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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Lecithinized superoxide dismutase attenuates phorbol myristate acetate-induced injury in isolated dog lung.

Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant human CuZn superoxide dismutase, has a higher affinity for cells such as polymorphonuclear leukocytes and endothelial cells than recombinant human CuZn superoxide dismutase has. We determined the protective effects of lecithinized superoxide dismutase on the increased microvascular permeability induced by phorbol myristate acetate (PMA) in isolated dog lungs. Microvascular permeability was assessed by the capillary filtration coefficient (Kf,c) and solvent drag reflection coefficient (sigma(f)). PMA (13.3 microg) increased microvascular permeability, as evidenced by an increase in Kf,c and the small sigma(f) value. Lecithinized superoxide dismutase at both low (4800 U) and high doses (48,000 U) inhibited the PMA-induced increase in Kf,c, but only the high dose of lecithinized superoxide dismutase attenuated the decrease in sigma(f). Recombinant human CuZn superoxide dismutase did not affect the PMA-induced increase in vascular permeability at either a low (4800 U) or a high dose (48,000 U). These findings suggest that lecithinized superoxide dismutase has a protective effect against oxygen radical-induced lung injury in isolated dog lungs.

Animals↗
PubMed1998

Meningeal melanocytoma in the left frontal region.

We report a rare case of meningeal melanocytoma in the left frontal region. A 45-year-old man complained of a headache. Magnetic resonance (MR) scanning showed characteristic patterns: a slightly high signal intensity mass in the left frontal region on the T1-weighted image and a low signal intensity on the T2-weighted image. The patient underwent gross total removal of the tumor. The postoperative course was uneventful. After two years, there was a small local recurrence. The histological finding of the tumor showed meningeal melanocytoma. To our knowledge, this is the second published report of a meningeal melanocytoma in the supratentorial region.

Brain Neoplasms↗
PubMed1998

Churg-Strauss syndrome (allergic granulomatous angitis) presenting with ileus caused by ischemic ileal ulcer.

We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10-15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis.

Adult↗
PubMed1998

Prenatally diagnosed cystic lymphangioma in infants.

BACKGROUND/PURPOSE: Prenatally diagnosed cystic lymphangioma (CL) is often associated with chromosomal anomalies, hydrops fetalis, and, in the case of cervical CL, occasionally respiratory distress just after birth. Often it is difficult to treat prenatally diagnosed CL because of the large size and associated symptoms. METHODS: Between 1988 and 1997, 11 cases of prenatally diagnosed CL were treated. Five pregnancies were terminated electively and one aborted spontaneously (nondelivered, non-D group), and another five delivered (delivered, D group). Thirteen infants nondiagnosed prenatally were also seen in the same period (prenatally nondiagnosed, without pre-D group). RESULTS: In the non-D group, massive CLs were diagnosed by ultrasound scan between 16 and 20 weeks' gestation. They occurred in the head and neck in all six cases, and four had associated pleural effusions or hydrops. In the D group, CL occurred in the face and neck in four cases. Three were born by cesarean section with neonatologists and surgeons standing by, then transferred to our hospital immediately after birth. Respiratory distress appeared in two cases; tracheostomy was carried out in one case. One patient with a huge CL in the chest and abdominal wall necessitated partial resection after OK-432 sclerotherapy. In the without pre-D group, there was CL in the face or neck in 10 cases, abdominal wall in two cases, and chest wall in one case. Respiratory distress was observed in three cases of cervical CL, and tracheostomy was required in two cases. One patient with hypoxic brain damage sequela died of pneumonia afterward. CONCLUSIONS: Prenatal diagnosis permits planned delivery, prompt postnatal resuscitation, and improve prognosis. Infants with massive CL diagnosed early in pregnancy have other associated anomalies as well as hydrops fetalis, and a poor outcome or difficult management can be expected.

Diagnosis, Differential↗
PubMed1998

Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema.

To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven patients with HAPE at its early stage. We measured cell counts, biochemical contents, and concentrations of pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid (BALF). All patients showed increased counts for total cells, alveolar macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary hypertension with normal wedge pressure. Both the driving pressure obtained as pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were significantly correlated with the concentrations of IL-6 and TNF-alpha in the BALF. These findings suggest that the inflammatory cytokines play a role at the early stage of HAPE and might be related to pulmonary hypertension.

Adult↗
PubMed1998

Pharmacokinetic and pharmacodynamic evaluation for tissue-selective inhibition of cholesterol synthesis by pravastatin.

The tissue-selective inhibition of cholesterol synthesis by pravastatin was evaluated pharmacokinetically and pharmacodynamically. Plasma, tissue, urine, and bile concentrations were measured after i.v. bolus injection of pravastatin to rats at various doses. The total body clearance and steady state volume of distribution decreased with increasing dose. A saturable biliary excretion was also observed. The time course of plasma and liver concentrations was described by a three-compartment model, consisting of a central compartment, a deep compartment with an nonsaturable uptake process, and a shallow compartment with saturable uptake and nonsaturable elimination processes. It suggests that a mechanism for the decrease in the total body clearance and distribution volume might be explained by a saturation of pravastatin uptake into the liver. Plasma concentration data after oral administration was also fitted to the same model by connecting an absorption compartment to the shallow compartment. The inhibitory activity of pravastatin against cholesterol synthesis in liver could be related to the concentration in the shallow compartment via a sigmoidal Emax model and the obtained pharmacodynamic parameters were comparable to those in vitro. Results suggest that the carrier-mediated hepatic uptake of pravastatin is actually responsible for the hepatoselective inhibition of cholesterol synthesis under physiological conditions.

Administration, Oral↗
PubMed1998

Coagulation abnormalities and thrombotic microangiopathy following bone marrow transplantation from HLA-matched unrelated donors in patients with hematological malignancies.

Thrombotic microangiopathy is a well-known heterogeneous disorder that occurs as a complication of allogenic bone marrow transplantation (BMT). We evaluated 12 consecutive patients receiving HLA-matched unrelated BMT and 12 consecutive recipients of HLA-identical related BMT for the development of bone marrow transplantation-associated thrombotic microangiopathy (BMT-TM) on days 30 and 60 following BMT. A diagnosis was made in four of 12 (33.3%) unrelated compared to none of 12 (0%) HLA-identical cases. Levels of serum lactic dehydrogenase (LDH), fibrin degraded products (FDP) and de novo thrombocytopenia were elevated in eight of 12 patients (66.7%) receiving unrelated donor BMT, and none of the patients receiving related donor BMT. Our findings suggest clinical or subclinical microangiopathic changes may occur frequently in unrelated donor BMT. FDP elevation is possibly an important marker of microangiopathic changes as early complications of BMT.

Adolescent↗
PubMed1998

Neurotransmitters of vestibular commissural inhibition in the cat.

The present study examined transmitters that regulate commissural inhibition. Extracellular spikes of a single vestibular neuron were recorded in decerebrated cats. Multibarreled electrodes were filled with transmitter candidates (GABA and glycine), their specific antagonists (bicuculline, strychnine) and 2 M NaCl for extracellular recording. After isolation of a type I neuron, chemicals were iontophoretically applied to examine their effects on the activity of the neuron. The results were as follows. Commissural inhibition caused by electrical stimulation of the contralateral labyrinth was not abolished by the application of strychnine (a glycine antagonist), but was abolished by bicuculline (a GABA antagonist). Commissural inhibition was not abolished by phaclofen. Some bicuculline-sensitive neurons, with a short-latency commissural inhibition (presumably disynaptic inhibition), showed spacial summation when the conditioning stimulation (contralateral vestibular nerve stimulation) was applied with the test stimulation (vestibular nucleus stimulation). It was concluded that commissural inhibition was activated by the GABAA receptor, but not by the GABAB receptor, that the inhibitory type I neurons located in the contralateral vestibular nucleus were GABAergic, and that inhibitory type II neurons were also GABAergic neurons.

Animals↗
PubMed1998

Spontaneous regression of primary mediastinal germ cell tumor.

A case of primary mediastinal germ cell tumor, which demonstrated spontaneous regression, is presented. The serum human chorionic gonadotropin level was elevated on admission and then decreased to the normal range with decrease in the size of the anterior mediastinal mass. Thoracotomy was performed with artificial replacement by grafts between the bilateral brachiocephalic veins and the right atrium. Histological diagnosis of combined teratoma with seminoma was made. After subsequent chemotherapy, the patient has remained alive without recurrence for over 10 years.

Adult↗
PubMed1998

Pharmacokinetic evaluation of amphotericin B in lung tissue: lung lymph distribution after intravenous injection and airspace distribution after aerosolization and inhalation of amphotericin B.

We have studied the pharmacokinetics of amphotericin B (AmB) in lung lymph circulation and bronchial-wash fluid after intravenous infusion and inhalation, respectively. For two experiments with awake sheep, we used lung lymph fistulas and tracheotomy. In experiment 1, AmB concentrations in plasma and lung lymph after intravenous infusion of AmB (1 mg/kg of body weight) over 1.5 h were measured. The mean peak in plasma level was 756.0 +/- 188.8 ng/ml at 3 h after the start of infusion, and the level then decreased gradually to 194.8 +/- 28.9 ng/ml at 24 h. The stable and maximal levels in lung lymph last 5 to 9 h after the start of AmB infusion. The concentrations in lung lymph after 9 h were slightly higher than those in plasma. Thus, the lung lymph-to-plasma ratio of AmB concentrations increased gradually during infusion, and the ratio was more than 1.0 after the end of infusion, suggesting that AmB could be easily moved from plasma to pulmonary interstitium and/or lung lymph circulation. In another experiment, 5 or 30 mg of aerosol AmB was inhaled, and the concentration of AmB in the bronchial-wash fluid was determined by bronchoalveolar lavage. The peak AmB concentration in the fluid was observed at 0.5 h. After that, AmB was slowly eliminated over 24 h. The area under the concentration-time curve for 30 mg of inhaled AmB was higher than that for 5 mg, but maximum concentrations of AmB in serum for 5 and 30 mg were almost similar. These observations identify the pharmacokinetic characteristics of AmB in the lung and may provide a new insight into the strategy for clinical treatment of fungal pneumonia.

Administration, Inhalation↗
PubMed1998

Pulmonary vasoconstriction induced by mitral valve obstruction in sheep.

We hypothesized that left atrial hypertension results in pulmonary vasoconstriction, which is obscured by the expected passive decrease in pulmonary vascular resistance. The objectives of this study were to demonstrate and quantify the vasoconstrictive changes that occur in the pulmonary circulation during experimental left atrial hypertension, to determine the site of vasoconstriction, and to explore its mechanism. Sheep were instrumented for measurement of pulmonary arterial (Ppa), left atrial (Pla), and systemic arterial pressures (Psa) with a Foley balloon catheter to variably obstruct the mitral valve. Distal pulmonary arterial wedge pressure (Ppaw) was determined by using a 5-Fr Swan-Ganz catheter that was advanced until it wedged with the balloon deflated. Cardiac output (CO) was estimated by thermodilution; pulmonary vascular resistances (PVR) were calculated as mean (Ppa - Pla)/CO = total PVR, (Ppa - Ppaw)/CO = upstream PVR, and (Ppaw - Pla)/CO = downstream PVR. We studied 15 awake sheep at baseline and during increases in Pla of 10 and 20 cmH2O, with and without inhalation of approximately 36 parts per million of nitric oxide. Left atrial hypertension resulted in elevation of Ppa. CO decreased only slightly at both levels of Pla elevation. Nitric oxide inhalation caused a significant decrease in PVR, which was greater as Pla increased. This vasodilator effect was most striking in downstream vessels. Experiments with phentolamine, atropine, and ibuprofen failed to reveal the mechanism of the reactive pulmonary vasoconstriction.

Administration, Inhalation↗
PubMed1998

Pulmonary infection with Mycobacterium avium-intracellulare leads to air trapping distal to the small airways.

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.

Airway Obstruction↗
PubMed1998

Inhaled nitric oxide reduces lung fluid filtration after endotoxin in awake sheep.

We studied the effect on lung fluid filtration of 37.6 ppm inhaled nitric oxide (NO) imposed for 1 h 2.5 h after endotoxin in seven awake sheep, with seven control subjects. The effects of NO on the longitudinal distribution of pulmonary vascular resistance (PVR) before and after endotoxin were specifically addressed in six sheep. Following endotoxin, sheep developed respiratory distress; PaO2, the alveolar-arterial oxygen tension difference (AaPO2) and venous admixture (Q S/Q T) changed significantly, as did the pulmonary artery pressure (Ppa), PVR, and lung lymph flow (Q L). Inhaled NO reduced Ppa and PVR by 50%; Q L decreased from 7.8 +/- 0.34 ml/15 min to 4.7 +/- 0.80 ml/15 min (mean +/- SEM), and lymph protein clearance from 4.9 +/- 0.18 ml/15 min to 3.6 +/- 0.75 ml/15 min. Lymph/plasma protein concentration ratio (L/P) increased from 0.63 +/- 0.016 to 0.72 +/- 0.006, concomitant with the decrease in Q L. The L/P - Q L relationships shifted from left, at baseline, to the right during endotoxemia, as did the permeability surface product (PS) isolines. The rightward shift was significantly less in the NO group. Inhaled NO significantly improved PaO2, AaPO2, and Q S/Q T, reduced the increase in pulmonary microwedge pressure back to baseline and decreased upstream and downstream PVR at 3.0 through 4. 0 h. We conclude that, in sheep, inhaled NO reduces lung fluid filtration by decreasing microvascular pressure and apparently also by declining the enhanced microvascular permeability during the late phase of endotoxemia.

Animals↗
PubMed1998

Pharmacokinetic and pharmacodynamic consequences of thiopental in renal dysfunction rats: evaluation with electroencephalography.

The purpose of this work was to investigate the disposition characteristics and pharmacodynamics of a barbiturate, thiopental, in renal dysfunction rats. Normal and renal dysfunction rats were infused with 40 and 20 mg/kg of thiopental, respectively. The quantitative electroencephalographic (EEG) method was used as the surrogate measure of pharmacological response. Signals from two electrodes fitted on the skull of rats were continuously measured, recorded and subjected to off-line analysis. Total amplitude (0.5-29.9Hz) from aperiodic analysis was taken as the EEG parameter. Thiopental concentration in plasma and cerebrospinal fluid (CSF) was assayed by an HPLC method. Steady-state volume of distribution was increased in renal dysfunction rats due to decreased plasma protein binding, while no change in clearance or volume of distribution based on the plasma unbound concentration was observed. Amplitude changes induced by thiopental in both normal and renal dysfunction rats were characterized by the sigmoidal Emax model. The unbound plasma concentration at half maximal effect was lowered by 30% in renal dysfunction rats as compared to the normal rats. In addition to considerable alteration in the pharmacokinetics of thiopental, it was also evident that renal impairment is associated with an increase in apparent pharmacological sensitivity, which is related to affinity.

Analysis of Variance↗
PubMed1998

Effects of lung volume reduction surgery on exercise pulmonary hemodynamics in severe emphysema.

STUDY OBJECTIVES: To clarify the effects of lung volume reduction surgery (LVRS) on pulmonary hemodynamics in severe emphysema and to evaluate the role of pulmonary circulation in the increased exercise performance after LVRS. DESIGN: In eight male patients with severe emphysema, we measured pulmonary artery (Ppa) and occlusion (Pop) pressures and cardiac output through a Swan-Ganz thermodilution catheter, and we calculated cardiac index (CI), pulmonary vascular resistance index, and driving pressure. The study was performed at rest and during exercise using a supine bicycle ergometer at 25 W, under room air and O2 inhalation. Exercise performance was expressed as endurance time in minutes. Pulmonary function tests were performed. The patients underwent an identical study before and 6 months after LVRS. RESULTS: The patients' exercise performance was significantly increased after LVRS (5.9+/-1.8 min) compared with that before LVRS (3.6+/-0.9 min). LVRS resulted in a significant increase in FEV1 and a significant decrease in residual volume. Before LVRS, Ppa was increased both at rest and during exercise. LVRS did not change rest or exercise Ppa. LVRS significantly decreased Pop during exercise from 24+/-10 mm Hg to 18+/-7 mm Hg. CI at rest and during exercise were significantly increased after LVRS. O2 administration significantly decreased Ppa during exercise both before and after LVRS. CONCLUSIONS: These findings suggest that LVRS does not improve pulmonary hypertension at rest or during exercise in patients with severe emphysema and that elevated Pop during exercise before LVRS is probably related to lung mechanic abnormalities.

Aged↗
PubMed1998

[Langerhans cell histiocytosis in the hypothalamus: a case report].

A case of Langerhans cell histiocytosis (LCH) in the hypothalamus is presented. A 52 year old man with eosinophilic granuloma of the lung was referred to our hospital. He complained of headache, easy fatigability, high fever, and voiding large quantities of urine, but was otherwise asymptomatic. T1-weighted images demonstrated a small mass in the hypothalamus. After about six months, the mass had grown to 2 cm in diameter. Surgery was performed by a pterional approach and a biopsy specimen was collected. Light microscopic examination of sections of the biopsy specimen showed polymorphous cellular infiltration by histiocytic cells, eosinophils, neutrophils, and lymphocytes. Electron microscopy showed Langerhans cells and Birbeck granules in the cytoplasm. The histological diagnosis was LCH, multifocal type. After low-dose radiation therapy, the mass gradually decreased in size. The clinicopathological features, neuroradiological findings, and treatment are briefly discussed.

Combined Modality Therapy↗
PubMed1998

Analysis of uveitogenic sites in phosducin molecule.

PURPOSE: Phosducin, a retinal photoreceptor protein, induces experimental autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptides. METHODS: Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC. First, 13 peptides covering the entire sequence of phosducin were synthesized, and each was injected into the hind footpad of Lewis rats for immunization, and induction of EAU was examined clinically and histologically. Next, peptides that appeared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. RESULTS: Of the 13 peptides used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior chamber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and serous retinal detachment was found in cases of severe inflammation. Infiltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino acid sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunized with these peptides also exhibited high value on lymphocyte proliferation assay. CONCLUSION: Phosducin has 5 uveitogenic sites. Among others, one of them has potent and others weak uveitogenicity.

Amino Acid Sequence↗