Search PubMed⌕ Search

Biomedical subjects

K Nakazawa

Publications and source records attributed to K Nakazawa.

At least 145 records · Page 8Linked to original sources

Regulatory effects of heat on normal human melanocyte growth and melanogenesis: comparative study with UVB.

Although energy-rich ultraviolet B (UVB) is considered to be primarily responsible for most of the effects associated with solar radiation, small energy recorded as heat appears to contribute to the biologic effects of solar radiation on the skin. We compared the effects of heat and UVB on normal human melanocyte functions. In monolayer culture the following was found. (i) Heat-treated melanocytes showed an increased dendricity and exhibited a larger cell body compared with nontreated melanocytes. (ii) After multiple treatments with UVB (20 mJ per cm2, 312 nm) or heat (42 degrees C for 1 h) for 3 d, melanocytes had a lower survival than nontreated melanocytes, but they resumed proliferation within 6 d in the same manner as seen in control. (iii) The expression levels of cell cycle regulators, p53 and p21 proteins, were increased after multiple treatments with UVB or heat. (iv) The tyrosinase (dopa-oxidase) activity per cell was increased after the multiple treatments with UVB or heat. (v) The number of dopa-positive melanocytes in coculture with keratinocytes in epithelial sheets was greatly increased by UVB or heat treatments. (vi) Similarly, the increased number of tyrosinase-related protein 1 positive melanocytes was seen in skin equivalents after UVB (100 mJ per cm2) or heat (42 degrees C for 1 h) treatments for 7 d. These results suggest that heat shares significant biologic activities with UVB in melanocyte functions. These results could be considered as one of the protective or adaptive responses of the skin pigmentary system to the environment.

Cell Division↗

Treatment of pulmonary hypertension and hypoxia due to oleic acid induced lung injury with intratracheal prostaglandin E1 during partial liquid ventilation.

BACKGROUND: Partial liquid ventilation using perfluorocarbon liquids may be of therapeutic benefit in patients with acute respiratory failure. This study investigated the effects of prostaglandin E1 (PGE1) delivered intratracheally during partial liquid ventilation on lung function and pulmonary circulation in rabbits with acute respiratory distress syndrome. METHODS: Lung injury was induced by intravenous oleic acid in adult Japanese white rabbits, 1 h after which they were divided into four groups of 10 animals. Group 1 received mechanical ventilation alone, group 2 received aerosolized PGE1 (5 microg followed by 0.1 microg x kg(-1) x min(-1)) under mechanical ventilation combined with 5 cm H2O positive end-expiratory pressure, and groups 3 and 4 received partial liquid ventilation with 15 ml/kg perflubron. Group 4 received a 5-microg bolus followed by 0.1 microg x kg(-1) x min(-1) PGE1 instilled intratracheally (not by aerosol) in combination with partial liquid ventilation. Measurements were performed at 30-min intervals for 120 min after lung injury. RESULTS: After lung injury, hypoxemia, hypercapnia, acidosis, and pulmonary hypertension developed in all animals and were sustained in groups 1 and 2 throughout the experiment. The partial pressure of oxygen in arterial blood of animals in group 3 improved with initiation of treatment, with statistical significance achieved at the 30 and 60 min time points as compared with controls. Group 4 animals had immediate and sustained increases in the partial pressure of oxygen in arterial blood that were significant compared with all other groups during the experiment. Statistically significant reductions in mean pulmonary artery pressure were seen only in group 4 animals compared with all other groups. CONCLUSIONS: These results suggest that PGE1 delivered intratracheally during partial liquid ventilation may be a useful therapeutic strategy for patients with the acute respiratory distress syndrome.

Animals↗

Behaviors of hypoglossal hyoid motoneurons in laryngeal and vestibular reflexes and in deglutition and emesis.

Reflex responses of hypoglossal motoneurons innervating the geniohyoid (GH) and thyrohyoid (TH) muscles from the superior laryngeal (SLN) and vestibular nerves and their behaviors during fictive swallowing and vomiting were examined by recording both the extracellular activities of 11 single cells in the hypoglossal nucleus and GH and TH muscle nerve activity in eight decerebrate, paralyzed, and artificially ventilated cats. The majority of TH motoneurons were either active and/or exhibited shortened antidromic latencies during early expiration. In contrast, GH motoneurons did not exhibit any respiratory-related activity. Electrical single-shock stimulation of the SLN never evoked an excitatory reflex response on GH or TH motoneurons but rather evoked inhibitory responses on the THs. Unlike other hypoglossal motoneurons, GH and TH motoneurons do not appear to receive vestibular inputs. However, they can exhibit robust activities during fictive swallowing and vomiting, particularly during expulsion. Thus these motoneurons may play an important role in airway protection during swallowing and vomiting but not in controlling upper airway patency regulated by vestibular afferents.

Animals↗

Formation of a spherical multicellular aggregate (spheroid) of animal cells in the pores of polyurethane foam as a cell culture substratum and its application to a hybrid artificial liver.

Monkey kidney cells (Vero), human embryonic kidney cells (293), human liver cells (PLC/PRF/5), and primary rat, dog, and porcine hepatocytes formed spherical multicellular aggregates (spheroids) in the pores of polyurethane foam which was used as a cell culture substratum. These spheroids of various cell types express high cell activity for a long period. A practical hybrid artificial live support system composed of a multi-capillary polyurethane foam packed-bed type cell culture module including primary hepatocyte spheroids was developed. The success of the system is indicated by an 80% recovery rate in hepatic failure rats which died in control experiments.

Animals↗

Amrinone improves right ventricular ejection fraction and oxygen delivery without deterioration of extravascular lung water in canine oleic acid pulmonary injury.

Fourteen mongrel dogs were anaesthetized and mechanically ventilated with oxygen. After oleic acid was administered intravenously, amrinone 1 mg/kg was intravenously administered to one group followed by a continuous infusion of 10 micrograms/kg/min for one hour (amrinone group, n = 7). Isovolumetric saline was administered to the control group (n = 7). Amrinone slightly lowered PaO2 but significantly increased oxygen delivery and improved gastric intramucosal pH (pHi) during the first 30 minutes (7.33 +/- 0.13) compared with the control group (7.21 +/- 0.06, P < 0.05). The pHi remained higher in the amrinone group (7.30 +/- 0.15) than in the control group (7.16 +/- 0.06, P < 0.05) after the drug was withdrawn. Extravascular lung water was significantly augmented after oleic acid injection and sustained in all animals for the remainder of the study.

Amrinone↗

Tracheal intubation through the intubating laryngeal mask airway (LMA-Fastrach) in patients with difficult airways.

The intubating laryngeal mask airway was used in 31 adult patients in whom tracheal intubation was known or suspected to be difficult. The intubating laryngeal mask airway was successfully inserted in 30 patients and provided a clinically patent airway. In the remaining one patient it was impossible to insert the device correctly. Tracheal intubation through the device was successful in 28 of 30 patients (93%). These results suggest that the intubating laryngeal mask airway has a potential role for tracheal intubation in adult patients with difficult airways.

Adolescent↗

The combination of partial liquid ventilation and inhaled nitric oxide in the severe oleic acid lung injury model.

STUDY OBJECTIVES: To elucidate the efficacy of the combination of inhaled nitric oxide (NO) and partial liquid ventilation (PLV) in ARDS. DESIGN: Prospective, randomized, controlled study. SETTING: A research laboratory at a university medical center. SUBJECTS: Thirty-two rabbits. INTERVENTIONS: Animals were anesthetized and ventilated via tracheostomy (tidal volume=40 mL; respiratory rate=25 breaths/min; fraction of inspired oxygen=0.99). After 0.08 mL/kg (0.071 g/kg) oleic acid was administered via the central venous route, animals were randomly divided into the following four groups depending on the ventilatory mode: (1) Gas ventilation (GV)-control group: GV was continued throughout the study; (2) GV-NO group: NO inhalation (10 ppm) was performed under GV; (3) PLV-control group: PLV using perflubron (15 mL/kg) was continued until the end of the study; and (4) PLV-NO group: NO inhalation (10 ppm) was performed under PLV. MEASUREMENTS AND RESULTS: NO inhalation improved PaO2 in the PLV-NO group (from 133+/-20 to 167+/-23 mm Hg; p=0.0008), but not in the GV-NO group (from 67+/-6 to 63+/-9 mm Hg), although pulmonary vascular resistance decreased both in the GV-NO (from 4,604+/-328 to 4,337+/-322 dyne x s x cm(-5); p=0.0116) and the PLV-NO group (from 4,727+/-665 to 4,112+/-560 dyne x s x cm(-5); p=0.0036). (Data were expressed as mean+/-SEM.) CONCLUSION: PLV augmented the effect of inhaled NO on pulmonary gas exchange. The combination of PLV and NO inhalation could be effective in severe ARDS.

Animals↗

A study on development of a home health care support information system.

As the need for home health care has been increasing with the rising number of the elderly in Japan, the application of medical informatics to home health care delivery is considered to be useful. Therefore, development of a home health care support information system was planned. The system can collect patient's PHD (Personal Health Data) such as data of ECG, complaints, etc. at patient's home and can send the PHD to medical facilities. We designed and constructed two subsystems on a trial basis. One subsystem has function of gathering, recording and transmitting vital signs of the aged such as ECG, physical activity rate, oxygen saturation rate in arterial blood. Another subsystem can collect and send image data of the old people at their home. Experiments for trial use of the system was conducted and it was recognized that the PHD can be smoothly collected and recorded at home of the elderly and can be sent to the medical facilities with good success by using the system.

Aged↗

[Immunohistochemical study on keratin no. 8, 18 and 19 expression of carcinoid tumors].

The purpose of this study is to evaluate keratin expression in neuroendocrine cells and carcinoid tumor of the gastrointestinal tract and lung. Neuroendocrine cells in the lung and the gastrointestinal tract reacted with low-molecular keratin strongly, but not with high-molecular keratin. The low-molecular keratin expression of carcinoid tumor in the lung and the gastrointestinal tract, which varied in degree, were identical to that of neuroendocrine cells. Keratin 8 and 18 were found abundantly in neuroendocrine tumor and carcinoid tumor of the gastrointestinal tract, and in a lesser amount in carcinoid tumor of the lung, whereas keratin 19 was found in all cases with variable amounts. Based on these results, the combination of antibodies for several types of keratin is useful for examining keratin expression as a marker of epithelium in carcinoid tumor.

Adult↗

[Anesthetic management of a patient with protein C deficiency associated with pulmonary thromboembolism].

A patient with protein C deficiency associated with massive pulmonary embolism underwent open heart tromboembolectomy. The operation was successfully performed under cardiopulmonary bypass using a usual dose of heparin 3 mg.kg-1. The effect of heparin was successfully reversed by the administration of protamine sulfate 6 mg.kg-1. Perioperative administration of fresh frozen plasma or protein C concentrates might be necessary to manage hypercoagulability in a patient with protein C deficiency.

Adult↗

[Usefulness of the intubating laryngeal mask airway for cases with predicted difficult intubation].

We evaluated the usefulness of the intubating laryngeal mask airway (ILMA) in patients who were predicted to have possible difficult airway. Patients with possible difficult airway were defined as those with limited head extension, Mallampati's classification of grade IV, thyro-mental distance < 4 cm, or Cormack grade III-IV on the laryngoscopy. The control group was consisted of the patients without these conditions or impaired mouth opening. Insertion of the ILMA was successfully performed in all patients of both groups. In the group of possible difficult airway, 83% of patients were intubated through the ILMA successfully, and in the control group, 86%. We conclude that the ILMA may become an additional tool in patients with difficult intubation.

Adult↗

Patched (ptch)-associated preferential expression of smoothened (smoh) in human basal cell carcinoma of the skin.

The discovery of specific overexpression of a gatekeeper gene, ptch, in basal cell carcinoma (BCC) led to a hypothesis that the human homologue of patched (PTCH) normally functions as a negative regulator of the signaling pathway that is initiated by hedgehogs (HHs) and activated by the human homologue of smoothened (SMOH); however, no evidence for the involvement of smoh and hhs has been provided. Here, we show novel evidence that smoh is also preferentially overexpressed in BCC, together with ptch (P < 0.002), and that Sonic hh was expressed in only some BCCs. Our data, therefore, indicate that such overexpression of smoh may be associated with overexpression or mutation of PTCH and that this overexpression subsequently stimulates the PTCH/SMOH signaling pathway. In an investigation of a possible regulation of ptch and smoh, we demonstrated that expression of exogenous p21WAF1 in immortalized keratinocytes down-regulates both ptch and smoh and that the down-regulation is accompanied by growth arrest, which suggests the involvement of p21WAF1 in regulation of the PTCH/SMOH signaling pathway.

Basal Cell Carcinoma↗

pH dependence of facilitation by neurotransmitters and divalent cations of P2X2 purinoceptor/channels.

The pH dependence of the facilitation by dopamine (10 microM), 5-hydroxytryptamine (10 microM), adenosine (1 and 100 microM), Zn2+ (10 microM) and Cd2+ (1 mM) of P2X2 purinoceptor/channels was tested by expressing these channels in Xenopus oocytes. In a pH range between 6.0 and 8.5, concentration-response curves for an inward current activated by ATP were shifted toward a lower concentration range at a more acidic pH, indicating that the sensitivity to ATP is pH-dependent. Comparison of the effects of the neurotransmitters and the divalent cations on the ATP-activated current was made using a concentration of ATP which activated 40-50% of the maximal current at each pH value. The current facilitation by dopamine was obvious at pH 7.1 and 7.7, but was not observed at pH 8.5. At pH 6.0, the current was inhibited upon first trials of dopamine, but it was facilitated upon second trials. With 5-hydroxytryptamine and adenosine, the current facilitation was most remarkable at pH 6.0, less remarkable at pH 7.1 and 7.7, and the facilitation was almost abolished at pH 8.5. On the other hand, the current facilitation by Zn2+ and Cd2+ was more remarkable at alkaline pH values (7.7 and 8.5), and the facilitation was almost abolished at pH 6.0. The results suggest that the facilitation of P2X2 purinoceptors depends on pH, and the pH dependence was different between the neurotransmitters and the divalent cations.

Adenosine↗

Vestibular inputs to bulbar respiratory interneurons in the cat.

Vestibular inputs to medullary respiratory interneurons were studied in decerebrated and artificially ventilated cats. Extracellular recordings were made from 40 neurons located in the area of pre-Bötzinger complex and activated antidromically from the contralateral ventral respiratory group. Neuronal populations analyzed included inspiratory and expiratory neurons with augmenting, constant and decrementing firing patterns, and a late inspiratory neuron. Seventeen neurons responded to ipsilateral and/or contralateral vestibular nerve electrical stimulation. These responses were observed in all seven cell types. Most neuronal reflex responses consisted of inhibition, while a few consisted of either excitation or a combination of both inhibition and excitation. These results indicate that pre-Bötzinger respiratory interneurons, which may be involved in respiratory rhythmogenesis, also participate in vestibulorespiratory responses.

Animals↗

Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a kidney transplant recipient.

A case of sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a cadaver renal transplant recipient is reported in this article. The patient underwent a kidney transplant at the age of 43 and was treated with various immunosuppressive agents after surgery. Twelve months after the transplantation, multiple tumors were found in the liver, and the patient died 8 months later. Pathological examination at autopsy revealed renal cell carcinoma with a sarcomatoid component in the right native kidney and metastases to liver and bones. It is unusual for renal cell carcinoma to undergo sarcomatous transformation and to metastasize to the liver before reaching other organs. We speculate that immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis in this case.

Adult↗

Potent inhibition by trivalent cations of ATP-gated channels.

The effects of La3+ and other trivalent cations on ATP-gated channels (P2X purinoceptor/channels) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing these channels. La3+, Gd3+, Ce3+ and Nd3+ (30-300 microM) inhibited an inward current activated by 30 microM ATP in PC12 cells. The concentration-response curve for the ATP-activated current was shifted by La3+ or Gd3+ toward a higher concentration range, and the slope of the curve became steeper, suggesting the inhibition is non-competitive. La3+ or Gd3+ did not affect the current component that was slowly activated upon hyperpolarization, and selectively inhibited the remaining 'voltage-independent' component. La3+ and Gd3+ also inhibited currents mediated through P2X1 and P2X2 purinoceptors expressed in Xenopus oocytes. The results suggest that La3+ and other trivalent cations inhibit P2X purinoceptors at low concentrations. The inhibition may at least partly be attributed to an allosteric inhibition.

Adenosine Triphosphate↗

Effects of neuroamines and divalent cations on cloned and mutated ATP-gated channels.

Sensitivities to dopamine, 5-hydroxytryptamine, Zn2+ and Cd2+ were studied in P2X1, P2X2, P2X3 and P2X4 purinoceptors and mutants of P2X2 purinoceptors expressed in Xenopus oocytes. Dopamine (10 and 100 microM) and 5-hydroxytryptamine (1 to 100 microM) enhanced the inward current activated by extracellular ATP through P2X2 and P2X4 purinoceptors. Zn2+ (1 to 100 microM) and Cd2+ (10 microM to 1 microM) enhanced the current through P2X2 purinoceptors. As for P2X4 purinoceptors, the ATP-activated current was, however, enhanced after the washout of Zn2+ (100 microM) or Cd2+ (1 mM). Three mutants of P2X2 purinoceptors were constructed by substituting negatively charged amino-acid residues. The magnitude of the enhancement by Zn2+, Cd2+ and dopamine was attenuated when Asp221 was replaced by histidine. The results suggest that dopamine, Zn2+ and Cd2+ require some common motif for the current enhancement.

Adenosine Triphosphate↗

Role of pre-inspiratory neurons in vestibular and laryngeal reflexes and in swallowing and vomiting.

Fifteen pre-inspiratory (Pre-I) neurons were extracellularly recorded in the pre-Bötzinger complex and their involvements in vestibular (VN) and superior laryngeal (SLN) nerve reflexes and in fictive swallowing and vomiting were tested in decerebrated and artificially ventilated cats. Both type I (1 of 9) and type II (1 of 6) pre-I neurons could project to the contralateral ventral respiratory group region. Pre-I neurons changed their firing during VN and SLN respiratory reflexes and fictive swallowing and vomiting; different response properties were observed among individual pre-I neurons. These results suggest that pre-I neurons are a population of heterogeneous and multi-functional propriobulbar neurons.

Animals↗