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1.
Pharmazie ; 73(10): 598-604, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30223925

ABSTRACT

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.


Subject(s)
Dietary Supplements/statistics & numerical data , Drug Utilization/statistics & numerical data , Nonprescription Drugs/administration & dosage , Aged , Delivery of Health Care/statistics & numerical data , Diet/statistics & numerical data , Female , Humans , Retrospective Studies , Self Medication/statistics & numerical data , Sex Factors , Socioeconomic Factors , Surveys and Questionnaires
2.
J Hand Surg Eur Vol ; 34(1): 115-20, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18936128

ABSTRACT

Experience with the use of the Universal Subcutaneous Endoscope (USE) system in surgical treatment of cubital tunnel syndrome in 35 patients is reported. Patients included in the study had pre- and postoperative clinical and electrophysiological data, and had undergone a minimum follow-up period of 13 months. Mean patient age was 59.5 years and the mean follow-up period was 25.9 months. The operation was performed under local anaesthesia without pneumatic tourniquet and on an out-patient basis. A 1.5 cm portal is made at the cubital tunnel and the USE system is inserted next to the ulnar nerve, first distally and then proximally. The nerve is endoscopically assessed and only the tissue that compresses the nerve is released, in keeping with the principles of minimally invasive treatment. Preoperative tingling sensations disappeared postoperatively in 63% of cases. Pain and sensory disturbance recovered to normal in 92% and 89% of cases, respectively. Abnormal motor nerve conduction velocities improved in 77%. Abductor digiti minimi weakness MMT 0, 1, 2 in 16 hands recovered to MMT 4 or 5 in eight. First-dorsal interosseous weakness in 18 hands recovered to MMT 4 or 5 in seven. There were no complications in this series. The endoscopic approach facilitates inspection of the ulnar nerve so that selective release of the tissue that compresses the nerve can readily be performed. The technique has proven effective in the treatment of cubital tunnel syndrome.


Subject(s)
Cubital Tunnel Syndrome/pathology , Cubital Tunnel Syndrome/surgery , Decompression, Surgical/methods , Endoscopy/methods , Minimally Invasive Surgical Procedures/methods , Ulnar Nerve/pathology , Ulnar Nerve/surgery , Adult , Aged , Aged, 80 and over , Anesthesia, Local , Cohort Studies , Cubital Tunnel Syndrome/physiopathology , Electrodiagnosis , Fascia/pathology , Fasciotomy , Female , Humans , Male , Middle Aged , Motor Neurons/physiology , Muscle, Skeletal/innervation , Neural Conduction/physiology , Neurologic Examination , Paresthesia/pathology , Paresthesia/physiopathology , Paresthesia/surgery , Postoperative Complications/physiopathology , Retrospective Studies , Sensory Thresholds/physiology , Touch/physiology , Ulnar Nerve/physiopathology
3.
Osteoarthritis Cartilage ; 16(7): 764-71, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18182309

ABSTRACT

OBJECTIVE: To investigate the in vitro and in vivo effects of interleukin (IL)-4 on mechanical stress-induced nitric oxide (NO) expression by chondrocytes, and destruction of cartilage and NO production in an instability-induced osteoarthritis (OA) model in rat knee joints, respectively. MATERIALS AND METHODS: Cyclic tensile stress (CTS; 0.5Hz and 7% elongation) was applied to cultured normal rat chondrocytes with or without pre-incubation with recombinant rat IL-4 (rrIL-4). Inducible NO synthase (iNOS) mRNA expression and NO production were examined with real-time polymerase chain reaction and the Griess reaction, respectively. OA was induced in rat knee joints by transection of the anterior cruciate and medial collateral ligaments and resection of the medial meniscus. rrIL-4 (10, 50, and 100 ng/joint/day) was injected intra-articularly, and knee joint samples were collected 2, 4, and 6 weeks after surgery. Cartilage destruction was evaluated by the modified Mankin score and Osteoarthritis Research Society International scoring system on paraffin-embedded sections stained with safranin O. Cleavage of aggrecan and NO production were examined by immunohistochemistry for aggrecan neoepitope (NITEGE) and of nitrotyrosine (NT), respectively. RESULTS: rrIL-4 down-regulated CTS-induced iNOS mRNA expression and NO production by chondrocytes. The intra-articular injection of rrIL-4 gave rise to a limited, but significant amelioration of cartilage destruction, prevention of loss of aggrecan, and decrease in the number of NT-positive chondrocytes, an effect that was not dose-dependent. CONCLUSION: The present study suggests that IL-4 may exert chondroprotective properties against mechanical stress-induced cartilage destruction, at least in part, by inhibiting NO production by chondrocytes.


Subject(s)
Arthritis, Experimental/prevention & control , Chondrocytes/drug effects , Interleukin-4/pharmacology , Nitric Oxide/biosynthesis , Osteoarthritis/prevention & control , Aggrecans/metabolism , Animals , Arthritis, Experimental/metabolism , Arthritis, Experimental/pathology , Cells, Cultured , Chondrocytes/metabolism , Dose-Response Relationship, Drug , Femur/pathology , Gene Expression Regulation, Enzymologic/drug effects , Injections, Intra-Articular , Interleukin-4/therapeutic use , Mechanotransduction, Cellular/drug effects , Nitric Oxide Synthase Type II/biosynthesis , Nitric Oxide Synthase Type II/genetics , RNA, Messenger/genetics , Rats , Rats, Wistar , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Reverse Transcriptase Polymerase Chain Reaction/methods , Stress, Mechanical , Tyrosine/analogs & derivatives , Tyrosine/metabolism
4.
Int J Hyperthermia ; 20(5): 529-38, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15277025

ABSTRACT

A phantom has previously been developed containing carrageenan, agarose and gadolinium chloride (called CAG phantom) for MRI with 1.5 T. T(1) and T(2) relaxation times of this phantom are independently changeable by varying concentrations of relaxation-time modifiers to simulate relaxation times of the various types of human tissues. The CAG phantom has a T(1) value of 202-1904 ms and a T(2) value of 38-423 ms, when the GdCl(3) concentration is varied from 0-140 micromol/kg and the agarose concentration is varied from 0-1.6%. A new phantom has now been developed (called CAGN phantom), made by adding an electric conductive agent, NaCl, to the CAG phantom for use in the areas of MRI and hyperthermia research. Dielectric properties of the CAGN phantom were measured and the results of experiments were expressed by the Cole-Cole equation in the frequency range of 5-130 MHz. The relationship between the conductivity of the CAGN phantom and the concentration of NaCl was expressed by a linear function in the frequency range of 1-130 MHz. The linear function involves a parameter of frequency and, when the frequency is 10 MHz, the conductivity of the CAGN phantom can be changed from 0.27-1.26 Sm(-1) by increasing the NaCl concentration from 0-0.7%. The CAGN phantom developed can be employed in basic experiments for non-invasive temperature measurement using MRI and as a loading phantom for MRI with up to 3 T.


Subject(s)
Hyperthermia, Induced , Magnetic Resonance Imaging , Phantoms, Imaging , Carrageenan , Electric Conductivity , Gadolinium , Gels , Humans , Models, Biological , Sepharose , Sodium Chloride
5.
Qual Life Res ; 13(1): 81-9, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15058790

ABSTRACT

BACKGROUND: Providing patients with disease- and treatment-related information is an important role of medical staff and is now reimbursed in Japan by the national health insurance system under the rubric 'patient education'. Evaluation of the effectiveness of patient education programs is necessary to ensure that limited health care resources are used efficiently. OBJECTIVE: The objective is to determine whether educating patients with Parkinson's disease (PD) is related to better health-related quality of life (HRQOL). DESIGN: A cross-sectional study was conducted. SETTING: Members of the Japan Association of Patients with Parkinson's disease were randomly selected. PARTICIPANTS: A total of 1200 patients with PD were asked to fill in written questionnaires and replies from 762 (63.5%) were analyzed. MEASUREMENTS: The questionnaire inquired about clinical characteristics, comorbidity, symptoms of PD, complications of therapy, HRQOL, and patient education. SF-36 was used to assess HRQOL. The section on patient education comprised one question each on patient-perceived satisfaction with information provided on (1) disease condition and pathophysiology, (2) effectiveness of drug therapy, (3) adverse drug reactions, (4) publicly available financial and social resources, and (5) rehabilitation and daily activities. Patient education score was defined as the sum of the individual scores for these five questions. The relationships between scores on the SF-36 subscales and the patient education score were examined. RESULTS: More satisfaction with patient education was associated with higher scores in all SF-36 subscales except physical functioning and bodily pain. The difference in score between the most satisfied and the least satisfied patients ranged from 8.4 points on the subscales of general health and 16.7 points on the subscale of role limitation due to emotional problems. CONCLUSION: The conclusion that patient education is associated with better HRQOL in patients with PD is drawn.


Subject(s)
Parkinson Disease/psychology , Patient Education as Topic/standards , Quality of Life , Sickness Impact Profile , Aged , Cross-Sectional Studies , Disease Management , Female , Humans , Japan , Linear Models , Male , National Health Programs , Parkinson Disease/complications , Patient Satisfaction , Program Evaluation , Surveys and Questionnaires , Treatment Outcome
6.
Int J Hyperthermia ; 20(8): 803-14, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15764343

ABSTRACT

The authors developed a phantom, designated as the CAGN phantom, compatible for MRI and hyperthermia that is useful in the fundamental studies of non-invasive MR thermometry. The ingredients of this phantom are carrageenan, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl as a conductivity modifier, NaN3 as an antiseptic and distilled water. Another phantom that was developed, the CAG phantom, has relaxation times that are adjustable to those of any human tissue. To use this phantom for electromagnetic heating, NaCl was added to change the conductivity of the phantom and clarified the relationship between the conductivity and NaCl concentration. This study examined the relationship between relaxation times and NaCl concentration of the CAGN phantom. The results showed that both T1 and T2 values were affected by NaCl and the experimental results led to the empirical formulae expressing the relationship between the relaxation rates (1/T1, 1/T2) and the concentrations of GdCl3, agarose and NaCl. The appropriate concentrations of T1 and T2 modifiers were calculated from these empirical formulae when making a specified phantom that has the required relaxation times and NaCl concentration.


Subject(s)
Carrageenan/chemistry , Hyperthermia, Induced/instrumentation , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging , Sodium Chloride/chemistry , Algorithms , Electric Conductivity , Electromagnetic Phenomena , Gadolinium/chemistry , Humans , Magnetic Resonance Spectroscopy , Sepharose/chemistry , Sodium Azide/chemistry , Water/chemistry
7.
Br J Ophthalmol ; 86(10): 1172-4, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12234901

ABSTRACT

BACKGROUND: The effectiveness of losartan for the treatment of leucocyte entrapment in the retinal microcirculation of diabetic rats was evaluated quantitatively. METHODS: After diabetes was induced by injection of streptozotocin (STZ), the rats were divided into two subgroups. The first subgroup (n = 6), received no medications; the second subgroup (n = 6) was given fresh drinking water supplemented with losartan (5 mg/kg/day) for 4 weeks. Six rats that were not injected with STZ or given medications served as controls. 4 weeks after intervention, leucocyte dynamics in the retina were observed using acridine orange digital fluorography. Leucocyte entrapment in the retina was compared among the three groups. RESULTS: In the untreated diabetic rats, the number of trapped leucocytes (6.1 (SD 1.4) cells/mm(2)) increased significantly compared with control rats (2.8 (1.2) cells/mm(2); p = 0.005) and diabetic rats treated with losartan (3.1 (0.9) cells/mm(2); p = 0.0002). CONCLUSIONS: Losartan, an AT1 angiotensin II receptor antagonist, inhibited increased leucocyte entrapment in the diabetic retina. The authors demonstrated that losartan may have therapeutic efficacy in preventing development of diabetic retinopathy. Further clinical studies of the effect of the angiotensin receptor antagonist on preventing development of diabetic retinopathy are needed.


Subject(s)
Angiotensin Receptor Antagonists , Diabetes Mellitus, Experimental/physiopathology , Leukocytes/drug effects , Losartan/pharmacology , Retinal Vessels/drug effects , Acridine Orange , Animals , Fluorescence , Male , Microcirculation/drug effects , Rats , Rats, Inbred BN
8.
Infect Immun ; 69(1): 386-91, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11119528

ABSTRACT

A large subunit of calpain, a calcium-activated neutral proteinase, from Schistosoma japonicum was cloned and expressed in Escherichia coli. When BALB/c mice were immunized with purified recombinant calpain (r-calpain) emulsified in complete Freund's adjuvant, a significant reduction in the number of recovered worms and also in egg production per female worm was observed (P<0.01). Spleen cells of the immunized mice showed enhanced production of gamma interferon (IFN-gamma) by activated CD4(+) T cells. Considering our observation of elevated expression of inducible nitric oxide synthase mRNA in immunized mice, r-calpain-induced IFN-gamma seemed to upregulate the production of nitric oxide by macrophages and subsequently mediated the killing of schistosomulae in the lung. On the other hand, spleen cells of immunized mice showed only faint interleukin-4 production in response to r-calpain in vitro, suggesting that immunization with r-calpain alters the Th1-Th2 balance in murine hosts even during a Th2-promoting S. japonicum infection. Furthermore, histopathological study of the livers of immunized mice showed that granulomas formed around eggs were diminished in both size and number. Egg production by female worms was clearly decreased in immunized mice, suggesting that r-calpain also has antifecundity effects. Taken together, these results point to S. japonicum calpain as a potential vaccine candidate for both worm killing and disease prevention, possibly through the induction of a strong Th1-dominant environment in immunized mice.


Subject(s)
Calpain/immunology , Schistosoma japonicum/immunology , Th1 Cells/immunology , Animals , Antibodies, Helminth/biosynthesis , Cytokines/biosynthesis , Female , Granuloma/pathology , Mice , Mice, Inbred BALB C , Nitric Oxide Synthase/genetics , RNA, Messenger/analysis , Recombinant Proteins/immunology , Vaccination
9.
Nihon Ronen Igakkai Zasshi ; 38(6): 780-4, 2001 Nov.
Article in Japanese | MEDLINE | ID: mdl-11774723

ABSTRACT

It is controversial whether pulmonary rehabilitation is effective in patients with chronic obstructive pulmonary disease (COPD). To test the effect of pulmonary rehabilitation, 7 patients with COPD (aged 76.0 +/- 2.6 years) were enrolled in pulmonary rehabilitation program for 6 weeks. The program consisted of relaxation, pursed lip breathing, diaphragmatic breathing, panic control, muscle stretch gymnastics, and exercise training. The distance of the 6-minute walking test increased significantly from 246.4 +/- 38.0 (m) to 304.3 +/- 28.4 (m) (p < 0.05). The minimum SpO2 during the 6-minute walking test increased from 86.0 +/- 2.8 (%) to 90.1 +/- 1.3 (%) and dyspnea as measured with Borg scale decreased from 5.6 +/- 1.1 to 4.6 +/- 0.5, although they were not significantly different. These results suggest that pulmonary rehabilitation might improve exercise tolerance in elderly patients with COPD.


Subject(s)
Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Respiration , Aged , Aged, 80 and over , Breathing Exercises , Exercise , Humans , Middle Aged , Relaxation Therapy , Walking
10.
Lipids ; 34(6): 583-9, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10405972

ABSTRACT

Feeding a diet with excess cystine to rats resulted in hypercholesterolemia. To understand the mechanism of the hypercholesterolemia, cholesterol synthesis and degradation, bile acid content of bile, and fecal steroids were determined. The in vivo incorporation of tritiated water into hepatic cholesterol, and activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in rats fed a high-cystine diet were significantly higher than those in rats fed a control diet. The activity of hepatic cholesterol 7 alpha-hydroxylase was similar between two groups. Little effect of cystine supplementation was found on fecal sterol excretion although there were some changes in biliary excretion of cholic acid derivatives. These results indicate that hypercholesterolemia caused by feeding of a high-cystine diet may be due to the stimulation of hepatic cholesterol synthesis.


Subject(s)
Cholesterol/biosynthesis , Cystine/administration & dosage , Diet , Animals , Bile/metabolism , Bile Acids and Salts/metabolism , Cholesterol/blood , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/metabolism , Hydrolysis , Hydroxymethylglutaryl CoA Reductases/metabolism , Kinetics , Liver/enzymology , Liver/metabolism , Male , Rats , Rats, Wistar , Tritium
11.
Phytochemistry ; 51(6): 819-23, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10389276

ABSTRACT

Investigation on the constituents of the fruit of Bupleurum falcatum L. resulted in the isolation of the three new glycosides, phenethyl alcohol 8-O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-apiofuranosyl-(1-->6)-b eta-D- glucopyranoside, phenethyl alcohol 8-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside and isopentenol 1-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside along with five known glycosides, icariside D1, icariside F2, saikosaponin a, saikosaponin c and saikosaponin d. The structures of these compounds were elucidated on the basis of interpretation of chemical and spectral data.


Subject(s)
Glycosides/isolation & purification , Plants, Medicinal/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Chromatography, Gel , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Glycosides/chemistry , Hydrolysis , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Spectrometry, Mass, Fast Atom Bombardment
12.
Eur J Pediatr Surg ; 9(6): 430-2, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10661860

ABSTRACT

We report a female newborn with Ondine's curse and Hirschsprung's disease--neurocristopathic syndrome. The female infant required endotracheal intubation and mechanical ventilation due to apnea which developed soon after birth. She had abdominal distension with bilious vomiting. A barium enema revealed a caliber change at the rectum and rectal biopsies showed no ganglion cells. Colostomy was performed at the age of 17 days. Hypoxemia with hypercapnia was noted during her sleep, and tracheostomy was performed at the age of 55 days. In addition, deafness and pupillary autonomic dysfunction were observed. The definitive surgery for Hirschsprung's disease was performed at the age of 4 months. She is now 2 years old with normal growth but needs ventilator support at home. In this case, we detected no mutation in the RET gene and EDNRB gene.


Subject(s)
Hirschsprung Disease/complications , Sleep Apnea, Central/complications , DNA Mutational Analysis , Female , Hirschsprung Disease/genetics , Humans , Infant, Newborn , Polymorphism, Single-Stranded Conformational , Respiration, Artificial , Sleep Apnea, Central/genetics , Sleep Apnea, Central/therapy , Syndrome
13.
J Hypertens ; 16(1): 111-8, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9533424

ABSTRACT

OBJECTIVE: To compare the effects of amlodipine and nifedipine on heart rate and parameters of sympathetic nerve activity during the acute and chronic treatment periods in order to elucidate their influence on cardiovascular outcome. DESIGN: A randomized and single-blind study. METHODS: We performed 24 h ambulatory electrocardiography and blood pressure monitoring of 45 essential hypertensive inpatients. Plasma and urinary catecholamine levels were measured during the control (pretreatment) period, on the first day (acute period) and after 4 weeks (chronic period) of administration of amlodipine and of short-acting nifedipine or its slow-releasing formulation. The low-frequency and high-frequency power spectral densities and low-frequency: high-frequency ratio were obtained by heart rate power spectral analysis. RESULTS: Blood pressure was significantly and similarly reduced by administrations of amlodipine, short-acting nifedipine and slow-releasing nifedipine during the chronic period. The total QRS count per 24 h, which remained constant during the chronic period of administration of slow-releasing nifedipine and was increased by administration of nifedipine, was decreased by 2.8% by administration of amlodipine. Administration of amlodipine decreased the plasma and urinary norepinephrine levels during the chronic period, whereas the levels were significantly increased by administration of short-acting nifedipine and not changed by administration of slow-release nifedipine. Although low-frequency: high-frequency ratio was increased significantly by administration of short-acting nifedipine and slightly by administration of slow-releasing nifedipine, administration of amlodipine reduced it during the acute and chronic periods. CONCLUSIONS: Administration of amlodipine did not induce an increase in sympathetic nerve activity in essential hypertensive patients during the chronic period, suggesting that beneficial effects on essential hypertension can be expected after its long-term administration. Administration of slow-releasing nifedipine induces milder reflex sympathetic activation than does that of short-acting nifedipine.


Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Heart Rate/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , Nifedipine/therapeutic use , Sympathetic Nervous System/drug effects , Adult , Aged , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Calcium Channel Blockers/administration & dosage , Circadian Rhythm/drug effects , Delayed-Action Preparations , Epinephrine/blood , Epinephrine/urine , Female , Humans , Male , Middle Aged , Nifedipine/administration & dosage , Norepinephrine/blood , Norepinephrine/urine , Single-Blind Method , Sympathetic Nervous System/physiopathology
14.
Article in English | MEDLINE | ID: mdl-11249000

ABSTRACT

Addition of excess cystine to a wheat gluten diet did not alter rat liver triacylglycerols or serum cholesterol. However, if the cystine-enriched diet was supplemented with lysine and threonine, rats accumulate triacylglycerols and show increased serum cholesterol. Increases in hepatic triacylglycerols can be prevented by the further addition of methionine. This diet further increases serum cholesterol. We conclude that accumulation of triacylglycerols in the liver might be due to an increased methionine requirement, induced by the addition of excess cystine, and therefore to choline deficiency.


Subject(s)
Amino Acids/pharmacokinetics , Fatty Liver/metabolism , Triglycerides/metabolism , Animals , Cystine/pharmacokinetics , Fatty Liver/pathology , Glutens/pharmacology , Liver/metabolism , Liver/pathology , Lysine/pharmacokinetics , Male , Methionine/pharmacokinetics , Organ Size , Rats , Rats, Wistar , Threonine/pharmacokinetics , Triticum
15.
J Biol Chem ; 272(27): 16884-8, 1997 Jul 04.
Article in English | MEDLINE | ID: mdl-9201996

ABSTRACT

The consensus primary amino acid sequence for mucin-type O-glycosylation sites has not been identified. To determine the shortest motif sequence required for high level mucin-type O-glycosylation, we prepared more than 100 synthetic peptides and assayed in vitro O-GalNAc transfer to serine or threonine in these peptides using a bovine colostrum UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferase (O-GalNAcT). We chose the sequence PDAASAAP from human erythropoietin (hEPO) for further systematic substitutions because it accepted GalNAc and was a fairly simple sequence consisting only of four kinds of amino acids. Several substitutions showed that threonine is approximately 40-fold better than serine as the glycosylated amino acid and a proline at position +3 on the C-terminal side is very important. To define the effect of proline residues around the glycosylation site, we analyzed a series of peptides containing one to three proline residues in a parent peptide AAATAAA. The results clearly indicated that prolines at positions +1 and +3 had a positive effect. The O-GalNAc transfer level of AAATPAP was increased approximately 90-fold from AAATAAA. The deletion of amino acids from the N-terminal side of the glycosylation site suggested that five amino acids from position -1 to +3 were especially important for glycosylation. Moreover, the influence of all 20 amino acids at positions -1, +2, and +4 was analyzed. Uncharged amino acids were preferred at position -1, and small or positively charged amino acids were preferred at position +2. No preference was observed at position +4. We propose a mucin-type O-glycosylation motif, XTPXP, which may be suitable as a signal for protein O-glycosylation. The features observed in this study also appear to be very useful for prediction of mucin-type O-glycosylation sites in glycoproteins.


Subject(s)
Mucins/metabolism , Acetylgalactosamine/metabolism , Amino Acid Sequence , Animals , Binding Sites , Cattle , Colostrum/chemistry , Erythropoietin/chemistry , Glycosylation , Humans , Kinetics , Molecular Sequence Data , Mucins/chemistry , Peptide Fragments/metabolism , Peptide Mapping , Proline/metabolism
16.
Neurosci Lett ; 208(2): 105-8, 1996 Apr 19.
Article in English | MEDLINE | ID: mdl-8859901

ABSTRACT

We have previously identified synaptotagmin, a synaptic vesicle membrane protein from rat brain, as a binding protein for Clostridium botulinum type B neurotoxin. In this report, rat synaptotagmin II was expressed by transfection in Chinese hamster ovary cells and interaction with the neurotoxin was studied. In stable transfectants, the NH(2)-terminal region of synaptotagmin was exposed to the extracellular medium. Synaptotagmin-expressing cells were shown to possess an extremely low binding activity for the radiodinated toxin. However, toxin-binding was markedly increased to cells which had been treated with gangliosides G T1b or G D1a. In synapses, the intravesicular NH(2)-terminus of synaptotagmin becomes exposed at the cell surface after following exocytosis. These findings suggest that the NH(2)-terminal domain of synaptotagmin II forms the binding site for type B neurotoxin by associating with specific gangliosides in presynaptic plasma membranes.


Subject(s)
Botulinum Toxins/metabolism , Nerve Tissue Proteins/genetics , Animals , Antibodies, Monoclonal , Antibody Specificity , Binding, Competitive/physiology , Botulinum Toxins/pharmacology , Botulinum Toxins, Type A , CHO Cells/chemistry , CHO Cells/metabolism , Carrier Proteins/genetics , Cricetinae , DNA, Complementary , Iodine Radioisotopes , Mice , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/immunology , Rats , Synaptotagmin II , Transfection
17.
Surg Today ; 26(9): 711-4, 1996.
Article in English | MEDLINE | ID: mdl-8883244

ABSTRACT

We report herein a case of perianal extramammary Paget's disease associated with primary linitis plastica of the rectum. An 82-year-old woman was admitted to our hospital for investigation and treatment of a perianal eczematous lesion. A skin biopsy of the lesion revealed perianal extramammary Paget's disease and a barium enema demonstrated diffuse narrowing with an irregular contour at the ampulla recti. Under a suspected diagnosis of linitis plastica of the rectum, an abdominoperineal resection was performed to resect both the rectal and perianal lesions with regional lymphadenectomy. Grossly, marked narrowing and wall thickness were observed at the lower rectum, and a histological diagnosis of signet ring cell carcinoma was confirmed. The perianal eczematous lesion revealed many atypical cells with clear cytoplasm, being Paget cells, throughout the entire epidermis. Sparse distributions of signet ring cells were also observed in the subcutaneous tissue beneath the perianal eczematous lesion. The pathogenesis of perianal extramammary Paget's disease in this patient was therefore considered to be an intraepidermal extension of primary linitis plastica of the rectum.


Subject(s)
Anus Neoplasms/complications , Carcinoma, Signet Ring Cell/complications , Linitis Plastica/complications , Paget Disease, Extramammary/complications , Rectal Neoplasms/complications , Aged , Aged, 80 and over , Anus Neoplasms/pathology , Carcinoma, Signet Ring Cell/pathology , Female , Humans , Linitis Plastica/pathology , Paget Disease, Extramammary/pathology , Rectal Neoplasms/pathology
18.
Gene ; 166(2): 303-6, 1995 Dec 12.
Article in English | MEDLINE | ID: mdl-8543180

ABSTRACT

Retinoic acid (RA), an important regulator of cell differentiation, is biosynthesized from retinol via retinal by a two-step oxidation process. We previously reported the purification and partial amino acid (aa) sequence of a rat kidney aldehyde dehydrogenase (ALDH) isozyme that catalyzed the oxidation of 9-cis and all-trans retinal to corresponding RA with high efficiency [Labrecque et al. Biochem. J. 305 (1995) 681-684]. A rat kidney cDNA library was screened using a 291-bp PCR product generated from total kidney RNA using a pair of oligodeoxyribonucleotide primers matched with the aa sequence. The full-length rat kidney ALDH cDNA contains a 2315-bp (501 aa) open reading frame (ORF). The aa sequence of rat kidney ALDH is 89, 96 and 87% identical to that of the rat cytosolic ALDH, the mouse cytosolic ALDH and human cytosolic ALDH, respectively. Northern blot and RT-PCR-mediated analysis demonstrated that rat kidney ALDH is strongly expressed in kidney, lung, testis, intestine, stomach and trachea, but weakly in the liver.


Subject(s)
Aldehyde Dehydrogenase/genetics , Retinaldehyde/metabolism , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA Primers/chemistry , DNA, Complementary/genetics , Gene Expression , Kidney/enzymology , Molecular Sequence Data , Oxidation-Reduction , RNA, Messenger/genetics , Rats , Substrate Specificity , Tissue Distribution
19.
Vis Neurosci ; 12(3): 493-500, 1995.
Article in English | MEDLINE | ID: mdl-7544607

ABSTRACT

Nitric oxide (NO) is known to be synthesized in several tissues and to increase the formation of cyclic GMP through the activation of soluble guanylate cyclases. Since cyclic GMP plays an important role in visual transduction, we investigated the presence of nitric oxide synthesizing activity in retinal rod outer segments. Bovine rod outer segments were isolated intact and separated into membrane and cytosolic fractions. Nitric oxide synthase activity was assayed by measuring the conversion of L-arginine to L-citrulline. Both membrane and cytosolic fractions were active in the presence of calcium and calmodulin. The activity in both fractions was stimulated by the nitric oxide synthase cofactors FAD, FMN, and tetrahydrobiopterin and inhibited by the L-arginine analog, L-monomethyl arginine. The Km for L-arginine was similar, about 5 microM for the enzyme in both fractions. However, the two fractions differed in their calcium/calmodulin dependence: the membrane fraction exhibited basal activity even in the absence of added calcium and calmodulin while the cytosolic fraction was inactive. But the activity increased in both fractions when supplemented with calcium/calmodulin: in membranes from about 40 to 110 fmol/min/mg of protein and in the cytosol from near zero to about 350 fmol/min/mg of protein in assays carried out at 0.3 microM L-arginine. The two enzymes also responded differently to detergent: the activity of the membrane enzyme was doubled by Triton X-100 while that of the cytosolic enzyme was unaffected. These results show that NO is produced by cytosolic and membrane-associated enzymes with distinguishable properties.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Nitric Oxide/biosynthesis , Photoreceptor Cells/metabolism , Retina/cytology , Rod Cell Outer Segment/metabolism , Amino Acid Oxidoreductases/metabolism , Animals , Calcium/pharmacology , Calmodulin/pharmacology , Cattle , Cell Membrane/drug effects , Cell Membrane/enzymology , Cytosol/drug effects , Cytosol/enzymology , Enzyme Activation , NADPH Dehydrogenase/metabolism , Nitric Oxide Synthase , Rod Cell Outer Segment/ultrastructure , Sodium-Potassium-Exchanging ATPase/metabolism
20.
Jpn J Antibiot ; 46(11): 953-8, 1993 Nov.
Article in Japanese | MEDLINE | ID: mdl-8309071

ABSTRACT

Pharmacokinetic, bacteriological and clinical studies on S-1108 were performed in children. The results were as follows: 1. A total of 11 patients were treated with S-1108. Each dose was 3 mg/kg, orally administered 3 times daily for 4-14 days. The clinical efficacies of S-1108 in 10 patients with bacterial infections (1 with bacteremia, 4 with pneumonia, 1 with acute maxillary sinusitis, 1 with scarlet fever and 2 with streptococcal pharyngitis) were evaluated as excellent in 8 patients and as good in 2 patients with an efficacy rate of 100%. Only one patient with staphylococcal scalded skin syndrome due to methicillin resistant Staphylococcus aureus (MRSA) who received gamma-globulin was not evaluated. Fourteen causative strains of 5 species were found in 10 patients. Three strains of Streptococcus pneumoniae out of 5, 2 of 3 Branhamella catarrhalis strains, none of Staphylococcus aureus and all 3 strains of Streptococcus pyogenes were eradicated. No adverse reaction was observed in any of the 11 patients. 2. MICs of S-1108 against 5 clinically isolated S. pneumoniae from cases of infections were examined. All of them were relatively highly resistant to penicillins. S-1108 was compared with cefteram pivoxil, cefpodoxime proxetil, cefaclor and cefixime, and it showed better antibacterial activity or than other cephems. 3. Double peaks were obtained in plasma levels of S-1108 orally administered at a dose of 3 mg/kg at 30 minutes after meal and were 1.03 microgram/ml and 0.74 microgram/ml at 1 and 4 hours after administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Bacterial Infections/drug therapy , Cephalosporins/therapeutic use , Bacterial Infections/blood , Bacterial Infections/microbiology , Cephalosporins/pharmacokinetics , Cephalosporins/pharmacology , Child , Child, Preschool , Drug Evaluation , Female , Humans , Infant , Male , Microbial Sensitivity Tests , Streptococcus pneumoniae/drug effects
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