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Biomedical subjects

M Sumi

Publications and source records attributed to M Sumi.

At least 73 records · Page 4Linked to original sources

Expression of a constitutively active Ca2+/calmodulin-dependent kinase in Aspergillus nidulans spores prevents germination and entry into the cell cycle.

The unique gene for Ca2+/calmodulin-dependent protein kinase (CaMK) has been shown to be essential in Aspergillus nidulans. Disruption of the gene prevents entry of spores into the nuclear division cycle. Here we show that expression of a constitutively active form of CaMK also prevents spores from entering the first S phase in response to a germinating stimulus. Expression of the constitutively active kinase induces premature activation of NIMEcyclin B/NIMXcdc2 in G0/G1. As NIMXcdc2 is present in spores, the elevation of maturation promotion factor activity may be secondary to the early production of NIMEcyclin B or post-translation modification of maturation promotion factor. The expression of the constitutively active CaMK also results in the appearance of NIMA kinase activity within 1 h of the germinating signal. These results support the contention that the activities of maturation promotion factor and NIMA are coincidentally regulated in A. nidulans and suggest that the unscheduled appearance of one or both of these activities may be sufficient to prevent A. nidulans spores from entering into DNA synthesis.

Aspergillus nidulans↗

Fractionated stereotactic radiotherapy for choroidal melanoma.

Stereotactic radiotherapy used for the treatment of choroidal melanoma made use of a 6-MeV linac with built-in multileaf collimators and a simple plastic head mold. The latter provided excellent head and ocular immobilization. The system resulted in highly localized dose distributions with a maximum 2-mm targeting error during fractionated treatments. Based on these techniques, sixteen patients with choroidal melanoma have so far been treated. Majority of patients received a total dose of 48 Gy in 8 fractions. Fourteen patients who presented with small- to moderate-sized tumors have remained free of relapse or major complications during the follow-up period of 3-42 months. Two patients who presented with an extensive tumor eventually required enucleation after irradiation. Technical precision required for stereotactic radiotherapy and reproducibility for fractionation appear adequate. Encouraging preliminary results justify further studies to evaluate its efficacy as an alternative to other conventional therapeutic approaches.

Adult↗

Technical considerations for fractionated stereotactic radiotherapy of hepatocellular carcinoma.

Technical aspects of fractionated stereotactic radiotherapy for solitary hepatocellular carcinoma have been investigated. Precise positioning of the patient and substantial reduction of the liver movement due to respiration were achieved by placing the patient ventrally on the treatment couch without a body cast. Repeated CT examinations were required for verification of tumor targeting. Though there were geometrical limitations on gantry rotation when the linac couch was rotated from its standard position, dose distributions obtained were found to be excellent. A patient with a small solitary lesion in the posterior segment of the liver received 52 Gy in 13 fractions over 29 days. He tolerated the treatment well without experiencing any morbidities or deterioration of liver functions. Three months later his alpha-fetoprotein value returned to normal and CT examinations revealed tumor shrinkage as well as a reduction in the viability of the tumor cells. The results suggest that it is possible to overcome technical difficulties associated with fractionated stereotactic radiotherapy of intraabdominal tumors.

Aged↗

The addition of phenylephrine contributes to the development of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine.

BACKGROUND: Recent reports indicate that transient neurologic symptoms commonly occur after single-injection spinal anesthesia with lidocaine. Information regarding tetracaine has been limited to a single case report. In addition, little is known about the cause of these symptoms or the cofactors that affect their occurrence. The present study sought to determine whether the presence of phenylephrine or the concentration of glucose in the anesthetic solution affects the incidence of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine. METHODS: One-hundred sixty patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for elective surgery on a lower limb or perineum were sequentially assigned to one of four equal groups to receive intrathecal 0.5% tetracaine in 7.5% or 0.75% glucose, with or without 0.125% phenylephrine. Patients were evaluated on postoperative day one for the presence of pain, dysesthesia, or both in the legs or buttocks by an investigator unaware of the drug given. RESULTS: Symptoms were present in 10 patients (12.5%) receiving a spinal anesthetic containing phenylephrine, but in only one patient (1.3%) receiving spinal anesthesia without phenylephrine. There was no significant difference in the incidence of symptoms between groups receiving 7.5% glucose and those receiving 0.75% glucose (8.8% and 5% of patients, respectively). CONCLUSIONS: These results suggest that adding phenylephrine to tetracaine for spinal anesthesia increases the potential for transient neurologic symptoms, but that the concentration of glucose does not affect their occurrence.

Adult↗

Effect of respiratory rate on respiratory patterns in patients with chronic obstructive pulmonary disease.

We enrolled 22 patients with chronic obstructive pulmonary disease (COPD) and 20 normal subjects as controls. Using a hot-wire flow meter, we obtained tidal volume (VT), duty ratio (Ti/Ttot), and mean inspiratory flow (VT/Ti) as measures of respiratory pattern at two different respiratory rates; 0.5 Hz and 1.5 Hz. At 0.5 Hz, there were significant differences in Ti/Ttot and VT/Ti. At 1.5 Hz, patients with COPD had significantly lower values of VT and VT/Ti. Furthermore, we calculated the change ratios from 0.5 Hz to 1.5 Hz in these parameters as new parameters of respiratory pattern change by respiratory rate. VT0.5/1.5 and VT/Ti0.5/1.5 significantly correlated with FEV1.0/FVC. The findings suggest that the parameters of the respiratory pattern may change depending on respiratory rates, and that the ratios of those parameters obtained at two different rates could be helpful in diagnosing airflow obstruction.

Aged↗

[Radiotherapy for non-small cell lung cancer].

Standard therapy for unresectable localized non-small cell lung cancer has been radiotherapy alone, but the treatment results were not satisfactory in terms of high incidence of distant metastasis and poor local control. Various kinds of prospective randomized clinical trials (RCT) were undertaken to solve the problems of encompassing the treatment field, total treatment dose, alteration of fractionation and combination of the chemotherapy drugs since 1970's. Radiation field which includes the primary site, ipsilateral hilar and mediastinal lymph nodes, and the total radiation dose of 60Gy in 6 to 7 weeks has been assumed as standard. However, with the advent of 3-dimensional treatment planning including the inverse planning method, particle radiotherapy and intraluminal brachytherapy, some trials are on-going to increase the total dose up to 70Gy or more in relation to the more confinement of the treatment field to the primary site only. Fractionation has also been studied to reduce the late normal tissue damage or to increase the total tumor dose, and is at present in favor of the accelerated hyperfractionation. Meta-analysis of the results of 11 RCT's revealed that the results with combination chemoradiotherapy including cisplatin yields longer MST, and higher 2-year survival rate.

Carcinoma, Non-Small-Cell Lung↗

[Improvement in function-preservation in radiotherapy for pediatric malignancies].

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery. Patients are not restricted in radioprotective area, and the overall treatment period is short enough. F-SRT is used either as the boost of conventional brain radiotherapy in primary brain neoplasms, or as hypofractionated F-SRT for control of metastatic brain tumors, with nearly perfect local control and maintenance of good quality of life. F-SRT is planned in 3-dimensional fashion from computed tomography images. Easily detachable, relocatable cast made for F-SRT is useful in pediatric patients.

Brachytherapy↗

Investigation of aortic CYP3A bioactivation of nitroglycerin in vivo.

Nitroglycerin (GTN) has been used to treat heart disease for many years. It is generally believed that GTN is a prodrug; however, the mechanism for GTN bioactivation remains unknown. Recent studies, using hepatic microsomes, have suggested the involvement of cytochrome P450 3A (CYP3A) in GTN biotransformation. Here, we used an animal model to test the hypothesis that aortic CYP3A plays a role in the bioactivation of GTN in vivo. Ketoconazole (KCZ), a potent CYP3A inhibitor, was given to rats (50 mg/kg i.p.) 1 hr before a bolus dose of GTN (2 mg/rat i.v.). KCZ decreased GTN-induced cGMP (cyclic guanosine monophosphate) levels by 20 to 30% (P < .05), without affecting basal or S-nitroso, N-acetyl penicillamine-induced levels of cGMP. When rats received dexamethasone (DEX, 30 mg/kg, 4 days i.p.), a strong CYP3A inducer, they exhibited a significant (approximately 50%) higher cGMP response to GTN than the control group. When rats received the combination treatment of both DEX and KCZ, they responded to GTN to the same extent as control rats. Although the effect of KCZ on aortic CYP3A activity cannot be detected (activity in control rats is below the detection limit), KCZ markedly inhibited CYP3A activity in rat livers (2.02 +/- 0.04 vs. 0.31 +/- 0.04 nmol/mg prot/min, P < .05, in control vs. KCZ-treated rats, respectively) and in DEX pretreated rat aorta (0.145 +/- 0.036 vs. 0.042 +/- 0.037 nmol/mg prot/min, P < .05, in rats treated with DEX alone vs. rats treated with both DEX and KCZ, respectively). KCZ did not elicit an effect on aortic glutathione S-transferases, another major metabolic enzyme responsible for GTN biotransformation. DEX enhanced the aortic GST mu activity by 3-fold. However, the activity of GST in aorta did not correlate with the cGMP response to GTN. In conclusion, our results demonstrate that CYP3A activity in aorta is correlated with GTN bioactivation in vivo, but the contribution of this enzyme to overall GTN bioactivation is limited.

Animals↗

[Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema].

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.

Aged↗

MR signal intensity of the perirolandic cortex in the neonate and infant.

Our purpose was the study the magnetic resonance (MR) signal intensity of the perirolandic gyri perinatally and to correlate it with the histological findings in formalin-fixed brains, focusing on myelination. MRI of 20 neurologically normal neonates and infants, of 37-64 weeks postconception (PCA), were studied retrospectively. We reviewed four formalin-fixed brains of infants 37-46 weeks PCA microscopically. The posterior cortex of the precentral gyrus (P-PRE) and the anterior cortex of the postcentral gyrus (A-PST) had different signal intensity from the adjacent surrounding cortex. On T1-weighted images P-PRE and A-PST gave higher signal 41-44 weeks PCA; on T2-weighted images, they gave lower signal 37-51 weeks PCA. Histological examination revealed very little myelination of the nerve fibres within both the P-PRE and the A-PST, while considerable myelination was present in the internal capsule and central corona radiata. The changes in signal intensity in the perirolandic gyri may reflect not only the degree of myelination but also the more advanced development of the nerve cells, associated with rapid proliferation and formation of oligodendroglial cells, synapses and dendrites. They could be another important landmark for brain maturation.

Age Factors↗

Comparison of glucose 7.5% and 0.75% with or without phenylephrine for tetracaine spinal anaesthesia.

PURPOSE: To investigate whether a marginally hyperbaric tetracaine solution with or without phenylephrine could produce consistent blocks as compared with a conventionally hyperbaric tetracaine solution injected at L3-4 interspace with the patient in the lateral position. METHODS: We studied 120 ASA I or II patients scheduled for elective surgery to the lower limb. Patients were randomly divided into four equal groups to receive spinal anaesthesia using tetracaine 0.5% in glucose 0.75% or 7.5%, with or without phenylephrine 0.125%. Neural block was assessed in a double-blind manner by cold, pinprick, and touch sensation, and a modified Bromage scale after the injection of the study drug. RESULTS: The median (10th, 90th percentiles) peak dermatomal level to pinprick obtained by the solutions in glucose 0.75% was T10 (L1, T5), which was lower than that obtained by the solution in glucose 7.5% extending to T5 (T10, T3) and T5 (T10, T2) with or without phenylephrine, respectively (P < 0.0001). The addition of phenylephrine prolonged the time to two-segment regression but did not change the maximum extent of blocks. CONCLUSIONS: A marginally hyperbaric tetracaine with or without phenylephrine produced consistent blocks with spread restricted to the lower thoracic segments when administered intrathecally at the L3-4 interspace with the patient in the lateral position.

Adult↗

In vitro interaction between tetracalcium phosphate-based cement and calvarial osteogenic cells.

Newly-developed tetracalcium phosphate-based cement (4CP cement) and cells derived from neonatal rat calvaria were cocultured to study the in vitro reaction of osteoblastic cells to the biomaterial at light and electron microscopic levels. Three-dimensional nodular structures covered with active osteoblastic cells were formed in the periphery of the test material and they contained a mineralized tissue that exhibited features closely resembling bone formed in vivo. Ultrastructurally, the test material was circumscribed with an electron-dense structure, and was immediately adjacent to elongated cyoplasmic processes with intact morphology or collagen fibrils with periodic structures. Furthermore, the mineralization of the extracellular collagenous matrix occurred directly on the surface of the material. These in vitro findings suggest the ability of 4CP cement to bind directly with newly-formed hard tissues.

Animals↗

[Invasive thymoma associated with pure red cell aplasia and lung cancer].

A 71-year-old man was admitted to our hospital with vertigo and general fatigue. Examination of his blood and bone marrow showed pure red cell aplasia. His chest X-ray film revealed an anterior mediastinal mass and a nodular shadow in the right lower lobe. Extended thymothymectomy and right lower lobectomy were done. The mediastinal mass appeared to be an invasive thymoma and the nodular shadow in the right lower lobe proved to be from an adenocarcinoma. The patient was treated with radiation and steroids. Thymoma, pure red cell aplasia, and lung cancer had not recurred and he was alive and well as of 2 years after surgery.

Adenocarcinoma, Papillary↗

[Effects of pulmonary rehabilitation on vital capacity in patients with chronic pulmonary emphysema].

To evaluate the effects of pulmonary rehabilitation on pulmonary function, 15 patients with chronic pulmonary emphysema underwent pulmonary rehabilitation for six weeks as inpatients. Pulmonary rehabilitation consisted of relaxation techniques, breathing retraining, thoracic massage, physical exercise, and walking. In 8 of the 15 patients vital capacity increased by more than 200 ml (over 10%), and in 7 of the 15 patients the load of maximal exercise increased by more than 5 watts (over 10%). Increases in vital capacity were not associated with increases in maximal exercise load. The percent change in vital capacity associated with pulmonary rehabilitation correlated significantly with the percent change in tidal volume and the percent change in expiratory minute ventilation at the maximal load. The percent change in tidal volume at the maximal load correlated significantly with the percent change in maximum oxygen uptake. We attribute the increase in vital capacity to an improvement in thoracic cage movement. These findings suggest that pulmonary rehabilitation can increase vital capacity in some patients with chronic pulmonary emphysema, and that such an increase is not directly connected to increases in exercise capacity.

Aged↗

[Psychological and physiological changes accompanying pulmonary rehabilitation in patients with chronic pulmonary emphysema].

In 14 patients with chronic pulmonary emphysema, the relations between changes in psychological status associated with pulmonary rehabilitation and exercise tolerance were studied with the Cornell Medical Index and the Yatabe-Guiford Personality Inventory. Although the scores on the latter did not change, the cardio-respiratory score on the Cornell Medical Index improved significantly (p < 0.05). The only index of exercise tolerance that improved significantly was the distance walked in 10 minutes (p < 0.05). The changes in the scores of "Lack of Objectivity" and "Rhathymia" correlated negatively with the change in the distance walked in 10 minutes (R = -0.80, p < 0.01; R = -0.81, p < 0.01). The change in psychological status that accompanied pulmonary rehabilitation has been related to the improvement in the distance walked in 10 minutes.

Aged↗