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Biomedical subjects

K Kudo

Publications and source records attributed to K Kudo.

At least 217 records · Page 12Linked to original sources

Simultaneous determination of nicotine and cotinine in various human tissues using capillary gas chromatography/mass spectrometry.

A reliable and sensitive method for the simultaneous determination of nicotine and cotinine concentrations in various human tissues was developed using capillary gas chromatography/mass spectrometry. Nicotine and cotinine were extracted using a 3-step solvent extraction procedure and quinoline as an internal standard. Quantification was carried out by single ion monitoring using ions of m/z 133 for nicotine, m/z 176 for cotinine and m/z 129 for quinoline. The lower limit of detection was 5 ng/g for nicotine and 10 ng/g for cotinine, in each tissue sample. The calibration curves of various tissues were linear in the concentration range from 5-1,200 ng/g for nicotine and 10-1,500 ng/g for cotinine. The accuracy and precision of this method were examined using human tissues and the results were satisfactory. The distribution of nicotine and cotinine was measured in tissues from 10 human autopsies. Nicotine was detected in every tissue examined at a level seen in habitual smokers. The nicotine concentration was high in the liver, kidney, spleen and lung, and low in adipose tissue. The cotinine level was highest in the liver. The tissue/blood concentration ratios of nicotine and cotinine were most stable in skeletal muscle, where the level of these drugs was close to that in whole blood. Skeletal muscle is, therefore, considered to be the most suitable tissue sample for toxicological examination, when acquisition of blood samples is not feasible.

Adipose Tissue↗

Insulin stimulates NaCl transport in isolated perfused MTAL of Henle's loop of rabbit kidney.

To elucidate the mechanism of Na+ retention by insulin in vivo, the direct tubular effect of insulin on NaCl transport in the in vitro microperfused medullary thick ascending limb of Henle (MTAL) was examined. Insulin at 10(-6) mol/l in the bath increased transepithelial voltage (Vte) from 3.1 +/- 0.3 to 5.7 +/- 0.3 mV (n = 12, P < 0.0001). The effect of insulin on Vte was dependent on its concentration, and the half-maximal effect of insulin was observed at 5 x 10(-9) mol/l. Insulin at 10(-6) mol/l also caused a significant decrease of luminal Cl- concentration from 85.4 +/- 5.0 to 62.8 +/- 3.0 mmol/l (n = 5, P < 0.002) when the lumen was microperfused constantly at less than 1 nl/min. Insulin at 10(-6) mol/l also increased net lumen-to-bath Cl- flux (JCl) from 143 +/- 15 to 292 +/- 37 pmol.mm-1.min-1 (n = 5, P < 0.004). When the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the basolateral membrane was blocked by 10(-4) mol/l ouabain, the insulin-mediated increase in Vte was completely suppressed. When the Na(+)-K(+)-2Cl- cotransporter in the luminal membrane of the MTAL was blocked by 10(-4) mol/l furosemide, the insulin-mediated increase in Vte was also abolished. To test whether adenosine 3',5'-cyclic monophosphate (cAMP) contributes to the action of insulin, we examined the effect of cAMP analogue and cAMP-dependent protein kinase inhibitor on the action of insulin. A maximal concentration (5 x 10(-4) mol/l) of dibutyryl-cAMP (DBcAMP) increased Vte and JCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Electrophysiological analysis of effect of propranolol in rabbit S2 proximal straight tubule.

The effect of dl-propranolol on the basolateral membrane potential (Vb) of in vitro microperfused S2 proximal straight tubules of the rabbit kidney was examined using conventional microelectrode techniques. In the steady-state condition, the average of 23 measurements of Vb was -44.8 +/- 2.0 mV. Addition of 10(-4) mol/l of dl-propranolol to the basolateral solution rapidly depolarized Vb by 12.1 +/- 1.3 mV in 20 sec (n = 15). The same dose of d-isomer of propranolol, which has no beta-blocking effect, also depolarized Vb to a similar extent. The non-selective beta-blocker nadolol, which possesses no membrane stabilising activity, had no effect on Vb. Depolarization of Vb by dl-propranolol in 20 seconds (propranolol-induced delta Vb) occurred in a dose-dependent manner. In the presence of 1 mmol/l Ba++ in basolateral solution, propranolol-induced delta Vb was strongly inhibited. The stilbene derivative DIDS at 1 mmol/l did not change propranolol-induced delta Vb, whereas the elimination of Cl- from the ambient conditions increased propranolol-induced delta Vb. The minimization of the luminal Na(+)-coupled organic solute transporter by collapsing of the lumen did not inhibit propranolol-induced delta Vb, indicating the lack of effect of propranolol on luminal Na(+)-coupled transporters. Ouabain at 10(-3) mmol/l in the bath did not eliminate propranolol-induced delta Vb, indicating the presence of a target transporter other than Na+/K+ ATPase for propranolol. These results suggest the following; 1) propranolol has a depolarizing effect on Vb in proximal tubule; 2) the effect of propranolol is independent of Cl- transport or Na(+)-coupled transporters in the luminal membrane; 3) propranolol depolarizes Vb by inhibiting the K+ channel in the basolateral membrane of S2 proximal tubule.

Animals↗

[Histopathological studies on paranasal mucosa from patients treated with erythromycin].

Low-dose and long-term administration of erythromycin (EM therapy) has been reported to be very effective for patients with intractable chronic sinusitis including sinobronchial syndrome. However, we sometimes encounter patients whose sinusitis is extremely resistant to EM therapy. Therefore, the present study was carried out to determine the correlation between the clinical efficacy of EM therapy and the histopathological features of the ethmoidal mucosa and nasal polyps of patients treated with erythromycin. Patients with significant lymphocytic infiltration in the submucosal area responded well to EM therapy. Furthermore, patients with neutrophilic infiltration within and beneath the ciliary epithelium tended to show improvement with this therapy. On the other hand, EM therapy was minimally effective in patients whose subepithelial layer showed marked eosinophilic infiltration. In patients showing excellent and good clinical results, histological changes in the paranasal mucosa after therapy were as follows: a decrease in the number of inflammatory cells, reduced interstitial edema, increased fibrosis and normalization of the secretory glands. From these results, we conclude that erythromycin may suppress chronic inflammation except for an allergic reaction characterized by marked eosinophilic infiltration.

Adolescent↗

[Locus of the retention benefits of variable practice in the motor learning].

Shea and Kohl (1990) reported that acquisition practice with variations of the criterion task leads to better retention than practice on the criterion task alone. The purpose of this study was to determine the locus of this retention benefits. Experimental task was the speed reproduction task. Eighty undergraduate male students were randomly assigned to eight practice conditions differing in the activities performed during the intertrial intervals. All subjects were administered retention test immediately and twenty-four hours after the practice. Results indicated that the retention benefits demonstrated by subjects provided variable practice was produced by the contextual interference effect not by the formation of motor response schema. Results also suggested that both of reconstruction of action plan and elaborative processing resulted in the retention benefits.

Adolescent↗

[Outcome of treatment protocol 8704T for childhood T cell leukemia and lymphoma].

We reported the treatment outcome of Protocol 8704T, which included repeated L-asparaginase, for childhood T cell malignancies. Fifteen cases of acute lymphoblastic leukemia (T-ALL) and 11 cases of non-Hodgkin's lymphoma (T-NHL), aged 3 to 14 yrs (median 6 yrs), were enrolled. Twelve T-ALL had mediastinal mass. Murphy's stages of T-NHL were 6 with III and 5 with IV. Types of histology consisted of 8 lymphoblastic and 3 large cell. Treatment was performed for 2 years. Observation periods were from 14 months to 78 months (median 42 months). Twenty-three achieved remission and 6 of them were transplanted with bone marrow or peripheral stem cells in the first remission. The protocol was continued in 17 cases. Fourteen of them remain in first remission, but one died of measles and 2 died of relapse. The 5-year event-free survival was 76.1% for ALL and 65.5% for NHL. In terms of histology, it was 87.5% for lymphoblastic NHL and 33.3% for large cell NHL (p = 0.19). In terms of phenotypes in ALL, it was 88.7% for ALL positive to CD2, 5 and 7, while 2 ALL positive to CD7 alone both failed. Therefore, it was shown that this treatment protocol is very effective for T-lymphoblastic leukemia and lymphoma.

Adolescent↗

Pharmacokinetics and postmortem changes of cimetidine in body tissues.

Cimetidine concentrations in body tissues were pharmacokinetically examined, together with their postmortem changes, to assess the toxicological effect of this drug from the aspect of forensic medicine. For the pharmacokinetic study, rats were pithed at 0.5, 1.0, 2.0, 4.0 or 8.0 hours after an intravenous injection of the drug (33.3 mg/kg), and their tissue samples were immediately collected to be analyzed by high-performance liquid chromatography (HPLC). The concentrations of cimetidine in the blood and muscle decreased below the lower detection limit at 8 hours after the injection, while the drug could still be detected in the brain, lung, liver, kidney, spleen and adipose tissue. The ratios of the cimetidine concentrations in the muscle, lung and spleen to that in the blood were nearly constant until 4 hours after the injection, while those in the liver, kidney and adipose tissue increased as time elapsed. Postmortem changes of cimetidine concentrations were examined using the tissue samples collected 0, 1 and 2 days after death. There was no statistical significance in the postmortem changes in cimetidine concentrations in the body tissues over the two-day period of examination. The experimental results indicated that the muscle, lung and spleen together can serve as samples for toxicological analysis to evaluate the effect of cimetidine, regardless of various postmortem factors, including the availability of blood.

Animals↗

Cytokine expression after the topical administration of substance P to human nasal mucosa. The role of substance P in nasal allergy.

Human nasal mucosal samples exposed in vitro to substance P or allergenic Ag were tested for the mRNA of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, and IFN-gamma using specific reverse transcriptase-polymerase chain reaction assays. After the administration of substance P, at dosages ranging from 10(-6) to 10(-9) M, an enhanced expression of the mRNA for IL-1 beta, -3, -5, -6, TNF-alpha, and IFN-gamma was observed in all mucosal samples of allergic subjects and in half of the nonallergic subjects. The expression of IL-2 and IL-4 was low. Mucosal samples of allergic subjects showed an increased expression of mRNA for cytokines after administration of specific Ag, whereas no enhancement was observed in samples from nonallergic subjects. Our data suggest that substance P may regulate allergic reactions via enhanced production of certain regulatory cytokines.

Administration, Topical↗

Simultaneous determination of paraquat and diquat in human tissues by high-performance liquid chromatography.

A simple, sensitive, reliable, and economical method for simultaneous determination of paraquat dichloride and diquat dibromide in human biological materials has been developed, using high-performance liquid chromatography. The drugs were extracted from the sample with a Sep-Pak C18 cartridge and applied to a chromatograph with the internal standard, L-tyrosine. Paraquat and diquat were clearly separated on the octadecylsilica column with a mobile phase of 0.5% potassium bromide in 5% methanol solution, containing triethylamine (1 ml/l). The pH of the mobile phase was adjusted to 3-4 with 1.3 M phosphoric acid. Two ultraviolet wavelengths were selected, 256 nm for paraquat as well as the internal standard, and 310 nm for diquat. The calibration curves were linear in the concentration range 0.1-10 micrograms/g, and the lower limit of detection was 0.05 microgram/g. We used this method to examine the concentrations of paraquat and diquat in tissues of an individual at autopsy.

Adult↗

Erythromycin therapy for otitis media with effusion in sinobronchial syndrome.

Chronic sinusitis is frequently associated with chronic lower respiratory tract diseases, and the association is referred to as sinobronchial syndrome (SBS). This study was carried out to determine the incidence of otitis media with effusion in the patients with sinobronchial syndrome and to investigate the efficacy of low-dose and long-term erythromycin therapy for otitis media with effusion associated with sinobronchial syndrome. We have found a high incidence of otitis media with effusion in patients with sinobronchial syndrome, the morbidity rate being 54% in 50 cases studied. This ear disease seems to be the major cause of hearing disturbance in patients with sinobronchial syndrome. Sixteen patients with both sinobronchial syndrome and otitis media with effusion were given low-dose and long-term erythromycin therapy (erythromycin base, 600 mg/d for more than 4 months); of these, 13 became effusion-free and most subjects showed improvement in the symptoms of sinobronchial syndrome. The erythromycin therapy thus seems to be exceedingly effective for the treatment of sinobronchial syndrome and associated otitis media with effusion.

Administration, Oral↗

Presence of respiratory syncytial virus genomic sequences in middle ear fluid and its relationship to expression of cytokines and cell adhesion molecules.

The presence of respiratory syncytial virus (RSV) and several cytokines and cell adhesion molecules in middle ear effusions and mucosal tissues was evaluated using polymerase chain reaction. RSV genomic sequences were detected in 23 (52.7%) of 44 middle ear effusions tested. The sequences were detectable at an even higher rate (82.4%) in effusions of children in whom infectious virus was detected in the nasopharynx. All samples with the RSV genome contained the mRNA for interleukin-1 beta and -6 and tumor necrosis factor-alpha. The messages for these cytokines, together with intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1, were detected in human middle ear mucosal organ cultures infected in vitro with RSV. Our results suggest that the enhanced synthesis of proinflammatory cytokines and cell adhesion molecules in the middle ear infected with RSV may contribute to the inflammatory processes in otitis media.

Base Sequence↗

Lipoprotein glomerulopathy. Report of a normolipidemic case and review of the literature.

Lipoprotein glomerulopathy is a disease characterized by intraglomerular lipoprotein thrombi and abnormal lipid metabolism similar to type III hyperlipoproteinemia. Recently, glomerular lesions compatible with lipoprotein glomerulopathy were found in a 38-year-old man. In this case, plasma apolipoprotein (apo) E level was elevated, and the apo E isoform was heterozygous E2/3, similar to most of the reported cases of lipoprotein glomerulopathy. However, the plasma levels of triglyceride and total cholesterol were within their respective normal ranges. Review in 11 cases revealed that lipoprotein glomerulopathy was not always associated with hyperlipidemia, and that apo E abnormality was always recognized. These findings suggest that lipoprotein thrombi associated with lipoprotein glomerulopathy are not induced via systemic hyperlipidemia but may be formed by intraglomerular accumulation of lipoprotein composed of abnormal apo E.

Adult↗

Direct evidence for the absence of active Na+ reabsorption in hamster ascending thin limb of Henle's loop.

The mechanisms of Na+ transport across cell membranes were investigated in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop using a fluorescent Na+ indicator sodium-binding benzofuran isophthalate. The intracellular Na+ concentration ([Na+]i) of the ATL cells was 17.1 +/- 1.7 mM (n = 22) when the ATL was microperfused in vitro with Hepes-buffered solution containing 204 mM Na+. Elimination of metabolites such as glucose and alanine from the basolateral solution increased [Na+]i. Applying either 5 mM cyanide or 5 mM iodoacetic acid to the bath also increased [Na+]i. The elimination of K+ and the addition of 10(-4) M ouabain in the bath increased [Na+]i by 25.0 +/- 5.0 mM (n = 5) in 3 min and by 10.7 +/- 2.4 mM (n = 4), respectively. The elimination of luminal and basolateral Na+ resulted in a decrease in [Na+]i, indicating Na+ permeability of both the luminal and basolateral cell membranes. The luminal Na+ permeability was not affected by furosemide. The presence of luminal Na+ permeability and the basolateral Na+/K+ ATPase suggests the presence of net active reabsorption of Na+, which is not a physiologically important amount, in our estimation.

Alanine↗

Lack of direct action of atriopeptidase inhibitor on cellular pH regulation in rabbit S2 proximal straight tubules.

While the in vivo diuretic and antihypertensive effects of the newly-developed drug Candoxatril (UK-79300), a prodrug of a selective atriopeptidase inhibitor UK-73967 (API) are well established, the mechanism of its diuretic action is not yet fully understood due to the lack of information about its direct effects on proximal tubules. To elucidate whether this atriopeptidase inhibitor has any direct effects on proximal tubules, we examined the effect of API on intracellular pH (pHi) of the in vitro microperfused proximal S2 segment of rabbit kidney, using the pH-sensitive fluorescent dye, (2',7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). In the steady-state condition, pHi was 7.13 +/- 0.02 (n = 19). Atriopeptidase inhibitor (API) at 100 microM added to the bath changed pHi by only 0.02 +/- 0.07 unit (n = 7, p > 0.05) in 10 min. The same concentration of API in the lumen changed pHi by 0.03 +/- 0.02 unit (n = 6, p > 0.05). To test whether the synergistic effects of API on the luminal and basolateral transport systems prevented the apparent change in pHi, we also examined the effect of API in the presence of amiloride in the lumen. The inhibition of Na+/H+ antiporter by the addition of 1 mM of amiloride to the lumen caused no change in pHi response to basolateral API application. API was without effect on pHi also in the presence of atrial natriuretic polypeptide (ANP). These results suggest that API per se has no significant effect on the process of proximal acidification over a short time period.

Animals↗

Coexisting acromegaly and a unilateral cortisol-producing adrenal adenoma: a possible variant of multiple endocrine neoplasia type I.

An unusual case of coexisting acromegaly and Cushing's syndrome is reported in a 34-yr-old female. There was no biochemical or morphological evidence to suggest the presence of other endocrinopathies. She did not have any family history to suggest a hereditary tendency to endocrine disorders. Her acromegaly and Cushing's syndrome were proven to be due to a pituitary somatotroph adenoma and a cortisol-producing adenoma in the right adrenocortex, respectively. Surgical removal of both tumors led to a marked biochemical improvement of the two endocrinopathies. To account for the simultaneous occurrence of the two endocrine tumors, at least two endocrine syndromes may be considered. One of them is Carney's complex. However, Cushing's syndrome in this complex is unexceptionally due to primary pigmented nodular adrenocortical disease, differing from the adrenal pathology of our patient. In addition, a lack in this case of any other characteristic suggestive of this syndrome appears to speak against this possibility. A second possibility is multiple endocrine neoplasia type 1. The absence of a parathyroid or pancreatic islet cell tumor does not strongly support this possibility, but adrenocortical lesions are not rare in this syndrome although they are only rarely functional. However, existence of similar case reports, although very few, in the literature leaves the possibility that she represents another rare variant of sporadic multiple endocrine neoplasia type I syndrome.

Acromegaly↗

Evaluation of mandibular reconstruction techniques following resection of malignant tumors in the oral region.

Over the past 15 years, reconstruction following excision of malignant oral tumors was performed on 27 patients with segmental resection and five patients with hemiresection of the mandible. Following segmental resection, the mandible was reconstructed using an autogenous bone graft in eight patients in whom the surrounding soft tissues were fairly well preserved. Bony union was achieved in six of them. In the remaining two, the graft was removed because of postoperative infection, and one patient underwent secondary bone grafting. A pedicled myocutaneous flap and bone graft was used in seven patients who underwent extensive resection of the surrounding soft tissue. Bony union was achieved in three patients, and one developed pseudoarthrosis. The graft was removed in the remaining three because of postoperative infection. Reconstruction with only a metallic plate for stabilization of the mandible was carried out in six aged or sarcoma-affected patients. In two of them, the postoperative course was uneventful for 4 to 7 years. In the remaining four patients, plate removal was required because of exposure or tumor recurrence. In 5 of 11 patients in whom reconstruction was carried out with a combination of a pedicled myocutaneous flap and metallic plate, the postoperative course was uneventful for 2 to 8 years. Two of these five patients underwent secondary bone grafting. In four of the remaining six patients, the plate was removed because of exposure or improper adaptation to the stump. Two others died of disseminated intravascular coagulation syndrome within 1 month. A prosthesis was used more frequently by patients when reconstruction was performed using a pedicled osteomyocutaneous flap. The metallic reconstruction plate was helpful for restoring mandibular contour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children.

The reverse transcriptase-polymerase chain reaction and the nested polymerase chain reaction were used for detection of respiratory syncytial virus (RSV) sequences in middle ear effusions collected from children with otitis media. Sequences of RSV were detected in 21 of 34 samples tested. These samples were collected during and/or after natural outbreaks of RSV infection in the community. In those patients from whose nasopharynges RSV was isolated, the viral sequences were highly detectable (75%) in the effusions. These observations suggest RSV as an important factor in the pathogenesis of otitis media with effusion.

Base Sequence↗