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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 901 records · Page 50Linked to original sources

Modulation of diethylnitrosamine-initiated placental glutathione S-transferase positive preneoplastic and neoplastic lesions by clofibrate, a hepatic peroxisome proliferator.

The effect of clofibrate (CF) on proliferation of diethylnitrosamine (DEN)-initiated glutathione S-transferase placental form (GST-P)-positive preneoplastic and neoplastic lesions as studied in male F344 rats. Animals were given a single i.p. injection of 200 mg/kg body weight of DEN, and then from 2 weeks later were given a diet containing 0.3% CF (group 1), or no supplement (group 2) until week 64. Group 3 received an injection of 0.9% NaCl instead of DEN and then a diet containing 0.3% CF, like group 1. Animals in all groups were subjected to partial hepatectomy at week 3 and killed at weeks 8, 20, 32, 49 or 64. The results showed that development of GST-P-positive lesions was significantly less in group 1 than in group 2 from week 8 (P less than 0.05). However, in group 1, morphologically distinguishable GST-P-negative preneoplastic lesions increased from week 20 (P less than 0.05), and the total number of GST-P-positive and -negative lesions was significantly greater than that in group 2 from week 32 (P less than 0.05). The induction of hepatocellular carcinoma (HCC) was greater in group 1 than in group 2 from week 49. All the HCCs induced in group 2 were GST-P-positive, whereas 38.9% (7/18) of those in group 1 were GST-P-negative. In group 3, only a few GST-P-positive and/or -negative preneoplastic lesions developed by week 64. These results suggest that CF has tumor-promoting activity, and that GST-P-positive cells induced by DEN changed to GST-P-negative cells on subsequent treatment with CF.

Animals↗

Proliferation kinetics of pepsinogen altered pyloric gland cells in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The cell kinetics of pepsinogen isozyme 1 altered pyloric gland (PAPG) cells with low pepsinogen isozyme 1 (Pg 1) content were analysed using double immunohistochemical staining for bromodeoxyuridine (BrdU) incorporation and Pg 1 in male WKY/NCrj rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After administration of 100 micrograms/ml MNNG for 10 weeks in the drinking water, carcinogenic insult was terminated and the animals killed two weeks later. BrdU was given either as a single i.p. injection (100 mg/kg b.w.) 1 h prior to death or continuously by osmotic minipump (120 micrograms/h) for 4, 7 and 10 days before killing. Immunogold-silver staining was used to detect BrdU and the avidin-biotin-peroxidase complex method adopted for demonstration of Pg 1. PAPG were found only in the MNNG treated group: their frequency was 4.1 +/- 0.6 per 100 pyloric glands. Almost no normal pyloric gland cells with high Pg 1 content demonstrated incorporation after BrdU flash labelling. However, a few pyloric gland cells in PAPG were labelled. The number of labelled cells in the pyloric columns containing PAPG was larger (P less than 0.05) than in normal pyloric columns. After continuous BrdU administration, the life span of cells comprising PAPG was estimated to be approximately 6-8 days while that of normal pyloric gland cells was approximately 11-13 days. Thus, the data indicate that PAPG cells demonstrate a degree of independence from surrounding pyloric glands with regard to proliferation kinetics, suggesting that PAPG is a preneoplastic lesion involved in gastric carcinogenesis.

Animals↗

Pulsatile insulin infusion and glucose-homeostasis in well-controlled type 1 (insulin-dependent) diabetic patients.

Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U kg-1 idealised body weight were given, each of 20 s duration, with intervals of 6 min, three times per day covered with adequate administration of glucose) on 2 successive days on glucose-tolerance in nine well-controlled Type 1 diabetic patients on continuous subcutaneous insulin infusion therapy (age 26 (7) years, mean (SD); duration of diabetes 10 (7) years; body mass index 23.4 (2.3) kg m-2; HbA1c 6.0 (0.6)%). On the days before and after the insulin pulsing, the patients were subjected to metabolic assessments by an oral glucose tolerance test (1 g glucose kg-1 body weight) 30 min after the subcutaneous injection of 0.15 U kg-1 body weight regular human insulin and a subsequent bicycle-ergometer test. During these metabolic assessments, plasma free insulin concentrations, plasma glucagon and the non-protein respiratory quotient remained unaffected by the insulin pulsing. However, glucose tolerance deteriorated significantly (maximal glucose concentration 120 min after glucose load was 10.0 mmol l-1 before and 13.9 mmol l-1 after insulin pulsing, P less than 0.01). In conclusion, the pattern of insulin pulsing used in this study did not ameliorate oral glucose homeostasis in well-controlled Type 1 (insulin dependent) diabetic patients.

Adult↗

[Recurrent thoracic abscess due to Salmonella typhi].

Abscess formation by Salmonella typhi is an unusual manifestation. A woman aged 62 suffered from recurrent abscess in the anterior thorax for 35 years, which was released by spontaneous pus drainage each time. Pus cultures grew S. typhi, and the CT scan revealed a large abscess enclosing the sternum and left ribs.

Abscess↗

[Clinical trial of T-3262 on acute enteritis. Japan Research Committee of T-3262, Research Group for Acute Infectious Enteritis].

For the purpose of evaluation of clinical efficacy, safety and usefulness on acute infectious enteritis (bacillary dysentery, and enteritis caused by Salmonella spp., Campylobacter spp., enteropathogenic E. coli, and so on), T-3262, a newly developed pyridone-carboxylic acid derivative, was administered to a total of 136 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). The daily dose of 450 mg of T-3262 was administered orally three times after meals for 5 days, with the exception of 7 day administration against Salmonella enteritis. A total of 89 cases were evaluated; 23 with Shigella spp., 30 with Salmonella spp., 15 with Campylobacter spp., 6 with enteropathogenic E. coli, and 15 cases with the other pathogens or pathogen-negative. The efficacy on clinical symptoms judging from duration of fever, and duration of diarrhea and abnormal stool character was 100% in all the enteritis except enteropathogenic E. coli enteritis, in which it was 50% (n = 2). Concerning bacteriological response, elimination of the causative organisms from the feces was 100% in Shigella spp. (n = 19), Salmonella spp. (n = 30), and enteropathogenic E. coli (n = 6), although 64.3% in Campylobacter spp. (n = 14). As an adverse effect, epigastric discomfort was observed in one (0.8%) of 130 cases. Deteriorations in laboratory findings were seen in five (6.2%) of 81 cases, consisting of two with elevated GOT and GPT, two with elevated GPT, and one with increased eosinophils count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Shigella spp, Salmonella spp., and Campylobacter spp., were 0.025, 0.05, and 0.78 microgram/ml, respectively. These values were lowest among the quinolone derivatives tested, except that the MIC90 against Campylobacter spp. was the same as that of ofloxacin.

4-Quinolones↗

[Comparison of clinical efficacy of lomefloxacin (LFLX, NY-198) and pipemidic acid (PPA) in the treatment of infectious enteritis by a double-blind method. The Japan Research Committee of Lomefloxacin Research Group Enteritis].

The clinical efficacy, safety and usefulness of lomefloxacin (LFLX, NY-198), a new quinolone antimicrobial agent, were compared with those of pipemidic acid (PPA) in the treatment of infectious enteritis (bacillary dysentery, enteropathogenic Escherichia coli enteritis and Campylobacter enteritis) by a double blind method. Daily dosage of LFLX and PPA was 600 mg and 2000 mg, respectively administered orally divided into 4 doses. The duration of the treatment was 5 days. Of 290 cases studied, 100 cases were excluded and 21 cases were dropped from analysis of effectiveness and usefulness. The effectiveness and usefulness was evaluated in 169 cases (LFLX group: 83, PPA group: 86). There was no significance difference between the two groups in any background characteristics. The results obtained were as follows: 1. In 73 symptomatic patients (LFLX group: 35, PPA group: 38) on the day of the beginning of administration, the clinical effect was 91.4% in the LFLX group and 84.2% in the PPA group with no significant difference between the two groups. 2. In a total of 184 strains (LFLX group: 90, PPA group: 94), the bacteriological effects of LFLX (93.3%) was superior to that of PPA (80.9%) with significant difference (p = 0.0153). 3. In 169 evaluable patients, the global clinical effects of LFLX (92.8%) was superior to that of PPA (79.1%) with a significant difference (P = 0.0144). 4. Side effects were observed in 1 (0.7%) of the 141 patients in the LFLX group and none of the 143 patients in the PPA group. Abnormal laboratory test values were noted in 10 (7.6%) of the 132 patients treated with FLLX and 7 (5.1%) of the 136 patients treated with PPA, but they as no significant difference between the two groups. 5. In 169 evaluable patients, the clinical usefulness of LFLX (91.6%) was superior to that of PPA (76.7%) with a significant difference (P = 0.0111). From these results, LFLX is considered to be a clinically useful medicine in the treatment of infectious enteritis including bacillary dysentery.

4-Quinolones↗

[Clinical trial of T-3262 (Tosufloxacin tosilate) on Salmonella enteritis, and fecal drug concentration and change in the fecal microflora in the acute diarrheal patients. Japan Research Committee of T-3262, Research Group for Acute Infectious Enteritis].

For the purpose of evaluation of clinical efficacy, safety and usefulness on Salmonella enteritis, T-3262 (Tosufloxacin tosilate), a newly developed pyridone-carboxylic acid derivative, was administered to a total of 103 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). And when T-3262 was administered to the patients of acute infectious enteritis, fecal drug concentration and their correlation to the changes in the fecal microflora were investigated. The daily dose of 450 mg T-3262 was administered orally three times after meal for 7 days. A total of 63 cases were evaluated (one case of mixed infection caused by Shigella flexneri and Salmonella sp. was included). The clinical efficacy was good in all the enteritis (N = 6). As the bacteriological effect, 60 out of 61 were eradicated, and eradication rate was 98.4%. Adverse effects were observed in four of 102 cases (3.9%), consisting of one with skin rash, one with nausea, headache and stomatitis and two with soft stools. Deteriorations in laboratory findings were seen in 5 of 23 cases (17.4%), consisting of one with elevated GOT, two with elevated GOT and GPT, one with elevated BUN and one with increased eosinophiles count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Salmonella spp. was 0.05 microgram/ml, which was the lowest among the quinolone derivatives tested. The values of the fecal drug concentration of 7 cases of acute infectious enteritis, to which T-3262 administered, were higher than that of MIC90 and recovery rates of T-3262 were distributed from 2.85 to 46.3%. The degrees of changes of the drug concentrations were dependent on individual cases, and did not show the same trend. In addition, changes in the fecal microflora with in 24 hrs after T-3262 administration did not show the same trend.

4-Quinolones↗

Synthesis of cis-bicyclo[4.3.0]non-2-ene derivatives. The potent homoisocarbacyclin analogs.

Synthesis of homoisocarbacyclin has been achieved efficiently by a general strategy with stereo- and regiochemical control. One of homoisocarbacyclin derivatives, 3-oxa homoisocarbacyclin analog (4), was shown to be potently active in inhibiting gastric ulcer. Another analog, conjugated diene derivative (5), was found to have a biological profile similar to prostacyclin.

Anti-Ulcer Agents↗

Reversal of rest asynergy during exercise in patients with coronary artery disease.

The diagnosis of ischemic heart disease by radionuclide ventriculography (RNV) is performed on the basis of an abnormal response of the left ventricular ejection fraction and the occurrence, or aggravation, of regional wall motion abnormality during exercise. However, the abnormal wall motion observed by RNV at rest is improved in some patients with coronary artery disease during exercise. We examined the clinical features of such patients who showed a paradoxical response of regional wall motion. The left ventricle was divided into 4 segments: anteroseptal, apical, inferior and posterolateral. The degree of wall motion of each segment was classified into 5 grades and scored according to a 5 point system: 4 = normokinesis, 3 = hypokinesis, 2 = severe hypokinesis, 1 = akinesis and 0 = dyskinesis. The wall motion score (WMS) was calculated as the sum of each segment score. If the WMS increased by 2 points or more during exercise, the case was defined as having shown significant improvement of wall motion. Improvement in WMS was found in 26 (12%) of 209 serial patients who underwent exercise RNV, exercise thallium myocardial scintigraphy and coronary angiography. Clinically, half of these patients had a variant form of angina pectoris. With respect to coronary lesions in the segments with reversible asynergy, 12 patients had 0 vessel disease, 8 had lesions with stenosis of less than 75% and 3 showed an adequate collateral circulation. Redistribution found on the exercise thallium myocardial scintigram at the same sites of improved wall motion was identified in only 1 patient. An analysis of patients with paradoxical improvement of wall motion during exercise suggests the involvement of coronary spasm, an improvement of coronary flow reserve, such as could be produced by regression or recanalization of the main lesions, or establishment of significant collateral circulation.

Coronary Angiography↗

Ruthenium red and magnesium ion partially inhibit silver ion-induced release of calcium from sarcoplasmic reticulum of frog skeletal muscles.

Effects of Ca2+-induced Ca2+ release blockers, ruthenium red (RR) and Mg2+, on Ag+-induced Ca2+ release were studied using skinned muscle fibers or fragmented heavy SR (HSR) prepared from frog muscle, and compared with those on caffeine-induced one. Exposure of the skinned fibers to 5 microM Ag+ produced a rapid and large contraction in the presence of 0.043 mM free Mg2+. When Mg2+ concentration was increased to 0.86 mM, Ag+ led to a large transient contraction, combined with a small tonic one. The transient component was completely blocked by high Mg2+ (3.64 mM), but the tonic one was not. Ca2+-ATPase activity was not stimulated by increase of Mg2+ from 0.86 to 3.64 mM. Ag+ and caffeine induced a rapid Ca2+ efflux from HSR in a dose-dependent manner. RR over a range from 1 to 10 microM dose-dependently inhibited the Ca2+ efflux induced by 10 microM Ag+. Despite increase of RR to 30 microM, however, further inhibition of the Ca2+ efflux was not produced any more (77.8 +/- 12.2% inhibition). A 10 mM caffeine-induced efflux of Ca2+ was blocked slightly by only 0.5 microM RR and almost completely by 3 microM. A slight inhibition (about 28%) of the Ca2+-ATPase activity was observed in the presence of 10 microM Ag+ in 0.5 mg SR protein/ml of medium. RR and caffeine did not affect the enzyme activity. These results indicate that frog SR could induce a rapid release of Ca2+ upon Ag+ and caffeine, suggesting that Ag+ may have two different binding sites to release Ca2+; one is on Ca2+-induced Ca2+ release channel and the other on RR-insensitive site.

Animals↗

Absorption of egg antigens by the gut observed by oral Prausnitz-Küstner (Walzer) reaction in atopic dermatitis.

Sera from 50 children (27 boys and 23 girls, under the age of 3 years) with atopic dermatitis allergic or not to hen's egg shown by skin test or radioallergosorbent test (RAST) were passively transferred to recipients which were then challenged with injection of egg antigen (Prausnitz-Küstner (P-K) test) or with ingestion of a raw egg (oral P-K test). Thirty-one patients showed positive P-K reaction with serum titers from 2 to 8,192. Fifteen of the P-K positive cases were also positive in the oral P-K test with titers from 2 to 256. The ratio of the oral P-K titer and the P-K titer in each positive case was from 1:2 to 1:32. The results indicate that a high percentage of atopic dermatitis patients with egg allergy have IgE antibody in the serum capable of reacting with an ingested egg.

Antigens↗

IgE antibody to sweat in atopic dermatitis.

Of 45 patients with atopic dermatitis skin-tested with their own sweat, 43 showed positive immediate-type skin reactions to titres between 1 and 256. Of 22 non-atopic patients 18 showed negative reactions. Skin reactivity of the atopic patients to the sweat and house dust did not run parallel. Radioallergosorbent test (RAST) using the sweat collected from a healthy subject detected IgE antibody in 24 atopic patients with a score from 0.5 to 3.5, whereas all the control subjects showed the score 0. This IgE antibody to sweat did not cross-react with the mite extract (Dermatophagoides farinae) or Staphylococcus aureus. These results indicate that atopic patients have specific IgE antibody to sweat.

Adolescent↗

[Developmental changes in judgment of weights addition].

As weight is invisible, some judgmental criteria are needed in judging weight. An experiment was carried out using the second, fourth, sixth, eighth graders and college students to reveal (1) what weights positions make subjects more errors in judgment of weights addition and (2) what relationships will be found between the judgments and judgmental criteria. Subjects were engaged in the tasks to judge weights addition in two conditions, height of weights and relative positions, and were asked the judgmental criteria in two situations, visual exteroceptive and realistic proprioceptive situations. Results showed clearly the developmental changes. The fourth graders dominantly produced errors in height of weights conditions and tended to depend on the criteria in realistic situations. In the contrast to this, the eighth graders committed errors in relative differences of weights positions and depended on the criteria in visual situations as well as realistic ones. Sex differences were also observed in terms of criteria. No relations between the judgments and judgmental criteria was found in girls' judgments of weights additions.

Adolescent↗

[Plasma histamine release following the intravenous administration of atracurium in man].

The purpose of this study was to measure plasma histamine concentration following the intravenous bolus injection of atracurium in surgical patients and to clarify any correlation of resultant cardiovascular change with plasma histamine release. Twelve elective surgical patients of ASA-I were studied after the approved informed consent. Twenty of blood samples were collected for the assay of plasma histamine at 1 minute before as the control and 1, 3, 5, and 10 minutes after the administration of atracurium 0.6mg.kg-1 or 1.2mg.kg-1 intravenously. Plasma histamine was measured by utilization of the modified single isotope radioenzymatic assay. Blood pressure, heart rate, EKG and cutaneous signs were observed continuously during the study. Intravenous bolus administration of 0.6mg.kg-1 and 1.2mg.kg-1 atracurium which is larger than 2 times of ED95 demonstrated significant changes in heart rate, blood pressure and histamine release. A significant increase in plasma histamine, a decrease in blood pressure and an increase in heart rate occurred at 1 to 3 minutes after the injection of atracurium. Plasma histamine release and cardiovascular changes had strong correlation with the intravenous dose of atracurium.

Atracurium↗

[Complete remission, obtained by multidisciplinary treatment of recurrent breast cancer with carcinomatous pleuritis, and cervical lymph node and diver metastasis].

A 46-year-old female, who had undergone a radical mastectomy for cancer of the breast 5 years previously at another institution presented a pleural effusion, in which malignant cells were detected, along with cervical lymph node metastasis. Although the patient initially responded to the H-CMcF regimen and intrathoracic injections of adriamycin (ADM), her condition subsequently was exacerbated, with metastasis occurring in the liver. A complete remission however, was achieved by local treatment, which included intrathoracic infusions of ADM and cis-platinum plus hepatic artery infusions of ADM and lipiodol, in addition to a systemic treatment consisting of a modification of the FEMP regimen employing UFT, CPA, MMC, and PDN, to which were added the immunopotentiators OK-432 and MPA. At present, 18 months after treatment, the patient is apparently disease free. The results obtained in this case suggest that even a distant metastasis can be controlled by aggressive local treatment for each metastatic lesion, in addition to a multidisciplinary treatment based mainly on intensive chemotherapy.

Adenocarcinoma↗

Treatment of upper gastro-intestinal bleeding with the H2-receptor antagonist famotidine.

Gastro-intestinal bleeding from peptic and stress ulcers is serious and life-threatening. Critically ill patients in intensive care units have many of the risk factors associated with bleeding from peptic and stress ulcers, including trauma, burns, sepsis, shock and multiple organ failure. This study investigated the results of treatment with famotidine, administered intravenously twice daily, to those in a control group that received treatment before the introduction of H2-receptor antagonists. The study was designed to determine whether famotidine reduced the need for emergency surgery in patients with bleeding ulcers and whether a reduction in mortality was associated with its use. The overall efficacy rate of famotidine was greater than 88%. The percentage of patients with a bleeding ulcer undergoing surgery was 24.5% compared with 50.3% in the historical control group. Twice daily intravenous administration of famotidine effectively stopped bleeding in patients with moderate to severe peptic ulcer and stress ulcer. Drug therapy for the treatment of upper gastro-intestinal bleeding, however, has limitations. Criteria for the use of famotidine include reduced mortality, rate of recurrent bleeding and rate of emergency surgery.

Anti-Ulcer Agents↗

[The effectiveness of Appleby's operation in advanced gastric carcinoma].

This study was undertaken in order to evaluate the effectiveness of Appleby's operation on the postoperative survival rate as compared with that of conventional total gastrectomy accompanying pancreatosplenectomy and that of subtotal gastrectomy with lymph node dissection of the conventional style preserving the spleen and the pancreas. In our study Appleby's operation was performed in 65 cases and the conventional procedures were in 41 cases and 50 cases, respectively. Both groups have almost identical prognostic backgrounds except for the lymph node status. The overall 5-year survival rate of Appleby's procedure group was higher (49.5%) than that of the conventional procedure group (23%) in spite of higher percentage of positive rate of the 2nd group of lymph node(n2+) in Appleby's procedure group. Furthermore, in the cases with serosal invasion(se) and positive metastasis in the 1st group of lymph node (n1+), the 5-year survival rate of Appleby's procedure group was higher (64%) than that of the conventional procedure group (32%), and the difference was statistically significant (p less than 0.01). On the other hand, no difference was observed in the 5-year survival rate between both groups in which the serosae were invaded and the 2nd group of lymph nodes were involved. Our study shows that Appleby's procedure salvaged further 32% of patients that would have been lost if they had undergone the conventional procedure.

Humans↗