that the peptide directly interacts with the enzyme with high affinity and inhibits its activity in a sequence-specific manner. This peptide itself could possibly be an effective agent for prevention of dental caries, although its effectiveness may be improved by further modification.

Amino Acid Sequence↗

Vestibular-pursuit interactions: gaze-velocity and target-velocity signals in the monkey frontal eye fields.

Visual information about a moving object is obtained by accurate tracking with the eyes using the smooth pursuit system, which must interact with the vestibular system during head movement. Such pursuit-vestibular interactions require calculation of gaze (i.e., eye in space) in order to match eye velocity in space to actual target velocity, using vestibular, retinal-image velocity, and eye-velocity information. To understand the role the frontal eye fields (FEFs) play in pursuit-vestibular interactions, we examined responses of pursuit-related neurons near the arcuate sulcus in head-stabilized monkeys during visual tracking tasks that dissociate eye movement in the orbit from that in space. The activity of the majority of pursuit-related neurons was related to gaze velocity. They also responded to passive body rotation in complete darkness. When the monkeys fixated the stationary target, similar modulation was observed, reflecting the velocity signal of a second test target. Muscimol infusion into the FEF pursuit areas severely impaired smooth gaze tracking. These results suggest that the region near the arcuate sulcus coordinates its various inputs to provide signals for target velocity in space and accurate gaze-velocity command during pursuit-vestibular interactions.

Animals↗

Quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer.

Quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhanced the Fenton reaction in phosphate buffer, respectively. The enhancement by quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction may be partly related to their respective actions in the biological systems such as a neurotoxic effect (quinolinic acid), a marked growth-inhibitory action on rice seeding (alpha-picolinic acid and fusaric acid), and an antiseptic (2,6-pyridinedicarboxylic acid). The ultraviolet-visible absorption spectrum of the mixture of alpha-picolinic acid with ferrous ion showed a characteristic visible absorbance band with a lambda(max) at 443 nm, suggesting that alpha-picolinic acid chelate of Fe2+ ion forms in the solution. Similar characteristic visible absorbance band was also observed for the mixture of Fe2+ ion with quinolinic acid (or fusaric acid, or 2,6-pyridinedicarboxylic acid). The chelation seems to be related to the enhancement by quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction. alpha-Picolinic acid was reported to be a toxic substance isolated from the culture liquids of blast mould (Piricularia oryzae CAVARA). On the other hand, it has also been known that chlorogenic acid protects rice plants from the blast disease. The chlorogenic acid inhibited the formation of the hydroxyl radical in the reaction mixture of alpha-picolinic acid, FeSO4(NH4)2SO4, and H2O2. Thus the inhibition may be a possible mechanism of the protective action of the chlorogenic acid against the blast disease.

Buffers↗

Plasma glicentin in diabetic and gastrectomized patients.

Recent successful synthesis of human glicentin prompted us to establish an immunoassay method for determination of human glicentin in plasma. Human glicentin in plasma was measured using a newly developed sandwich ELISA. The mean fasting levels of human glicentin were 18.6+/-2.4 and 19.7+/-2.1 pM in normal subjects and diabetic patients, respectively. In diabetic patients with renal failure, plasma glicentin was elevated, exceeding 100 pM. In normal subjects, plasma glicentin increased to a peak level of about 130 pM at 60 min after an oral glucose load, and then decreased. In patients who underwent gastrectomy, plasma glicentin rapidly increased to a peak of about 300 pM at 30 min after oral glucose load. In a patient with short bowel syndrome plasma glicentin did not change following an oral glucose load. These results correspond with previous findings for gut glucagon-like immunoreactive materials (GLI) or enteroglucagon. We conclude that glicentin is secreted from the small intestine in response to intraluminal glucose stimulation in humans.

Blood Glucose↗

Amniotic fluid alpha-fetoprotein testing in native Japanese women.

Owing to differences in maternal serum alpha-fetoprotein, human chorionic gonadotrophin and oestriol levels between native Japanese and Caucasian women screened in this laboratory, a study was conducted to measure amniotic fluid alpha-fetoprotein (AFAFP) levels in native Japanese pregnancies. When the native Japanese AFAFP levels were compared with a United States (non-Black) population, the Japanese medians did not decrease as rapidly over the 14 to 22 weeks of gestation period investigated. At 14 weeks, the difference was negligible, graduating to a difference of 20 per cent by 22 weeks' gestation. Native Japanese pregnancy AFAFP levels should be interpreted based upon population data from that group alone. From these findings, prenatal screening laboratories should be encouraged to collect preliminary data for comparison before screening is initiated for a defined ethnic group.

Amniocentesis↗

Monitoring and antibacterial treatment for postoperative bacterial overgrowth in Crohn's disease.

PURPOSE: Bacterial overgrowth sometimes complicates the clinical course of Crohn's disease and may lead to inappropriate treatment. To clarify the effect of antibiotic therapy, we monitored the hydrogen concentration in expiratory breath after fasting. METHODS: We evaluated 18 patients (15 males; median age, 32.7; range, 22.3-60 years) for postoperative bacterial overgrowth symptoms and for intestinal dilation by plain abdominal x-ray. Five patients had ileitis and 13 patients had ileocolitis. Various intestinal resections were performed in all, and strictureplasties were done at the same time in 13 patients. The median postoperative period was 10.2 (range, 1.2-102) months. Nine patients, who had symptoms such as bloating, nausea, vomiting, or pain, were classified as the symptomatic group, whereas nine other patients, who had no symptoms, were classified as the symptom-free group. Sixteen patients who had undergone intestinal resections for noninflammatory bowel disease served as the control group. After overnight fasting, hydrogen concentration in end-expiration, breath was measured with gas chromatography. At the same time clinical examinations of white blood cell count, hemoglobin, total protein, serum albumin, iron, sialic acid, and C-reactive protein in the peripheral blood were performed. To assess the effect of antibacterial treatment, changes in symptoms were assessed in eight patients who received antibacterial treatment. Hydrogen concentration was measured repeatedly before and after treatment in six patients. RESULTS: The symptomatic group had an expiratory hydrogen concentration level significantly higher (median, 40; range, 20-139 ppm) than the control group (median, 3; range, 1-6 ppm) and the symptom-free group (median, 4; range, 1-10 ppm). After the antibiotic treatment the symptoms were improved in all of the patients, and the hydrogen concentration level was significantly reduced (median, 4.5; range, 2-13 ppm). CONCLUSIONS: Antibacterial treatment was useful in the postoperative patients whose assessments were complicated by bacterial overgrowth. Using a hydrogen breath test, bacterial overgrowth was effectively monitored and managed, effecting a change in clinical symptoms.

Adult↗

Management of urinary complications in Crohn's disease.

Among the 127 patients who underwent surgical treatment for Crohn's disease at Tohoku University Hospital, urinary complications were noted in 13 patients (10.2%), including urolithiasis in 6 patients (4.7%), a ureteral obstruction in 4 (3.1%), and urinary fistula in 3 (2.4%). In patients with urolithiasis, conservative therapy was effective. An ureteral obstruction was detected on the right side in all 4 of these cases because of the inflamed terminal ileum. In 2 of the 4 cases, the symptoms improved by either preoperative total parenteral nutrition or elemental diet therapy. A resection of the inflamed intestine was necessary in all cases. In patients with urinary fistulas, a resection of the inflamed intestine combined with a reconstruction of the urinary tract was carried out after total parenteral nutrition. In conclusion, conservative therapy with preoperative total parenteral nutrition or elemental diet therapy proved to be effective for a ureteral obstruction since it improved the intestinal inflammation. As a definitive treatment, surgery is still necessary for the management of urinary fistulas and ureteral obstruction. Based on our findings, patients with urolithiasis in Crohn's disease should thus be treated conservatively in the same way as patients without Crohn's disease.

Adolescent↗

Turcot syndrome with colonic obstruction and small intestinal invagination: report of a case.

We report herein the case of a 16-year-old boy diagnosed as having Turcot syndrome, otherwise known as glioma-polyposis syndrome. The patient was transferred from the Department of Neurosurgery where he was undergoing investigation of a brain tumor, to the Department of Medicine for investigation of gastrointestinal symptoms. The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. A subtotal colectomy with side-to-end ileoproctostomy and release of the invaginations was carried out. Multiple polyps were found in the colon, two of which, including a large polyp that obstructed the colonic lumen, were confirmed histologically to be adenocarcinoma. The remaining polyps were adenomas. A biopsy of the brain tumor confirmed a diagnosis of astrocytoma (WHO grade II). This case report describes the characteristic features of Turcot syndrome presented by this patient.

Adenocarcinoma↗

Surgical treatment for patients with lung cancer complicated by severe pulmonary emphysema.

Ten patients with lung cancer complicated by severe pulmonary emphysema, underwent lung reduction surgery between 1995 and 1997. Patients meeting the following criteria were defined as having severe pulmonary emphysema: (1) forced expiratory volume in 1 s (FEV1%) of < 55% and (2) characteristic, severe findings of emphysema in chest x-rays and chest computed tomography scans. 9 men and 1 woman (mean age: 70.8; range: 59-78 years), were all smokers (smoking index: 500-2450). Preoperative lung function showed an average percent vital capacity of 87.8% (range: 67-108%) and an average FEV1% of 35.9% (range: 27-54%). The histological types of lung cancer were squamous cell carcinoma (4 patients), adenocarcinoma (5 patients), and large cell carcinoma (1 patient). Four patients were in clinical stage IA, 3 in stage IB, and 1 each was in stages IIA, IIIA, and IIIB. Lobectomy was conducted in 3 cases and partial resection in the remaining 7. Five of the 10 patients underwent thoracoscopic resection. After surgery, patients died one at 2 months and the other at 17; 3 survived but 3 suffered cancer recurred; and 5 patients without recurrence. In complications, bronchial air leakage requiring postoperative treatment. Postoperative lung function showed an average percent vital capacity of 71.4% (range: 41-90%) and an average FEV1% of 41.3% (range: 28-61%). We found an important relationship between the location of the perfusion defect (target area) in pulmonary perfusion scintigram in relation to the lung cancer site and postoperative improvement of lung function. One patient with lung cancer associated with severe respiratory obstruction underwent lobectomy after confirmation of the perfusion defect by pulmonary perfusion scintigram. Postoperative FEV1% in this patient was restored to the preoperative level. In general, partial thoracoscopic resection was effective in patients with early-stage lung cancer.

Adenocarcinoma↗

Clinical evaluation of SITA: a new family of perimetric testing strategies.

PURPOSE: To perform a clinical comparison of the Humphrey Full Threshold strategy with its intended replacement, SITA Standard, regarding testing time, reproducibility, and measured threshold sensitivity in normal subjects and glaucoma patients. METHODS: Thirty-eight healthy volunteers and 80 patients with primary open-angel glaucoma underwent central 30-2 testing with both Full Threshold and SITA strategies using a Humphrey HFA 2 Model 740 perimeter. The testing time, reproducibility, and measured threshold sensitivity of the two strategies were compared. RESULTS: The testing time for measurements with SITA was 56% lower in normal subjects and 45% lower in glaucoma patients than with Full Threshold. Cases having higher mean sensitivity or cases requiring longer testing time for Full Threshold had a greater percentage reduction in testing time for SITA. The test-retest variability studied in normal subjects was lower, but not significantly so, with SITA (2.9%) than with Full Threshold (3.4%). The mean sensitivities of SITA were higher (1 dB) than those of Full Threshold not only in normal subjects but also in glaucoma patients. This higher sensitivity in SITA was found irrespective of the order of the two tests both in normal subjects and glaucoma patients. Analysis by each testing point revealed that the difference was not dependent on the test point position or the sensitivity at the point. CONCLUSION: SITA has greater patient acceptability than the Full Threshold strategy. However, the difference in sensitivity can be considerable in a serial comparison of one patient's fields tested by Full Threshold and SITA.

Adolescent↗

Colonization of microflora in mice: mucosal defense against luminal bacteria.

To investigate the pathogenesis of inflammatory bowel disease, it is critical to develop a system that uses simple and reproducible models for analyzing the "normal" mucosal defense mechanism. In the present study, germ-free mice were conventionalized by the oral administration of microorganisms prepared from the feces of genetically identical mice. Histological assessment and mucin characterization of small intestine and colon were then carried out. Histological findings in the gut were site-dependent and clearly time-dependent. Acute inflammation was most evident in the cecum. The cecal mucosa exhibited hyperplastic changes in epithelial cells, infiltration of polymorphonuclear cells, crypt abscesses, and epithelial projections on the epithelial surface 7 days after conventionalization. Some of the changes were similar to those seen in human ulcerative colitis. The histological findings in the conventionalized mice were comparable to those in specific pathogen-free mice after 28 days. Mucin histochemistry revealed that bacterial colonization altered the number of rectal goblet cells and the mucin composition in a time-dependent fashion. Although this model shares only some characteristics of human inflammatory bowel disease, it is unique in demonstrating the acquisition of mucosal defense. Understanding of this process is critical for the elucidation of inflammatory bowel disease pathogenesis.

Animals↗

Latency of cross-axis vestibulo-ocular reflex induced by pursuit training in monkeys.

To examine the latency of smooth pursuit induced, short-term modifications of the vestibulo-ocular reflex (VOR), Japanese monkeys were rewarded for tracking a vertically moving target spot synchronized with horizontal whole body rotation. Eye movements induced by equivalent rotation in complete darkness were examined before and after training. Before training, the horizontal trapezoidal rotation (peak acceleration approximately 78%/s2) resulted in a collinear VOR with a mean latency of 15.3 ms, and no orthogonal component in any of the three monkeys tested. After training, the collinear VOR remained unchanged but an orthogonal, cross-axis VOR developed. It had a mean latency of 42.4 ms with gain (eye/chair) of 0.19, followed by a decaying phase that had a mean time constant of 80 ms. These results suggest that the cross-axis VOR induced by pursuit-vestibular interaction is different from previously reported cross-axis VOR induced by optokinetic-vestibular interaction.

Adaptation, Physiological↗

Course and outcome of tubulointerstitial nephritis and uveitis syndrome.

We report here the clinical features and outcomes of 10 patients, aged 11 to 21 years (median, 13.0), with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU syndrome). The initial symptoms were visual impairment in 7 patients and prolonged fever, anemia, or asthenia in 4 patients. An increase in urinary beta(2)-microglobulin was noticed at the initial checkup in all patients, including 2 patients who showed the normal ranges of 24-hour protein excretion. Creatinine clearance was decreased in 8 patients. TIN was found simultaneously with ocular symptoms in 7 patients and preceded these symptoms in the remaining 3 patients. Percutaneous renal biopsy indicated tubulointerstitial lesions in varying degrees. The histological grade of TIN was correlated with urinary beta(2)-microglobulin levels. Systemic steroid therapy was performed in 7 patients because of the progression of uveitis. The 10 patients were followed-up for 16 to 94 months (median, 31.0 months). In all patients, creatinine clearance recovered to the normal ranges (>/=70 mL/min/1.73 m(2)) mostly within 1 year. Urinary beta(2)-microglobulin excretion gradually declined but was slightly elevated in 4 patients at the latest checkup. Uveitis recurred in all 10 patients, which did not affect the renal status. Our findings indicate that early referral of patients from ophthalmologists and determination of beta(2)-microglobulin in the urine is helpful for the early discovery of TINU syndrome. In children and adolescents with this syndrome, TIN spontaneously resolves and its long-term prognosis is good, but uveitis often relapses. Systemic steroids may be required for uveitis, but not for TIN.

Adolescent↗