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Biomedical subjects

T Tashiro

Publications and source records attributed to T Tashiro.

At least 91 records · Page 5Linked to original sources

Adenovirus-mediated transfer of human acid maltase gene reduces glycogen accumulation in skeletal muscle of Japanese quail with acid maltase deficiency.

Acid maltase deficiency (AMD) causes a lysosomal glycogenosis inherited as an autosomal recessive trait. The infantile type of AMD (Pompe disease) leads to early death due to severe dysfunction of cardiac and respiratory muscles and no effective therapy is available. Replication-defective adenovirus vectors offer a promising tool for in vivo gene delivery and gene therapy. We constructed a recombinant adenovirus containing the human acid maltase (AM) cDNA downstream of the CAG promoter, composed of modified chicken beta-actin promoter and CMV IE enhancer (AxCANAM). Japanese quail with AMD was used for this study as an animal model for human AMD. When cultured fibroblasts from AMD quail were infected with AxCANAM, AM activity in the cells increased in proportion to the multiplicity of infection (MOI). When AxCANAM (4.5 x 10(8) PFU) was injected into unilateral superficial pectoral muscle of AMD quail, PAS staining showed that glycogenosomes disappeared and stainability of acid phosphatase was reduced in the injected area as compared with the contralateral muscle of the same birds. Biochemically, AM activity increased and glycogen content decreased in the injected muscle. Western blot analysis showed that AMD quail muscle injected with AxCANAM expressed human AM protein processed to active forms. These results suggest that the human AM cDNA transferred by an adenovirus vector was sufficiently expressed, leading to a marked reduction of the glycogen accumulation in the skeletal muscle of AMD quail.

Adenoviridae↗

Lymphocytic adenohypophysitis: skull radiographs and MRI.

We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass.

Adenoma↗

Midterm results of free internal thoracic artery grafting for myocardial revascularization.

BACKGROUND: This study investigated the midterm results after free internal thoracic artery (FITA) grafting for coronary artery bypass grafting. METHODS: Between 1988 and 1995, coronary artery bypass grafting and postoperative graft angiography were performed in 337 patients, of whom 56 patients were treated with 57 FITA grafts. We examined the postoperative graft patency of FITA grafts compared with in situ internal thoracic artery (IITA) grafts, and the late results in the patients receiving at least one FITA graft (FITA group) were compared with those in the patients receiving only IITA graft (IITA group). RESULTS: The early postoperative graft patency rate was 93.2% for the FITA grafts and 96.0% for the IITA grafts (not significant [NS]). Patients underwent sequential graft angiography at 29.5 months postoperatively (25 FITA and 89 IITA). The late graft patency rate was 100% and 92.1%, respectively (not significant). The cardiac death-free survival rate at 5 years was 93.5% in the FITA group and 96.6% in the IITA group (not significant), and the angina-free survival rate at 5 years was 80.6% and 83.2%, respectively (not significant). CONCLUSIONS: The FITA provides late results comparable with those attained with IITA.

Anastomosis, Surgical↗

Infections caused by multiple strains of methicillin-resistant Staphylococcus aureus--a pressing epidemiological issue.

The genotype of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from several foci in the same patient was studied to identify the rate of infections caused by multiple MRSA strains during hospitalization. Twenty-one patients with MRSA bacteraemia and other specimens diagnosed between 1990-1994 were studied. Clinical data were retrospectively collected from the medical records. Genotyping of 113 MRSA isolates was performed by pulsed-field gel electrophoresis (PFGE), using the Gene Navigator System. More than one type of MRSA was detected from different foci in eight of 21 (38%) patients, and three types were identified in a single patient. Our results indicate that epidemiological investigations must be conducted carefully, especially in immunocompromised hosts with MRSA bacteraemia, as the probability of infection with multiple strains among these patients is relatively high.

Adult↗

CT and MR imaging of cerebral tuberous sclerosis.

Tuberous sclerosis is a heredofamilial neurocutaneous syndrome, or phakomatosis, with multisystem involvement including the brain, kidney, skin, retina, heart, lung, and bone. The brain is the most frequently affected organ in tuberous sclerosis. Brain lesions in tuberous sclerosis are of three kinds; cortical tubers, white matter abnormalities, and subependymal nodules. We review the computed tomography (CT) and magnetic resonance (MR) features of the brain lesions in patients with tuberous sclerosis. CT clearly demonstrates calcified subependymal nodules. MR imaging demonstrates more clearly cortical, and white matter lesions than CT, since MR imaging shows excellent image contrast between various normal structures and high sensitivity in detecting pathological states due to intrinsic differences in proton density and in particular, in proton relaxation times of tissues. Possible pathogenesis of this disorder is also discussed.

Brain↗

Effects of a newly developed fat emulsion containing eicosapentaenoic acid and docosahexaenoic acid on fatty acid profiles in rats.

A new fat emulsion of symmetrical triacylglycerols, containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. The effects of this preparation on serum and liver fatty acid composition were investigated. Male Sprague-Dawley rats were fed a fat-free oral diet for 2 wk and were then divided into two groups. Seven rats were infused for 7 d with 1 mL of the new fat emulsion, which accounted for 1% of total caloric intake. The other 7 rats received saline. Both groups of rats received a fat-free diet during the infusion. EPA and DHA decreased to one third to one fifth of normal value after 2 wk on a fat-free diet. EPA and DHA of serum and liver remained at a low level in the control group throughout the study. But in the rats administered with the new fat emulsion, EPA and DHA increased rapidly and exceeded normal values in both serum and liver after 7 d of infusion. Decreased arachidonic acid with increased 20:3n-9 resulted in the rise of the triene/tetraene (T/T) ratio to greater than 0.4, indicating an n-6 essential fatty acid deficiency in the control rats. In the group administered the new fat emulsion, however, 20:3n-9 and total content of monounsaturated fatty acids decreased significantly, and the T/T ratio was less than than 0.4 in both serum and liver. In conclusion, the intravenous use of a newly developed fat emulsion containing EPA and DHA is useful in improving the EPA and DHA status of serum and liver without any harmful effects. Beneficial effects are expected in the modulation of inflammatory and stress response.

Animals↗

n-3 versus n-6 polyunsaturated fatty acids in critical illness.

The effects of n-6 and n-3 polyunsaturated fatty acids (PUFA) on protein metabolism, cell-mediated immunity, and production of cytokines and prostanoids were studied in experimental animals and patients with esophageal cancer. In the experimental study using a rat burn model, n-6 PUFA increased serum interleukin-6 (IL-6) and tumor necrosis factor (TNF), alpha (P < 0.05), and decreased nitrogen balance (NB) (P < 0.05), when compared with a fat-free control. But addition of n-3 PUFA reduced TNF-alpha and IL-10 (P < 0.05) and improved NB (P < 0.05). Suppressed delayed type hypersensitivity (DTH) induced by burn injury, which was not influenced by n-6 PUFA, was significantly improved by the administration of n-3 PUFA. n-6 PUFA tended to increase, and n-3 PUFA significantly decreased the endotoxin translocation. DTH, granulocyte-macrophage colony-stimulating factor, and eicosapentaenoic acid (EPA) content increased proportionately with the intravenous dose of fish oil emulsion. The effects of n-6 and n-3 PUFA were studied in the patients who underwent surgery for esophageal cancer. In the group of patients fed by total parenteral nutrition with soybean oil emulsion, the serum IL-6 significantly increased at 2 and 6 h after operation (P < 0.05). Oral/enteral supplementation of EPA ethyl ester (1.8 g/d) significantly reduced the postoperative IL-6 production (P < 0.05 at 1, 2, and 6 h after operation), and improved cell-mediated immune function 3 wk after operation (P = 0.05). During the chemoradiation therapy, cell-mediated immune function was improved significantly in the patients fed enterally with EPA ethyl ester (n = 5), when compared with the patients without EPA (n = 14).

Animals↗

Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.

We compared the in-vitro antimycobacterial activities of rifabutin and KRM-1648, two rifamycin derivatives, with that of rifampicin against 163 strains of Mycobacterium tuberculosis. We also evaluated the correlation between the level of resistance to rifampicin, rifabutin and KRM-1648 and genetic alterations in the rpoB gene. All 82 strains susceptible to rifampicin or resistant to rifampicin with MICs < or = 16 mg/L were susceptible to rifabutin and KRM-1648 with MICs < or = 1 mg/L. Seventy-six of 81 strains resistant to rifampicin with MICs > or = 32 mg/L were resistant to both rifabutin and KRM-1648, but with lower MICs than those of rifampicin. KRM-1648 showed more potent antimycobacterial activity than rifabutin against organisms with low MICs (< or = 1 mg/L), while rifabutin was more active than KRM-1648 against organisms with high MICs (> or = 2 mg/L). A total of 96 genetic alterations around the 69 bp core region of the rpoB gene were detected in 92 strains. Alterations at codons 515, 521 and 533 in the rpoB gene did not influence the susceptibility to rifampicin, rifabutin and KRM-1648. Point mutations at codons 516 and 529, deletion at codon 518 and insertion at codon 514 influenced the susceptibility to rifampicin but not that to rifabutin or KRM-1648. With the exception of one strain, all alterations at codon 513 and 531 correlated with resistance to the three test drugs. The resistant phenotype of strains with an alteration at codon 526 depended on the type of amino acid substitution. Our results suggest that analysis of genetic alterations in the rpoB gene might be useful not only for predicting rifampicin susceptibility, but also for deciding when to use rifabutin for treating tuberculosis. Further studies may be required to determine the usefulness of KRM-1648.

Amino Acid Sequence↗

Analysis of genetic relationships and antimicrobial susceptibility of verotoxin-producing Escherichia coli strains isolated in Nagasaki Prefecture, Japan in 1996.

A total of 19 Escherichia coli O157 isolates were obtained in Nagasaki Prefecture, in the south-western part of Japan, between 1990 and 1996. Pulsed-field gel electrophoresis (PFGE) and computer-assisted analysis were applied to determine genetic relationships among these strains. Fragment patterns of the isolates in Nagasaki, as determined by PFGE, were compared with those of isolates in other areas where large outbreaks and sporadic cases of E. coli O157 infection occurred. Similarity values of all the strains isolated in Nagasaki Prefecture were over 0.65 except for E. coli O26. Some strains were identical to the strains isolated from the areas where large outbreaks occurred. All strains were susceptible to ampicillin, fosfomycin, minocycline, amikacin, ofloxacin and sulfamethoxazole-trimethoprim.

Anti-Bacterial Agents↗

[Analysis of utility of the phenotyping method on detection of cases infected by multiple strains of methicillin-resistant Staphylococcus aureus (MRSA)].

In this study, we compared the types of methicillin-resistant Staphylococcus aureus (MRSA) isolated from several foci of the same patient to find the incidence of multiple strain infection of MRSA in bacteremia cases. We will also evaluate the utility of the typing methods of phenotyping and genotyping for the above mentioned objective and judge the dissimilarity of clinical characteristics between the single strain infection and multiple strains infection. We studied 21 cases of MRSA bacteremia who were culture-positive both from blood and other foci in the same patient at Nagasaki University Hospital during 1990-1994. Clinical data were retrospectively collected from the patients' records. Phenotyping of all 113 MRSA isolates were done by coagulase typing (I-VIII), production of enterotoxins (SEA-SED) and toxic shock syndrome toxin-1 (TSST-1), hemolysis typing and antibiogram (MIC). In addition, typing of the same isolates were done by Pulsed-Field Gel Electrophoresis (PFGE), using Gene Navigator System as the genotyping. Several types of MRSA were found from different foci in the same patient in 8 of 21 cases (38%) by phenotyping. The same typing results were obtained in 7 of 8 the multiple strains isolated cases by PFGE. Two types were obtained from another case by phenotyping, but by PFGF, 3 types were obtained. We consider that phenotyping method is convenient and reliable for judgment of the difference in types isolated from different foci in the same patient, but PFGE possibly provide us more detailed epidemiological information. The epidemiological investigation must be done very carefully, especially in immunocompromised hosts as MRSA bacteremia cases, because the chance of multiple strains infection is relatively high among these cases.

Bacteremia↗

Long-circulating immunoliposomal amphotericin B against invasive pulmonary aspergillosis in mice.

We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.

Amphotericin B↗

Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Amphotericin B↗

Detection of Mycobacterium tuberculosis in preserved tuberculous lymph nodes by polymerase chain reaction.

We evaluated the usefulness of three types of polymerase chain reaction (PCR) targeting 16S rRNA, protein antigen b and IS6110 in detecting Mycobacterium tuberculosis in preserved tuberculous lymph nodes. The detection limit of all PCR methods was 100 colony forming unit (CFU) of M. tuberculosis in tissue. The test samples included eight paraffin-embedded tuberculous lymph nodes containing microscopical epithelioid cell granuloma with caseous necrosis and Langhans giant cells. Although acid-fast stained organisms in lymph node tissue were not detected in any sample, all three types of PCR tests were positive in four of eight lymph nodes. Our results suggest that PCR is not only a rapid and sensitive diagnostic method for tuberculous lymphadenitis, but also clinically significant in retrospective study for detecting M. tuberculosis even in some preserved lymph node tissues without evidence of acid-fast stained organisms.

Antigens, Bacterial↗

[Severe mycosis-factors with fungus and host].

The deep-seated mycosis occurred in immunocompromized patients. Normally, the deep-seated mycosis became sever infection because of the defects of host defense or the adverse effects of antifungal agents. The major factors of the reason on the severity of the deep-seated mycosis depends on the pathogenesity and the drug resistance for antifungal agents in infected fungi. The clinical factors related with hosts defenses are important to the other reason on the severity. We investigated that the multiple drug resistant (MDR) mechanism may be one of the major roles plays in the azole resistant Candida albicans strains isolated form the patients with oropharyngeal candidiasis infected HIV. We analyzed which clinical factors are related with the prognosis of the patients with pulmonary cryptococcosis and aspergilloma. The titer of cryptococcal capsular antigen was earlier improve in the patient without underline disease than in the patients with underline diseases diagnosed pulmonary cryptococcosis. CRP was higher in the death cases in the patients with pulmonary aspergilloma, compared with alive cases.

AIDS-Related Opportunistic Infections↗

[Sudden decrease in the level of consciousness due to subarachnoid bleeding attack in a patient undergoing ophthalmic surgery under retrobulbar anesthesia].

We experienced a case of intraoperative subarachnoid bleeding attack under retrobulbar anesthesia in a 71 year-old female. Immediately after retrobulbar anesthesia with bupivacaine, the patient showed a sudden decrease in her level of consciousness, respiratory depression, convulsions and her blood pressure increased to 258/63 mmHg. The clinical symptoms and onset of the attack were very similar to those of acute local anesthetic intoxication, where local anesthetics reached the central nervous system through cerebrospinal fluid or via ophthalmic artery. We gave oxygen and provided ventilatory assist by bag and mask, and administered anticonvulsant and antihypertensive agents. After we confirmed recovery of consciousness and stability of hemodynamics and respiration, the extracapsular lens extraction began. The same attack reoccurred 20 minutes later, and we treated the patient with the same procedure as in the first attack and asked the surgeon to shorten the operation. After surgery the patient was diagnosed by computed tomography as having subarachnoid bleeding from a ruptured aneurysm of the anterior cerebral artery. When a patient's level of consciousness suddenly decreases under local anesthesia, we recommend terminating the surgery to clarify the cause. In such cases, serious cardio- and cerebrovascular disorders might be involved, rather than complications due to local anesthetic intoxication.

Aged↗

[N-3 polyunsaturated fatty acids in surgical nutrition].

Recent surgical nutrition includes the management of mediator to induce the stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA) were reported to increase the survival rate, and to improve the nutritional and immune status of septic or burned animals. N-3 PUFA also inhibited the proliferation and metastasis of cancer, and improved the cancer cachexia. N-3 PUFA decreased the production of cytokine and eicosanoid originated from n-6 PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity was suppressed with the reduction of cytokine. But in the stressed state, N-3 PUFA ameliorated the stress induced immunosuppression. Alteration of transcription of cytokine mRNA, changes of membrane fluidity, and reduced expression of adhesion molecule were proposed to interpret these effects. In conclusion, n-3 PUFA can be applied for the surgical patients, especially for the critically ill patients.

Animals↗

[Spontaneous resolution of pulmonary cryptococcosis--report of 2 cases].

We encountered two patients with pulmonary cryptococcosis that resolved spontaneously without antifungal treatment. A 59-year-old man (patient 1) and 37-year-old man (patient 2) were admitted to our hospital for the examination of abnormal shadows on their chest x-ray films. Transbronchial lung biopsies were performed, and cryptococci were detected in both patient's lung tissues. Latex aggultination tests for cryptococcal antigen were positive (1:16 and 1:4, respectively). The size of the shadows reduced spontaneously and the titers of the cryptococcal antigen in sera decreased within three months although no antifungal therapy was performed. Bronchoalveolar lavage fluid (BALF) was obtained from each patient and examined. In patient 1, the lymphocyte to CD 4/8 ratio was high in the BALF obtained on admission and the lymphocyte count was low; however, the CD 4/8 ratio was still high in a BALF sample obtained 3 months after discharge. In patient 2, the findings of the BALF analysis on admission were almost normal. The analysis of BALF may contribute to the immunological conditions to in the patients with pulmonary cryptococcosis.

Adult↗