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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 865 records · Page 48Linked to original sources

[Clinical usefulness of the combined empirical therapy with flomoxef and fosfomycin for intractable respiratory tract infections. With a background of increasing MRSA incidence].

We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

Aged↗

[Early cytomegalovirus retinitis].

We report the clinical course of cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS) from the initial onset. The patient was a 40-year-old human immunodeficiency virus antibody-positive male with hemophilia A. He was diagnosed as having AIDS on the basis of pneumocystis carinii pneumonia. Ophthalmoscopic examination disclosed a small white punctate lesion at the macular area in his right eye. Because the lesion enlarged gradually with hemorrhages, it was suspected to be CMV retinitis. However, further examination was impossible due to his severe general condition. He died five months later and the autopsy disclosed disseminated CMV infection. Ocular histopathological examination revealed CMV retinitis. The earliest sign of CMV retinitis is supposed to be a white punctate retinal lesion, which becomes a small white patchy lesion resembling a cotton-wool spot. It may gradually progress to diffuse retinal involvement, frequently associated with hemorrhages.

Acquired Immunodeficiency Syndrome↗

[Coronary artery bypass grafting in a patient with right aortic arch associated with retroesophageal anomalous left subclavian artery].

A rare case of coronary artery bypass grafting in a patient with right aortic arch was presented. A 62-year-old man was admitted to our hospital with angina pectoris. Coronary angiography revealed total obstruction of left anterior descending artery and jeopardized collateral from right coronary artery. Aortography disclosed right aortic arch associated with retroesophageal anomalous left subclavian artery. As the symptom of neither the vascular ring nor the subclavian steal syndrome was recognized, left internal thoracic artery along with the saphenous vein was used for bypass conduit. The patient is doing well without any troubles 7 months after the operation. Attention should be made to use left internal thoracic artery in a patient with right aortic arch.

Aorta, Thoracic↗

[A case report of surgical repair of a ruptured aneurysm of the sinus Valsalva in an aged person with cardiac cachexia].

A 71-year-old woman underwent surgical repair of a ruptured aneurysm of the sinus Valsalva. She had an aneurysm of the right coronary sinus ruptured into the right atrium. There was no VSD. The patient suffered from heart failure for 38 years and went into cardiac cachexia. Direct closure from the right atrium was performed and the patient has resumed full physical activities. As far as we know, this is one of the oldest patients who underwent successful surgery for this disease in this country.

Aged↗

[Growth inhibition of the emulsion from to Brucea javanica cultured human carcinoma cells].

We studied the growth inhibitory activity of the emulsion from Brucea javanica fruit of B. javanica to human squamous cell carcinoma cells. The dose of 250 micrograms/ml at 96 hrs after drug exposure, it showed 42% growth inhibition, and at 500 micrograms/ml inhibited 56% of the cell growth. The effect of more than 50% of the growth inhibition was evident at more than 7 hrs after drug exposure. In the analysis of mechanism of the drug using a flow cytometry, the arrest in G1 phase of cell cycle was found during incubation of cancer cells with drug. These results suggested that the oil of B. javanica is useful as an anticancer drug.

Antineoplastic Agents, Phytogenic↗

[Phase I clinical study for 111In-DTPA-IgG].

A phase I study was performed in three health volunteers to evaluate the safety and biodistribution of 111In-DTPA-IgG, a newly developed imaging agent for inflammation/infection. No adverse effect was observed. There were no clinically significant changes in blood chemistry, hematology, and urinalysis parameters, physical examinations or vital signs. 111In-DTPA-IgG in blood exhibited a biexponential disappearance, consisting of a fast component (t1/2 alpha) ranging from 5.72 to 8.51 hours, and a slow component (t1/2 beta) ranging from 34.0 to 35.5 hours. Twelve percent of the injected dose was eliminated in the urine within 72 hours. Dosimetry estimates indicated that up to 80 MBq of 111In-DTPA-IgG can be safely administered to subjects without exceeding generally accepted absorbed dose for other scintigraphic procedures for inflammation/infection. The organs receiving the highest absorbed dose was the liver followed by the kidneys, heart, and lungs. Each of these organs received less than 40 mGy per 80 MBq administered. The safety data and dosimetry estimates indicated that it is safe to proceed with phase II studies with a 40-80 MBq dose of 111In-DTPA-IgG.

Adult↗

Two regulatory elements in the 5' region of the mouse mitochondrial malate dehydrogenase gene.

We previously reported that the promoter region of the mouse mitochondrial malate dehydrogenase gene is located within the 160 base-pairs (bp) region upstream from the initiation codon, named P1, and that the -160/-131 bp region contains sequence(s) essential for the promoter activity of mitochondrial malate dehydrogenase gene. To define more precisely the regulatory mechanism of this gene, a 3' deletion analysis was performed using constructs with a constant 3' boundary at -130 bp. We obtained evidence of an additional positive regulatory element located between -393/-249 bp, named P2, the function of which can be separated from that of the P1. DNase I footprinting and gel-sift mobility experiments showed that nuclear protein binding to the P2 was not inhibited in the presence of the P1 sequences.

3T3 Cells↗

[Lung transplantation from non-heart-beating donor following brain death in canine model].

Candidates for pulmonary transplantation have been limited because of extreme susceptibility to lung infections and pulmonary edema in the brain-dead donor. To ameliorate the donor shortage, two possibilities for expanding the donor source have been presented, i.e. xenotransplantation and transplantation from cardiac-dead donors. The present study was conducted to evaluate the possibility of lung transplantation from a non-heart-beating donor following brain death, using a canine model. Six mongrel dogs were put into a state of brain death by elevating intracranial pressure with a balloon catheter. Following the intravenous administration of methylprednisolone and heparin used for 6-hour management following brain death mechanical ventilation was discontinued leading to cardiac arrest with in a few minutes. Excision of the left lung was scheduled for twenty minutes after cardiac arrest, followed by washing out the pulmonary vasculature with cold Ep4 solution, and orthotopic transplantation into the recipient animal. Immunosuppression was achieved with methylprednisolone and azathioprine. A right pulmonary arterial occlusion test (RPAO) was performed to assess graft function immediately and 7 days postoperatively. All but one animal survived and three animals had an uneventful postoperative course, with the transplants alone according to immediate and 7 day postoperative, respectively, RPAO results. These outcomes indicate the possible feasibility of lung transplantation from non-heart-beating donors following brain death.

Animals↗

Gene targeting by a vector with hairpin-shaped oligonucleotide caps.

To improve the efficiency of gene targeting, a linearized vector containing part of the mouse transthyretin (ttr) gene, a bacterial neomycin-resistance gene and a herpes simplex virus thymidine kinase gene was capped with hairpin-shaped oligonucleotides. The capped vector not only improved the efficiency of positive-negative selection about 3.5-fold, but also increased about 2.5-fold the ratio of ttr gene targeted clones to the selectants.

Animals↗

Altered levels of erythrocyte calcium-binding proteins in essential hypertensives with genetic predisposition: correlation with ambulatory blood pressure.

OBJECTIVE: To examine whether changes in calcium-binding proteins, one of the components of the calcium ion handling mechanism, occur in humans with essential hypertension. DESIGN: We measured the levels of cytosolic calcium-binding proteins purified from human erythrocytes using a felodipine fluorescence assay, and examined the correlation between this parameter and the ambulatory blood pressure (ABP). We divided 127 subjects into four age-matched groups according to their mean ABP levels and whether they had a family history of both hypertension and stroke [group A hypertensives with a positive family history (n = 30), group B hypertensives with no family history (n = 31), group C normotensives with a family history (n = 31) and group D normotensives with no family history (n = 35) of hypertension and stroke]. RESULTS: The erythrocyte cytosolic level of calcium-binding proteins in group A was significantly lower than that in group B, as was that in group C compared with group D. There was no significant correlation between the erythrocyte level of calcium-binding proteins and casual blood pressure values in any group. However, in group A significant negative correlations between the erythrocyte level of calcium-binding proteins and systolic and mean ABP were observed (r = -0.34, P < 0.05 and r = -0.39, P < 0.05, respectively). No significant correlations between the ABP and erythrocyte levels of calcium-binding proteins were observed in the other groups. When each group was subdivided according to sex, there were significant negative correlations between the erythrocyte level of calcium-binding proteins and the systolic and mean ABP in the males of groups A and C, but no correlations were found in any of the female subgroups or the males of groups B and D. Reducing the blood pressure by antihypertensive drug therapy did not affect the erythrocyte calcium-binding proteins level in 13 patients from groups A and B. Analysis using anion-exchange fast-performance liquid chromatography on a Mono-Q column and sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that the calcium-binding proteins in human erythrocytes, the levels of which were low in group A, formed a single protein band with a molecular weight of 17,000, which was assumed to be a calmodulin. CONCLUSIONS: These results suggest that there are subgroups of hypertensive patients with low erythrocyte cytosolic levels of calcium-binding proteins, which are genetically determined. Furthermore, our data suggest that the erythrocyte level of calcium-binding proteins and ABP in male subjects with hypertension and normotensives with a genetic predisposition are correlated strongly, whereas no such correlation was observed in any female subgroup. This indicates that the regulatory mechanism or mechanisms involved in the control of blood pressure in men and women may be different.

Aging↗

[Foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome].

A 41-year-old man with acquired immunodeficiency syndrome (AIDS) developed cytomegalovirus (CMV) retinitis. Intravenous administration of ganciclovir arrested progression of the retinitis, but it was discontinued due to side effects of severe anemia, neutropenia, and thrombocytopenia. Reactivation of CMV retinitis occurred two weeks after stopping ganciclovir, and then forscarnet was given intravenously. The response was prompt with resolution of the retinitis. There was no progression of retinitis during the treatment. The patient experienced renal dysfunction as a side effect of foscarnet, but it was reversible. As with ganciclovir, foscarnet appeared to be an effective drug for CMV retinitis associated with AIDS. Both drugs have severe adverse events: foscarnet causes renal dysfunction and ganciclovir causes myelosuppression, that necessitated discontinuation of the therapy. We suggest that alternating ganciclovir and foscarnet administration, switching to other treatment on the basis of the clinical response and side effects of the drugs, is an efficacious regimen for the treatment of CMV retinitis associated with AIDS.

AIDS-Related Opportunistic Infections↗

[Clinical effect of arbekacin on MRSA infections after gastrointestinal surgery].

From January 1991 to July 1993, 58 patients with MRSA infections in our clinic at Wakayama Medical College and six affiliated hospitals were administered with arbekacin (ABK). The clinical results were as follows: 1. The clinical efficacy rates of ABK were 84% in pneumonia, 100% in both wound infections and hepatobiliary tract infections, and 85% in total. The bacteriological efficacy rate was 83%. 2. Regarding the administration route, the clinical efficacy rates were 60-79% by the intravenous treatment and inhalation therapy. Especially by the local administration with ABK, MRSA was eradicated in all cases. 3. The sufficient efficacy was obtained by the treatment of ABK alone (89%) and by the combined treatment with ABK (82%) and another antibiotics. From these results, it is concluded that ABK is useful for the treatment of MRSA infections after gastrointestinal surgery.

Administration, Inhalation↗

[Problems in coping with intractable bacterial infections].

The development of new antimicrobial agents has succeeded to overcome most of the bacterial infections. However, the success has, at the same time, accompanied with the increase of intractable infections by drug-resistant pathogens such as methicillin resistant Staphylococcus aureus or multi-drug resistant Mycobacterium tuberculosis. To cope with these infections, we have to settle quite a lot of problems. In this paper, we described these problems adopting chronic respiratory tract infection as an example. The problems discussed here are (1) determination of causative agent, (2) dynamics of bacterial flora, and (3) pathogenic role of extracellular protease from Pseudomonas aeruginosa.

Bacteria↗

Perioperative blood transfusion promotes recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND: Recent advances in liver surgery have reduced operative blood loss drastically, and in more than one half of the patients in our hospital, the liver resection can be accomplished without blood transfusion. METHODS: Two hundred fifty-two patients who underwent complete resection for hepatocellular carcinoma (HCC) were evaluated to assess the effect of perioperative blood transfusion on the recurrence of carcinoma. RESULTS: Carcinoma recurred in 55 (74.3%) of the 74 patients who received a transfusion, but in only 89 (50%) of the 178 patients who did not receive a transfusion (p = 0.0001). This effect was significant even when only a small amount of blood was transfused (p = 0.0001). Based on multivariate analysis, perioperative blood transfusion was a significant predictor for accelerated recurrence (p = 0.003), as were tumor invasiveness (vascular invasion or intrahepatic metastasis) (p = 0.0008) and background liver cirrhosis (p = 0.04). The recurrence-promoting effect of blood transfusion was markedly significant when the patient had either noninvasive HCC (p = 0.0005) or a cirrhotic liver (p < 0.0001). CONCLUSIONS: These results strongly suggest that perioperative blood transfusion substantially promotes the recurrence of HCC after hepatectomy. This effect must be considered and added to the risks of perioperative blood transfusion when formulating a surgical strategy for HCC.

Adult↗

[Heparan sulfate proteoglycan of endothelial cells: homocysteine suppresses anticoagulant active heparan sulfate in cultured endothelial cells].

The endothelial surface plays an important role in the pathogenesis of atherosclerosis and the regulation of coagulation. It has become increasingly clear that while perturbed endothelial cells generate procoagulant activity, under normal conditions they possess multiple antithrombotic and anticoagulant mechanisms, including generation of prostacyclin and plasminogen activators and synthesis of thrombomodulin as a cell surface cofactor for thrombin-catalyzed activation of protein C. In addition, anticoagulantly active heparan sulfate proteoglycans, including heparin-like molecules are apparently present on the vascular surface. Previous studies showed that homocysteine, a thromboatherogenic and atherogenic agent, inhibits an endothelial thrombomodulin-protein C anticoagulant pathway. We examined whether homocysteine might affect another endothelial anticoagulant mechanism; i.e., heparin-like glycosaminoglycan-antithrombin III interactions. Incubations of cultured endothelial cells with homocysteine reduced the amount of antithrombin III bound to the cell surface in a dose- and time-dependent fashion. In contrast with a marked reduction in the maximal antithrombin III binding capacity, the radioactivity of [35S] sulfate incorporated into heparan sulfate on the cell surface was minimally reduced. Although neither net negative charge nor proportion in total glycosaminoglycans of cell surface heparan sulfate was altered by homocysteine treatment, a substantial reduction in antithrombin III binding capacity of heparan sulfate isolated from homocysteine-treated endothelial cells was found using both affinity chromatography and dot blot assay techniques. The antithrombin III binding activity of endothelial cells decreased after preincubation with homocysteine, cysteine, or 2-mercaptoethanol, containing a sulfhydryl group; no reduction in binding activity was observed after preincubation with methionine, alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗