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Biomedical subjects

A Higa

Publications and source records attributed to A Higa.

At least 19 recordsLinked to original sources

Prevention and reversal of experimental colitis by a monoclonal antibody which inhibits leukocyte adherence.

The role of neutrophils in the pathogenesis of acute colitis was investigated using a rabbit model. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid in 30% ethanol. Myeloperoxidase activity was measured at various times after induction of colitis as an index of neutrophil infiltration, and this was confirmed by histology. The permeability of the colonic epithelium to [51Cr]EDTA was also measured at various times after induction of colitis. The most marked increase in neutrophil infiltration of the colon occurred during the period 3-6 h after induction of colitis. This was also the period in which the greatest increase in colonic permeability was observed. Pretreatment with a monoclonal antibody (IB-4) directed against the leukocyte adhesion molecule, CD18, markedly suppressed neutrophil infiltration into the colonic tissue after induction of colitis. This pretreatment also significantly reduced the extent of epithelial injury. Administration of IB-4 to rabbits 12 h after induction of colitis resulted in a rapid decline in tissue myeloperoxidase activity. When measured 12 h after IB-4 administration (3 mg/kg), colonic myeloperoxidase activity was reduced by about 80% compared to the control group treated with the vehicle. These results are consistent with the hypothesis that neutrophils contribute significantly to the epithelial dysfunction that characterizes colitis and suggest that antibodies directed against adhesion molecules may represent a novel approach to the treatment of intestinal inflammatory disorders.

Acute Disease

[Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children].

Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections

[Pharmacokinetic, bacteriological and clinical studies on meropenem in children].

Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30-minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Gastric mucosal microcirculation measured by laser Doppler velocimetry in patients with gastric ulcer.

In order to evaluate the role of gastric mucosal blood flow in patients with gastric ulcer, we applied laser Doppler velocimetry to the human gastric mucosa to study the regional microcirculatory mechanism. We measured 5 spots each in 34 control stomachs, and in 47 patients with gastric ulcer at the angle and antrum of the stomach, 2 additional spots around the ulcer. During the healing process, mucosal blood flow around the gastric ulcer increased as compared to that of the active or scarring stages. Compared with that of surrounding mucosa, mucosal blood flow around the gastric ulcer increased significantly during healing stage. Mucosal blood flow at the ulcer margin in healing stage (H1 stage) was 52% more than in the active stage. The increase in mucosal blood flow in the ulcer margin during healing stages (H1 and H2 stage) was 45% in cases with initial ulcer and 22% in cases with recurrent ulcer. It was concluded that increased blood flow in the ulcer margin during healing stages promotes healing of the ulcer. Laser Doppler velocimetry is useful in measuring mucosal blood flow sequentially in various stages of gastric ulcer, and also provides effective evaluation of medical treatment.

Adult

The possible role of LTC4 in the pathogenesis of ethanol-induced gastric lesions in mice and their prevention by 5-lipoxygenase inhibitor AA-861, and leukotriene receptor antagonist FPL-55712.

The extent of acute gastric lesions produced by intragastric administration of ethanol in mice paralleled gastric leukotriene (LT) C4 levels. Furthermore, an inverse dose-response relationship was observed between the extent of gastric lesions and the number of mast cells in the gastric mucosa. When mice were pretreated with the 5-lipoxygenase inhibitor, AA-861, both the extent of ethanol-induced gastric lesions and the level of gastric LTC4 decreased dose-dependently. In contrast, when mice were pretreated with the LTC4 receptor antagonist, FPL-55712, the extent of ethanol-induced gastric lesions was depressed without significant reduction of gastric LTC4 level. These results indicate that both production of LTC4 and also subsequent binding of LTC4 to the receptors is important for the pathogenesis of gastric lesions and suggest that mast cell-derived LTC4 plays a major role in the development of ethanol-induced gastric lesions.

Animals

Natural resistance of W/Wv mice to ethanol-induced gastric lesions and its abrogation by bone marrow grafting: possible role of mast cells and LTC4.

The extent of ethanol-induced acute gastric lesions, gastric leukotriene C4 (LTC4) levels, and the number of gastric mucosal mast cells were examined in mast cell-deficient W/Wv mice, normal litter-mate +/+ mice, and bone marrow-reconstituted W/Wv mice. After administration of ethanol, +/+ mice developed gastric lesions and elevation of gastric LTC4 levels in a dose dependent manner. In mast cell-deficient W/Wv mice, the extent of gastric lesions was far less than that of +/+ mice and the level of gastric LTC4 was not significantly altered. This difference was not due to anemia because blood-transfused non-anemic W/Wv mice were still resistant to ethanol-induced gastric lesions. When W/Wv mice were reconstituted with +/+ bone marrow cells, their natural resistance against ethanol-induced gastric lesions was abrogated. The extent of gastric lesions of bone marrow-reconstituted W/Wv mice paralleled with the increase in number of gastric mucosal mast cells and also with the level of gastric LTC4. Furthermore, ethanol-induced gastric lesions in bone marrow-reconstituted W/Wv mice was inhibited by pretreatment with 5-lipoxygenase inhibitor, AA-861, in a dose dependent manner. These results suggest that LTC4 may, even if it is not a prerequisite factor for ethanol induced acute gastric lesions, act as the amplitier in the sequential events of the pathogenesis.

Animals

Characterization of two bacteriocins produced by Clostridium perfringens.

Two types of bacteriocins were shown to be produced in succession by a strain of Clostridium perfringens SN-17. They were separated by diethylaminoethyl cellulose (DEAE) column chromatography at pH 8.5 with a linear concentration gradient of NaCl. One type of bacteriocin (named SN-a) was eluted at 0.07 M and the other type (named SN-b) was at 0.12 M. Each of these was partially purified in a series of column chromatographies: DEAE, Sephadex G-200 (or Bio Gel P-150), and hydroxyapatite. Specific activities of SN-a and SN-b after the last chromatography were at most 30- to 50-fold that of culture filtrate of the organisms. Chromatographed SN-a migrated as a single zone in polyacrylamide gel electrophoresis (PAGE) and the zone showed high biological activity. On the other hand, PAGE pattern of SN-b revealed the presence of a few contamination materials. The activity of SN-b after the last chromatography was hardly recovered from the gel but inactivated SN-b was identified in the gel by examining bacteriocin activity of the DEAE fractions recovered from the gel. The molecular weight of the SN-a and SN-b was determined to be about 70,000 and 100,000, respectively, by molecular sieve chromatography. These bacteriocins were very sensitive to protease but insensitive to DNase and RNase. Bacteriocins were both completely inactivated at 55 C and they were more stable in alkaline pH than in acidic pH. SN-a and SN-b were adsorbed in different ways on the surface of the producer and insensitive strains. Several differences and similarities between these 2 bacteriocins are discussed with special reference to the relationship between them.

Bacteriocins

Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara canis-infected mice.

Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the livers of Toxocara canis-infected mice. At the peak of the response (day-13 after infection), the majority of hepatic hemopoietic foci were of the eosinophil lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day 13 contained large numbers of hemopoietic stem cells, more than half of which were cycling. When W/Wv mice, which are genetically deficient in multipotent hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci were rare throughout the course of infection. This impaired response of W/Wv mice was restored by bone marrow grafting from normal +/+ littermates. These results indicate that, in response to the increased demand, eosinophils are generated in the liver by the differentiation from multipotent stem cells, not only from the committed precursors.

Animals

Extramedullary eosinophilopoiesis in the liver of Schistosoma japonicum-infected mice, with reference to hemopoietic stem cells.

Extramedullary hemopoiesis recognized as hemopoietic foci increased in the liver of Schistosoma japonicum-infected mice in parallel with kinetic changes in periovular granuloma formation. At the peak of the response, about 65% of the hepatic hemopoietic foci were of eosinophil lineage. When S. japonicum-infected mice were irradiated, hepatic hemopoietic foci rapidly disappeared within 3 days, whereas inflammatory cells in the periovular granulomas slowly reduced in number. When the number of hemopoietic stem cells in the liver were examined by spleen-colony assay, kinetic changes in the number of hemopoietic stem cells in hepatic nonparenchymal cells paralleled those of hepatic hemopoietic foci. Hemopoietic stem cells were rare in the granuloma cells. These results indicate that in response to the increased demand for eosinophils and other inflammatory cells, the liver acts as an extramedullary hemopoietic organ in which inflammatory cells are generated from hemopoietic stem cells.

Animals

Effects of Toxocara canis infection on hemopoietic stem cells and hemopoietic factors in mice.

The effects of Toxocara canis infection on hemopoietic stem cells and hemopoietic factors were examined in mice. Severe eosinophilia was observed with a peak 14 days after infection. When the numbers of hemopoietic stem cells in peripheral blood, spleen, and bone marrow were examined by spleen colony assay (CFU-S), those in peripheral blood and spleen increased in parallel with peripheral blood eosinophilia. On the other hand, CFU-S in bone marrow did not alter significantly throughout the course of infection. Interleukin (IL)-3, which is known as multi-colony-stimulating factor and is involved in the growth/differentiation of various blood cells including stem cells, was produced by spleen cells of infected mice. The time course study showed that concanavalin A stimulated IL-3 production peaked on day 7 after infection, whereas that with excretory secretory antigen peaked on day 14. Even without stimulation, spleen cells obtained on day 21 after infection produced IL-3 spontaneously. IL-5, which is known to have eosinophil differentiation factor activity, was also produced by spleen cells obtained on day 13 after infection. These results suggest that in response to increased demand for eosinophils, hemopoietic stem cells migrate into various extramedullar hemopoietic organs where they grow/differentiate into mature eosinophils, depending on the hemopoietic factors.

Animals

[Clinical evaluation of clarithromycin, a new macrolide antibiotic in children].

A new oral macrolide, clarithromycin (TE-031, A-56268), was evaluated for its safety, efficacy and pharmacokinetics in 33 children. TE-031 was effective in all cases of mycoplasmal pneumonia, pneumococcal pneumonia, streptococcal pharyngitis, pertussis and Campylobacter gastroenteritis. The pharmacokinetic availability of TE-031 granule and tablets was much better than the older macrolides; serum half-lives of TE-031 averaged 3.2 +/- 0.25 hours (for the granule preparation). No clinical adverse reaction was encountered, but cases of transient mild elevation of the serum GPT (2 cases) and eosinophilia (2 cases) were encountered. From these preliminary data, TE-031 seems to have a place in the treatment of pediatric infectious diseases.

Adolescent

[Bacteriological, pharmacokinetic and clinical studies on clarithromycin in the pediatric field. Pediatric Study Group of Clarithromycin].

Clarithromycin (TE-031, A-56268), a new macrolide antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Absorption and excretion Pharmacokinetics of TE-031 was examined by single oral administration of 10% granules and 50 mg tablets at doses of 1, 5, 10 and 15 mg/kg. There were no significant differences between 10% granules and 50 mg tablets, and between administrations before and after meal. Peaks and half-life periods of blood level of TE-031 given once at doses of 5, 10 and 15 mg/kg (10% granules) before meal were 1.58, 4.37 and 3.79 micrograms/ml, and 2.53, 3.17 and 2.20 hours, respectively, and the urinary excretion in 6 hours after the administration were about 20-30%. 2. Antibacterial effects TE-031 was proved to have excellent antibacterial effect, i.e., inhibiting growth over 80% of strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.10 micrograms/ml, Branhamella catarrhalis at 0.39 micrograms/ml, and Campylobacter jejuni at 0.78 micrograms/ml. Against Staphylococcus aureus, TE-031 showed very similar activity spectrum to EM, and EM resistant strains were also resistant to TE-031. 3. Clinical results A total of 764 cases was studied. Clinical effects of TE-031 were evaluated in 717 cases out of the 764, excluding drop-outs and cases which did not meet specified protocols. Clinically, efficacies of TE-031 were "excellent" in 265 cases and "good" in 161 cases out of 453 cases of Group A in which causal agents were identified, with an efficacy rate of 94.0%, and out of 264 cases of Group B in which pathogens were not detected, clinical effects of TE-031 were "excellent" in 115 cases and "good" in 124 cases, with an efficacy rate of 90.5%. In terms of clinical effects of TE-031 classified by diseases when Group A and B were combined, efficacy rates were 91.6% for upper respiratory tract infection (217/237), 90.0% for bacterial pneumonia (108/120), 97.4% for Mycoplasma pneumonia (111/114), 100% for Chlamydia pneumonia (4/4), 85.0% for pertussis (34/40), 100% for scarlet fever (16/16), 83.9% for skin and soft tissue infection (26/31), and 98.9% for Campylobacter enteritis (87/88).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

A case of generalized juvenile gastrointestinal polyposis associated with gastric carcinoma.

A case of generalized juvenile gastrointestinal polyposis associated with gastric adenocarcinoma is described. A 31-year-old male patient developed polyposis of the stomach complicated by gastric carcinoma and multiple polyps in the colon. Polyps of the stomach and colon were pathologically consistent with juvenile polyp, but adenomatous changes were also present in a very small percentage of the juvenile polyps. This case strongly suggests the possibility of carcinoma developing in patients with generalized juvenile gastrointestinal polyposis.

Adenocarcinoma

Immunological and clinical effects of interferon-gamma on Crohn's disease.

Five patients with Crohn's disease (CD) confined to the small intestine were studied to determine whether intravenous administration of interferon (IFN)-gamma to normalize immunological imbalance produces clinical improvement. A daily dose of 12 million IU of IFN-gamma was intravenously infused for four weeks. Laboratory data, immunological responses, clinical and radiologic findings were evaluated after administration. Laboratory data showed no significant change after treatment. Immunological studies also failed to demonstrate any significant change except for a significant increase of natural killer (NK) cell activity after IFN-gamma infusion. Clinical assessment by Crohn's disease activity index as well as radiologic findings disclosed no definite improvement. This study suggests that enhancement of NK cell activity or augmentation of immunological imbalance induced by IFN-gamma does not play an important role in the pathogenesis of CD.

Adult

Technetium-99m serum albumin measurement of gastrointestinal protein loss in a subtotal gastrectomy patient with giant hypertrophic gastritis.

Gastrointestinal protein loss was measured using Tc-99m labeled human serum albumin in a patient with giant hypertrophic gastritis. Gastric secretion was aspirated via a nasogastric tube and measured for radioactivity after intravenous injection of Tc-99m albumin. Assessment of radioactivity of the collected gastric secretion yielded a total radiocount of 98.7 kilocounts per minute within 6 hours, which is equivalent to 1.1% of the total dose. Therefore, at least 1.1% of the circulating albumin was excreted into the gastric cavity within 6 hours, and, since simultaneous abdominal imaging did not demonstrate obvious accumulation of tracer in the gastrointestinal tract, protein loss was thought to be due to giant gastric rugae of the resected stomach. It was concluded that Tc-99m albumin is a valuable means for detection of the site of protein loss in patients with protein-losing gastroenteropathy. This method has several advantages in the clinical setting; it is less time consuming, easy to perform, and provides quantitative and qualitative assessment of protein loss.

Female