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Biomedical subjects

H Akamatsu

Publications and source records attributed to H Akamatsu.

At least 55 records · Page 3Linked to original sources

Suppressive effect of ultraviolet (UVB and PUVA) radiation on superantigen production by Staphylococcus aureus.

It is well known that Staphylococcus aureus (S. aureus) proliferates on the moist skin lesion of atopic dermatitis. Reduction of bacteria colonization from skin lesions by antibiotics has been reported to be effective for the treatment of atopic dermatitis. S. aureus produces superantigens which can activate T cells and possibly enhance the inflammatory reaction. Photo(chemo)therapy has been successfully used for the treatment of severe cases of atopic dermatitis. We have previously reported that photo(chemo)therapy had bacteriostatic effect on S. aureus. Now we examined the effect of UVB and psoralen plus UVA (PUVA) on superantigen production from S. aureus. We isolated S. aureus from six atopic dermatitis patients. S. aureus was irradiated in vitro with UVB (0, 5, 10 mJ/cm2) or PUVA (0.001% psoralen plus 0, 5, 10 mJ/cm2 UVA) and incubated 4 h with 100 strokes per min. After incubation, the amounts of superantigens in the supernatant were measured using ELISA kit. The production of superantigens decreased in an ultraviolet dose-dependent manner. The suppressive effects of UV radiation on superantigen production may be involved in the therapeutic efficacy of photo(chemo)therapy for atopic dermatitis.

Dermatitis, Atopic↗

The effects of clonidine and dexmedetomidine on human neutrophil functions.

UNLABELLED: Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2-agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils. IMPLICATIONS: Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation.

Adjuvants, Anesthesia↗

The effects of cimetidine, ranitidine, and famotidine on human neutrophil functions.

UNLABELLED: Neutrophil functions, which play an important role in the antibacterial host defense system, are inhibited by various anesthetics and surgical procedures. Histamine H2-receptor antagonists are perioperatively used as a prophylaxis against acid aspiration syndrome or stress ulceration. We examined the effect of cimetidine, ranitidine, and famotidine, at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil function using an in vitro system. The three H2-receptor antagonists did not impair neutrophils' chemotaxis or phagocytosis. Cimetidine and famotidine inhibited superoxide (O2-) and hydrogen peroxide (H2O2) production of the neutrophils in a dose-dependent manner, although the inhibitory effects were minimal. In contrast, ranitidine failed to change O2- or H2O2 production of neutrophils. The three H2-receptor antagonists did not scavenge these reactive oxygen species generated by the xanthine-xanthine oxidase system. The increase in intracellular calcium concentrations in neutrophils by a stimulant were dose-dependently attenuated with cimetidine or famotidine. This decreasing effect of the drugs on [Ca2+]i in neutrophils may represent one of mechanisms responsible for inhibition of reactive oxygen species generation. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that cimetidine and famotidine slightly reduced the O2- or H2O2 production of neutrophils in a dose-dependent manner, although ranitidine failed to do so. At least ranitidine does not seem to have any deleterious effect on neutrophil function, which is clearly an important consideration in its use in severely ill patients.

Calcium↗

Mediastinal fibromatosis presenting with superior vena cava syndrome.

We encountered a fatal case of mediastinal fibromatosis in a 67-year-old female in whom there was aggressive infiltration into the large vessels, nerves and pericardium. She presented with the superior vena cava syndrome, Horner's syndrome, paralysis of bilateral vocal cords and diaphragm and heart failure. Mediastinoscopical examination revealed an extremely firm tumor adhering to the sternum, trachea and brachiocephalic artery. She died of severe heart failure due to the disturbed dilatation of the heart and ventilatory insufficiency. Although mediastinal fibromatosis is very uncommon and sometimes difficult to diagnose at an early stage, physicians should be aware of this disease for the differential diagnosis of mediastinal tumors.

Aged↗

[A case of successful resection of pulmonary arteriovenous fistula with a high shunt ratio].

We report on a 25-year-old cyanotic man who was diagnosed as having a pulmonary arteriovenous fistula. His chief complaint had been shortness of breath since childhood. Polycythemia (Hb 21.4 g/dl) was detected during a health checkup at his company. A chest X-ray showed an abnormal mass in the left lung. Blood gas analysis showed severe hypoxia with PaO2 of 38.6 mmHg at room air. Angio-CT showed a large aneurysmal lesion at S6 of the left lung with a large feeding artery and vein. Oxygen saturation was 75.2% in the radial artery and 62.5% in the right atrium. The right-to-left shunt ratio was therefore calculated as 62%. The aneurysmal lesion was resected by segmentectomy of the left S6 following division of A6 and V6. After a successful operation, the patient no longer had shortness of breath or cyanosis and blood gas analysis showed PaO2 as 84.3 mmHg at room air. Pulmonary angiography showed no residual shunt lesion.

Adult↗

The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.

UNLABELLED: We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. IMPLICATIONS: Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.

Anesthetics↗

Propofol inhibits human neutrophil functions.

UNLABELLED: Neutrophils play important roles in the antibacterial host defense mechanism and in the pathogenesis of tissue injury. Propofol has been reported to impair the production of reactive oxygen species from neutrophils. We examined the effect of propofol (2,6-diisopropylphenol), at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil functions using an in vitro system. Propofol significantly inhibited chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, propofol suppressed these neutrophil functions, but it did not decrease ROS generation by the cell-free (xanthine-xanthine oxidase) system. Increase in intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine was dose-dependently attenuated by propofol. This decreasing effect on [Ca2+]i in neutrophils may represent one of the mechanisms responsible for the inhibition of neutrophil functions by propofol. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that at clinically relevant concentrations, propofol impaired neutrophil functions. Further studies may determine whether this impairment, observed in vitro, leads to clinical immunological suppression.

Anesthetics, General↗

Inhibitory effect of shofu-san, a Japanese kampo medicine, on neutrophil functions in vitro.

The effect of Shofu-san (TJ-22), an oral Japanese kampo medicine, on several inflammatory parameters of human neutrophils, including reactive oxygen species (ROS) generation, chemotaxis, and calcium concentration, [Ca2+]i in neutrophils was examined in vitro. In addition, ROS generated in a cell-free, xanthine-xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). TJ-22 significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. The medicine also markedly inhibited neutrophil chemotaxis and [Ca2+]i in neutrophils. In addition, three kinds of ROS generated in the cell-free system was reduced in the presence of TJ-22. Our results indicate that TJ-22 may exert an anti-inflammatory action by inhibiting the neutrophil functions and scavenging ROS, leading to a reduction in oxidative tissue injury.

Calcium↗

The human sebocyte culture model provides new insights into development and management of seborrhoea and acne.

Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin 1 alpha expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5 alpha-reductase and metabolized testosterone to androstenedione, 5 alpha-androstanedione, 5 alpha-dihydrotestosterone, androsterone and 5 alpha-androstanediol, whereas the levels of 5 alpha-reductase activity were probably not feedback regulated. 4,7 beta-Dimethyl-4-aza-5 alpha-cholestan-3-one, a type 1 5 alpha-reductase inhibitor, induced an early, marked down-regulation of 5 alpha-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 10(3)-fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.

Acne Vulgaris↗

The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation.

The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.

Acne Vulgaris↗

Establishment of a tissue culture system for hamster sebaceous gland cells.

BACKGROUND: A human sebaceous gland culture system is very useful in studying the functions of the sebaceous glands at the cellular level. On the other hand, the success rates for culture systems and the experimental results from these human culture systems exhibit significant fluctuations, depending on the condition of the donor skin. OBJECTIVE: The purpose of this study was to establish a stable culture system in order to investigate the functions of the sebaceous glands under uniform conditions. METHODS: Sebaceous glands from the auricles of 5-week-old hamsters were isolated and seeded onto a 3T3 cell feeder layer. The proliferation, lipid production and response to androgens of these sebaceous-gland-derived cells (SGDC) were then examined. RESULTS: The SGDC showed outgrowth, formed colonies and became confluent in a 35-mm dish culture after 14 days in primary culture. The amount of intracellular lipids significantly increased following the peak of the cell proliferation. The composition of the intracellular lipids from the hamster SGDC was identical to human SGDC, except that the hamster SGDC did not contain any squalene. Testosterone and 5alpha-dihydrotestosterone markedly stimulated the proliferation of these SGDC in a dose-dependent manner. CONCLUSION: This tissue culture system will be a useful tool for the study of sebaceous gland function at the cellular level.

3T3 Cells↗

Mediastinal lymph node metastasis in patients with clinical stage I peripheral non-small-cell lung cancer.

Our aim in this study was to determine the mediastinal areas where lymphadenectomy should be done at the time of surgical resection of clinical stage I lung cancer. Between 1984 and 1994, 575 patients with clinical stage I non-small-cell lung cancer underwent lobectomy and systematic mediastinal lymphadenectomy. Mediastinal lymph nodes were pathologically positive for disease in 79 patients (14%), and positive nodes appeared normal intraoperatively in 54 patients (68%). Thirty-three percent of those patients with positive N2 (mediastinal) nodes had negative lobar (N1) nodes. In cancer of the right upper lobe, all N2 cases had the lymph node metastases in the superior mediastinal compartment. In cancer of the right middle lobe, all N2 cases but one had the metastases in subcarinal or anterior mediastinal nodes. In cancer of the right lower lobe, all N2 cases but one the metastases in subcarinal nodes. In cancer of the left upper lobe, all N2 cases had the lymph node metastases in the subaortic compartment. In cancer of the left lower lobe, all N2 cases but one had the lymph node metastases in the subcarinal area or subaortic compartment. In conclusion, systematic staging of mediastinal lymph nodes is necessary for all patients with resectable clinical stage I lung cancer. The location of the primary tumor determines the mediastinal areas where lymphadenectomy should be done to examine all lymph nodes.

Adult↗

The best site for bronchial stapling in left and right upper lobectomies: a comparative study.

Bronchial stapling and postoperative bronchoscopy was performed in 22 left upper lobectomies (LUL) and 18 right upper lobectomies (RUL). Seven LUL cases and 15 RUL cases with staples positioned 2 bronchial rings (BR) from the entrance to the upper lobe bronchus (ULB) had no residual cartilaginous rings at the stump (RCRS). Deformity of the residual bronchus (DRB) was found in 6 of these 7 LUL cases, and 3 of these 15 RUL cases (p < 0.01), with a high rate of suffering from a severe cough. The remaining 15 LUL cases and 3 RUL cases had staples positioned 3 to 4 BR from the entrance to the ULB resulting in one or two RCRS. Only one LUL case with one RCRS was accompanied by DRB and coughing. These facts strongly imply a connection between cough and DRB. DRB was frequently seen in LUL cases with no RCRS (86%), was less likely to occur in cases with one RCRS (10%), and was absent in cases with two RCRS (p < 0.01). We conclude that bronchial staples applied during a LUL should be positioned 3 or 4 bronchial rings distal from the entrance to the left ULB.

Aged↗

Reduction of Staphylococcus aureus in atopic skin lesions with acid electrolytic water--a new therapeutic strategy for atopic dermatitis.

The subjects studied were 22 pediatric patients newly diagnosed with atopic dermatitis (AD); 11 were treated with acid electrolytic water (AEW), which has a strong bactericidal activity (AEW group), and the other 11 with tap water (placebo group). AEW or tap water, 1 ml/cm2 (body surface area), was sprayed on their skin lesions with a spray gun each twice a day for a week. There were no significant differences between the two groups in regard to sex, age, serum IgE, peripheral eosinophil counts, grading scores of AD, and duration of AD. The study was designed as a randomized, placebo-controlled, double-blind clinical trial. Colony counts of Staphylococcus aureus on skin lesions in the AEW group, both 3 min after spraying (P < 0.05) and after 1 week of skin treatment (P < 0.01), were significantly decreased as compared with colony counts before treatment, while there was no significant difference in the placebo group before and after treatment. Grading scores of AD also decreased in the AEW group (P < 0.01), but not in the placebo group. Both the subjects' guardians' evaluation and a referee physician's evaluation of treatment effect were significantly higher in the AEW group than in the placebo group (P < 0.01). AEW may be potentially effective in preventing a staphylococcal chronic inflammation in AD because of its strong bactericidal activity.

Acids↗

Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils.

BACKGROUND: Reactive oxygen species (ROS) generated from neutrophils accumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto-injury. Lidocaine has been shown to reduce the injury. We investigated the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS production by neutrophils using an in vitro system. METHODS: We measured the production of superoxide (ferricytochrome c method), hydrogen peroxide (H2O2: scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas method) by neutrophils isolated from human adult volunteers in the absence and presence of lidocaine (2-200 micrograms/mL), mepivacaine (3-300 micrograms/mL), and bupivacaine (3-300 micrograms/mL). We also measured the ROS generation in a cell-free (xanthine-xanthine oxidase) system. RESULTS: Lidocaine and mepivacaine at higher levels significantly decreased the production of ROS by neutrophils. However, these local anaesthetics at clinically relevant blood concentrations had no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to reduce ROS generated by the cell-free system. Bupivacaine did not decrease ROS generation by either generating system. CONCLUSION: In conclusion, in the present in vitro system, only concentrations of lidocaine and mepivacaine 100-fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically relevant blood concentrations had no suppressive effect. Further studies using in vivo systems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings.

Adult↗

Effects of a single exposure to UVB radiation on the activities and protein levels of copper-zinc and manganese superoxide dismutase in cultured human keratinocytes.

Ultraviolet B irradiation has been believed to decrease or impair the activity of reactive oxygen species (ROS) scavenging enzymes such as superoxide dismutase (SOD) in the skin. It has been recently reported that two isozymes of SOD, namely copper-zinc SOD (Cu-Zn SOD) and manganese SOD (Mn SOD), exist in mammalian cells and that the two enzymes play different roles in living systems. The aim of this study was to investigate changes in SOD activities and protein levels in cultured human keratinocytes after acute UVB irradiation. In addition, the protein levels of Cu-Zn SOD and Mn SOD were quantified separately. A single exposure to UVB irradiation produced an increase in SOD activity and protein level that peaked immediately after UVB irradiation, after which a decline was observed, with subsequent recovery to baseline levels 24 h after irradiation. In individual assays of Mn SOD and Cu-Zn SOD, the amount of Mn SOD protein decreased and then gradually recovered 24 h after irradiation. In contrast, the amount of Cu-Zn SOD protein increased immediately after UVB irradiation, and then gradually declined. To evaluate the mechanisms of these changes, we examined the effects of the cytokines, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), which can be secreted from keratinocytes after UVB irradiation, on the SOD activity and protein levels in keratinocytes. Interleukin-1 alpha and TNF-alpha enhanced both the SOD activity and protein level of Mn SOD, while these cytokines had no effect on Cu-Zn SOD protein levels in cultured human keratinocytes after incubation for 24 h. Furthermore, when neutralizing antibodies against IL-1 alpha and TNF-alpha were added separately or together to the culture medium before UVB irradiation, the recovery of total SOD activity and Mn SOD protein level were markedly inhibited 24 h after irradiation. Our results suggest that significant increases in SOD activity and protein level occur as a cutaneous antioxidant defense mechanism that protects against the cytotoxicity as a result of UVB irradiation, and that this increase in SOD is attributed to Cu-Zn SOD. The Cu-Zn SOD and Mn SOD protein levels changed in a different manner after UVB irradiation. The former may participate in an early phase and the latter in a late phase defense mechanism directed against oxidant cytotoxicity through UVB irradiation. In addition, the recovery of Mn SOD to baseline levels 24 h after UVB irradiation seems to be mediated through cytokines such as IL-1 alpha and TNF-alpha, which are secreted from keratinocytes.

Cell Line↗