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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 667 records · Page 37Linked to original sources

Activated eosinophils increase vascular permeability and resistance in isolated perfused rat lungs.

The effects of eosinophils activated with phorbol myristate acetate (PMA) on isolated perfused rat lungs were examined. Eosinophils were obtained from lungs of rats infected with Toxocara canis by bronchoalveolar lavage, incubated with PMA, and administered to an isolated perfused rat lung preparation. Vascular endothelial permeability was assessed by measuring the capillary filtration coefficient (Kf,c) in the perfused lungs. In lungs receiving either no eosinophils (control) or nonactivated eosinophils, there were no changes in pulmonary hemodynamics or Kf,c. However, in lungs receiving 2 x 10(6) eosinophils activated with PMA, there was a transient 4.8-fold increase in pulmonary vascular resistance that peaked at 30 min, primarily due to the constriction of small arteries and veins. After the initial pressor response, Kf,c was increased to 7.5 times control at 130 min and resulted in marked lung edema, increased wet-dry weight ratios, and edema on histologic examination. Pulmonary arterial pressure and Kf,c responses were dose related for eosinophil numbers between 1 x 10(6) and 4 x 10(6) cells. Peak airway pressure (Paw) during constant tidal volume ventilation also increased in lungs receiving activated eosinophils compared to the control and nonactivated eosinophil groups. These findings indicate that activated eosinophils are potent effector cells and can cause pulmonary vasoconstriction, bronchoconstriction, and vascular endothelial injury without widespread plugging of capillaries by aggregated eosinophils.

Animals↗

Synthesis and biological evaluation of quinocarcin derivatives.

Cyanation of quinocarcin readily opened the oxazolidine ring to provide DX-52-1 (2), which was a key compound in the synthesis of quinocarcin derivatives. Various electrophilic reactions toward aromatic ring of DX-52-1 were examined, and 10-substituted (e.g., halogen, nitro, formyl, cyano, hydroxy, etc.) analogs were prepared. Dehydrocyanation of the derivatives could be achieved to reproduce the oxazolidine ring upon treatment with HCl or AgNO3. 10-Chloride 10 and 10-bromide 11 were the most promising among the derivatives prepared. Antitumor activity of 10 was extended to B-16 melanoma.

Animals↗

Studies on orally active cephalosporin esters. V. A prodrug approach for oral delivery of 3-thiazoliomethyl cephalosporin.

Oral delivery of 3-thiazoliomethyl cephalosporin 1 was attempted through a prodrug approach by applying thiamine chemistry. The 3-thiazoliomethyl group was modified to a ring-opened structure with no ionic charge, and the 4-carboxyl group was converted to pivaloyloxymethyl ester. Lipophilicity of the resulting derivatives (8-10) was suitable for passive absorption from the intestinal tract, and chemical stability in phosphate buffer solution (pH 6.86) was moderate. When administered orally to mice, these derivatives were mainly transformed to a novel 3-spiro cephalosporin 11, and desired reconversion to the 3-thiazoliomethyl cephalosporin was minor. Isomerization to delta 2-cephalosporin 14 was also observed. These results showed that the derivatives (8-10) tested in this study did not serve as orally active prodrugs of 3-thiazoliomethyl cephalosporin 1.

Administration, Oral↗

Comparative studies on the antitumor and immunosuppressive effects of the new fluorouracil derivative N4-trimethoxybenzoyl-5'-deoxy-5-fluorocytidine and its parent drug 5'-deoxy-5-fluorouridine.

N4-Trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro 09-1390), a new prodrug of 5'-deoxy-5-fluorouridine (5'-dFUrd), was synthesized for the purpose of finding a drug with less intestinal toxicity than the parent compound. The present study compared the antitumor activity and immunotoxicity of Ro 09-1390 with those of 5'-dFUrd, 5-fluorouracil (5-FUra) and tegafur in various transplantable tumor models. The antitumor efficacy of Ro 09-1390 was comparable to 5'-dFUrd and these two agents were much more effective than the others. However, Ro 09-1390 was much less toxic to the intestinal tract and less immunosuppressive in both humoral and cellular immune reactions than 5'-dFUrd. Consequently, Ro 09-1390 showed higher therapeutic indices and higher efficacy than 5'-dFUrd at high dosages. The antitumor spectrum of Ro 09-1390 was somewhat different from that of 5'-dFUrd, though it shows the efficacy after it converts to 5'-dFUrd. The activity of Ro 09-1390 was partly associated with cytidine deaminase in the tumors treated. Ro 09-1390 appeared to be more effective against tumors with a high concentration of the enzyme by which the major metabolite 5'-deoxy-5-fluorocytidine (5'-dFCyd) is metabolized to 5'-dFUrd.

Animals↗

[The changes of serum gamma-Sm level in acute prostatitis].

gamma-Sm, the specific antigen of the prostate, is useful for the diagnosis and following-up of prostatic cancer. It is recognized as the tumor marker. The serum gamma-Sm is increased in some cases of acute prostatitis. We evaluated the serum gamma-Sm in patients with acute prostatitis. Serum gamma-Sm, PAP, CRP and WBC count were measured before treatment with antibiotics and 3 to 5 days and 1 week thereafter. In the acute phase of inflammation (before treatment) serum gamma-Sm increased in 62.5% of the cases. Then it decreased quickly and was within the normal range 3 to 5 days later. This change of serum gamma-Sm is similar to that of WBC count, fever and urinalysis. But the decrease of serum gamma-Sm is earlier than that of CRP. PAP does not increase in any phase of inflammation. It suggests that the serum gamma-Sm reflects cell damages of the prostatic gland or increased permeability due to prostatitis.

Acute Disease↗

Studies on orally active cephalosporin esters. VI. Synthesis and antimicrobial activity of 3-(3-isoxazolyl)oxymethylcephalosporin derivatives.

The synthesis and biological activities of a series of 3-(isoxazol-3-yl)oxymethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3- [(isoxazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid (7a) showed potent activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species. Its pivaloyloxymethyl ester provided a good urinary recovery after oral administration to mice.

Bacteria↗

Role of lymphocyte activation by substance P in rheumatoid arthritis.

Peripheral mononuclear cells taken from rheumatoid arthritis (RA) patients, which had previously been treated in vitro with the neuropeptide Substance P (SP) followed by stimulation with the mitogen PHA, showed a significantly higher percent positivity of lymphocytes with the double-markers CD4+ CD2+, CD8+ CD25+, CD4+, HLA-DR+ and CD8+ HLA-DR+ than those of the cells untreated by SP. No effect of SP was detected in normal controls, except that the cells with the double-marker CD4+ CD25+ were slightly increased. Furthermore, in RA patients the percentage of CD4+ CD45R- cells was increased, while that of CD4+ CD45R+ cells was decreased, by pre-treatment with SP and stimulation with PHA. Monocytes of patients with rheumatoid arthritis after the treatment with SP released a significantly higher amount of oxygen-intermediate than those of normal controls with or without SP. From these results, it could be considered that SP plays an important role in RA inflammation.

Antigens, CD↗

Transport of lipid and apolipoproteins A-I and A-IV in intestinal lymph of the rat.

Intestinal lipid absorption is associated with marked increases in the synthesis and secretion of apolipoprotein A-IV (apoA-IV) by the small intestine. Whether the increased intestinal apoA-IV synthesis and secretion results from increased fat uptake, increased cellular triglyceride (TG) content, or increased secretion of TG-rich lipoproteins by the enterocytes is unknown. Previous work from this laboratory has shown that a hydrophobic surfactant, Pluronic L-81 (L-81), is a potent inhibitor of intestinal formation of chylomicrons (CM), without reducing fat uptake or re-synthesis to TG. Furthermore, this inhibition can be reversed quickly by the cessation of L-81 infusion. Thus L-81 offers a unique opportunity to study the relationship between lymphatic TG, apoA-I and A-IV secretion. In this study, we studied the lymphatic transport of TG, apoA-I, and apoA-IV during both the inhibitory phase (L-81 infused together with lipid) and the subsequent unblocking phase (saline infusion). Two groups of lymph fistula rats were used, the control and the experimental rats. In the experimental rats, a phosphate-buffered taurocholate-stabilized emulsion containing 40 mumol [3H]triolein, 7.8 mumol of phosphatidylcholine, and 1 mg L-81 per 3 ml was infused at 3 ml/h for 8 h. This was then replaced by glucose-saline infusion for an additional 12 h. The control rats received the same lipid emulsion as the experimental rats, but without L-81 added, for 8 h. Lymph lipid was determined both by radioactivity and by glyceride-glycerol determination, and the apoA-I and apoA-IV concentrations were determined by rocket electroimmunophoresis assay. L-81 inhibited the rise in lymphatic lipid and apoA-IV output in the experimental rats after the beginning of lipid + L-81 infusion. Upon cessation of L-81 infusion, the mucosal lipid accumulated as a result of L-81 treatment was rapidly cleared into lymph as CM. This was associated with a marked increase in apoA-IV output; the maximal output was about 3 times that of the fasting level. There was a time lag of 4-5 h between the peak lymph lipid output and the peak lymph apoA-IV output during the unblocking phase in the experimental rats. There was also a comparable time lag between the maximal lipid and apoA-IV outputs in the control animals. Incorporation studies using [3H]leucine showed that apoA-IV synthesis was not stimulated during lipid + L-81 infusion, perhaps explaining the lack of increase in lymphatic A-IV secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Clinico-statistical and pathological observation on sialolithiasis over 11 years at Department of Dentistry and Oral Surgery, Nagoya National Hospital (1978-1988)].

A clinico statistical and pathological study was made on 21 cases of the sialolithiasis patients who has been examined at the Department of Dentistry and Oral Surgery, Nagoya National Hospital between April, 1978 and December 1988. There were more male patients than female patients (12 males and 9 females) with a male to female ratio of 1.3:1. According to age group the majority (28.6%) were in their youngest was 17 years old, and the oldest was 72 years old. The left to right ratio was 1.4:1. The earliest visit was made 5 days after onset and the longest was 11 years. The majority was seen within one month (28.6%). The medical institution with which the patient consulted most often prior to visiting our department, was the private dentist's which accounted for 52.4% of all institutions. In the radiograph of the salivary gland tissue extracted together with the salivary calculus, slight lymphocyte cellular infiltration, moderate atrophy of the acinus and fibrous degeneration, and chronic sialitis such as ductus dilatation and others were observed.

Adolescent↗

Establishment of a B-lymphoblastoid cell line infected with Epstein-Barr-related virus from a cynomolgus monkey (Macaca fascicularis).

A B-lymphoblastoid cell line (Ts-B) was established from lymph nodes of an apparently healthy cynomolgus monkey. The cells were demonstrated to contain Epstein-Barr virus-related antigens. Moreover, herpesvirus particles were found in the cells by electron microscopy. The cell-free culture medium transformed lymphocytes of cynomolgus rhesus monkeys, and of Japanese monkeys.

Animals↗

Experimental infection of African green monkeys and cynomolgus monkeys with a SIVAGM strain isolated from a healthy African green monkey.

An infection occurred in all African green monkeys and cynomolgus monkeys experimentally inoculated with SIVAGM [TYO-1], as demonstrated by the appearance of an antibody to SIVAGM [TYO-1] and the isolation of the virus. No monkey exhibited overt clinical disorders throughout the experimental period of 42 weeks. Thus, SIVAGM was not pathogenic to its original host or to macaques. This system is proposed as a model for HIV infection manifesting no overt disease.

Animals↗

[Hilar and mediastinal lymph node metastases from lung cancer; detection with CT and MR imaging].

Sixty-one patients with primary lung cancer, who had CT and MR imaging before surgery, were studied. MR imaging used spin-echo sequences with T1 weighted image and T2 weighted image (C-MRI), and included STIR technique (Stir-MRI). The accuracy of diagnosis of mediastinal lymphadenopathy (regarding 10 mm or larger in short transverse diameter as positive) was 89% by CT, 84% by C-MRI and 89% by Stir-MRI. The accuracy of diagnosis of hilar lymphadenopathy was 42% by CT, 67% by C-MRI, and 75% by Stir-MRI. The accuracy of diagnosis of mediastinal lymph node metastases was 89% by CT, 94% by C-MRI and 96% by Stir-MRI. The accuracy of diagnosis of hilar lymph node metastases was 78% by CT, 87% by C-MRI and 89% by Stir-MRI. The possibility of enhancement of diagnostic accuracy of lymph node metastases from lung cancer was suggested by combining MR imaging included STIR technique with CT.

Adenocarcinoma↗

[Arachidonic acid metabolites on peripheral blood plasma in patients with bronchial asthma].

To assess the role of arachidonic acid metabolites in pathogenesis of bronchial asthma, we measured thromboxane B2 (TxB2), 6-keto PGF1 alpha, leukotriene (LT) C4, and LTB4 in venous blood plasma in patients with bronchial asthma and in controls. The level of TxB2 was significantly higher in 18 asthmatics with attacks than that in 11 controls (77.3 +/- 48.8 pg/ml vs 48.8 +/- 9.4 pgml). The levels of 6-keto PGF1 alpha in both asthmatics with attacks (17.8 +/- 6.7 pg/ml) and without an attack (16.4 +/- 9.7) were significantly higher than that in controls (11.6 +/- 3.9 pg/ml). The levels of LTC4 in asthmatics with attacks (0.84 +/- 0.11 ng/ml, n = 11) were significantly higher than that in controls, furthermore the level of LTC4 in asthmatics without an attack. The level of LTB4 was significantly higher in asthmatics with attacks (295.0 +/- 160.7 pg/ml, n = 26) than that in controls (161.7 +/- 25.3 pg/ml, n = 12) and asthmatics without an attack (182.4 +/- 97.9 pg/ml, n = 22). These findings suggest that the arachidonic acid metabolites are related to the asthma attack and are associated with the pathogenesis of bronchial asthma.

6-Ketoprostaglandin F1 alpha↗

[A case of metastatic renal tumor: review of 74 cases reported in Japan].

A 76-year-old man, who had undergone surgery for lung cancer, was referred to our department for further examination for left renal mass. Exploration was done through a transperitoneal approach and the left kidney was removed. A metastatic renal tumor originating from a pulmonary squamous cell carcinoma was diagnosed histologically. There have been 73 reported cases with metastatic renal tumor in Japanese literature and we reviewed the pathogenesis and treatment of this rare entity.

Aged↗

[Abrupt onset and rapid deterioration in the course of congenital ornithine transcarbamylase deficiency: a case report].

We report a 17-year-old female case of ornithine transcarbamylase (OTC) deficiency who died of brain edema due to hyperammonemic attack. The patient had a brother with OTC deficiency who had died of hyperammonemia at 17 years of age. She firstly had a symptom of headache, nausea, vomiting and myalgia at 14 years old and twice thereafter. On admission she had a severe disorientation and vomiting. The plasma ammonia level was 89 micrograms/dl, then increased to 400 micrograms/dl in five hours. In addition to plasma exchange, hemodialysis and then peritoneal dialysis for next 5 days, parenteral sodium benzoate and arginine were administered. Although the plasma ammonia level improved gradually, her consciousness never returned and she died of severe brain edema with uncontrollable hypotension on day 8. Histology of a necropsy liver sample showed fatty metamorphosis of hepatocytes mainly with fine lipid droplets. Electron micrograph of hepatocytes showed crystalloid inclusions in mitochondria. Significance of the clinical course and the treatment during hyperammonemic crisis was discussed.

Acute Disease↗

[Melatonin secretion in intracranial tumor].

UNLABELLED: The secretion of melatonin (MLT) was examined in 6 ICT patients, 2 men and 4 women, who showed marked midline shift of CT scan findings with intracranial hypertension signs (headache, nausea, vomiting). Their ages ranged from 22 to 40 years. The controls, 6 healthy men and 4 healthy women (follicular stage) were aged from 18 to 35. With the subject recumbent, blood was drawn at 14, 20, 02 and 08 hour (Lights out, 9 pm; sunrise, 6 am). After separation of plasma by centrifugation, MLT was extracted by SEP-PAK C18 cartridge and determined by radioimmunoassay (RIA). ( METHOD: The extracted MLT, the antiserum and the 3H-MLT were incubated overnight at 4 degrees C, the antibody-combined and free 3H-MLT were separated using ammonium sulfate, and the radioactivity of the precipitate containing combined 3H-MLT was measured by liquid scintillation.) Plasma MLT concentrations of controls were 42.5 +/- 7.0 (Mean +/- SEM) pg/ml at 14 hr, 50.9 +/- 8.2 pg/ml at 20 hr, 165.1 +/- 22.7 pg/ml at 02 hr, and 49.1 +/- 5.4 pg/ml at 08 hr. The value of 14 hr. significantly differed from 02 hr, (P less than 0.01) showing a diurnal rhythm. The patients' MLT levels (pg/ml) were 19.8 +/- 6.2 at 14 hr, 15.9 +/- 5.2 at 20 hr, 52.0 +/- 17.2 at 02 hr, and 20.3 +/- 3.5 at 08 hr. These values were significantly lower than in controls (P less than 0.01) except at 14 hr. (P less than 0.05), showing no diurnal rhythm except 2 cases. In conclusion, in ICT with midline shift of CT scan melatonin secretion was inhibited and diurnal rhythm disappeared in four cases (67%).

Adolescent↗