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Biomedical subjects

T Komatsu

Publications and source records attributed to T Komatsu.

At least 217 records · Page 12Linked to original sources

Structure and solution properties of lipidheme-microsphere.

Triglyceride microsphere emulsified with phospholipid derivative of heme (5,10,15,20-tetrakis[alpha,alpha,alpha,alpha-o-[2,2-dimethyl-20- [2-(trimethylammonioethoxy) phosphonatoxy]eicosanamido]phenyl]porphinatoiron(II); lipidheme) provides a totally synthetic artificial red cell (lipidheme-microsphere; LH-M). Its structure, solution properties and O2 binding ability are described. The particle diameter of the LH-M was ca. 90 nmø elucidated by electron microscopy. Viscosity of the LH-M suspension (approximately 1.5 cP) was much lower than that of human blood and the viscosity of mixed system of LH-M/human blood (1/1(v/v)) was 2.5 cP. Specific gravity, osmotic pressure, and colloid osmotic pressure of the LH-M suspension also satisfied the physiological needs. The LH-M can bind O2 reversibly in response to O2 pressure (P50(O2): 41 torr (pH 7.4, 37 degrees C)). O2 solubility of the LH-M was more than that of human blood caused by its high heme concentration.

Blood Substitutes↗

Two types of totally artificial red blood cell substitutes liposome embedded heme(L/H) and lipidheme/microsphere(LHM).

Two types of totally artificial oxygen carriers were produced (1)by embedding synthetic lipidhemes (as oxygen carriers) in bilayers of liposomes as vehicles of lipidhemes (L/H) and (2)by covering clinically available fat droplets (triglyceride microspheres) with synthetic lipidhemes (LHM). Fat droplets were used as vehicles of lipidhemes. Their oxygen carrying ability in vivo was examined in beagles undergoing hemorrhagic shock. L/H delivered 15.7 to 19.2% of total oxygen delivery. From 12.7 to 24.4% of total oxygen consumption was from L/H. LHM delivered 11.6 to 7.3% of total oxygen delivery. From 13.1 to 16.4% of total oxygen consumption was from LHM. These totally synthetic red blood cell substitutes can be candidates for future clinical testing.

Animals↗

Lipidheme-microsphere (LH-M). A new type of totally synthetic oxygen carrier and its oxygen carrying ability.

We have succeeded in synthesizing a new type of totally artificial oxygen carrier which was produced by covering oil droplets (microsphere) with synthetic hemes (LH-M). We studied its oxygen-transporting ability in hemorrhagic dogs. Four beagles weighing about 8 kg were studied. Under controlled ventilation, exchange-transfusion of 30 ml/kg was carried out. Cardiac output, hemoglobin and LH-M concentration in the blood, and blood gas were measured to 5 hours after intravenous injection of LH-M solution. LH-M delivered 15.7 to 22.3 ml/min (11 to 16%) of oxygen to the tissue and 5.5 to 8.2 ml/min (11 to 17%) of oxygen was consumed from LH-M to 5 hours after intravenous injection. Its half-life time in the blood stream was about 12 hours. It was confirmed that LH-M transported oxygen and released it to the tissue in vivo.

Animals↗

[A case of suspected occupational asthma in an orthopedist, due to cast materials containing MDI].

A 38-year-old male presented complaining of an asthma attack. He had a past history of allergic rhinitis and conjunctivitis, family history of bronchial asthma and atopic dermatitis. He was an orthopedist who had been using cast materials containing methylene diphenyl isocyanate (MDI) for one year, and had developed an early asthmatic response while handling the casts. An acetylcholine inhalation test was done and his value was 20000 micrograms/ml. The scratch test for the cast materials was negative though the inhalation challenge test was positive. We suspected that the patient was suffering from bronchial asthma induced by MDI contained in the cast materials. Studies using isocyanates conjugated with human serum albumin were performed. The results were as follows: IgE-RAST negative, ELISA demonstrated the existence of specific IgG for both toluene diisocyanate (TDI) and MDI, as well as IgG4 for both TDI and MDI. The cast contained MDI but not TDI. We therefore considered TDI to be cross-reactant. It was likely that chronic exposure enhancing specific IgG4 and specific IgG might have caused the high IgG4 value. This is the first case of occupational asthma in an orthopedist due to isocyanates.

Adult↗

[Changes in urine oxygen tension (PuO2) during anesthesia with isoflurane and sevoflurane].

Leonhardt and coworkers have suggested that PuO2 may indicate degree of renal medullary perfusion and function. The changes in PuO2 during N2O-O2-isoflurane anesthesia (GOI) and N2O-O2-sevoflurane anesthesia (GOS) were studied in 20 patients (GOI group: 10 cases, GOS group: 10 cases) who underwent elective surgeries. In the GOI group, PuO2 decreased significantly 30 and 60 minutes after the beginning of surgical incision, and it returned to the previous value immediately after the cessation of isoflurane. In the GOS group PuO2 decreased starting 30 minutes after the beginning of surgical incision until 10 minutes after the cessation of sevoflurane. These results suggest that isoflurane and sevoflurane administration caused a reduction in renal medullary perfusion, and that the low perfusion during sevoflurane anesthesia lasted longer than during isoflurane anesthesia. Measurement of PuO2 has a number of problems, but we believe that PuO2 is useful as an indicator of renal medullary blood flow.

Adult↗

Neurotoxic effects of 2,5-hexanedione on rapidly growing unmyelinated peripheral nerve axons of a rat fetus: dose-effect relationship.

To investigate the potential neurotoxicity of 2,5-hexanedione (2,5HD) on developing axons we examined peripheral nerves of rat fetuses. Pregnant female Sprague-Dawley rats were injected subcutaneously with 680 mg/kg of 2,5HD once a day from Day 12 of gestation (GD12) to GD16 in one group and with 340 mg/kg of 2,5HD once a day from GD12 to GD20 in the other group. On GD20 live fetuses were removed from the uteri and their sciatic nerves were examined morphologically. By electron microscopical observations, affected nerves revealed axons which were aggregated and fused together, but there were no axons aggregated with neurofilaments. The diameter distributions of axons revealed an increase in the number of small-size axons in the nerves of the 340 mg/kg group and showed an enlargement of part of the axons in the nerves of the 680 mg/kg group, suggested by the appearance of a second peak at a diameter larger than that of the first peak.

Animals↗

Immunohistochemical analysis of p53 protein over-expression in endometrial carcinomas: inverse correlation with sex steroid receptor status.

Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with over-expression of p53 protein. To examine the significance of p53 gene alteration in endometrial carcinomas, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 30 endometrial carcinomas as well as in 64 normal endometria. The presence or absence of correlation of p53 over-expression with the clinicopathological features and with the immunohistochemical expression of sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in none of 64 normal endometria, but was identified in 5 of the 30 (16.7%) endometrial carcinomas. All 5 of the p53-positive tumours developed in women more than 3 years post-menopause, whereas the carcinomas in 5 pre-menopausal women and 3 women less than 3 years post-menopause were p53-negative. None of the 5 p53-positive carcinomas was associated with adjacent endometrial hyperplasia. Two of the 5 p53-positive tumours showed non-endometrioid histology: serous papillary and clear cell carcinomas. In contrast, 6 carcinomas accompanied by adjacent hyperplasia were p53-negative. In addition, ER and/or PR expression was found in none of the 5 p53-positive tumours, but was present in 21 of the 25 p53-negative tumours (p < 0.01). These clinicopathological features of p53-positive carcinomas and the inverse correlation of p53 immunoreactivity with sex steroid receptor status suggest that p53 over-expression is frequent in a specific category of endometrial carcinoma, presumably oestrogen-unrelated tumours.

Adult↗

Anastomosis of occipital artery to anterior inferior cerebellar artery with interposition of superficial temporal artery. Case report.

A 56-year-old man with vertebrobasilar insufficiency and associated findings including quadriparesis, dysarthria, cerebellar ataxia, nystagmus, and somnolence underwent left occipital artery (OA) to anterior inferior cerebellar artery (AICA) anastomosis with interposition of a superficial temporal artery (STA) graft. This procedure was chosen because cerebral angiograms demonstrated occlusion of the right vertebral artery (V3) and severe stenosis of the V4 segment of the left vertebral artery, with perfusion of the territory of the left posterior inferior cerebellar artery via the ipsilateral AICA, and because dissection of the OA is a relatively difficult and time-consuming procedure. Dissection of the STA, on the other hand, is much easier. Preoperative measurements of local cerebral blood flow in the vertebrobasilar circulation before and after intravenous administration of acetazolamide (500 mg) were obtained, and demonstrated low flow and hemodynamic compromise in the posterior circulation. The patient's hemodynamic and neurological status improved following surgery. In this report, we present a new and simplified method of OA-AICA anastomosis with interposition of STA graft.

Anastomosis, Surgical↗

Synthesis of porphinatoirons having an alkyl amphiphilic chain and their O2 binding properties in lipid bilayers.

Synthesis and characterization of two amphiphilic tetraphenylporphinatoiron complexes having a glycerophosphocholine or an alkyl phosphoserine group are described. These porphinatoiron(II) complexes with 1-dodecyl-2-methyl-imidazole (L2MIm) were efficiently embedded in the bilayer of a phospholipid vesicle due to their high compatibility with lipids, similar to the heme substituted with four alkyl amphiphilic chains (lipid-heme). Oxygen transporting ability of the phospholipid vesicles embedded with hemes were similar to that of hemoglobin (Hb) in red blood cells.

Carbon Monoxide↗

Transient unilateral catalepsy and right parietal damage.

We describe the appearance of transient catalepsy of the left upper extremity in a patient without previous psychiatric illness after a right parietal subcortical hemorrhage. This case, and five other available cases in the relevant literature, demonstrates that catalepsy can be produced by right parietal damage.

Aged↗

Purification of a factor which provides a costimulatory signal for gamma interferon production.

A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose. It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis. It induced IFN-gamma production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate- and nylon wool-adherent cells. Anti-CD3 MAb induced the highest level of production of the three. The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-gamma in these cells. The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA. However, the factor failed to stimulate IFN-gamma production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed. Treatment with pronase or heat abolished these activities. These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-gamma production in resting T or natural killer cells. It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).

Animals↗

Characterization of a temperature-sensitive influenza B virus mutant defective in neuraminidase.

ts5, a temperature-sensitive mutant of influenza B virus, belongs to one of seven recombination groups. When the mutant infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious virus was produced at very low levels compared with the yield at the permissive temperature (32 degrees C) and hemagglutinating and enzymatic activities were undetectable. However, viral protein synthesis and transport of hemagglutinin (HA) and neuraminidase (NA) to the cell surface were not affected. The NA was found as a monomer within cells even at 32 degrees C, in contrast to wild-type virus NA, existing mostly as an oligomer, but the mutant had oligomeric NA, like the wild-type virus. Its enzymatic activity was more thermolabile than that of wild-type virus. Despite the low yield, large aggregates of progeny virus particles were found to accumulate on the cell surface at the nonpermissive temperature, and these aggregates were broken by treatment with bacterial neuraminidase, with the concomitant appearance of hemagglutinating activity, suggesting that NA prevents the aggregation of progeny virus by removal of neuraminic acid from HA and cell receptor, allowing its release from the cells. Further treatment with trypsin resulted in the recovery of infectivity. When bacterial NA was added to the culture early in infection, many hemagglutinable infectious virus was produced. We also suggest that the removal of neuraminic acid from HA by NA is essential for the subsequent cleavage of HA by cellular protease. Nucleotide sequence analysis of RNA segment 6 revealed that ts5 encoded five amino acid changes in the NA molecule but not in NB.

Amino Acid Sequence↗

Assessment of the variability in coupling intervals of ventricular premature contractions.

BACKGROUND: The coupling interval of ventricular premature contraction is relatively constant in some patients, while it varies in others. The clinical implications of this variability in the coupling intervals of ventricular premature contractions remains to be clarified. METHODS: Ambulatory electrocardiograms were recorded in 48 patients who had 2000 or more ventricular premature contractions per day. In each subject, 24 h ambulatory electrocardiograms were recorded in the absence of antiarrhythmic drug (control), and during treatment with various antiarrhythmic drugs. Data on R-R intervals were obtained using a Marquette 8000T, and transmitted to a personal computer. For each of the control recording, an R-R interval scatterplot was constructed by plotting the coupling intervals of ventricular premature contractions as a function of the preceding R-R intervals of normal sinus beats. The standard deviation of the coupling intervals (SDNV), that of the preceding R-R intervals (SDNN), and their ratio (SDNV/SDNN) were calculated. RESULTS: At control recording, two primary R-R scatterplot patterns were recognized; 1) Fixed, where the coupling intervals remained constant at various preceding R-R intervals (SDNV/SDNN < 0.5 and SDNV < 50 msec) (n = 29), and 2) Variable, where the coupling intervals showed a much greater (n = 19). The prevalence of organic heart disease was higher in the Variable group than in the Fixed group (47% vs 14%, p < 0.05). SDNV/SDNN was higher in patients with organic heart disease than in those without (0.62 +/- 0.34 vs 0.44 +/- 0.23, p < 0.05). The efficacy of antiarrhythmic drugs was compared between the two groups. A reduction of 80% or more in the total number of ventricular premature contractions was considered effective. Class Ia, Ib, and Ic drugs had almost the same efficacy in the Fixed and Variable groups (Ia, 43% and 41%; Ib, 36% and 22%; Ic, 64% and 63%, respectively). Class II drugs (beta-blockers) were more effective in the Fixed group than in the Variable group (50% vs 0%, p < 0.05). CONCLUSION: The R-R interval scatterplot of ambulatory electrocardiograms was useful in exploring the variability in the coupling intervals of ventricular premature contractions, and may help to predict the efficacy of antiarrhythmic drugs.

Adolescent↗

Epizootiological study of hantavirus infection among Rattus norvegicus in Tokyo Bay area, Japan.

The prevalence of antibodies against hantavirus in 413 rats (Rattus norvegicus) captured in eight regions of the Tokyo Bay area from 1983 to 1992 were examined by the indirect fluorescent antibody test. Antibody-positive rats were found in Tokyo Port in 1983 (34.8%), 1984 (25.9%), 1985 (22.0%) and 1986 (15.6%), in Kasai Seaside Park in 1989 (3.2%) and 1990 (4.2%) and in Chiba Port in 1990 (6.7%). In Tokyo Port, antibody-positive rats were found in any season in 1984 and 1985, and seroprevalences among two age groups, i. e., less than six months and six or more months of age were 18.1% and 28.4%, respectively. Three virus strains were isolated from rats captured on reclaimed land No. 13 in Tokyo Port in 1985 and named TQR-23, TQR-48 and TQR-50. These strains were antigenically identical with other rat strains, e. g., strain SR-11 and TR-352 but were discriminated from 76-118 strain by the neutralization test. Until 1990, persistence of hantavirus among rats inhabiting the Tokyo Bay area was demonstrated and hantavirus may be continuously prevalent in rats in this area.

Animals↗