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Biomedical subjects

I Kobayashi

Publications and source records attributed to I Kobayashi.

At least 181 records · Page 10Linked to original sources

[Usefulness of combination therapy with expandable metallic stent replacement and FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide and cisplatin) for advanced esophageal cancer invading the bronchus: a case report].

A 63-year-old male with an esophageal cancer invading the bronchus was treated with radiation therapy (70 Gy) from November 1995, resulting in the disappearance of the lesion. He was later readmitted due to dysphagia from the recurrence of the esophageal cancer. We diagnosed, by endoscopic and chest CT scan findings, that the esophageal cancer was invading the right bronchus. We inserted an expandable metallic stent endoscopically, and the patient could eat well. We performed two courses of FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide and cisplatin) from November 12, 1997. He then suffered from an esophagobronchial fistula, but was cured by a covered expandable metallic stent replacement. No esophageal stenoses or recurrences were seen endoscopically and he could eat well on December 7, 1998. The standard modality of treatment for patients with advanced esophageal cancer invading adjacent structures is not yet established, and the prognosis for such patients remains quite poor. We performed combination therapy with an expandable metallic stent replacement and FLEP chemotherapy, and improved the patient's quality of life. This form of therapy was thus proved useful for patients with esophageal cancer invading adjacent structures.

Antineoplastic Combined Chemotherapy Protocols↗

[In vitro bactericidal activities of new oral penem, faropenem against the various clinical isolates].

The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of faropenem (FRPM) more compared with those of various oral beta-lactams against 15 isolates each of 6 species of microorganism. FRPM possessed potent in vitro antibacterial activity against both aerobic and anaerobic Gram-positive bacteria tested. FRPM showed the same activity as new oral cephems such as cefdinir, cefditoren and cefcapene against all Gram-negative bacteria, but K. pneumoniae strains were less susceptible. The MBC of FRPM against S. pneumoniae and the other strains tested equal and were within 1 dilution the MIC of that, respectively. These results suggest that FRPM has excellent in vitro bactericidal activity against clinical isolates and is a clinically useful for the chemotherapy of bacterial infections.

Anti-Bacterial Agents↗

[Microsomal antibody].

Microsomal antibody is an antibody for the section of a microsome in thyroid cells. There are two methods of measurements of microsomal antibodies, the semiquantitative microtiter particle agglutination test(MCHA) and the high sensitive assay(RIA, ELISA) for the anti thyroid peroxidase(TPO-Ab). MCHA is broadly useful for the diagnosis of autoimmune thyroid diseases and TPO-Ab is mainly measured in the occult autoimmune thyroiditis. TPO-Ab is expensive to compare with MCHA, in Japan. We recommend that MCHA is used in the routine test and TPO-Ab should be measured in the cases of patients with thyroid goiter and MCHA negative.

Autoantibodies↗

Serum thrombomodulin as a prognostic marker of disseminated intravascular coagulation.

Disseminated intra-vascular coagulation (DIC) is associated with severe bleeding tendency and organ failure, the extent of which is thought to be related to the prognosis of DIC patients. Thrombomodulin (TM) is a high-affinity thrombin receptor on vascular endothelial cells. Clinical importance of soluble TM is still controversy as a diagnostic and prognostic indicator in patients with disseminated intravascular coagulation (DIC). We compared plasma levels of TM with fibrin degradation product (FDP) in patients with DIC through the clinical course. The significant elevation of circulating TM in nonsurvivors with DIC compared with survived patients with DIC(TM 3.1+/-1.52 vs 8.1+/-3.89 FU/ml), as well as FDP (12.9+/-12.12 vs 49.8+/-55.42 microg/ml) but the levels of FDP were not different between the two groups. The measurement of circulating TM was a relatively good prognostic marker of patients with DIC.

Adult↗

Comparative accuracy of automated computer analysis versus physicans in training in the interpretation of electrocardiograms.

We compared the interpretation of an electrocardiogram (ECG) made by computer with that made by physicians in training, as well as with the diagnosis made by cardiologists. ECGs were collected from 1058 Japanese adults (812 men and 246 women, mean age 49 +/- 19 years). With the computer program, the incidence of false-negative reports was 10.5% while that of false-positive reports was 16.5%, when compared with the physician's diagnosis. The incidence of a false-positive diagnosis with the computer was 18 times higher than that found by the physicians in training. The results show the advantages and the limitations in the use of computers for analysis of ECGs.

Adult↗

Nurses' perspectives concerning do-not-resuscitate (DNR) orders.

The purpose of this study was to investigate the views of the nursing staff concerning do-not-resuscitate (DNR) orders at the Tokai University Hospital where a controversial incident occurred several years ago. A 'Questionnaire on DNR Orders' was circulated and the anonymous answers were collected two weeks later. The questionnaire was returned by 706 of 780 (90.5%) nurses from every ward/specialty, which revealed that 87% of the nurses felt that DNRs were occasionally necessary, with more than 40% of the nurses answering that they took part in DNR. Further, 36% of the nurses stated that patient consent was indispensable, and 64% thought that the patient's family and physician could decide DNR in the event the patient was physically unable to give consent. Moreover, 66% of the nurses expected the establishment of a DNR order sheet to be formulated as a matter of hospital policy; only 5% of the nurses thought that such an order sheet would not be necessary. Comparing these results with a previous study polling physicians at the Tokai University Hospital, nurses are more likely than physicians to think that patient consent is indispensable, and want the establishment of a standardized DNR order sheet as hospital policy. There is, in fact, a "tacit understanding" between physicians and patients' families in medical practice in Japan. However, DNR is definitely a medical decision. Therefore it should be clearly stated in a standardized format, although such a procedure presently seems unlikely, in view of the Japanese traditional value system.

Adult↗

[In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates].

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.

Ampicillin↗

N-acetyl-beta-D-glucosaminidase is not a predictor, but an indicator of kidney injury in patients with cardiac surgery.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was evaluated in terms of its ability to predict renal failure following open-heart surgery. Twenty-two patients were divided into three groups; 6 patients with post-operative renal failure (RF group), 9 without renal failure (non-RF group) and 7 who underwent non-cardiac surgery (non-ECC group). NAG levels during operation were significantly higher in the non-RF group than in the non-ECC group (2.28 +/- 0.50 U vs. 0.39 +/- 0.06 U, p < 0.01). NAG levels in the RF group were not significantly different from those in the non-ECC group (1.12 +/- 0.28 U/hr vs. 0.39 +/- 0.06 U/hr, p > 0.1), and in the non-RF group (1.12 +/- 0.28 U/hr vs. 2.28 +/- 0.50 U/hr, p > 0.1). Post-operative NAG levels were not significantly different between the RF and non-RF groups, whereas post-operative creatinine clearance values were significantly different (on 2, 6 and 7 post-operative day, p < 0.05). Our data suggest that the kidney is predisposed to renal failure by cardiopulmonary bypass and the chance of renal failure depends in some part on post-operative patient management.

Acetylglucosaminidase↗

Glutamine is involved in the dependency of brain neuron survival on cell plating density in culture.

The mechanism by which neuronal cell viability in culture is dependent on cell plating density is unclear. To address this question, dissociated cells from the neonatal rat cortex were cultured in a chemically defined medium. Medium conditioned with cortical cells plated at high density (2000 cells/mm2) promoted the survival of neurons grown at low cell density (100 cells/mm2) in a dose-dependent manner. Data obtained from molecular sieving suggested that the molecule(s) promoting the survival of neurons was smaller than 1000 Da. Amino acid analysis of the conditioned medium revealed the release of a mass of glutamine from cortical cells in culture. L-Glutamine mimicked the conditioned medium in action promoting the viability of neurons. These findings suggest that the effect of plating density on neuronal cell viability is mediated at least in part by glutamine released from cultured cells.

Amino Acids↗

Contribution of brainstem hypoperfusion to the tracheal and phrenic nerve responses to high-pressure lung inflation in the dog.

Lung inflation to high airway pressure is known to produce tracheal constriction following an initial dilation. This is attributed to stimulation of various pulmonary receptors. In an attempt to find cause of this response, we investigated in 20 decerebrated, tracheostomized and paralyzed dogs changes in the tracheal smooth muscle tension, arterial pressure and the phrenic nerve activity to high-pressure lung inflation. A high-pressure lung inflation evoked a contraction of tracheal smooth muscle following its short-lasting relaxation, and a persistent hypotension. After hilar denervation which eliminated all pulmonary afferents, a high-pressure lung inflation still evoked contraction of tracheal smooth muscle (an increase of 3.7 times) and augmented amplitude and frequency of phrenic bursts. Bilateral transections of sympathetic fibers to the lung, or blockade of arterial perfusion to the carotid sinus and denervation of the carotid sinus bilaterally did not alter the tracheal muscle and phrenic responses to a high-pressure lung inflation. We further found that severe hypotension alone caused similar responses of the tracheal smooth muscle contraction and augmented phrenic activity. Finally, when blood supply to the brainstem was transiently obstructed by clamping both the vertebral and internal carotid arteries bilaterally, the same responses were observed. In contrast, when blood hypoperfusion to the brainstem was prevented by means of extracorporeal circulation, a high-pressure lung inflation failed to evoke such contraction of tracheal smooth muscle and or increased phrenic activity. After transection of the vagus nerves bilaterally at the cervical level the tracheal muscle response to lung inflation was abolished but that of phrenic nerve was preserved. We concluded that the tracheal smooth muscle contraction and phrenic responses induced by high-pressure lung inflation may be in part attributed to brainstem hypoperfusion.

Animals↗

Restriction-modification gene complexes as selfish gene entities: roles of a regulatory system in their establishment, maintenance, and apoptotic mutual exclusion.

We have reported some type II restriction-modification (RM) gene complexes on plasmids resist displacement by an incompatible plasmid through postsegregational host killing. Such selfish behavior may have contributed to the spread and maintenance of RM systems. Here we analyze the role of regulatory genes (C), often found linked to RM gene complexes, in their interaction with the host and the other RM gene complexes. We identified the C gene of EcoRV as a positive regulator of restriction. A C mutation eliminated postsegregational killing by EcoRV. The C system has been proposed to allow establishment of RM systems in new hosts by delaying the appearance of restriction activity. Consistent with this proposal, bacteria preexpressing ecoRVC were transformed at a reduced efficiency by plasmids carrying the EcoRV RM gene complex. Cells carrying the BamHI RM gene complex were transformed at a reduced efficiency by a plasmid carrying a PvuII RM gene complex, which shares the same C specificity. The reduction most likely was caused by chromosome cleavage at unmodified PvuII sites by prematurely expressed PvuII restriction enzyme. Therefore, association of the C genes of the same specificity with RM gene complexes of different sequence specificities can confer on a resident RM gene complex the capacity to abort establishment of a second, incoming RM gene complex. This phenomenon, termed "apoptotic mutual exclusion," is reminiscent of suicidal defense against virus infection programmed by other selfish elements. pvuIIC and bamHIC genes define one incompatibility group of exclusion whereas ecoRVC gene defines another.

Apoptosis↗

Combination of OK432 and human interferon-alpha for treating viral-induced diabetes mellitus in mice.

We investigated the therapeutic effects of OK432 (picibanil; CAS39325-1-4), an immunomodulator that is derived from the Su strain of Streptococcus pyogenes. This agent was administered alone or combined with human interferon-alpha in a murine model of insulin-dependent diabetes mellitus. Interferon-alpha inhibits viral replication, reducing the incidence of virus-induced IDDM. Groups of DBA/2 mice (N = 25 per group) received an intraperitoneal injection of OK432 and interferon-alpha daily for 16 d beginning 1 d after inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). The dose of OK432 was one clinical unit (corresponding to 0.1 mg dried cells) per mouse, and that of interferon-alpha was 1 x 10(4) u/g. The animals were killed at random at 3 or 7 d after inoculation with EMCV. The survival rate of mice treated with the combination of OK432 and with interferon-alpha was significantly greater than that of the non-treated infected control animals (P < 0.01). Fasting levels of blood glucose were significantly lower in the mice administered the combination, than in the controls, both on day 3 (68 +/- 21 mg/dl vs. 270 +/- 135 mg/dl, P < 0.01) and on day 7 (101 +/- 29 mg/dl vs. 219 +/- 112 mg/dl, P < 0.01). Serum levels of insulin were significantly higher in the treated mice than in the controls (65 +/- 5 vs. 55 +/- 1 microU/ml, P < 0.05). However, in the mice treated with OK432 or interferon-alpha alone, the survival rate and the blood level of glucose and insulin did not differ from those of infected controls. Natural killer (NK) cell activity was significantly higher in the mice treated with the drug combination than in the controls on both days evaluated: day 3, 65 +/- 5 vs. 55 +/- 1%, n = 3, P < 0.05; day 7, 44 +/- 3 vs. 22 +/- 8%, n = 3, P < 0.05). Serum levels of murine interferon in the treated mice exceeded those in controls on both days evaluated (day 3, 671 U/ml vs. 442 U/ml; day 7, 57 U/ml vs. 43 U/ml). There were no significant differences in NK cell activity or in the interferon level in mice treated with either OK432 or interferon-alpha alone as compared with the infected, non-treated controls. Results suggest that the combination of OK432 and interferon-alpha protects against virally induced IDDM by increasing the activity of NK cells as well as the plasma level of interferon.

Animals↗

Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency.

Ten patients with adenosine deaminase deficiency (ADA-) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990. We describe a Japanese ADA- severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN. The percentage of peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% during the 12 months since the fourth infusion. ADA enzyme activity in the patient's circulating T cells, which was only marginally detected before gene transfer, increased to levels comparable to those of a heterozygous carrier individual and was associated with increased T-lymphocyte counts and improvement of the patient's immune function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA-SCID.

Adenosine Deaminase↗