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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 361 records · Page 20Linked to original sources

Problems of neuroblastoma screening for 6 month olds and results of second screening for 18 month olds.

Nationwide neuroblastoma mass screening for 6-month-old infants (first screening) was introduced in Japan in 1985. About 110 neuroblastoma cases are detected annually by the first screening and treated, with a survival rate of 97%. Sensitivity of the first screening (positive cases/positive cases+false negative cases) is about 75%, and the prognosis of false-negative cases is unfavorable. A second screening at 18 months of age was started to rescue false-negative cases in Miyagi Prefecture in May 1992. Of 62 neuroblastoma cases treated in our hospital since 1985, 40 cases had received the first screening. Twenty cases were positive at first screening, 18 cases were false negative, and 2 cases were false negative and picked up by the second screening. Age distribution of false-negative cases ranged from 12 to 83 months and included 12 cases younger than 36 months old. Only 5 of 18 false-negative cases are alive without the disease. From May 1992 to November 1993, 14,282 infants had received the second screening (compliance rate: about 75%), and 2 neuroblastoma cases were detected. The first case was stage III with paraortic lymph node metastases, Shimada UH, aneuploidy and negative N-myc amplification. The second case was stage II with Shimada FH, aneuploidy, and negative N-myc amplification. Both cases are alive now without the disease after undergoing radical operation and chemotherapy. The first screening is effective for early detection of neuroblastoma cases, but the sensitivity is insufficient; the authors recommend a second screening to rescue false-negative cases.

Adrenal Gland Neoplasms↗

Mesenteric teratoma in an 8-month-old girl.

The authors report the case of a solid, mature teratoma of the mesentery occurring in an 8-month-old girl. The tumor was enucleated from the ileocecal mesentery. Histologically the tumor included all three embryonal layers. This is the youngest patient reported to have mesenteric teratoma.

Female↗

Effect of intramedullary procaine injection on tracheal tone and phrenic neurogram.

To map the superficial locations which are involved in the control of respiration and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized, paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial layer (from the rostral part of the trapezoid body to the caudal hypoglossal rootlets and lateral from the pyramids to 5.5 mm from the midline), which included rostral, intermediate and caudal areas, and the area lateral to the hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was decreased by procaine injection to the intermediate area and the area lateral to the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to the intermediate area. In the intermediate area, some injections decreased either phrenic output alone or tracheal tone alone. These results suggest that the two ventral medullary areas, i.e. the intermediate and caudolateral parts, contain neural structures which are involved in the shaping of phrenic output, but only the intermediate area is involved in the regulation of tracheal tone. It is also suggested that, in the intermediate area, the structures responsible for the maintenance of respiration and tracheal tone are, at least in part, separable.

Animals↗

Submental stimulation and supraglottic resistance during mouth breathing.

We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals and 6 patients with obstructive sleep apnea. We then examined the most effective sites of stimulation in the submental regions, and the relationships between Rsg and stimulation frequency and voltage in the supine position. Inspiratory and expiratory Rsg's were obtained as the slope of the linear portion of the pressure-flow relation determined at zero flow. Before stimulation, inspiratory and expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L-1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L-1.sec, respectively, in patients. Stimulation in the proximal half submental region with surface electrodes 1 cm apart decreased inspiratory and expiratory Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in this submental region showed a stimulation frequency-and voltage-dependency in both groups, but expiratory Rsg did not. These findings suggest that submental stimulation in the proximal half region widens the supraglottic airway during mouth breathing and probably involves the upper airway muscles.

Adult↗

Lymph node metastases in gastric cancer invading the submucosal layer.

We investigated the incidence of lymph node metastasis in 80 patients with early gastric cancer invading the submucosal layer and the relation of metastasis to other clinicopathological variables. All patients underwent curative gastric resection with lymphadenectomy. Lymph node metastasis was detected histologically in 15 patients. The incidence of nodal involvement showed significant increase paralleling the depth of cancer invasion. There was no relation between nodal involvement and histological differentiation. No patients died of gastric cancer during the follow-up. We conclude that gastrectomy with R2 lymphadenectomy is an appropriate operative method for early gastric cancer in which precise diagnosis of cancer invasion cannot be confirmed preoperatively.

Adult↗

Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice.

Murine (m) IL-5 induces proliferation and differentiation of both Ly-1+ B cells and activated conventional B cells. X-linked immunodeficient (XID) mice do not respond to thymus-independent type II antigens, and have an abnormal response to a variety of activation signals through Ig receptors, CD40 and cytokine receptors. Furthermore, XID mice show a B cell specific defect, reflected in decreased numbers of IL-5R alpha+ B cells and reduced responsiveness of IL-5R alpha+ B cells to mIL-5. We generated IL-5R alpha transgenic (5R alpha-Tg) mice in which B cells expressed recombinant IL-5R alpha. We crossed male 5R alpha-Tg mice with female XID mice and used their offspring to determine the IL-5 responsiveness of these B cells. All B cells of F1 male mice carrying the xid gene together with the transgene expressed the recombinant IL-5R alpha. However, those mice lacked Ly-1 B cells and their B cells acquired responsiveness to mIL-5. Interestingly, XID-5R alpha-Tg B cells, but not XID B cells, acquired mIL-5 proliferative and Ig-secretory responsiveness only in the presence of suboptimal doses of lipopolysaccharide. Stimulation of these B cells with mIL-5 plus phorbol myristate acetate induced proliferation, but not Ig secretion. These results indicate that the impaired mIL-5 responsiveness of B cells in XID mice is due to an abnormality of IL-5R-mediated signaling which may correlate with the xid gene mutation, alteration of a single amino acid of Bruton's tyrosine kinase.

Agammaglobulinaemia Tyrosine Kinase↗

Synthesis and self-cleavage reaction of a chimeric molecule between RNase P-RNA and its model substrate.

We synthesized a chimeric RNA between the catalytic RNA subunit of RNase P from Escherichia coli (M1 RNA) and a model substrate of the enzyme. The model substrate is the smallest substrate of RNase P, having a simple stem-loop structure. This model substrate was added to the 3'-end of M1 RNA. This chimeric molecule, which we call M1 RNA-MS, is a self-cleaving RNA and is cleaved much more efficiently than the M1 RNA-pre-tRNA, an artificial self-cleaving RNA previously synthesized [Kikuchi et al. (1993) Nucleic Acids Res. 21, 4685-4689], that consists of a full-size tRNA precursor and the M1 RNA. The self-cleavage of M1 RNA-MS at 10 mM Mg2+ was an intramolecular reaction (cis-cleavage). Ca2+ supported the self-cleavage of M1 RNA-MS as effectively as Mg2+, although the self-cleavage of M1 RNA-pre-tRNA proceeded with low efficiency in the presence of Ca2+ as the only metal ion. Future application of the M1 RNA-MS molecule to the in vitro evolution of the M1 RNA and other experiments is proposed.

Base Sequence↗

Sleep disturbance in elderly patients with cognitive impairment, decreased daily activity and periventricular white matter lesions.

We investigated how sleep disturbance is correlated with brain lesions, cognitive impairment and decreased daily activity (ADL). Two hundred and four chronically ill patients including patients with vascular dementia were classified into eight groups based on cognitive function, ADL and grades of PVL (periventricular lucency) as shown by computerized tomography. Visual monitoring of the sleep/wake state was performed hourly for 14 consecutive days and the daytime sleep hours and the nighttime sleep hours were determined based on detected disturbances in the sleep/wake pattern. Whether any specific infarcted regions were correlated with sleep disturbance was also evaluated. We found that daytime sleep hours were increased and nighttime sleep hours were decreased by three single factors: cognitive impairment, decreased ADL and the severe grade of PVL. As for an interactive effect of the two factors, daytime sleep hours were increased by dementia with decreased ADL (independent of PVL) and increased by decreased ADL with the severe grade of PVL (independent of dementia). Although three factors affected sleep independently, ADL has an interactive effect on sleep with dementia and with PVL. No specific cortical regions related to sleep disturbance were found.

Activities of Daily Living↗

Effect of phenytoin on smoke inhalation injury in sheep.

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.

Animals↗

Cloning of the rat homologue of the von Hippel-Lindau tumor suppressor gene and its non-somatic mutation in rat renal cell carcinomas.

Recently, von Hippel-Lindau (VHL) gene mutations were detected in non-inherited, sporadic human renal cell carcinomas (RCs) at a high frequency. In order to determine whether or not the VHL gene is also a critical gene in rat RCs, we cloned and sequenced the rat homologue of human VHL gene and searched for mutations of the VHL gene in rat RCs. Mutations in the VHL gene were not detected in spontaneous RCs of the Eker rat model or in ferric nitrilotriacetate-induced rat RCs using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. These data indicate that mutation of the VHL tumor suppressor gene is not an event in rat renal carcinogenesis, at least in our present systems.

Amino Acid Sequence↗

Allelic loss at the tuberous sclerosis (Tsc2) gene locus in spontaneous uterine leiomyosarcomas and pituitary adenomas in the Eker rat model.

Hereditary renal carcinomas (RCs) develop in virtually all Eker rats by the age of one year. Investigation of extra-renal primary tumors co-occurring in Eker rats late in life (at 2 years) additionally revealed enhanced development of hemangiosarcomas of the spleen, uterine leiomyosarcomas and pituitary adenomas, although the demonstrated predilection for these extra-renal tumors was not as complete as with RCs. We identified the germline mutated tuberous sclerosis (Tsc2) gene as the predisposing Eker gene and revealed the tumor suppressor nature of Tsc2 gene function in renal carcinogenesis. In the present study, we examined allelic loss at the Tsc2 gene locus in uterine leiomyosarcomas and pituitary adenomas developing in hybrid F1 rats carrying the Eker mutation as well as in pituitary adenomas from non-carrier rats. We detected loss of heterozygosity in 4 of 11 uterine leiomyosarcomas (36%) and 11 of 31 pituitary adenomas (35%) from Eker rats but in none of 9 pituitary adenomas from non-carrier rats (P < 0.05), suggesting that inactivation of the Tsc2 gene is also a critical event in the pathogenesis of these extra-renal tumors. Our present data indicate that there might be different pathways for tumorigenesis of pituitary adenomas between Eker and

Adenoma↗

Cardiac pacing in fetal lambs: intrauterine transvenous cardiac pacing for fetal complete heart block.

To evaluate the feasibility of intrauterine transvenous cardiac pacing, the right ventricular output was measured during pacing in six fetal lambs. Under maternal anesthesia, the uterus was opened, and, under local anesthesia, the pacing lead (Medtronic Capsure SP4023) was inserted via the fetal left internal jugular vein. Right ventricular output was estimated using an Aloka SSD-730 ultrasound device, and tricuspid valve regurgitation was evaluated with an Aloka SSD-880 using the transuterine approach. The ultrasonic right ventricular cardiac output was measured under three different conditions: (1) with the tip of the pacing lead in the superior vena cava (control); (2) with the tip of the pacing lead in the right ventricle; and (3) with pacing at 200 beats/min. The right ventricular output decreased when the pacing lead was inserted into the right ventricle, as well as during pacing at 200 beats/min ([1] = 107 +/- 13.2 mL/kg per min; [2] = 73.8 +/- 17.5 mL/kg per min; and [3] = 78.3 +/- 23.6 mL/kg per min). Tricuspid regurgitation did not change under any of the conditions tested. Intrauterine transvenous cardiac pacing was successfully achieved. Insertion of the pacing lead into the right ventricle decreased the ventricular output without increasing tricuspid valve regurgitation.

Animals↗

Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea.

BACKGROUND: Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS: The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS: The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS: The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea.

Adult↗

Unsei-in inhibits rheological activity of leukocytes: mechanism of action in neutrophil-related skin diseases.

To investigate the efficacy of Unsei-in on skin diseases such as Behçet's disease, palmoplantar pustulosis and psoriasis vulgaris, the rheological activity of leukocytes as manifested by adhesiveness, deformability and aggregability was studied in vitro using a micropore filtration method. Unsei-in inhibited the rheological activity of leukocytes at a statistical significance of p < 0.01 in normal individuals whose leukocytes had been stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). It did not, however, inhibit the activity of cells that had not been stimulated by FMLP. In contrast, in Behçet's disease, Unsei-in inhibited rheological activity of non-stimulated leukocytes (p < 0.01) but did not inhibit the rheological activity of FMLP-stimulated leukocytes. In a study using Ouren-gedoku-to and Shimotsu-to, the main constituents of Unsei-in, the latter inhibited the activity of FMLP-stimulated leukocytes in normal individuals (p < 0.02). These results indicate that Unsei-in has an inhibitory effect on rheologically-activated neutrophils, which are involved in the healing mechanisms of the above skin diseases, and it also has a satisfactory effect in the form of a mixture of Shimotsu-to and Ouren-gedoku-to.

Adult↗

Superficial esophageal cancer: multicenter analysis of results of definitive radiation therapy in Japan.

PURPOSE: To assess the effectiveness of definitive radiation therapy in patients with superficial esophageal cancer. MATERIALS AND METHODS: Method of irradiation, local control rate, survival rate, and complications were assessed in 105 patients (89 men, 16 women; age range, 50-88 years) with superficial esophageal cancer treated with definitive radiation therapy at 15 hospitals in 1981-1990. RESULTS: All lesions were confirmed to be squamous cell carcinoma. The overall 5-year survival rate was 38.7%; the 5-year disease-specific survival rate was 71.0%. The 2-year local control rate was 83.0%. Late complications occurred in 16 patients. The prevalence of complications was relatively high in the group treated with intraluminal radiation therapy. CONCLUSION: Local control and survival rates in patients treated with radiation therapy were excellent, especially in the group treated with external and intraluminal radiation therapy; however, the optimal dose and optimal combination of external and intraluminal radiation therapy should be further assessed.

Aged↗

Chronic lung lymph fistula that only drains the left lung.

We developed a chronic lung fistula that drains only the left lung, allowing for evaluation of injury in a single lung. To remove lymph drainage from the right lung into the caudal mediastinal lymph node, the right lower pulmonary ligament was severed. Pneumatic occluders were placed on the left pulmonary arteries and veins. To ensure that lymph drained from only the left lung, we increased the right pulmonary arterial pressure (RPAP) from 21.2 +/- 0.5 to 36.5 +/- 0.6 mmHg. The left pulmonary arterial pressure (LPAP) was kept at wedge pressure level for 1 h by inflating pneumatic occluders. Lymph flow from the left lung fistula was stable during this occlusion. Six hours after recovery was increased the LPAP from a baseline level of 19.1 +/- 1.0 to 36.4 +/- 0.9 mmHg and the RPAP from 21.2 +/- 0.5 to 38.0 +/- 0.8 mmHg for 2 h by inflating the pneumatic occluders on the left and right pulmonary veins. Lymph flow increased from 5.3 +/- 1.0 to 28.0 +/- 2.9 ml/h. Reflection coefficient was calculated at 0.80 +/- 0.02.

Animals↗

Hypoglossal nerve stimulation affects the pressure-volume behavior of the upper airway.

To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.

Animals↗