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Biomedical subjects

N Konno

Publications and source records attributed to N Konno.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characterization of high-affinity binding sites for diisopropylfluorophosphate (DFP) from chicken spinal cord membranes.

The delayed neurotoxic organophosphate [3H]diisopropylfluorophosphate ([3H]DFP) binds with high affinity to membrane-bound proteins from the chicken spinal cord. The DFP binding proteins were solubilized from membrane preparations, using a detergent (CHAPS). The protein(s) sites that labeled with a low concentration of [3H]DFP, e.g. 10(-10)-10(-9) M, were defined as the high-affinity binding sites. The density (or concentration) of the high-affinity binding sites in protein(s) was determined by the difference between total and non-specific binding. The high-affinity binding sites were saturable, and the maximal amount of binding sites was estimated at 400 fmol/mg protein. [3H]DFP binding to solubilized proteins was not completely reversible. Concentration-dependent curves suggested that the [3H]DFP binding sites differ from the active sites of acetylcholinesterase, butyrylcholinesterase, and neuropathy target esterase, as well as from muscarinic acetylcholine receptors. The amount of DFP binding sites after a neurotoxic dose of tri-o-cresyl phosphate (TOCP) decreased markedly in membrane preparations from the chicken spinal cord. These results indicate that a TOCP metabolite(s) interacts with the DFP binding sites in vivo. Gel filtration chromatography of the solubilized membranes indicated at least two major high-affinity DFP binding proteins with apparent molecular weights of 300 and 110 kDa. The DFP binding sites corresponding to the 110 kDa protein were insensitive to eserine, a potent anti-cholinesterase agent.

Animals↗
PubMed1994

Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan.

The prevalence of thyroid dysfunction in relation to iodine intake was studied in adults (n = 1061) in five coastal areas of Japan that produce iodine-rich seaweed (kelp). The prevalence of hyperthyroidism (TSH < 0.15 mU/L) was similar in these areas, whereas that of hypothyroidism (TSH > 5.0 mU/L) varied from 0-9.7%. The relative frequency of above normal iodide concentration in the morning urine (> or = 75 mumol/L) [high urinary iodide (UI)] varied from 3.7%-30.3%. Together with previously reported results of a noncoastal city, the frequency of high UI correlated significantly with that of hypothyroidism with negative thyroid autoantibody (r = 0.829, n = 6, P < 0.05) but not with positive thyroid autoantibody (r = 0.278, NS) or with that of hyperthyroidism (r = 0.038, NS). Hypothyroidism was more prevalent in thyroid autoantibody-negative subjects with high UI (group II, 12.1%) than with normal UI (group I, 2.3%) (P < 0.001). The TSH [21.9(6.5-73.7)mU/L] (mean +/- SD) and thyroglobulin [288 (182-456) micrograms/L] levels in group II were significantly higher than the respective levels in group I [9.6(3.7-25.3)mU/L and 123 (38-399) micrograms/L] (P < 0.05). Free T4 of group II (9.9 +/- 3.9 pmol/L) was significantly lower than in group I (14.2 +/- 3.9 pmol/L) (P < 0.05). These results indicate that 1) the prevalence of hypothyroidism in iodine sufficient areas may be associated with the amount of iodine ingested; 2) hypothyroidism is more prevalent and marked in subjects consuming further excessive amounts of iodine; and 3) excessive intake of iodine should be considered an etiology of hypothyroidism in addition to chronic thyroiditis in these areas.

Adult↗
PubMed1994

[Screening for thyroid dysfunction in adults residing in Hokkaido Japan: in relation to urinary iodide concentration and thyroid autoantibodies].

The prevalence of thyroid dysfunction and its relation to thyroid autoantibodies (TAA) and urinary iodide concentration (UI) was studied in apparently healthy adults in Sapporo (n = 4110) (Sapporo group), and in five coastal areas of Hokkaido (n = 1061) (coastal group) which produce iodine-rich seaweed (kelp). The frequency of above normal UI (high UI) in the morning urinary samples of coastal group was 10.8%, significantly higher than that of Sapporo group (6.4%) (p < 0.001). Frequency of positive TAA in both groups were similar. In Sapporo group TAA was positive in 6.4% of males and 13.8% of females with an age-related increase. The overall prevalence of hyperthyroidism (TSH < 0.15 mU/L) in coastal group (0.6%) was similar to that in Sapporo group (1.1%), while that of hypothyroidism (TSH > 5.0 mU/L) in coastal group (3.8%) was significantly higher than that in Sapporo group (1.3%) (P < 0.001). The frequency of high UI correlated significantly with that of hypothyroidism with negative TAA (r = 0.829, P < 0.05), but not with positive TAA, or with that of hyperthyroidism. Hypothyroidism was more prevalent in TAA negative subjects with high UI than with normal UI. Moreover, serum TSH and thyroglobulin levels were higher and free T4 level was lower in former than in latter group. These results indicate that 1) the prevalence of TAA negative hypothyroidism in iodine sufficient areas may be associated with the amount of iodine ingested, 2) this hypothyroidism is more prevalent and marked in subjects consuming further excess amounts of iodine, and 3) excessive intake of iodine should be considered an etiology of hypothyroidism in addition to chronic thyroiditis in these areas.

Adult↗
PubMed1993

Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations.

OBJECTIVE: The present study was designed to investigate the prevalence of thyroid dysfunction and its relation to thyroid autoantibodies and urine iodide concentration in apparently healthy people residing in Sapporo, a city of northern Japan, where the iodine intake is high. DESIGN AND SUBJECTS: Serum TSH and thyroid autoantibodies, and urine iodide were measured in 4110 people (2931 men and 1179 women) (age 45.6 +/- 10.3 years (mean +/- SD)) who were recruited at the hospital for medical examinations. RESULTS: The thyroid autoantibodies were positive in 6.4% of males and 13.8% of females with an age-related increase. Of the people with positive antibodies, 87.2% had normal TSH values (0.15-5.0 mU/l) as measured by a sensitive assay. The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves' disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidenced by supranormal TSH, was 0.68% for males and 3.13% for females with an age-related increase. Of those with hypothyroidism, 45.5% were autoantibody positive. The overall prevalence of Hashimoto's thyroiditis was 13.11% for females and 6.15% for males. The urine iodide levels of hypothyroidism with a positive autoantibody of 38.5 (17.7-83.9) mumol/l and a negative autoantibody of 34.9 (17.9-67.9) mumol/l were both significantly higher than that of normal subjects (26.9 (14.6-49.6) mumol/l) (P < 0.01). When iodine intake was restricted for 6-8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group. CONCLUSIONS: This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing latent hypothyroidism.

Adult↗
PubMed1993

Clinical evaluation of the iodide/creatinine ratio of casual urine samples as an index of daily iodide excretion in a population study.

To assess the daily iodine intake in a population study, we have compared the validity and degree of reliability of the urine iodide/creatinine ratios and iodide concentrations of casual samples as a representative index of daily urine iodide excretion. The morning urine samples were obtained from apparently healthy 2,956 men and 1,182 women residing in Sapporo, Japan, and urine iodide was measured by an iodide selective electrode. The iodide/creatinine ratios was higher in women than in men, increasing more steeply with age in women than in men, due to a concomitant decrease in the urine creatinine level with age. The iodide concentration showed no age-related change. Similarly the daily urine iodide excretion measured in 22 control subjects by collecting 24-h urine specimens did not vary with age, while the iodide/creatinine ratio of these subjects increased with age. The correlation coefficient(r) of the iodide concentration with daily iodide excretion in the 95 observations of the 22 subjects was 0.832 (P < 0.001), higher than that of iodide/creatinine ratio with daily iodide excretion (0.699, P < 0.001). The 95% range of the iodide concentration in morning urine samples in the population (n = 4,138) was 9.0-70.3 mumol/L with a mean of 27.1 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Mitochondrial dysfunction observed in situ in cardiomyocytes of rats in experimental diabetes.

OBJECTIVE: The aim was to investigate effects of experimental diabetes and insulin treatment on heart myocytes, particularly on the mitochondrial function studied in situ in isolated cardiomyocytes. METHODS: 20 male Sprague-Dawley rats (140-160 g) were made diabetic by intraperitoneal streptozotocin, 70 mg.kg-1. Ten then received daily subcutaneous injections of ultra lente insulin (starting dose of 3 units.d-1) for 7-15 d from the 20th day after streptozotocin. There was a control group of 11 rats. The rats were killed 21-35 d after the induction of diabetes, and heart myocytes were isolated by collagenase digestion. The 45[Ca]2+ uptake of mitochondria in situ in permeabilised myocytes, the transmembrane potential gradient of mitochondria, and the respiration of myocytes, as well as the cell yield and cell [45Ca]2+ uptake, were examined. RESULTS: Mitochondrial uptake of [45Ca]2+ was significantly decreased in the diabetic group compared to control at cytosolic calcium concentrations between 760 nM and 44.6 microM. The mitochondrial potential of diabetic myocytes, estimated from the distribution of [3H]triphenylmethylphosphonium+, was slightly but significantly decreased from the control value. Cell respiration, measured polarographically in the presence of pyruvate and malate or succinate as oxidisable substrates, and with or without 2,4-dinitrophenol, was decreased by diabetes. The rapidly exchangeable [45Ca]2+ content in the myocyte with intact sarcolemmal membrane ("cell Ca2+ uptake") and the yield of cells from heart tissue were also diminished in diabetic rats. These changes were returned to normal by insulin treatment of 7 d or longer. CONCLUSIONS: Insulin deficiency at early stages causes defects of mitochondrial function detectable in situ in cardiomyocytes. This suggests the possibility that such alterations are causative factors in the development of diabetic cardiomyopathy.

Animals↗
PubMed1992

Study on reperfusion injury on sarcoplasmic reticulum in acute myocardial ischemia.

Reperfusion injury in early myocardial ischemia was studied in the dog with special reference to sarcoplasmic reticulum (SR) and contraction bands. Acute myocardial ischemia (I) was induced by occlusion of the left anterior descending coronary artery (LAD) for 10, 20 and 30 min followed by reperfusion for 15 min (R). Ca(++)-ATPase activity of SR in 10-min-R-Group was significantly reduced to 60% of control activity, but activity of 10-min-I-Group remained near the control level in subendomyocardium (Endo). ATPase activity in 30-min-I-Group diminished to 60% of control activity in Endo and it was similar for 30-min-R-Group. In ischemic myocardium, composition of major ATPase protein decreased significantly in 30-min-I-Group and similar reduction was observed in 20-min-R-Group in Endo. In morphology proportion of appearance of contraction bands in Endo was significantly increased in 20-min or longer-R-Groups. These results suggest that reperfusion injury is likely to occur when coronary artery is reflowed after 10 min of ischemia. This may be caused by increased intracellular Ca++ at a very early stage of reperfusion period, and reperfusion injury may be induced due to acceleration in the necrotic process of the membrane system in the myocytes during ischemia.

Animals↗
PubMed1992

Impairment of sarcolemmal permeability in the acute ischemic myocardium--a study with ionic lanthanum probe method.

Impairment of sarcolemmal permeability after the initiation of acute ischemic myocardial injury was studied using an ionic lanthanum (La3+) probe in electron microscopy. Acute ischemic myocardium was induced by ligation of the left anterior descending coronary artery in dogs. In normal cardiac myocytes La is localized exclusively in the extracellular space. i.e. on the glycocalyx, in the T-system and in intercalated discs, with normal fine structures. In ischemic myocardial cells, La deposits were found in the cytosolic space in 22% of subendocardial cells with mild to moderate, but non-necrotic, fine structural changes as early as 30 min. The number of myocytes with La deposition increased with advancing ischemic injury, and necrotic fine structural changes were recognized following ischemia for 60 min. These results indicate that deposition of La occurs before the appearance of irreversible morphologic alterations in ischemic myocardial cells, and suggest an increased permeability of the sarcolemma for Ca2+ and the development of degradation of plasma membrane integrity.

Animals↗
PubMed1991

Effects of hydrogen peroxide and hypochlorite on membrane potential of mitochondria in situ in rat heart cells.

Hydrogen peroxide (H2O2) and hypochlorite (HOCl) cause a variety of cellular dysfunctions. In this study we examined the effects of these agents on the electrical potential gradient across the inner membrane of mitochondria in situ in isolated rat heart myocytes. Myocytes were prepared by collagenase digestion and incubated in the presence of H2O2 or HOCl. Transmembrane electrical gradients were measured by distribution of [3H]triphenylmethylphosphonium+, a lipophilic cation. The particulate fraction was separated from the cytosolic compartment first by permeabilization using digitonin, followed by rapid centrifugal sedimentation through a bromododecane layer. We found that the mitochondrial membrane potential (161 +/- 7 mV, negative inside) was relatively well maintained under oxidant stress, i.e., the potential was decreased only at high concentrations of HOCl and H2O2 and gradually with time. The membrane potential of isolated rat heart mitochondria was affected similarly by H2O2 and HOCl in a concentration- and time-dependent manner. High concentrations of oxidants also reduced the cellular ATP level but did not significantly change the matrix volume. When the extra-mitochondrial free calcium concentration was increased in permeabilized myocytes, the transmembrane potential was decreased proportionally, and this decrease was potentiated further by H2O2. These results support the view that heart mitochondria are equipped with well-developed defense mechanisms against oxidants, but the action of H2O2 on the transmembrane electrical gradient is exacerbated by an increase in cytosolic calcium.

Animals↗
PubMed1991

[A comparison of measurements of serum free thyroxine concentration by equilibrium dialysis and ultrafiltration using undiluted serum].

We have examined the clinical usefulness for free thyroxine (FT4) measurement by equilibrium dialysis of undiluted serum and by radio-immunoassay of T4 concentration in the dialysate (ED/RIA). The results were compared with those by ultrafiltration of undiluted serum (UF/RIA), which is believed to offer the best possible approach towards estimation of in vitro serum level of FT4. The precision with both methods was excellent. There was a high degree of correlation of FT4 concentration by both methods (r = 0.831, p less than 0.001, n = 99). FT4 concentration by ED/RIA and UF/RIA methods agreed well for hyperthyroidism, hypothyroidism, normal pregnancy, and for low T4-binding globulin concentration. In nonthyroidal illness (NTI), FT4 levels were all within or above normal for UF/ED method, while some FT4 values in low T4 syndrome were below normal for ED/RIA method. The effect of progressive serum dilution on FT4 concentration was also examined for both methods. There was no fall in FT4 concentration in sera from normal, hyperthyroid patient and in serum with low T4 syndrome for both methods, but in a serum from low T3 syndrome, there was a fall in FT4 concentration by dilution with UF/RIA method, indicating that serum dilution with ED/RIA method might underestimate FT4 concentration in some NTI sera. From these results it is concluded that the present ED/RIA method is adaptable to clinical laboratory use as a reference standard method for FT4 measurement.

Adult↗
PubMed1990

Effects of age on susceptibility of chickens to delayed neurotoxicity due to triphenyl phosphite.

Triphenyl phosphite (TPP), which is widely used in the chemical industry, is known to produce delayed neurotoxicity in some experimental animals. The effects of aging on the susceptibility to TPP, its disposition and pharmacokinetics, and its in vitro degradation by liver homogenate were studied in chickens. Chickens aged 60 days or less at administration were not affected, but 10 of 15 chickens aged 90 to 180 days developed ataxia 10 to 12 days after the intravenous injection of TPP (50 mg/kg). TPP clearance from the blood and most of the tissues examined was faster in 45-day-old chickens than in 135-day-old chickens. The biological half-life of TPP in the blood was 23.2 min. in the younger group and 30.5 min. in the older group. In the in vitro experiment, the initial TPP concentration of 1.6 x 10(-5) M fell to less than half this level within 60 min. during incubation with liver homogenates from 45-day-old chickens, whereas with homogenates from 135-day-old chickens the level remained high. These results suggested that the age-specific susceptibility to TPP was related to the differences of the tissue load, which derived in part from differing levels of metabolic activity in the liver.

Aging↗
PubMed1989

Delayed neurotoxicity of triphenyl phosphite in hens: pharmacokinetic and biochemical studies.

The organophosphorus compound, triphenyl phosphite (TPP), caused ataxia in chickens 8-14 days after single po or iv administration. The po and iv ED50 values were 1414 and 35.4 mg/kg, respectively. Chickens which developed ataxia lost 14.4 +/- 2.5% (mean +/- SEM, n = 14) of their initial weight at 28 days and the paralyzed birds showed a severe reduction of 29.3 +/- 2.9% (n = 13) of their initial weight at death or at 28 days after dosing. For the first 4-hr interval after iv injection of 50 mg/kg, the elimination of TPP from plasma consisted of at least two exponential phases; the half-lives of the first and second phases were approximately 30 and 60 min, respectively. When the birds received 100 mg/kg (iv) fatty tissue showed the highest TPP concentration, e.g., 215 micrograms/g fresh wt at 6 hr postdosing. The half-life was approximately 24 hr. Among neural tissues, the sciatic nerve had the highest concentration, followed by the spinal cord, the cerebellum, and the cerebrum. The red muscles, such as adductor magnus, contained about 4-30 times as much TPP as did the white muscles, such as biceps brachii, 6 hr after treatment. Time course effects of TPP treatment on mitochondrial enzymes in leg skeletal muscles were examined by treating hens with 50 mg/kg (iv) and euthanizing the birds at 6 hr to 8 days postdosing. The creatine kinase (CK) activities of the adductor and the soleus were significantly decreased at 2 (48 hr), 4, and 8 days, and at 4 and 8 days postdosing, respectively. Adductor magnus and soleus succinate dehydrogenase (SDH) activities were decreased markedly at 24 and 48 hr, and at 2 (48 hr), 4, and 8 days, respectively. Cytochrome oxidase (COD) activity in adductor magnus and soleus did not decrease during the time course. Biceps femoris CK, SDH, and COD activities were not affected by TPP treatment at this dosage. These results suggest that TPP administration affects the mitochondrial metabolism in skeletal muscle, especially red muscle of chickens.

Animals↗
PubMed1989

Protection of acute ischemic myocardial injury by pharmacological intervention.

Pharmacological protection of acute ischemic myocardial injury was studied using diltiazem, bunazosin, coenzyme-Q10 (Co-Q), and nicorandil, in dogs of which the left anterior descending coronary artery was ligated for 60 min. Drugs were given intravenously prior to and/or during coronary ligation. Co-Q, bunazosin and diltiazem suppressed degradation of sarcoplasmic reticulum (SR) expressed as inhibitions of reduction in Ca++-dependent ATPase activity and degradation of major ATPase protein. Fine structures of ischemic myocardial cells were simultaneously retained as well. On the contrary, the effects of nicorandil on ischemic myocardial injury were few. It is likely that protection of ischemic myocardial injury could be expected with drugs which react with ischemic myocardium directly and inhibit excess inflow of extracellular Ca++ in ischemic myocardium.

Adenosine Triphosphatases↗
PubMed1989

Delayed neurotoxicity and toxicokinetics of leptophos in hens given repeatedly by low-dose intravenous injections.

The repeated intravenous injections (RIVInj) of 5 mg/kg/day leptophos [O-(4-bromo-2, 5-dichlorophenyl) O-methyl phenylphosphonothioate] for 3 consecutive days caused delayed ataxia in 4 out of 9 hens (44.4%). And one out of 9 hens (11.1%) given RIVInj of 3 mg/kg leptophos for 5 days was affected with ataxia. Twenty hens, however, which received a single intravenous injection (SIVInj) of 15 mg/kg leptophos did not exhibit any delayed neuropathic signs at all. Thus, delayed neurotoxicity was increased by the subdividing RIVInj of the critical dose which was shown in the SIVInj of leptophos. The leptophos concentration in plasma and liver decreased very rapidly after finish of either SIVInj or RIVInj. Although no significant differences were observed in the biological half life of leptophos in plasma by different dosages, the mean level of leptophos decreased significantly with frequency of injections. On the contrary, the evident accumulation of leptophos was observed in only sciatic nerve with RIVInj. Leg muscle maintained relatively high level of leptophos after the last injection. These results suggest that leptophos seems to transfer from blood to affinitive tissues such as sciatic nerve or leg muscles and to accumulate there easily in initial stage after repeated iv injections, and that this causes the enhancement of neuropathy with repeated administrations of divided critical dose of leptophos in both iv and oral administration.

Animals↗
PubMed1989

Concentration of free thyroxin in serum during nonthyroidal illness--calculation or measurement?

We measured the free thyroxin (FT4) concentration in serum from 79 patients with nonthyroidal illnesses (NTI), using two analog RIAs and two calculation methods, and compared the results with those by ultrafiltration (UF) as a reference. The percentage of NTI patients with subnormal concentrations of FT4 was 10.1% by UF; 20.3% by mathematical calculation (MC) according to mass-action theory; 19.0% by FT4 index (FT4I), calculated by the triiodothyronine-albumin uptake method expressed as the bound:free ratio; 37.2% by Amerlex M FT4 (P less than 0.001 vs UF, P less than 0.025 vs MC); and 33.3% by Coat-A-Count FT4 with albumin blocker (P less than 0.001 vs UF, P less than 0.025 vs MC). No significant correlations were found between FT4 (UF) and T4-binding proteins (TBP) in serum, but FT4 (MC) correlated with T4-binding globulin (TBG) (r = 0.383, P less than 0.001), FT4I with TBG (r = 0.345, P less than 0.001), FT4 (Amerlex M) with albumin (r = 0.491, P less than 0.001), and FT4 (Coat-A-Count) with TBG (r = 0.636, P less than 0.001). All FT4 measurements correlated well with each other, but correlations were stronger between both calculated FT4 values and FT4 (UF), r = 0.702 to 0.760, than between both values for RIA and FT4 (UF), r = 0.475 to 0.665. These results indicate that in comparison with the UF method, both calculated FT4 values are little affected by TBP concentrations, and FT4 (MC) or FT4I by T3-albumin uptake may be more appropriate than analog RIA for evaluation of circulating FT4 concentration in NTI.

Adult↗
PubMed1989

[Evaluation of fine needle aspiration cytology in the diagnosis of thyroid diseases].

The role of fine needle aspiration cytology (FNA) was examined in 384 patients with thyroid diseases referred to the thyroid clinic from May 1984 to June 1988. The cytological diagnoses were 65 (16.9%) malignant neoplasms, 137 (35.7%) benign neoplasms, 135 (35.2%) chronic thyroiditis, 20 (5.2%) thyroid cysts, and 27 (7.0%) other thyroid diseases including Graves' disease and subacute thyroiditis. Ninety-eight patients were selected for thyroidectomy based on criteria, which included clinical and cytological diagnosis, and the following pathological diagnoses of resected specimens were obtained: 45 (45.9%) papillary carcinoma, 9 (9.2%) follicular carcinoma, 26 (25.5%) follicular adenoma, 1 (1.0%) papillary adenoma, 14 (14.3%) adenomatous goiter, and 3 (3.1%) Hürthle cell adenoma. The accuracy of diagnosis of goiter by FNA was examined by comparing with that by histological findings. False negative rate, false positive rate, true positive rate, and true negative rate of FNA were 5.7%, 10.0%, 94.3%, and 90.0% respectively. The calculated sensitivity, specificity, and accuracy of FNA were 92.6%, 92.3% and 92.5% respectively. These results indicate that the FNA is a safe and reliable method for routine use in the evaluation of nodular thyroid disease.

Adult↗