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Biomedical subjects

Y Kondoh

Publications and source records attributed to Y Kondoh.

At least 37 records · Page 2Linked to original sources

Decreased expression of the metastasis suppressor gene KAI1 in gastric cancer.

KAI1 was immunohistochemically detected in the lower part of fundic glands and intestinal metaplasia in non-cancerous gastric tissues, while only 11.0% (8/73) of cancerous tissues were shown to be positive. The relationship between various clinicopathological characteristics of patients with gastric cancer and KAI1 expression in their tumors was then analyzed to reveal that the incidence of positivity was 16.6% (8/48) of patients with stage Ia-IIIa and 0% (0/25) of patients with stage IIIb-IVb (P < 0.05) and that the incidence of peritoneal or hepatic metastasis tended to be lower in KAI1-positive tumors than in negative ones. These results suggest that decreased KAI1 expression may be related to the progression of gastric cancer.

Adenocarcinoma↗

A simple, two-color fluorescence detection method for membrane blotting analysis using alkaline phosphatase and horseradish peroxidase.

We have developed a one-step, two-color fluorescence detection method using simultaneously two fluorogenic substrates for both Southern and Western blots on nylon membranes. For this enzyme-mediated reporter system, a mixture of (i) 3-hydroxy-N-2'-biphenyl-2-naphthalenecarboxamide phosphate ester (HNPP), a substrate for alkaline phosphatase and (ii) N-(4-amino-5-methoxy-2-methylphenyl)benzamide (AMMB), a fluorogenic substrate for horseradish peroxidase was used. The reaction with these substrates produces blue (HNPP) and yellow (AMMB) fluorescent signals under ultraviolet light (302 nm). Therefore, this simple method allows the simultaneous visualization of two different targets on a single nylon membrane, e.g. nucleic acids or proteins.

Alkaline Phosphatase↗

Immunotherapy and combined assay of serum levels of carcinoembryonic antigen and acute-phase reactants.

Our previous studies have revealed that gastric and esophageal cancer patients with abnormal sialic acid levels had a better response than those with normal levels if they received polysaccharide K (PSK), a nonspecific immunomodulator. Serum levels of carcinoembryonic antigen (CEA) and acute-phase reactants (APR) such as immunosuppressive acidic protein, acid-soluble glycoproteins, alpha1-antichymotrypsin, and sialic acid were analyzed in 872 gastric cancer patients who had undergone resection from March 1979 to September 1993 at the Department of Surgery of Tokai University. The patients were categorized into four groups according to the preoperative serum levels: group A had normal levels of both CEA and APR, group B had abnormal CEA and normal APR levels, group C had a normal CEA level and normal levels of one or more APR, and group D had abnormal levels of both CEA and of one or more APR. Patients in group D who received PSK showed significantly better survival than those without PSK (29.3% versus 6.9%; log-rank test, P = 0.0015; Breslow test, P = 0.0042). CEA-positive patients receiving PSK therapy exhibited a significantly better survival rate than those without PSK (38.1 % versus 18.6%; log-rank test, P = 0.0136; Breslow test, P = 0.0125). Cox's regression analysis showed that PSK therapy was significantly related to survival in group D, but not in the other groups. We conclude that the combined assay of tumor-associated factors (such as CEA) and various nonspecific reactants to the presence of cancer (such as immunosuppressive acidic protein, alpha1-antichymotrypsin, acid-soluble glycoproteins and sialic acid) provides a good set of preoperative indicators on which to base the selection of treatment for individual gastric cancer patients.

Acute-Phase Proteins↗

Chronic ischemic colonic lesion caused by phlebosclerosis with calcification.

We report here two patients in both of whom ileus finally developed and chronic ischemic colonic lesion caused by phlebosclerosis with calcification was diagnosed. We believe that phlebosclerosis is an old-fashioned diagnostic term, but appropriate here because of the remarkable calcification of the sclerotic walls of the colic veins that seems to be one of the most important hallmarks of this previously unrecognized, "new" condition. Phlebosclerosis could be a novel type of ischemic colitis because of its unique clinical presentations, although the pathogenesis of this unusual venopathy remains unknown.

Adult↗

Misery perfusion with preserved vascular reactivity in Alzheimer's disease.

To elucidate the hemodynamic pathophysiology underlying Alzheimer's disease (AD), cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction fraction (OEF) were measured with positron emission tomography in 10 patients with probable AD and in 20 age-matched normal volunteers. By the 15O intravenous bolus injection method, CBF was measured during resting state, CO2 inhalation (hypercapnia) and hyperventilation (hypocapnia), and the vascular reactivity (VR) was estimated by comparing the CBF changes (delta CBF%/PaCO2 mmHg) in the hyper- or hypocapnic to the resting state. By the 15O2 single-breath method or 15O steady-state method, CMRO2 and OEF were measured during resting state. Based on 26 regions of interest, local CBF, CMRO2 and OEF were compared statistically between the two groups. As compared with the control group, the mean CBF and CMRO2 decreased to as low as 77.0% and 88.4% of the normal values, respectively, while the mean OEF increased by 12.1% (p < 0.05) in AD patients. These changes were most pronounced in the supramarginal and superior temporal gyri. There was no focal change in VR in the AD group, and no significant difference was seen in VR to either hyper- or hypocapnia between AD and control groups. The results may suggest a vascular involvement, possibly at the capillary level, that might cause a relative misery perfusion syndrome accompanied by preserved vascular reactivity in AD.

Adult↗

Disopyramide improves the balance between myocardial oxygen supply and demand in patients with hypertrophic obstructive cardiomyopathy.

We evaluated the effects of disopyramide in terms of the balance between myocardial oxygen supply and demand in patients with hypertrophic obstructive cardiomyopathy (HOCM). The myocardial oxygen supply was evaluated by measuring coronary flow velocity and the myocardial oxygen demand was assessed by the pressure-volume area (PVA). The time velocity integral of coronary flow did not change significantly (20 +/- 6 to 21 +/- 8 cm), but the peak left ventricular pressure and left ventricular external work decreased significantly (206 +/- 44 to 157 +/- 37 mmHg, P < 0.001; 1.09 +/- 0.33 to 0.80 +/- 0.23 J/beat, P < 0.001) after disopyramide administration. From theoretical analysis using these data, we concluded that disopyramide improves the myocardial oxygen supply-demand balance in patients with HOCM.

Adult↗

Aortic blood momentum--the more the better for the ejecting heart in vivo?

OBJECTIVES: The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function. METHODS: The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available. RESULTS: The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56). CONCLUSION: The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.

Aged↗

Fasudil (HA1077), an intracellular calcium antagonist, improves neurological deficits and tissue potassium loss in focal cerebral ischemia in gerbils.

The effects of an intracellular calcium antagonist fasudil (HA 1077) on protein synthesis, ion derangement, brain edema, and the neurological signs associated with focal cerebral ischemia, were investigated via a nine-hour occlusion of the left common carotid artery (CCA) in Mongolian gerbils. Protein synthesis was evaluated by the amount of incorporation of [14C]methionine into the tissue. Intravenous infusion of fasudil hydrochloride (1 mg kg-1) just after CCA ligation was effective in reducing neurological deficits six and nine hours after CCA ligation, as well as loss of tissue potassium. However, fasudil did not ameliorate the brain edema or the accumulation of sodium in the tissue. On the other hand, fasudil improved the uptake of [14C]methionine, but not its incorporation into the tissue. The improved uptake of tracer into the tissue may indicate the facilitation of collateral blood flow by fasudil. These results suggest that fasudil may mitigate ischemic damage in the penumbral zone, possibly by ameliorating collateral blood flow and preventing calcium-related cell damage.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Dynamics of neurons controlling movements of a locust hind leg II. Flexor tibiae motor neurons.

Imposed movements of a proprioceptor that monitors the relative position of the tibia about the femur, the femorotibial chordotonal organ (FeCO), evoke resistance reflexes in the motor neurons that control the movements of the tibia of the locust. The response dynamics of one pool of motor neurons, the flexor tibiae motor neurons, which are located in three groups (anterior, lateral, and posterior), have been analyzed by the Wiener kernel method. First- and second-order kernels that represent the linear and nonlinear responses, respectively, were computed by a cross-correlation between the intracellularly recorded synaptic responses in the motor neurons and the white noise stimulus applied to the FeCO, and were used to define the input-output characteristics of the motor neurons. The posterior fast, intermediate, and slow and the anterior fast and intermediate flexor tibiae motor neurons had biphasic first-order kernels with initial negative phases, indicating that they are velocity sensitive. The falling phases of the kernels had distinct shoulders, indicating that the responses of the motor neurons also had delayed low-pass components, i.e., position sensitivity. The anterior slow flexor motor neuron had a monophasic, low-passed, first-order kernel, indicating that it is position sensitive. The linear component of the motor neuron responses, predicted by convolving the first-order kernels with the stimulus signal, strongly resembled the actual response, whereas the second-order nonlinear component was small, particularly at > 10 Hz. The power spectra of the fast motor neurons showed that they had the highest cutoff frequencies (at > 8 Hz), whereas the slow flexor motor neurons had a gradual roll-off at 1 Hz. The intermediate flexor motor neuron had an intermediate cutoff frequency of approximately 2-3 Hz. The linear responses of the flexor motor neurons could be decomposed into low- and high-frequency components. The high-frequency components (> 10 Hz) were velocity dependent and linear, whereas the low-frequency components (< 10 Hz) were position dependent and nonlinear. The nonlinearity was a signal compression (or half-wave rectification). The results show that although the flexor motor neurons receive many common inputs during FeCO stimulation, each individual has specific dynamic response properties. The responses of the motor neurons are fractionated so that a given individual within the pool will respond best to position, whereas others will respond better to velocity. Likewise, some motor neurons respond best at low frequencies, whereas others respond best at higher frequencies of stimulation.

Animals↗

Dynamics of neurons controlling movements of a locust hind leg. III. Extensor tibiae motor neurons.

Imposed movements of the apodeme of the femoral chordotonal organ (FeCO) of the locust hind leg elicit resistance reflexes in extensor and flexor tibiae motor neurons. The synaptic responses of the fast and slow extensor tibiae motor neurons (FETi and SETi, respectively) and the spike responses of SETi were analyzed with the use of the Wiener kernel white noise method to determine their response properties. The first-order Wiener kernels computed from soma recordings were essentially monophasic, or low passed, indicating that the motor neurons were primarily sensitive to the position of the tibia about the femorotibial joint. The responses of both extensor motor neurons had large nonlinear components. The second-order kernels of the synaptic responses of FETi and SETi had large on-diagonal peaks with two small off-diagonal valleys. That of SETi had an additional elongated valley on the diagonal, which was accompanied by two off-diagonal depolarizing peaks at a cutoff frequency of 58 Hz. These second-order components represent a half-wave rectification of the position-sensitive depolarizing response in FETi and SETi, and a delayed inhibitory input to SETi, indicating that both motor neurons were directionally sensitive. Model predictions of the responses of the motor neurons showed that the first-order (linear) characterization poorly predicted the actual responses of FETi and SETi to FeCO stimulation, whereas the addition of the second-order (nonlinear) term markedly improved the performance of the model. Simultaneous recordings from the soma and a neuropilar process of FETi showed that its synaptic responses to FeCO stimulation were phase delayed by about -30 degrees at 20 Hz, and reduced in amplitude by 30-40% when recorded in the soma. Similar configurations of the first and second-order kernels indicated that the primary process of FETi acted as a low-pass filter. Cross-correlation between a white noise stimulus and a unitized spike discharge of SETi again produced well-defined first- and second-order kernels that showed that the SETi spike response was also dependent on positional inputs. An elongated negative valley on the diagonal, characteristic of the second-order kernel of the synaptic response in SETi, was absent in the kernel from the spike component, suggesting that information is lost in the spike production process. The functional significance of these results is discussed in relation to the behavior of the locust.

Animals↗

Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.

This study was designed to investigate possible involvement of type IV collagenolytic matrix metalloproteinases (MMPs; 72-kDa type IV collagenase [MMP-2], 92-kDa type IV collagenase [MMP-9]), and the respective specific tissue inhibitors of these MMPs (TIMP-2 and TIMP-1) in the development of adult respiratory distress syndrome (ARDS). We determined the concentrations of these enzymes in the bronchoalveolar lavage fluid (BALF) from patients with ARDS using newly developed sensitive one-step sandwich enzyme immunoassay methods. BALF obtained from the 17 patients and eight healthy volunteer control subjects were also used for the analysis of the number of the cellular component. Concentrations of the 7S portion of type IV collagen and laminin in the BALF were measured as markers of basement membrane disruption. In the BALF from the ARDS patients, the concentrations of MMP-2 (66.7 +/- 57.0 ng/ml versus < 7.0 ng/ml for controls, p < 0.01) and MMP-9 (118.0 +/- 309.3 ng/ml versus 9.0 +/- 9.5 ng/ml for controls, p < 0.05), and the specific inhibitor of MMP-9 (TIMP-1) (161.0 +/- 145.0 ng/ml versus < 50 ng/ml for controls, p < 0.01) were significantly higher compared with those for healthy control subjects. In the ARDS patients, the concentrations of MMP-2 correlated both with those of 7S collagen and laminin; MMP-9 with the concentration of 7S collagen and the number of neutrophils. These findings suggest that the increased concentration of collagenolytic MMPs in lung plays a role in the pathogenesis of ARDS.

Adult↗

Classification of hypothalamic progestin-nonresponsive amenorrhea by secretion pattern of serum LH.

The pathogenesis of hypothalamic progestin-nonresponsive amenorrhea is unclear and this disease often fails to respond to treatment. The pulsatile patterns of diurnal and nocturnal secretion of serum LH as well as serum levels of melatonin were examined to improve the understanding of the pathogenesis and to develop strategies for the management of a severe type of hypothalamic amenorrhea. Four types of LH pulsatile patterns were observed: a) no pulse during the day or night (Group 1); b) more than 1 pulse only at night (Group 2); c) only 1 pulse during the day and more than 2 pulses at night (Group 3); and d) more than 2 pulses during the day and at night (Group 4). Serum estradiol was less than 30 pg/mL, and the serum PRL and PRL response to TRH did not differ among the four groups. The basal level and the pulse amplitude of LH increased successively from Group 1 to Group 4. The serum level of melatonin at night was noticeably increased in Group 1 and correlated negatively with the LH pulse frequency at night. After 6-month hormone replacement therapy with estrogen and progesterone, the rate of improvement in ovarian function were 0%, 33.3%, 57.1% and 67.0% in Groups 1, 2, 3, and 4, respectively. In 5 patients, the LH pulse pattern was re-examined at 6 months, the LH pulsatile pattern was changed from that of Group 1 to that of Group 4, with a decrease in serum concentrations of nocturnal melatonin, indicating improved ovarian function. In conclusion, classification of patients according to the LH secretion pattern is useful in establishing the severity of hypothalamic disturbance in hypothalamic progestin-nonresponsive amenorrhea and in predicting its prognosis; in addition nocturnal melatonin can be used as a marker for severer cases of hypothalamic amenorrhea.

Adolescent↗

[Effect of intraperitoneal therapy in gastric cancer with peritoneal dissemination].

Eighty gastric cancer patients with peritoneal dissemination were analyzed to evaluate the effect of intraperitoneal chemo- and/or immunotherapy on abdominal ascites. Among them, 19 were treated with intraperitoneal chemo- and/or immunotherapy, and 21.1% of them showed decreased ascites and better QOL. Patients treated with intraperitoneal administration with OK-432 showed good survival. Among patients with OK-432 administration, those receiving postoperative chemotherapy showed better survival than those given immunochemotherapy. Conversely, among patients with chemotherapy, those given postoperative immunochemotherapy showed better survival than those on chemotherapy. Patients with HLA-type I and III, and those with preoperative normal immune status showed good response when they received intraperitoneal therapy.

Adult↗

[Outcomes of noninvasive positive-pressure ventilation in patients with acute hypercapnia complicating chronic respiratory failure].

We used noninvasive positive-pressure ventilation to treat hypercapnea due to acute exacerbations of chronic respiratory failure (21 episodes in 19 patients; COPD, 4; pulmonary tuberculosis sequelae, 4; silicosis, 3; silicotuberculosis, 3; bronchiectasis, 3; others, 2). All patients had acute onsets of severe hypercapnea (PaCO2 > 45 Torr), acute decreases in pH (< 7.35), and tachypnea, paradoxical breathing or both. During the first 2 to 4 hours of bi-level positive airway pressure, PaCO2 decreased from 72 to 61 Torr (p < 0.0005), pH increased from 7.26 to 7.31 (p < 0.001), and respiratory rate decreased from 30 to 25 breaths/min (p < 0.005). In three cases leakage of air through the mouth prevented improvement in the patients' conditions, but in two of those a face mask was then used successfully. In 17 of the 21 episodes (81%) gas exchange improved and intubation was not necessary. In those 17, the mean duration of noninvasive positive-pressure ventilation was 6.3 days. We conclude that noninvasive positive-pressure ventilation can improve gas exchange in patients with acute hypercapnea complicating chronic respiratory failure.

Acute Disease↗

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates].

Cefozopran (CZOP) was administered to nine newborn patients with infections at a dose of 20 mg/kg twice or three times daily for 5 to 6 days to evaluate the efficacy, safety and pharmacokinetics of cefozopran. 1. Blood concentrations CZOP was intravenously given to 6 newborn patients by drip infusion at a dose of 20 mg/kg over 30 minutes. The maximum blood concentrations (Cmax) were 38.4 micrograms/ml in a patient aged 0 day, 37.7 and 54.3 micrograms/ml in two patients aged 1 day, 51.3 and 64.1 micrograms/ml in two patients aged 3 days and 51.0 micrograms/ml in a patient aged 5 days. Cmax was lower in the patient aged 0 day. The elimination half life (T 1/2) was 9.2 hours in the patient aged 0 day, 4.9 and 3.7 hours in the patients aged 1 day, 3.1 and 2.4 hours in the patients aged 3 days and 2.9 in the patient aged 5 days, showing a prolongation of T 1/2 in patients of lower age. 2. Urinary excretion Of the 6 patients given CZOP at a dose of 20 mg/kg by intravenous drip infusion over 30 minutes, urine was collected in 5 patients. The cumulative excretion rate within 6 hours after infusion was as low as 19.8% of dose in the patient aged 0 day. The rates were elevated as high as 46.3 and 57.0% of dose in the patients aged 1 day. In the patient aged 3 days, the recovery within 4 hours after infusion was 47.3%. It was 70.6% of dose within 6 hours after dosing in the patient aged 5 days. The urinary recovery within 6 hours after dosing increased with the advance of age. 3. Clinical results Efficacy was evaluable in 7 patients. Of them, 3 had suspected septicemia, 2 pneumonia, 1 intrauterine infection and 1 urinary tract infection. The clinical efficacy was judged "excellent" in all the evaluable patients. Neither adverse drug reactions of signs and symptoms nor abnormal alterations of the laboratory test values were recognized in the 9 patients evaluable for safety. These results suggest that CZOP is an effective and safe drug for treatment of infections in the newborns. As for the dosage and method of administration from the view of the pharmacokinetic data obtained, intravenous drip infusion of 20 mg/kg once or twice daily was considered to be sufficient for patients aged 0 day. For patients aged 1 to 7 days and those aged 8 days or elder, the administration of twice to 3 times daily and 3 to 4 times daily were considered to be sufficient, respectively.

Bacterial Infections↗

Neural circuitry underlying linear representation of wind information in a nonspiking local interneuron of the cockroach.

In the cercal system of the cockroach Periplaneta americana, primary sensory interneurons exhibiting a sharp directional sensitivity respond to wind in a linear manner whereas those exhibiting an omnidirectional sensitivity respond nonlinearly. For example, the wind-evoked response in an identifiable, nonspiking local interneuron, 101, which responds preferentially to wind from the left versus the right, is characterized exclusively by a differential first-order (linear) kernel. However, the slow potential response in a cercal giant interneuron, GI-1, is omnidirectional, and characterized by a second-order (nonlinear) kernel with an elongated depolarizing peak on the diagonal with two off-diagonal valleys. We here examined the neural circuitry underlying the linear and nonlinear representations of wind information by the deprivation of inputs from particular sets of cercal hair afferents. Electrical stimulation of the ipsilateral (related to the soma) cercal nerve elicited a depolarizing potential in 101, which was followed by delayed hyperpolarization. A continuous flow of 10(-4) M picrotoxin, which selectively blocked this delayed hyperpolarization, resulted in a significant change in the 101 response from linear to nonlinear. Because no frequency-doubling response was observed, the nonlinearity is due to signal compression (or rectification) that reflects the mechanical property of cercal afferents. This is consistent with the hypothesis that the linear representation in 101 is based on a subtraction process between two subsets of particular column hairs, whose best optimal directions are opposite to each other.

Animals↗

Changes in diastolic regional stiffness of the left ventricle before and after coronary artery bypass grafting.

To evaluate the effect of coronary artery bypass grafting (CABG) on regional diastolic function of the left ventricular wall, we applied the concept of the stiffness constant to the diastolic sigma-ln (1/H) relation, where sigma is the mean wall stress, and H is the wall thickness of the region of concern, and ln (1/H) is the natural logarithm of the reciprocal of wall thickness. We assessed 12 cardiac regions in six patients with coronary artery disease who underwent CABG at the Cardiovascular Hospital of Central Japan between May 1994 and January 1995. Left ventricular pressure and regional wall thickness were measured simultaneously, with a micromanometer-tipped catheter and by two-dimensional echocardiography, respectively, before and after CABG. The stiffness constant (K) was obtained by fitting the diastolic sigma-ln (1/H) data points to an exponential curve with zero asymptote: sigma = Cexp[Kln (1/H)]. Preoperatively, the stiffness constant in the affected region (CABG region) was greater than that in the unaffected region (non-CABG region) (4.79 +/- 2.56 vs 2.95 +/- 0.72). Postoperatively, the stiffness constant in the CABG region was significantly decreased, to 3.21 +/- 1.22. The stiffness constant, which is derived from the sigma-ln (1/H) relation, is useful for the assessment of LV regional diastolic function.

Aged↗