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Biomedical subjects

T Fukuoka

Publications and source records attributed to T Fukuoka.

At least 19 recordsLinked to original sources
PubMed1996

Organization of the chicken histone genes in a major gene cluster and generation of an almost complete set of the core histone protein sequences.

We present a detailed picture of the disposition of the histone genes in the chicken genome and an almost complete set of the core histone protein sequences. Thirty-nine histone genes, six H1, nine H2A, eight H2B, eight H3 and eight H4, were located within a histone gene cluster of 110 kb, which was covered by five cosmid clones and two lambda clones. Results of our sequence analyses, together with those reported previously, generated a set of the core histone amino acid sequences as follows: three H2A variants, four H2B variants, two H3 variants and an H4 protein.

Amino Acid Sequence↗
PubMed1996

Effects of different triggering systems and external PEEP on trigger capability of the ventilator.

OBJECTIVE: The triggering capability of both the pressure and flow triggering systems of the Servo 300 ventilator (Siemens-Elema, Sweden) was compared at various levels of positive end-expiratory pressure (PEEP), airway resistance (R(aw)), inspiratory effort and air leak, using a mechanical lung model. DESIGN: The ventilator was connected to a two bellows-in-series-type lung model with various mechanical properties. Lung compliance and chest wall compliance were 0.03 and 0.121/cmH2O, respectively. R(aw) was 5, 20 and 50 cmH2O/l/s. Respiratory rate was 15 breaths/min. To compare the triggering capability of both systems, the sensitivity of pressure and flow triggered pressure support ventilation (PSV) was adjusted to be equal by observing the triggering time at 0 cmH2O PEEP and 16 cmH2O of pressure support (PS) with no air leak. No auto-PEEP was developed. In the measurement of trigger delay, the PS level ranged from 16 to 22 cmH2O to attain a set tidal volume (V(T)) of 470 ml at a R(aw) of 5, 20 and 50 cmH2O/l/s. The PEEP level was then changed from 0, 5 and 10 cmH2O at a PS level of 17 cmH2O and R(aw) of 5 and 20 cmH2O/l/s, and the trigger delay was determined. The effect of various levels of air leak and inspiratory effort on triggering capability was also evaluated. Inspiratory effort during triggering delay was estimated by measurements of pressure differentials of airway pressure (Paw) and driving pressure in the diaphragm bellows (Pdriv) in both systems. MEASUREMENTS AND RESULTS: There were no significant differences in trigger delay between the two triggering systems at the various PEEP and R(aw) levels. At the matched sensitivity level, air leak decreased trigger delay in both systems, and additional PEEP caused auto-cycling. A low inspiratory drive increased trigger delay in the pressure sensing system, while trigger delay was not affected in the flow sensing system. The Paw and Pdriv differentials were lower in flow triggering than in pressure triggering. CONCLUSIONS: With respect to triggering delay, the triggering capabilities of the pressure and flow sensing systems were comparable with and without PEEP and/or high airway resistance at the same sensitivity level, unless low inspiratory drive and air leak were present. In terms of pressure differentials, the flow triggering system may require less inspiratory effort to trigger the ventilator than that of the pressure triggering system with a comparable triggering time. However, this difference may be extremely small.

Lung↗
PubMed1996

Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone.

We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q- in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids is rare. Combination therapy might therefore be advantageous in MDS.

Anti-Inflammatory Agents↗
PubMed1996

Detection of an aberrant fragment in growth hormone gene cluster in a girl with congenital generalized lipodystrophy.

The etiology of congenital generalized lipodystrophy (CGL) is unknown, but one of the clinical features is an accelerated rate of growth. In order to determine whether this abnormality is related to an abnormality of the GH or the IGF-I gene, we studied the DNA of lymphocytes of a girl with CGL. The IGF-I gene autoradiographic patterns of this patient were found not to differ from those of normal subjects, but after BamHI digestion, this patient's GH gene cluster had an aberrant 5.7 kb fragment in addition to the constant 8.3, 6.7, 5.3, 3.8, 2.9 kg fragments. The new 5.7 kb fragment was not detected in any of 60 unrelated Japanese individuals. In conclusion, the CGL patient carries an abnormal GH gene cluster, but further studies are needed to clarify whether this abnormal fragment is specific to CGL or just a rare polymorphic fragment.

Autoradiography↗
PubMed1995

The platelet activating factor as a pivotal mediator of shock after liver ischemia.

Liver failure is often accompanied by shock, which is usually refractory to conventional vasopressive therapy, and it is believed that some potent chemical mediators are involved in this process. The platelet activating factor (PAF) is a newly discovered inflammatory mediator that has a remarkable hypotensive action. In the present study, the possible role of PAF in shock after ischemic liver failure was investigated. Partial hepatic ischemia was induced in Wistar rats by clamping the hepatic afferent vessels to almost 70% of the whole liver for 90 min. One group of rats was pretreated with 10 micrograms/kg of TCV-309, a PAF antagonist. Pretreatment with TCV-309 inhibited the shock that ultimately occurred in the untreated rats; the survival rate 16 h after hepatic ischemia was 20% in the untreated control group but 100% in the group pretreated with TCV-309. The level of PAF in the plasma after hepatic ischemia was 2,939 +/- 2,412 pg/ml, which was significantly higher than that of the surgical control (920 +/- 188 pg/ml). These findings strongly suggest that anoxical disintegration of the liver derives PAF which causes shock. Thus, a PAF antagonist is expected to be an effective prophylactic treatment for patients who are at risk of developing shock from an ischemic liver.

Animals↗
PubMed1995

Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors.

In order further to identify the prevalence of anti-receptor autoantibodies in the sera of patients with dilated cardiomyopathy (DCM), we attempted to detect autoantibodies against a series of G-protein-coupled cardiovascular receptors in a well-defined population of DCM patients from Japan. Peptides corresponding to the sequences of the second extracellular loops of the human beta 1 and beta 2 adrenoceptors, alpha 1 adrenoceptors, M2 muscarinic acetylcholine receptors and angiotensin II-1 (AT1) receptors were used as antigens in an enzyme immunoassay to screen the sera from patients with DCM (n = 28). Nine sera from patients with DCM (32%) and 2 sera from healthy subjects (9%) recognized the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor had autoantibody against the M2 receptor. However, no significantly high frequencies of autoantibodies against the beta 2 adrenoceptor, alpha 1 adrenoceptor and AT1 receptor were found in DCM patients. Our results demonstrate that a subgroup of patients with DCM have a specific spectrum of autoantibodies which are specifically directed against the second extracellular loops of the beta 1 adrenoceptors and M2 muscarinic receptors rather than other cardiovascular receptors.

Adult↗
PubMed1995

Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons.

Using in situ hybridization and the retrograde tracer, Fluorogold, we examined the expression of preprotachykinin (PPT) mRNA in the rat dorsal root ganglion neurons projecting to the gracile nucleus. Seven days after unilateral sciatic nerve transection, some medium- to large-sized neurons in the rat dorsal root ganglia projecting to the gracile nucleus express PPT mRNA, whereas very few gracile nucleus-projecting neurons on the contralateral side express PPT mRNA. Immunohistochemistry revealed an increase in substance P (SP) immunoreactivity in the gracile nucleus and large myelinated fibers in the dorsal root 2 weeks after unilateral sciatic nerve transection. The results suggest that medium to large DRG cells that project to the gracile nucleus express PPT mRNA de novo in response to peripheral nerve injury, and increased SP is transported to the gracile nucleus through large myelinated fibers. To determine whether the increased SP might affect the excitability of the gracile nucleus neurons postsynaptically, Fos expression after electrical stimulation of the injured sciatic nerve was examined. Multiple injections of the NK-1 receptor antagonist, CP-96,345, suppressed stimulus-induced Fos expression in gracile nucleus neurons including thalamic relay neurons. The inactive enantiomer, CP-96,344, had no effect on stimulus-induced Fos expression. These data indicate that the de novo synthesized SP in the lesioned primary afferent neurons may be involved in an augmentation of excitability in the dorsal column-medial lemniscus sensory pathway. This hyperexcitability may play a role in the pathogenesis of abnormal neuropathic sensations following peripheral nerve injury.

Animals↗
PubMed1994

Effect of the combination of hyperthermia and irradiation on human colon cancer cells.

The combination of hyperthermia and radiation is considered to have a synergistic effect on mammalian cells, which depends on temperature and duration of time of the hyperthermia and on the sequence in which the modalities are given. The response of cultured colon cancer cells to hyperthermia and ionizing radiation was evaluated using the flow cytometry method by measuring DNA damage. The enhanced DNA damage after combined treatment with hyperthermia and irradiation was recognized after both sequences: heat followed by radiation as well as radiation followed by heat. The results demonstrated that the sequence of radiation plus heat produced more DNA damage on colon cancer cells than did the reverse order. The clinical application of these results is discussed.

Colonic Neoplasms↗
PubMed1994

A case of toxic megacolon in ulcerative colitis associated with cytomegalovirus infection.

Cytomegalovirus (CMV) infection, which has been shown to complicate the course of ulcerative colitis (UC), has been implicated as a possible etiologic factor in the exacerbation of UC, especially in toxic megacolon. However, CMV infection in patients with UC accompanied by toxic megacolon has rarely been reported. Here we report a case of CMV infection of the colon accompanied by toxic megacolon occurring in UC. A 38-year-old woman had been treated with intravenous hydrocortisone, rectal steroid, and central venous alimentation for 6 weeks under the diagnosis of UC. She was transferred to Akita University Hospital because of increasing bloody diarrhea and abdominal pain. Toxic megacolon was identified by examinations on admission, and she underwent a total colectomy. Examination of the surgical specimen showed severe inflammation of the colon. Microscopically, cytomegalic inclusions were observed in and around the endothelial cells in the inflamed submucosal layer. It can be assumed that CMV infection was a secondary, opportunistic invader superimposed on UC, and that it played an important role in altering the clinical course of the patient.

Adult↗
PubMed1994

[Lipid peroxidation and tubular disorder in experimental acute renal failure-enzymochemical study in the rat kidney].

Acute renal failure induced by the administration of gentamicin (GM) was studied enzymochemically in comparison with that in rats with tubular disorder resulting from postischemic reperfusion. Renal ischemia was caused by clamping the renal artery for 30 minutes to create complete ischemia and reflow. The activities of renal tissue glutathione peroxidase (GSH-Px) and the values to the renal contents of glutathione (GSH) and malondialdehyde (MDA) were measured in each sample. In order to confirm whether GSH plays an important role in the intrinsic anti-oxidant system in this model, buthionine sulfoximine (BSO), which is a gamma-glutamylcysteine synthetase inhibitor, was administered intraperitoneally to decrease the renal GSH content before the procedure in renal ischemia. On the other hand, the GM-induced ARF model was made by injection with GM 100 mg/kg during a period of 5 days. In the GM group, a significant increase in MDA and a reduction in the sphigomyelin (SPH)/phosphatidylcholine (PC) ratio and inactivation of PLA2 were observed. In the kidney tissue obtained 15 min. after reperfusion, the renal content of MDA was elevated markedly in the BSO-preadministered group. A reduction of SPH/PC ratio was also observed in the reperfusion model. PAL2 hydrolyzes the acyl group at the 2-position containing much of the highly unsaturated fatty acids that are easily oxidized. Further, PLA2 is considered to act directly on one of PC or phosphatidylinositol. Phospholipidosis thesauruses, noted in acute renal failure induced by GM, is considered to be caused by reduced liberation of lysosomal intramembranous phospholipid into the cytoplasm and accelerated peroxidation of intramembranous lipid.

Acute Kidney Injury↗
PubMed1993

The size of regional lymph nodes does not correlate with the presence or absence of metastasis in lymph nodes in rectal cancer.

We evaluated the relationship between the size of regional lymph nodes and the presence of metastasis in them in rectal cancer. Of 1,064 lymph nodes in 46 specimens, 133 (13%) were found to have metastases. A half of the positive nodes and most of the negative ones were less than 5 mm in diameter. Therefore, we must find lymph nodes smaller than 5 mm in diameter for assessment of lymph node metastasis. Although positive nodes were larger than negative ones, there was no significant difference. However, when comparing the size of lymph nodes in relation to their location, the epi- and pararectal lymph nodes larger than 10 mm in diameter were highly suggestive of metastases, but the size of the lymph node was not a reliable indicator of lymph node metastases in other situations.

Humans↗
PubMed1993

Protective effect of the calcium channel blocker diltiazem on hepatic function following warm ischemia.

The purpose of this study was to investigate the protective effect of a calcium channel blocker diltiazem (DTZ) on hepatic ischemic injury using a canine model. Hepatic ischemia was induced by temporary clamping of hepatic afferent blood vessels for 60 min with establishment of a portojugular bypass. The administration of DTZ at a dose of 70 micrograms/kg bolus i.v. injection before hepatic ischemia and thereafter via the portal vein at a dose of 10 micrograms/kg/min well restored the hepatic blood flow (HBF, 92 +/- 5%; P < 0.01) and arterial ketone body ratio (AKBR, 1.15 +/- 0.16; P < 0.01) 1 hr after interruption compared with untreated controls (HBF, 61 +/- 7%; AKBR, 0.53 +/- 0.09). In addition, the increase of plasma lactate level and the decrease of mean arterial pressure were significantly suppressed after ischemia (P < 0.05). We concluded that DTZ has a protective effect on ischemia-induced hepatic damage and might be useful in the prevention of primary graft failure caused by warm ischemia in liver transplantation.

Animals↗
PubMed1993

The clinical significance of regional variations in histologic differentiation within carcinomas of the colorectum.

The clinical significance of the presence or absence of regional variations in histologic differentiation within a primary colorectal carcinoma was investigated in this study. Regional variations in histologic differentiation were judged to be present when the low power field of a microscope was occupied by cancer tissue cytologically and architecturally different from that of the surrounding area. Regional variations in histologic differentiation were noted in 153 (42%) of 368 primary carcinomas. Carcinomas with regional variations were of an anaplastic histologic type and had a higher incidence of lymph node metastasis and a worse prognosis than those without regional variations. Thus, the histologic diversity within a carcinoma is thought to be important for determining the prognosis of patients with colorectal cancer.

Adenocarcinoma↗
PubMed1993

Activity of the carbapenem panipenem and role of the OprD (D2) protein in its diffusion through the Pseudomonas aeruginosa outer membrane.

Evidence of permeation of panipenem through the OprD (D2) channel of Pseudomonas aeruginosa outer membrane was shown by using OprD protein-producing and -nonproducing strains which contained plasmid pHN4, which codes for L-1 beta-lactamase of Xanthomonas maltophilia. Permeation by panipenem was determined by measuring hydrolysis of the carbapenem by beta-lactamase in the periplasmic space. Permeation by panipenem was also determined by counting uptake of [14C]panipenem into P. aeruginosa PAO1 and its OprD protein-deficient mutant, and this permeation of PAO1 was inhibited by L-lysine. These results indicate that panipenem, as well as imipenem, uses the OprD channel, which functions as a specific channel for diffusion of basic amino acids. Panipenem and imipenem showed stronger activities against PAO1 and clinical isolates in human serum than in Mueller-Hinton broth, which contains more amino acids than human serum does. The activities of the carbapenems were reduced by addition of L-lysine to human serum. Similar results were obtained with mouse serum and ascitic fluid. In contrast, such a change in the activities of carbapenems was not observed with an OprD protein-deficient mutant, suggesting that the main reason for the strong activities of carbapenems in biological fluids is a decrease in competition between the antibiotics and basic amino acids for permeation through the OprD channel. Panipenem and imipenem showed much stronger therapeutic efficacies against experimental infections with P. aeruginosa in mice than did the reference antibiotics. Their in vivo activities were more consistent with their MICs in biological fluids than with those in Mueller-Hinton broth.

Animals↗
PubMed1993

Safety and accuracy of dipyridamole thallium myocardial scintigraphy in elderly patients.

This study examined mainly the adverse effects of 201Tl myocardial scintigraphy with dipyridamole (D-Tl) in 73 elderly patients over 70 years old in comparison with those in 65 younger patients. Fifty-five of 73 elderly patients (75%) and 49 of 65 younger patients (75%) had a persistent or dipyridamole-induced perfusion defect on D-Tl. The hemodynamic changes induced by dipyridamole as well as the incidence of cardiac and noncardiac adverse effects were similar in both groups and no serious adverse effect occurred in either group. Secondly, we examined the procedure's usefulness for detecting ischemic heart disease in elderly and younger patients. Dipyridamole induced perfusion defect was noted in 21 elderly patients and in 24 younger patients (N.S.). Among the patients in whom coronary angiography was performed, significant coronary artery stenosis was found in 5 of 8 elderly patients and 17 of 20 young patients (N.S.). In patients with one or two-vessel disease, the area with dipyridamole induced ischemia was concordant with the stenotic area seen on coronary angiography in 3 of 3 elderly patients and 12 of 13 younger patients (N.S.). Thus, the safety and usefulness of D-Tl for detecting myocardial ischemia were comparable in elderly and young patients.

Age Factors↗