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K Nakazawa

Publications and source records attributed to K Nakazawa.

At least 163 records · Page 9Linked to original sources
PubMed1997

Evidence for UV-associated activation of telomerase in human skin.

Telomerase activation plays a crucial role in the immortalization of human cells and carcinogenesis; however, the temporal and pathophysiological aspects of the activation in vivo are poorly understood. We found telomerase activity not only in malignant tumors (91%) but also in most benign (60%) and premalignant (89%) skin tumors. This suggests the involvement of telomerase activation in a crucial biological step of human skin carcinogenesis. Because UV light is a major factor in skin carcinogenesis, we further examined telomerase activity in normal skin samples and in normal skin samples adjacent to benign, premalignant, and malignant skin lesions. Data for chronically sun-exposed body sites were compared with those for covered sites. Among normal skin samples, 39% (26 of 67) had telomerase activity, and this activity was unrelated to neighboring lesions but strongly associated with the level of sun exposure. Fifty-four % (21 of 39) of normal skin samples from chronically sun-exposed sites were telomerase-positive, compared with only 12% (3 of 26) of samples from covered sites. When we examined telomerase activity and CC to TT mutations at codons 247/8 of the p53 gene (which are considered to be UV specific) in the same normal skin samples, only 43% (7 of 16) of telomerase-positive normal skin samples at sun-exposed sites contained the p53 mutations, whereas all (7 of 7) of the samples with UV-specific p53 mutations showed telomerase activity (P = 0.019). These data suggest that telomerase activation is involved at an early stage of human skin carcinogenesis and that activation may precede the acquisition of UV-associated p53 mutations in the skin. Telomerase activity was also found in plucked hair follicles and enzymatically separated epidermis, which may be associated with the presence of stem cells in the skin.

Enzyme Activation↗
PubMed1997

Short- and long-latency reflex responses during different motor tasks in elbow flexor muscles.

Stretch reflex responses in three elbow flexor muscles - the brachioradialis and the short and long heads of the biceps brachii - were studied during different motor tasks. The motor tasks were iso-velocity (8 deg/s) elbow flexion movements in which the muscles performed shortening or lengthening contractions, or were isometric contractions. Care was taken to maintain constant background electromyographic (EMG) activity in the brachoradialis muscle at a 50-deg elbow angle across the tasks by changing the magnitude of the initial load. During each task, mechanical perturbations (duration 170 ms) were applied at pseudorandom intervals when the elbow angle was 50 deg. The magnitude of the perturbation was varied across tasks in order to induce an elbow extension velocity of 80 deg/s over the first 50 ms after the onset of perturbation. The stretch reflex EMG responses in all muscles varied across the three tasks, despite a constant EMG level and similar perturbation-induced angular velocity in the direction of elbow extension. In particular, both the short- and long-latency reflex EMG components were reduced during the lengthening contractions. Further, the task-dependent variations in the early (M2) and the late (M3) components of the long-latency reflex were different, i.e., the magnitude of M3 was considerably enhanced during the shortening task as compared with that of M2. These findings suggest that central modification was responsible for the task-dependent modulation of late EMG responses.

Adult↗
PubMed1997

Does nitric oxide mediate plasma extravasation induced by electrical stimulation of the superior salivatory nucleus in cat nasal mucosa?

The effects of electrical stimulation, applied to the superior salivatory nucleus (SSN) or the cervical sympathetic nerve, on vascular permeability in nasal mucosa were studied in 16 cats. Plasma extravasation was quantified by using Evans blue. Vascular permeability in the cat nasal mucosa was increased by the electrical stimulation of SSN. Plasma extravasation induced by SSN stimulation was reduced by administration of nitric oxide synthase (NOS) antagonist, N(omega)-nitro-L-arginine methyl ester (L-NAME). Administration of atropine did not affect increased vascular permeability by SSN stimulation. We conclude that neurogenic plasma extravasation in cat nasal mucosa evoked by the parasympathetic nerve is not mediated by cholinergic fibers but rather by nitric oxide.

Animals↗
PubMed1997

Role of pulmonary afferent inputs in vocal on-switch in the cat.

The purpose of this paper is to elucidate the possible role of pulmonary afferent inputs in triggering inspiratory-vocal (I-V) and Vocal-inspiratory (V-I) transitions during periaqueductal gray (PAG)-induced vocalization. Under ketamine anesthesia, we investigated the effects of changes in pulmonary afferent inputs on the PAG-induced vocal motor pattern by transection and electrical stimulation of the cervical vagus nerve in non-paralyzed cats and by lung inflation and deflation in paralyzed cats. After bilateral vagotomy, PAG stimulation induced apneusis; strong suppression of the I-V transition disrupted the vocal rhythmicity. Electrical stimulation of the central end of the cut vagus nerve during PAG stimulation immediately caused an I-V transition. In paralyzed cats during the withholding of lung inflation, the I-V transition was also suppressed during PAG stimulation. Lung inflation during PAG stimulation caused a phase switch from inspiration to fictive vocalization, i.e. I-V transition. In contrast, this fictive vocal phase maintained by lung inflation was terminated by lung deflation, i.e. V-I transition. These findings suggest that pulmonary vagal afferent feedback plays an important role in triggering and terminating vocalization.

Afferent Pathways↗
PubMed1997

Potent and voltage-dependent block by philanthotoxin-343 of neuronal nicotinic receptor/channels in PC12 cells.

1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 microM inhibited an inward current activated by 100 microM ACh. The current inhibition was relieved by depolarizing steps, and augmented at negative potentials, suggesting that PhTX-343 blocks the channel in a voltage-dependent manner. Joro spider toxin-3 (JSTX-3) also exerted voltage-dependent inhibition of ACh-activated currents in a similar concentration range, but argiotoxin636 did not affect the currents. 3. Analysis of the current decay during hyperpolarizing steps indicated that the current inhibition by 100 nM PhTX-343 develops in an order of several hundres of milliseconds. On the other hand, the recovery from the current inhibition during depolarizing steps developed in an order of about 100 ms. 4. The results suggest that PhTX-343 blocks neuronal nicotinic receptor channels in PC12 cells at concentrations lower than those required for channel block in non-mammalian cells, and the block exhibits clear voltage-dependence. Estimated from the voltage-dependence, the binding site of PhTX-343 may be located near the outer mouth of the channel.

Acetylcholine↗
PubMed1997

Visual evaluation of train-of-four and double burst stimulation, fade at various currents, using a rubber band.

The sensitivity of train-of-four (TOF) or double burst stimulation3,3 (DBS3,3) was examined to detect fade by visual inspection, at varying stimulating currents, using the thumb of the investigated arm maintained abducted by the use of a rubber band. One-hundred adult patients were allocated randomly to (1) train-of-four-rubber band (TOF-RB), (2) train-of-four-control (TOF-control), (3) double burst stimulation-rubber band (DBS-RB), or (4) double burst stimulation-control (DBS-control) group. Each group contained 25 patients. The thumb of the investigated arm was kept abducted using a rubber band in the TOF-RB band and DBS-RB group and was free in the TOF-control and DBS-control. TOF stimuli were delivered in the TOF-RB and TOF-control groups, and DBS3,3 in the TOF-RB and TOF-control at 50, 30 and 20 mA. The probability of visual detection of TOF fade was the same in the TOF-RB and TOF-control groups. In contrast, when measured TOF ratio was 0.51-0.80, at the stimulating current of 50 or 30 mA, the likelihood of visual detection of fade in the DBS-RB group was significantly higher than in the DBS-control group (P < 0.05). With a TOF ratio of 0.61-0.70, in the DBS-RB group the probability of visual detection of fade at 50 or 30 mA was significantly higher than at 20 mA (P < 0.05). This study suggests that when using a rubber band, fade in response to the DBS3,3 is detected by visual inspection more readily at a stimulating current of 50 or 30 mA than without the rubber band.

Adult↗
PubMed1997

Modification of proteoglycan synthesis by corneal stromal cells on co-culture with either epithelial or endothelial cells.

Corneal stromal cells, prepared from 2-day-old chicks and embedded in collagen gel on an insert dish, were co-cultured with corneal epithelial cells or endothelial cells on a fibronectin-coated companion plate. Cell growth and proteoglycan synthesis, as determined as the incorporation of [35S] sulfate and [3H] glucosamine, were examined for each cell type in both combinations. In comparison with single cultures, growth was affected little, while proteoglycan synthesis was appreciably altered in both combinations. Stromal and epithelial cells stimulated proteoglycan synthesis by each other, while endothelial cells stimulated the synthesis by stromal cells, but stromal cells reduced that by endothelial cells to some extent. Endothelial cells alone synthesized proteoglycans much more actively than did epithelial or stromal cells. Analysis of the radiolabeled proteoglycans revealed that endothelial and epithelial cells had different effects on proteoglycan synthesis by stromal cells: the former tended to increase keratan sulfate synthesis by stromal cells, while the latter tended to increase chondroitin sulfate/dermatan sulfate synthesis. Proteoglycan synthesis in the corneal stroma in vivo might thus be controlled by the balance between the antipodal actions of the epithelial and endothelial cell layers.

Animals↗
PubMed1997

Evaluation of residual neuromuscular block using train-of-four and double burst stimulation at the index finger.

We examined the percentage of tactile detection of fade in response to train-of-four (TOF), double burst stimulation3,3 (DBS3,3), or DBS3,2 at the index finger compared with that at the thumb during continuous infusion of vecuronium. One hundred five adult patients were studied. At TOF ratios (T4/T1) of 0.41-0.70, fades in response to TOF were more frequently identified by tactile means at the index finger than at the thumb (58% vs 26%, P < 0.05). Similarly, at TOF ratios of 0.61-0.90, fades in response to DBS3,3 were more frequently detected at the index finger than at the thumb (55% vs 15%, P < 0.05), and at TOF ratios of 0.81-1.00, the percentage of detection of fade in response to DBS3,2 was higher at the index finger than at the thumb (72% vs 40%, P < 0.05). In addition, baseline displacement of the index finger or thumb during tactile assessment of fade in response to neurostimulation was measured videographically. The baseline displacement of the index finger was significantly less than that of the thumb (P < 0.05). In summary, the percentage of tactile detection of fade in response to neurostimulation at the index finger is higher than at the thumb, and the absence of fade in response to DBS3,3 at the index finger is a good indicator of adequate recovery from neuromuscular block. This is probably because of the smaller baseline displacement of the index finger.

Adult↗
PubMed1997

Evaluation of residual neuromuscular blockade using modified double burst stimulation.

BACKGROUND: To assess the degree of residual neuromuscular blockade, double burst stimulation (DBS) is commonly applied in the clinical setting. However, fades in response to DBS3,3 can rarely be identified manually when train-of-four (TOF) ratios are > or = 0.70, and, in contrast, fades in response to DBS3,2 are felt manually in an undesirably high proportion of cases, even at TOF ratios greater than 0.7. We investigated whether a new monitoring method, modified DBS, would be useful to determine an adequate degree of recovery from neuromuscular blockade. For modified DBS, two burst stimuli were applied at an interval of 750 ms. The first stimulation in the modified DBS consisted of two stimuli of 0.3 ms duration at 50 Hz and the second of two stimuli of 0.2 ms duration at 50 Hz. METHODS: Forty-five adult patients undergoing elective nitrous oxide-oxygen-isoflurane anesthesia were randomly divided into one of three groups: DBS3,3 group (n = 15), DBS3,2 group (n = 15), or modified DBS group (n = 15). During recovery from vecuronium-induced neuromuscular blockade, on both forearms, DBS3,3, DBS3,2, and modified DBS were delivered in the DBS3,3 group, DBS3,2 group, and modified DBS group, respectively. One hand and forearm (fixed arm) were immobilized to quantify the degree of neuromuscular blockade mechanically, and the contralateral arm (free arm) was unrestrained. An observer determined tactiley on the free arm the presence or absence of fade in response to the three DBS patterns. RESULTS: Probabilities of detection of fade in response to the DBS3,3 were 67% (TOF ratio of 0.51-0.60), 40% (0.61-0.70), 19% (0.71-0.80), 5% (0.81-0.90), and 0% (0.91-1.00). Those to the DBS3,2 were 95% (0.51-0.60), 93% (0.61-0.70), 83% (0.71-0.80), 65% (0.81-0.90), and 38% (0.91-1.00). Those to modified DBS were 90% (0.51-0.60), 86% (0.61-0.70), 65% (0.71-0.80), 25% (0.81-0.90), and 3% (0.91-1.00). Those modified DBS was more sensitive in diagnosing residual neuromuscular blockade than DBS3,3 at the TOF ratio of 0.51-0.90, but was less sensitive than DBS3,2 at the TOF ratio of 0.81-1.00 (P < 0.05). CONCLUSION: Our results indicate that the modified DBS may be a useful stimulation pattern to diagnose the adequacy of recovery from neuromuscular blockade.

Adult↗
PubMed1997

Pigmented human skin equivalent: new method of reconstitution by grafting an epithelial sheet onto a non-contractile dermal equivalent.

We have established a new protocol for reconstituting a pigmented human skin equivalent (PSE) and have evaluated its functional responses to environmental stimulus, UVB. The PSE is reconstituted by grafting an epithelial sheet consisting of keratinocytes and melanocytes onto a porous non-contractile dermal equivalent populated with mitotically and metabolically active fibroblasts. i) The PSE has a multilayered, well-differentiated epidermis with cuboidal basal cells and highly organised dermis with newly synthesised extracellular matrix components. ii) Ki67-positive proliferating keratinocytes (18.1 +/- 7.4%) were detected on the basal layer of the epidermis. iii) Melanocytes located exclusively within the basal layer were detected by monoclonal antibody against tyrosinase-related protein (TRP-1). iv) After exposure to UVB (100 mJ/cm2 per day) for 7 consecutive days, the intensity of TRP-1 staining was increased in the PSE, showing their functional state, whereas the number of melanocytes was not changed. This non-contractile and functioning new PSE is potentially useful as a model for studying the role of melanocyte-keratinocyte-fibroblast interactions in photoprotection of the skin in more complex cutaneous microenvironment than monolayer culture, and for developing in vitro disease models and therapeutic protocols with genetically altered cells both in epidermis and dermis.

Cells, Cultured↗
PubMed1997

Voltage-dependent gating of ATP-activated channels in PC12 cells.

The possibility that P2X receptors exhibit voltage-dependent gating in a similar manner to nicotinic receptors was investigated in rat pheochromocytoma cells with the use of whole cell voltage-clamp techniques. In the presence of extracellular ATP, slowly activating inward currents were elicited by stepping from -50 mV to potentials more negative than -80 mV; these currents had a time constant of approximately 60 ms at -120 mV. This slowly activating component (as a fraction of the total ATP-induced current) increased with membrane hyperpolarization from -80 to -100 mV and was much increased when depolarizing prepulses were applied, although the time constant of activation was not altered by depolarizations. The fraction of the slowly activating current and its time constant were decreased as the ATP concentration was increased from 10 to 300 microM. Thus it has been demonstrated that voltage-dependent gating of ATP-activated channels does occur in PC12 cells, and that this gating is modified by agonist concentration. It is possible that such gating may serve as a postsynaptic mechanism to facilitate excitatory neurotransmission by contributing to the inward rectification of the ATP-activated currents.

Adenosine Triphosphate↗
PubMed1997

A new concept of dynamic orthosis for paraplegia: the weight bearing control (WBC) orthosis.

A new concept of device, termed the weight-bearing control (WBC) orthosis, has been designed with three major needs in mind; a rigid frame that supports the user's body weight, a special hip joint device that reciprocally propels each leg forward, a gas powered foot device that varies the sole thickness of the device for foot/floor clearance, and control system of the orthosis. A paraplegic (T7 level complete paraplegia, sensory evoked potential silent, response to electro-stimulation on the cortical area of the brain also silent) who has tested this WBC orthosis has been able to walk without fatigue at a high speed for a greater distance than before. In walking tests of this WBC orthosis, he achieved a maximum walking speed of 34.1 m/min for a distance of 10 metres. The walking distance reached 521 m with an average walking speed of 21.2 m/min without rest on one small tank of CO2 liquid gas, measuring 10 cm in length and 3 cm in diameter.

Adult↗
PubMed1997

Effects of long term bed rest on stretch reflex responses of elbow flexor muscles.

Stretch reflex responses of m. biceps brachii and m. brachioradialis of ten normal adults were studied before and after 20 days of strict bed rest. A standard torque perturbation (15 Nm, 170 ms) was applied to the forearm to induce reflex electromyographic (EMG) activities of the two muscles investigated. Totally 30 perturbations were applied during submaximal isometric elbow flexion movements at 80 deg flexed joint angle, and ensemble averaged EMG waveforms were calculated by aligning the signal to the onset of perturbations. All subjects showed that both short and long latency stretch reflex FMG activities of m. biceps brachii were reduced immediately after 20 days bed rest, and then recovered gradually to pre-bed rest levels at one- to two-months after bed rest, whereas there was no such variation in the stretch reflex induced in m. brachioradialis. It was demonstrated that the muscle stretch reflex gain might be reduced with long-term inactivity, but the effects on stretch reflex gains were different in the two tested muscles.

Adult↗
PubMed1997

[A study of the effects of antidepressants on the GABAA receptor and its complex based on the drug actions on the power-spectral changes of rat hippocampal EEG induced by GABA antagonists and inverse agonists].

To analyze the effects of antidepressants on the GABAA receptor, we investigated how the chronic administration of antidepressants (10 mg/kg twice a day for three or seven days, ip) influenced the power-spectral changes induced by pentylenetetrazol (PTZ; a GABA antagonist; 27.5 mg/kg) or beta-carboline-3-carboxylic-acid-methylester (beta-CCM; an inverse agonist; 1 mg/kg) on rat hippocampal EEGs. PTZ and beta-CCM are known to inhibit the chloride ionophore and benzodiazepine receptor (GABAA receptor complex), respectively. After the ip injection of both compounds, the EEG power under 12 Hz increased to about five times that before injection. Between the rats that did not receive any antidepressants and all those injected with the drugs for 3 days or treated with desipramine (DMI) for 7 days, there were no apparent changes in the effect of PTZ or beta-CCM. However, in the rats treated with imipramine, fluoxetine or trazodone for 7 days, the increase in power after the injection of PTZ or beta-CCM was apparently suppressed. In these rats, the power values were less than three times those before the dosing of PTZ or beta-CCM. DMI is known to inhibit the re-uptake of norepinephrine (NE), while the other three antidepressants inhibit that of serotonin (5-HT). Trazodone is also reported to block the 5-HT2 sites. These observations might indicate that the chronic administration of antidepressants prompted the function of the GABAA receptor complex. Moreover, it is also suggested that, to that action, the effect of antidepressants on the 5-HT system or interaction between the 5-HT system and GABA receptors might play some role.

Animals↗
PubMed1997

[A survey of radioactive levels of agricultural products in Saitama Prefecture].

Past atmospheric nuclear testing which have been conducted frequently, have caused environmental pollution due to the diffusion of radioactive substances into the atmosphere and from the radioactive fallout. The environmental pollution from nuclear testing into the atmosphere has resulted in the radioactive contamination in agricultural products and has continued for a long time. The radioactive contamination of agricultural products occurs through air, water and soil which were contaminated by radioactive fallout. In this paper, for the purpose of analyzing the extent of the radioactive contamination levels in the agricultural products of Saitama Prefecture, spinach, green soybeans, dried shiitake and welsh onion, were selected among products, as the amount of the harvest is abundant in all of Japan. Radioactivity concentration was investigated by gamma ray spectrometry and radiochemical analysis. The radioactivity concentrations of artificial radioactive nuclides, cesium-137 (137Cs) and strontium-90 (90Sr), were detected in the range which is considered to be the result of radioactive fallout. Moreover, in order to examine the effect on radioactivity concentrations in agricultural products by culinary processing, the raw agricultural products were boiled, and their radioactivity concentrations were compared with the raw produce. The radioactivity concentrations in the boiled were lower than those in the raw produce.

Cesium Radioisotopes↗
PubMed1997

[Effects of thiopental and sevoflurane on hemodynamics during anesthetic management of electroconvulsive therapy].

The effect of thiopental and sevoflurane (1 MAC, 2 MAC) on hemodynamics was assessed in a randomized study involving 38 adult patients undergoing electroconvulsive therapy (ECT). Blood pressure, heart rate and electrocardiogram (ECG) were monitored during the ECT procedure. After oxygenation, hypnosis was induced with a bolus injection of thiopenal (TPS) 4 mg.kg-1. Muscle relaxation was achieved by succinylcholine, 1 mg.kg-1 intravenously before ECT procedure. Ventilation was assisted using a face mask with 100% oxygen (TPS group), 1.7% sevoflurane (1 MAC group) or 3.4% sevoflurane (2 MAC group), plus 50% nitrous oxide and 50% oxygen. Thereafter, an electrical stimulus was administered. A total of 150 treatment sessions were evaluated. The rate pressure product increased in every group right after ECT, but the use of sevoflurane (2 MAC) significantly diminished the response compared with sevoflurane (1 MAC) and thiopental. In the sevoflurane (2 MAC) group, no ventricular arrhythmias were observed. In general, it seems that sevoflurane (2 MAC) is as effective as thiopental and sevoflurane (1 MAC) as an induction agent for ECT.

Adult↗
PubMed1997

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

Adolescent↗