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Biomedical subjects

H Koh

Publications and source records attributed to H Koh.

At least 37 records · Page 2Linked to original sources

New bronchoscopic microsample probe to measure the biochemical constituents in epithelial lining fluid of patients with acute respiratory distress syndrome.

OBJECTIVE: A noninvasive bronchoscopic microsampling (BMS) probe was developed to sample biochemical constituents of the epithelial lining fluid in small airways. DESIGN: Observational, controlled study. SETTING: Intensive care unit of academic medical center. PATIENTS AND PROCEDURE: BMS was applied in a control group of seven patients who had hemoptysis or small solitary peripheral nodules but no hypoxemia or other signs of acute inflammation and in four patients with acute respiratory distress syndrome (ARDS), to test whether BMS can ascertain the presence of acute pulmonary inflammation without complications. MEASUREMENTS AND RESULTS: Complications, including a significant decrease in arterial oxygen saturation, were observed neither during nor after BMS. In the ARDS group, albumin, lactate dehydrogenase, interleukin-6, basic fibroblast growth factor, and neutrophil elastase concentrations in epithelial lining fluid were significantly higher (p <.0001, p =.012, p <.0001, p <.0001, and p <.0001, respectively) than in the control group. Serial BMS was safely performed in one patient with ARDS, allowing us to observe a correlation between changes in the concentration of inflammation-related biochemical markers and clinical course of the disease. CONCLUSIONS: These results suggest that BMS is safe and useful to monitor pulmonary biochemical events in ARDS.

Adult↗

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.

PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.

Adult↗

[Giant cystic pheochromocytoma: a case report].

The patient, a 59-year-old woman, was referred to our University Hospital for evaluation of a left mass. Ultrasonography revealed a left adrenal cystic mass. On excretory urograms, the left kidney was pressed downward by a suprarenal mass, and computerized tomography (CT) and magnetic resonance imaging (MRI) confirmed an adrenal cyst. 131I-meta-iodo-benzylguanidine (MIBG) scintigraphy showed prominent accumulation in the left adrenal mass and the capsule. Considering the elevation of catecholamines in both blood and urine samples, we performed a left adrenalectomy with a presumptive diagnosis of pheochromocytoma (tumor size: 11.6 x 7.5 x 6.5 cm, tumor weight 720 g). The subsequent pathological examination confirmed a left giant cystic pheochromocytoma. 131I-MIBG scintigraphy was the most useful tool in the diagnosis of the cystic pheochromocytoma.

3-Iodobenzylguanidine↗

Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.

Akt is stimulated by several growth factors and has a major anti-apoptotic role in the cell. Therefore, we hypothesized that a pathway leading to the inhibition of Akt might be utilized in the process of apoptosis. Accordingly, we used a yeast two-hybrid screening assay to identify the proteins that interact with and possibly inhibit Akt. We found that the C-terminal region of protein kinase C-related kinase 2 (PRK2), containing amino acids 862 to 908, specifically binds to Akt in yeast and mammalian cells. During early stages of apoptosis, the C-terminal region of PRK2 is cleaved from the inhibitory N-terminal region and can bind Akt. The protein-protein interaction between Akt and the PRK2 C-terminal region specifically down-modulates the protein kinase activities of Akt by inhibiting phosphorylation at threonine 308 and serine 473 of Akt. This inhibition of Akt leads to the inhibition of the downstream signaling of Akt in vivo. The PRK2 C-terminal fragment strongly inhibits the Akt-mediated phosphorylation of BAD, a pro-apoptotic Bcl-2 family protein, and blocks the anti-apoptotic activities of Akt in vivo. These results provide direct evidence that the products of protein cleavage during apoptosis inhibit pro-survival signalings, leading to the amplification of pro-apoptotic signalings in the cell.

Animals↗

Extracellular zinc activates p70 S6 kinase through the phosphatidylinositol 3-kinase signaling pathway.

We have studied a possible role of extracellular zinc ion in the activation of p70S6k, which plays an important role in the progression of cells from the G(1) to S phase of the cell cycle. Treatment of Swiss 3T3 cells with zinc sulfate led to the activation and phosphorylation of p70S6k in a dose-dependent manner. The activation of p70S6k by zinc treatment was biphasic, the early phase being at 30 min followed by the late phase at 120 min. The zinc-induced activation of p70S6k was partially inhibited by down-regulation of phorbol 12-myristate 13-acetate-responsive protein kinase C (PKC) by chronic treatment with phorbol 12-myristate 13-acetate, but this was not significant. Moreover, Go6976, a specific calcium-dependent PKC inhibitor, did not significantly inhibit the activation of p70S6k by zinc. These results demonstrate that the zinc-induced activation of p70S6k is not related to PKC. Also, extracellular calcium was not involved in the activation of p70S6k by zinc. Further characterization of the zinc-induced activation of p70S6k using specific inhibitors of the p70S6k signaling pathway, namely rapamycin, wortmannin, and LY294002, showed that zinc acted upstream of mTOR/FRAP/RAFT and phosphatidylinositol 3-kinase (PI3K), because these inhibitors caused the inhibition of zinc-induced p70S6k activity. In addition, Akt, the upstream component of p70S6k, was activated by zinc in a biphasic manner, as was p70S6k. Moreover, dominant interfering alleles of Akt and PDK1 blocked the zinc-induced activation of p70S6k, whereas the lipid kinase activity of PI3K was potently activated by zinc. Taken together, our data suggest that zinc activates p70S6k through the PI3K signaling pathway.

3T3 Cells↗

Cloning and characterization of a nuclear S6 kinase, S6 kinase-related kinase (SRK); a novel nuclear target of Akt.

Akt is stimulated by several growth factors, and mediates their cell survival signals. Recent studies have shown that Akt may play an intermediate role between phosphatidylinositol 3-kinase (PI3K) and p70 S6 kinase (p70S6K). Here we show that a novel nuclear p70S6K-related kinase (SRK) exists and that its in vivo function is also augmented by over-expression of Akt. Conceptual translation of the SRK cDNA revealed that the catalytic domain of SRK was highly homologous to that of p70S6K, and that the treatment of wortmannin or rapamycin strongly inhibited the phosphorylation and the activation of SRK, as in p70S6K. However, the N- and C-terminal domains of SRK were quite different from those of p70S6K. In immunolocalization analyses, we demonstrated a constitutive nuclear localization of SRK and the presence of a nuclear localization signal in its C-terminus. In vitro S6 phosphotransferase activities of SRK were stimulated with a slower kinetics by a variety of agonists to p70S6K. Interestingly, over-expression of the proto-oncogene Akt resulted in EGF-independent activation of SRK, while over-expression of kinase-dead Akt actually had an inhibitory effect. This relationship between Akt and SRK suggests that SRK may be a novel target of Akt and perhaps an important downstream component in the nuclear function of Akt.

Catalytic Domain↗

No psychological emergence reactions in schizophrenic surgical patients immediately after propofol, fentanyl, and ketamine intravenous anesthesia.

PURPOSE: We attempted to determine the frequency of adverse psychological events after total intravenous anesthesia with propofol-fentanyl-ketamine (PFK) in surgical schizophrenic patients. METHODS: PFK was used in 25 schizophrenic patients undergoing various surgical procedures from 1995 to 1997. Adverse events occurring during and after anesthesia were recorded. Psychiatric follow-up was also done during the first 3 postoperative weeks at least. RESULTS: One patient died postoperatively of airway obstruction from concomitant severe malignant thyroid disease, but in the remaining patients neither respiratory nor cardiovascular states during or after anesthesia became unstable. None of the patients developed adverse psychological emergence reactions immediately after anesthesia. Two patients undergoing major surgical procedures exhibited delirium in the early postoperative days despite taking their routine antipsychotic drugs postoperatively. CONCLUSIONS: We suggest that PFK maintains stable respiratory and cardiovascular states, and causes no psychological emergence reactions in schizophrenic surgical patients. However, adverse psychological events may occur postoperatively, probably due to continued psychic stress. We therefore recommend appropriate perioperative management and further psychological studies for such patients.

Journal Article↗

Effect of carbohydrate intake on serum 3,5,3'-triiodothyronine-response to glucose ingestion and its relation to glucose tolerance in lean non-insulin-dependent diabetic patients.

This study was conducted to know the effect of carbohydrate intake on serum 3,5,3'-triiodothyronine (CAS 6893-02-3, T3)-response to glucose ingestion and its relation to glucose tolerance in lean non-insulin-dependent diabetes mellitus (NIDDM) patients. Ten patients, body mass index: 21.8 +/- 2.2 (mean +/- SD) kg/m2, were given a control diet (2012 kcal/day(d); carbohydrate (CHO): 299 g/d) on admission. Several days later, they were given a low-calorie and low-CHO diet (Low-CHO) (1156 kcal/d; CHO: 139 g/d) and 2 weeks later, they received a low-calorie and high-CHO diet (High-CHO) (1154 kcal/d; CHO: 176 g/d) and another 2 weeks later, they were given Low-CHO again for 2 weeks. They received oral 75 g glucose tolerance tests after completion of each diet. sigma dGlucose (mmol/l) decreased from 54.3 +/- 11.9 (control) to 42.5 +/- 7.5 after Low-CHO and reached 34.5 +/- 10.4 after High-CHO but increased to 36.4 +/- 11.1 after the 2nd Low-CHO (F = 7.46, p = 0.0005). sigma dT3 (nmol/l) increased from -0.18 +/- 0.52 (control) to 0.12 +/- 0.67 after Low-CHO and reached 0.92 +/- 0.59 after High-CHO but decreased to 0.36 +/- 0.65 after the 2nd Low-CHO (F = 5.92, p = 0.0022). Serum insulin and body weight remained unchanged throughout the study. Negative correlation between sigma dT3 and sigma dGlucose (r = -0.493, n = 40, p = 0.0012) was found throughout the diet modification. Carbohydrate intake affected serum T3-response to glucose ingestion and the response was closely related to glucose tolerance in lean NIDDM patients.

Blood Glucose↗

A comparison of commercial and in-house ELISAs for antineutrophil cytoplasmic antibodies directed against proteinase 3 and myeloperoxidase.

This study compares the concordance of results in different ELISAs for antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) or myeloperoxidase (MPO). Sera were considered "true positives" if they were positive according to the manufacturer's criteria in a least three of the five PR3-ANCA ELISAs, or in at least four of the six MPO-ANCA ELISAs. Of the 26 sera that demonstrated cytoplasmic fluorescence (C-ANCA), 23 (89%) contained PR3-ANCA and three (11%) had MPO-ANCA. Two sera that were negative by indirect immunofluorescence (IIF) contained PR3-ANCA. Of the 26 sera with perinuclear fluorescence (P-ANCA), 19 (73%) contained MPO-ANCA, and one (4%) had PR3-ANCA. Six sera with P-ANCA did not have PR3- or MPO-ANCA. No serum that was negative by IIF contained MPO-ANCA. For the different PR3-ANCA ELISAs, sensitivities ranged from 88 to 100%, and specificities from 91 to 100%. For the MPO-ANCA ELISAs, sensitivities varied from 59 to 100% and specificities from 83 to 100%. The highest sensitivity and specificity for both the PR3- and MPO-ANCA ELISAs were obtained with the IBL and Eurodiagnostica assays. The in-house PR3-ANCA ELISA performed slightly less well than the commercial assays, but the performance of the in-house MPO-ANCA assay was comparable or better.

Antibodies, Antineutrophil Cytoplasmic↗

[A comparison of the incidence of postoperative nausea and vomiting after propofol-fentanyl anesthesia and that after nitrous oxide-isoflurane anesthesia].

We compared the incidence of postoperative nausea and vomiting after total intravenous propofol-fentanyl anesthesia (TIVA group) and that after thiamylal-nitrous oxide-isoflurane anesthesia (GOI group) in 60 ASA physical I and II patients for elective abdominal simple total hysterectomy. When the patients returned to the ward, the incidence of nausea was lower in TIVA group than in GOI group (P < 0.05), but no difference was found in the incidence of vomiting between the two groups. There were no differences in the incidence of nausea and vomiting 6 hours after the operation and on the next morning between the two groups. Postoperative pain scores were similar between the two groups, while total postoperative evaluation scores (nausea, vomiting, pain, fever, and sleep disturbance) were lower in TIVA group (P < 0.05). We conclude that TIVA with propofol-fentanyl reduced the incidence of nausea and improved total evaluation scores in the immediate postoperative period.

Adult↗

[Two cases of circulatory failure after local infiltration of epinephrine during tonsillectomy].

We experienced two cases of circulatory failure after local infiltration of 0.0005% epinephrine solution for the purpose of prophylactic hemostasis during tonsillectomy under sevoflurane anesthesia. Case 1: A 14 year-old girl developed ventricular bigeminy, tachycardia and hypertension following infiltration of the epinephrine solution 6ml around the tonsil. Sinus rhythm returned with intravenous lidocaine 40 mg and propranolol 0.4 mg. However, the patient showed gradually decreasing heart rate, depressed ST segments and inverted T waves and poor peripheral circulation. Her blood pressure decreased abruptly at the same time and finally the pulsation of the radial and femoral arteries was not palpable. She was treated with intravenous ephedrine in vain. Therefore, she received intravenous epinephrine and cardiac massage, and then recovered from the circulatory failure with her ECG showing normal sinus rhythms. Emergence from the anesthesia was smooth. Her cardiac failure may have been caused by the decreasing cardiac contraction and the increasing afterload due to the vasoconstriction after the intravenous beta-blocker. Case 2: An eleven year-old boy showed ventricular tachycardia and hypertension after infiltration of the epinephrine solution 11.5 ml around the tonsil. Lidocaine was given intravenously. This restored sinus rhythm but the ST segments on his ECG were elevated. ST segments became normalized after intravenous nitroglycerin. However, pulmonary edema developed suddenly, and it was cured by intensive treatment. His ventricular tachycardia and hypertension after the local administration of epinephrine were presumably responsible for the acute heart failure causing the pulmonary edema. Our experience suggests that the maintenance of cardiac function and the reduction of afterload are important to overcome the circulatory disaster following the local infiltration of epinephrine.

Adolescent↗

Effect of temporary closure of oronasal fistulae on levator veli palatini muscle activity.

OBJECTIVE: The objective of this study was to clarify electromyographically the effects of closing an oronasal fistula on levator muscle activity and oral air pressure in patients with velopharyngeal incompetence and in those with adequate velopharyngeal function. SUBJECTS: Five patients with adequate velopharyngeal function and six patients with velopharyngeal incompetence were studied. All subjects had an oronasal fistula at the anterior third portion of the hard palate in spite of primary palatal closure using palatal push-back operation. OUTCOME MEASURES: The smoothed electromyographic activity of the levator veli palatini muscle was measured with the fistula closed with a cotton swab dipped in saline and with the fistula left open. RESULTS: Under the closed fistula condition, oral air pressure was greater than that observed under the open fistula condition irrespective of velopharyngeal function. Levator veli palatini muscle activity was significantly lower in magnitude under the condition of closure than under the open condition in the patients with adequate velopharyngeal function, whereas in those with velopharyngeal incompetence, it was not significantly changed. CONCLUSIONS: The results suggest that velopharyngeal function is affected by temporary closure of an oronasal fistula, and that the magnitude of the effect is greater for subjects with adequate velopharyngeal function than for subjects with velopharyngeal incompetence.

Adolescent↗

Immunophenotypic identification of Sezary cells in peripheral blood.

Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+.

Antigens, CD7↗

Preoperative serum prostate-specific antigen, clinical stage and Gleason sum as basis for predicting final pathological stage in Japanese patients with prostate cancer.

By logistic regression analysis and log-likelihood ratio chi-square test, the usefulness of preoperative variables (prostate specific antigen [PSA], clinical stage and biopsy Gleason sum) for predicting the final pathological stage was assessed in 77 patients with clinically resectable prostate cancers. Pathologically, 32 (41.6%) had organ-confined disease. Extracapsular extension was found in 41 (53.2%), seminal vesicle involvement in 30 (39.0%), positive pelvic lymph nodes in 10 (13.0%) and a positive surgical margin in 27 (35.1%). Each preoperative variable was found to be significantly associated with the final pathological stage. Any combination of these variables was more predictive for extraprostatic disease, compared with each individual variable. Extraprostatic spread was found more frequently in patients with lower serum PSA in this Japanese elderly male population compared with North American males. These preoperative variables considered in combination may provide valuable information for management decisions related to prostate cancer. Serum PSA alone cannot reliably predict pathological stage on an individual basis except in patients with a PSA level of 20 ng/ml or greater. The high incidence of extraprostatic spread at intermediate PSA underscores the importance of selecting an ideal cutoff value for PSA-based screening in a Japanese male population.

Aged↗

Measurement of the free form of TFPI antigen in hyperlipidemia. Relationship between free and endothelial cell-associated forms of TFPI.

Tissue factor pathway inhibitor (TFPI), a protease with three tandem Kunitz-type (K1, K2, and K3) domains, inhibits the initial reaction of the TF-mediated coagulation pathway. TFPI occurs in a free and a lipoprotein-associated form in plasma as well as an endothelial cell-associated form on vascular walls. In a previous study we had demonstrated that free-form TFPI activity was lower in hyperlipidemic patients. In the present study we established a new enzyme immunoassay method for measuring free-form TFPI antigen; this new method uses a monoclonal antibody that recognizes the K3 domain of free-form TFPI but not lipoprotein-associated TFPI. Free-form TFPI antigen was significantly lower in hyperlipidemic patients compared with those in normolipidemic individuals. We applied this new method to measure the amount of endothelial cell-associated TFPI, which can be released by heparin injection, as "free-form TFPI." We found that free-form TFPI antigen in plasma was positively correlated with the endothelial cell-associated form. These results indicate that both of these forms of TFPI are in equilibrium in vivo and that our new method can be used for assessing changes in the levels of endothelial cell-associated TFPI antigen and, hence, for assessing thrombotic tendencies in various disease states.

Adolescent↗

[A case of the foreign body due to "coring"].

A case of the foreign body due to coring from the rubbercap of a 50 ml Diprivan vial was reported. Furthermore, how the fragment is made and how to decrease the incidence are discussed. The incidence of coring should decrease by improvement of the needle and by sticking vials vertically. However, even if the improvement of the rubber, needles and sticking technique is achieved, the occurrence of coring can not be eliminated completely. The best way to avoid coring will be to furnish "50 ml syringes containing Diprivan" commercially.

Foreign Bodies↗

Does the initial distribution volume of glucose reflect plasma volume after haemorrhage in dogs?

To test the hypothesis that the initial distribution volume of glucose (IDVG) reflects plasma volume, the relationship between the IDVG and indocyanine green (ICG) assessments of plasma volume (Vd-ICG) were evaluated simultaneously both before and after induced haemorrhage (30 ml.kg-1) in eight mongrel dogs. The IDVG and the Vd-ICG were calculated with a one-compartment model from repeated measurements of plasma glucose three to seven minutes, and of plasma ICG three to nine minutes after simultaneous infusions of both glucose 100 mg.kg-1 and ICG 0.5 mg.kg-1. The IDVG calculated with a one-compartment model (IDVG-OCM) was also compared with a two-compartment model within 15 min (IDVG-TCM) on nine occasions among a total of 12 determinations. Using Bland and Altman analysis to compare the two analytical models, the IDVG-OCM tends to overestimate the IDVG-TCM by an average of 0.04 L. Although the IDVG-OCM was two to three times larger than the Vd-ICG at each corresponding point, a correlation was obtained between the IDVG-OCM and the Vd-ICG before and after induced haemorrhage (r = 0.85, n = 16, P < 0.001). We conclude that the IDVG reflects plasma volume in normal and hypovolaemic dogs, although the IDVG cannot be used directly to estimate plasma volume.

Animals↗

Tissue factor pathway inhibitor activity in human plasma. Measurement of lipoprotein-associated and free forms in hyperlipidemia.

Tissue factor pathway inhibitor (TFPI), a protease inhibitor that is present in free and lipoprotein-associated forms in plasma and that also occurs as an endothelial cell-associated form, can inhibit the initial reactions of the tissue factor-mediated coagulation pathway. Although a positive correlation between plasma TFPI activity and cholesterol concentration in human plasma has been demonstrated, levels of the various forms of TFPI, ie, the LDL/VLDL-associated form, the HDL-associated form, and the free form, have not yet been completely determined in hyperlipidemia. We therefore established a method for the measurement of each of these forms of TFPI in plasma by gel filtration of plasma in buffer containing 1 mol/L NaCl. The recovery of TFPI activity in the free form was markedly greater as assessed by the new method than the recovery reported when other methods have been used. We employed the new method to analyze TFPI activity in 19 hyperlipidemic patients and compared the results with those for normal control subjects. The level of LDL/VLDL-associated TFPI in hyperlipidemic patients was significantly increased compared with control subjects' levels (0.383 +/- 0.112 versus 0.237 +/- 0.077 U/mL), whereas the level of the free form of TFPI in hyperlipidemic patients was significantly decreased (0.381 +/- 0.132 versus 0.495 +/- 0.106 U/mL), the former being positively correlated with cholesterol level, while the latter was negatively correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗