Relationships between transepidermal water loss, cutaneous microcirculatory function and autonomic nervous activity.

OBJECTIVE: Several studies have shown that a deterioration of skin properties, an impaired cutaneous microcirculatory function and an imbalance of autonomic nervous activity are observed in smokers and in patients with diabetes mellitus or Raynaud's phenomenon. These observations suggest that skin properties are associated with cutaneous microcirculatory function and autonomic nervous activity in pathological conditions. However, there is no published evidence to support the concept that these two functions have any relationship with skin properties even in healthy subjects. To investigate the hypothesis that these properties are related, we conducted a survey of healthy adult subjects to investigate the relationships between cutaneous microcirculatory function and autonomic nervous activity and skin properties. METHODS: The hydration of the stratum corneum and transepidermal water loss (TEWL) were investigated as skin properties, and the responsiveness of skin blood flow (SkBF) to local warming was examined as an index of cutaneous microcirculatory function in 19 healthy adult male subjects. Electrocardiograms were monitored for 24 h and heart rate variability was analysed considering low-frequency power (LF: 0.04-0.15 Hz), high-frequency power (HF: 0.15-0.40 Hz) and a ratio of low- to high-frequency power (LF/HF) as indices of autonomic nervous activity; HF is an index of parasympathetic activity, whereas LF/HF is an index of sympathovagal balance. The relationships between those indices were then analysed. RESULTS: A moderate negative correlation was found between TEWL and the relative maximum rate of increases in the responsiveness of SkBF on local warming. A moderate positive and a moderate negative correlation were observed between TEWL and LF/HF or HF, respectively. Moreover, a moderate negative and a moderate positive correlation were shown between the responsiveness of SkBF and LF/HF or HF, respectively. The hydration of the stratum corneum showed no correlations with any indices of microcirculation or autonomic nervous activity. CONCLUSION: These results indicate that skin barrier function, cutaneous microcirculatory function and autonomic nervous activity are mutually associated in healthy adults.

[Surgical treatment for Pancoast tumors--significance of surgical approach and induction chemoradiotherapy].

We analyzed 46 patients with Pancoast tumor who underwent surgical resection. Anterior approach was employed for 16 patients and hook approach for 30 patients. Twenty-one patients received preoperative treatment; chemotherapy for 1 patient, radiotherapy for 11 patients, and chemoradiotherapy for 9 patients. Complete resection was achieved in 59% (27/46) of patients. The overall 5-year survival rate was 10.9%. Five-year survival was significantly higher in the patients received complete resection than the patients received incomplete resection (18.5 vs 0%, p=0.0016). The complete resection rate has improved in recent cases, and one of the reasons seems to be the adoption of preoperative chemoradiotherapy. But postoperative complications occurred more frequently in patients who received induction therapy than the others. Optimal selection of surgical approach and induction chemoradiotherapy for Pancoast tumors appear to provide improved complete resection rate and long term survival.

[Evaluation of tracheobronchoplasty for lung cancer].

Tracheobronchoplasty has become one of the standard procedures for lung cancer. In this study, we examined the incidence of complications and survival of tracheobronchoplasty and compared with these of pneumonectomy. In 119 patients underwent tracheobronchoplasty, bronchopleural fistula occurred in 6 (5.0%) and anastomotic stenosis occurred in 5 (4.2%). Five-year survival rate of 119 patients underwent tracheobronchoplasty was 47.3%, and the median survival time was 49.3 months. We compared the sleeve or wedge lobectomy and pneumonectomy, the incidence of complications and 30-days death were similar, but the rate of in-hospital death and the prognosis of the sleeve or wedge lobectomy were better than these of pneumonectomy. So to preserve a respiratory function, we should use a bronchoplastic procedures to avoid pneumonectomy.

[Assessment of surgery for stage IV non-small cell lung cancer].

We assessed the survival of surgery for stage IV non-small cell lung cancer. Forty-two patients were operated on lung cancer for stage IV from 1986 to 2005. Overall median survival time (MST) was 12.3 months and 5-year survival rate was 9.8%. There was significant difference in survival between pulmonary metastasis (pm2) and other sites metastasis (p<0.05). In pm2 patients there was significant difference between ipsilateral metastasis and contralateral metastasis (MST 21.9 months, 2-year survival rate 48.6%, 5-year survival rate 21.6% and MST 12.3 months, 2-year survival rate 0%) [p<0.05], and between complete resection and incomplete resection (MST 36 months, 2-year survival rate 64.8%, 5-year survival rate 28.8% and MST 12.3 months, 2-year survival rate 0%) [p<0.01]. In patients with brain metastasis, surgery of brain metastasis was better prognosis than radiation therapy (MST 12.5 months, 3-year survival rate 33.3% and MST 8.3 months, 2-year survival rate 0%) [NS].

[A study of high-resolution computed tomography (HRCT) findings of resected small pulmonary nodules 2 cm or less in diameter with reference to the malignant nature].

To identify the characteristics of peripheral small lung mass lesions on high-resolution computed tomography (HRCT) and discriminate between malignant and benign, 223 mass lesions 2 cm or less resected surgically were evaluated about following points. 1) Density : 90.7% of lesions with mixed solid and ground-glass opacity (GGO) components were adenocarcinomas. Pure GGO lesions without scale-down between several months were all adenocarcinomas or atypical adenomatous hyperplasia (AAH). Thereby, patients with these findings are good candidates for surgical resection. 2) Spicular or pleural indentation :75.2% (88 of 117 cases) of adenocarcinomas and all squamous cell carcinomas (18 cases) showed these findings, but 26.6% (41 of 154 cases) of positive cases were benign lesion (non-specific inflammation, mycobacterisis, and so on). Accordingly, they are not peculiar to malignancy. 3) Satellite lesion : all lesions with this one showed benign, therefore it was thought that this finding could exclude malignant lesion. Thus, recognition of certain characteristics at HRCT can be helpful in discrimination between small malignant mass and benign mass.

[The effect of multimodality induction therapy for locally advanced non-small cell lung cancer].

In this study we analyzed induction therapy for locally advanced non-small cell lung cancer. Eligible patients had mediastinoscopic proven N2 disease and T4 with mediastinal involvement. From January 1997 to May 2005, 56 patients entered the study. They received 2 cycle chemotherapy (platinums based 2 or 3 drugs), in 32 patients with concurrent radiotherapy followed by surgery. Response rates were 57.1%. Fifty-one patients underwent surgery. A radical resection was possible in 39 patients. Complication occurred in 14 patients (27.5%). Overall 5-year survival was 27.5%. In N2 disease, there was no statistically significant difference in survival between the induction group and the historical group. In T4 disease, overall 5-year survival was 30.2% for the induction group and 5.2% for historical group. There was significant difference in survival between the groups (p < 0.05).

Effect of phorbol ester and calcium ionophore on human thymocytes.

Positive selection of immature thymocytes is a developmental process in which TCR ligation with low avidity induces generation of mature T cells. In mouse thymocytes, CD4(+)8(+) double-positive (DP) cells which were treated with a proper combination of calcium ionophore ionomycin and phorbol 12-myristate 13-acetate (PMA) have been reported to differentiate into CD4 single positive cells. However, in human thymocytes the effects of PMA and ionomycin have remained unclear. Here we report that DP cells that were treated with PMA and ionomycin up-regulated bcl-2 and down-regulated CD1 expression. However, CD3 expression remained low. This treatment induced prolonged CD4 down-regulation in DP cells which was an effect also seen in mature peripheral blood T cells. PMA/ionomycin-treated DP cells showed high cell proliferation and resistance to dexamethasone-induced apoptosis. These results indicate that PKC activation and calcium elevation may be part of the biochemical signals that induce positive selection of human DP cells and the system described in this paper may be a useful model to study the signals involved in the selection of human thymocytes.

Expression of the cdc25B gene as a prognosis marker in non-small cell lung cancer.

There is an evidence to suggest that cdc25B phosphatase is an oncogenic. We hypothesized that cdc25B gene may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of cdc25B messenger RNA was evaluated by reverse transcription polymerase chain reaction in 55 non-small cell lung carcinomas and adjacent histological normal lung samples using LightCycler. The data was analyzed in reference to clinicopathological data and survival data. There was no difference of cdc25B expression level between the NSCLC tissue and normal lung tissue. There was no relationship between cdc25B gene expression and age, gender, N or T-status and clinical stage. However, the NSCLC patients with high cdc25B expression had significantly poor survival than the patients with low cdc25B expression (P=0.0173). Thus we suggest that cdc25B may predict poor survival.

Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating.

Three types of calcium phosphate coating were formed on polyethersulphone (PES) rectangular plates using a biomimetic method: a 20 microns thick amorphous calcium phosphate (ACP 20) coating, a 50 microns thick amorphous calcium phosphate (ACP 50) coating, and a 50 microns thick highly crystalline hydroxyapatite (hHA 50) coating. Uncoated PES plates were used as a control group. These materials were implanted in the tibiae of rabbits and subcutaneously in rats, and the samples were harvested 8 and 16 weeks thereafter, and were examined histologically. The tensile failure loads at the bone-implant interfaces were determined using the detaching test. Each ACP coating was more degradable than the hHA 50 coating. However, newly formed bone came into direct contact with underlying materials as the coating degraded. No coating degraded in subcutaneous tissue. Soft tissue intervening was seen in uncoated samples. Failure load of ACP 20-, ACP 50- and hHA 50-coated samples were all relatively higher than that of the uncoated samples at each period. Significant increase of failure load was seen in hHA 50-coated samples by 16 weeks, however, no increase was seen in either the uncoated or ACP-coated samples. If coating longevity is desired, then the hHA coating is preferable. However, if only the osteoconducive property of calcium phosphate coating is desired for initial fixation of porous materials, the ACP coating may be advantageous.

Ultrastructural study of an apatite layer formed by a biomimetic process and its bonding to bone.

A dense and uniform apatite layer about 20 microns thick was formed on a poly(ether sulphone) (PESF) substrate treated with glow discharge in O2 gas by a biomimetic process. The apatite-polymer composite obtained was implanted into a rabbit tibia and the structure of the PESF-apatite-bone interface was observed under a scanning and a transmission electron microscope 8 weeks after implantation. The apatite layer formed by the biomimetic process was confirmed to consist of small crystals of apatite with a structure similar to that of apatite in bone. The apatite layer remained on the substrate in the body, and bonded to the apatite in bone directly. This type of apatite-organic polymer composite expected to be useful as bone-repairing material.

Effects of NKH477 on renal nerve stimulation-induced responses in anesthetized dogs.

We evaluated the effects of an adenylate cyclase activator, N, N-dimetyl-beta-alanine[3R-(3alpha,4alphabeta,5beta+ ++,6beta,6aalpha, 10alpha,10abeta,10balpha)]-5(acetyloxy)-3-eth enyldodecahydro-10, 10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho[2, 1-b]pyran-6-yl ester hydrochloride (NKH477), on neural control of renal functions in anesthetized dogs. Renal nerve stimulation (2 Hz) increased renal norepinephrine efflux and reduced renal blood flow, glomerular filtration rate, urine flow rate, urinary Na(+) excretion and fractional Na(+) excretion. Intrarenal arterial infusion of NKH477 (300 ng/kg/min) suppressed the stimulation-induced reductions in renal blood flow and glomerular filtration rate and attenuated the reductions in urine flow rate and urinary Na(+) excretion but not the changes in renal norepinephrine efflux and fractional Na(+) excretion. Infusion of NKH477 did not affect the urinary responses induced by renal nerve stimulation at a lower frequency (0.5-1 Hz) which had little influence on renal blood flow and glomerular filtration rate. The present results demonstrate that NKH477 inhibits renal vasoconstriction and hypofiltration but not the enhanced tubular Na(+) reabsorption during activation of the renal sympathetic nervous system.

Effects of NKH477 on renal functions and cyclic AMP production in anesthetized dogs.

The present study was undertaken to evaluate the effects of an adenylate cyclase activator N,N-dimethyl-beta-alanine[3R-(3alpha, 4alphabeta, 5beta, 6beta, 6aalpha, 10alpha, 10abeta, 10balpha)]-5(acetyloxy)-3-ethenyldodecahydro-10, 10b-dihydroxy-3, 4a, 7, 7, 10a-pentamethyl-1-oxo-1H-naphtho [2,1-b] pyran-6-yl ester hydrochloride (NKH477) on renal functions and cyclic AMP production in the dog kidney. The intrarenal arterial infusion of NKH477 (30, 100 and 300 ng kg(-1) min(-1)) increased renal blood flow, glomerular filtration rate, urine flow rate, urinary Na+ and cyclic AMP excretion, fractional Na+ excretion and arterial and renal venous plasma cyclic AMP concentrations in a dose-dependent manner. The intrarenal arterial infusion of rolipram (0.3 microg kg(-1) min(-1)), a cyclic AMP-specific phosphodiesterase inhibitor, also caused the same renal responses as NKH477. The increasing effects of NKH477 on renal blood flow, fractional Na+ excretion and renal venous plasma cyclic AMP concentration were facilitated in the presence of rolipram. NKH477 reduced glomerular filtration rate and filtration fraction in the presence of rolipram. The increasing effects of NKH477 on urine flow rate and urinary Na+ excretion were not affected by rolipram. The present results suggest that NKH477 increases glomerular filtration and suppresses tubular sodium reabsorption through activation of cyclic AMP production, and thereby induces natriuresis. The results also demonstrate that renal cyclic AMP level during the activation of adenylate cyclase is regulated by phosphodiesterase IV in both the vascular and tubular sites.

Synthesis of 2-deoxy-4-O-phosphono-3-O-tetradecanoyl-2-[(3R)- and (3S)-3-tetradecanoyloxytetradecanamido]-D-glucose: a diastereoisomeric pair of 4-O-phosphono-D-glucosamine derivatives (GLA-27) related to bacterial lipid A.

The diastereoisomeric, 4-O-phosphono-D-glucosamine derivatives named in the title have been synthesized, starting from benzyl 2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside and (3RS)-3-hydroxytetradecanoic acid.

Evaluation of new TNM lung cancer classification.

OBJECTIVE: A new staging system for lung cancer was proposed by the Union Internationale Contre le Cancer in 1997, with Stages I and II subdivided and T3N0M0 assigned as stage IIB. We studied the usefulness of this new classification. METHODS: Subjects were 753 patients with non-small-cell lung cancer undergoing pulmonary resection and follow-up data were retrospectively reviewed. RESULTS: A significant difference was seen between stage IA and IB survival--70.4% vs 52%. No significant difference was seen between survival for T3N0M0, T1N1M0 and T2N1M0--35.3%, 42.3%, and 43.8%--at 5 years. We found, however, that the prognosis for T3N2M0 tumors--6.5% 5-year survival--is too poor to be grouped with other N2 diseases having a better prognosis--23.9% 5-year survival. Significant differences were also seen in the survival of T3N0 or T3N1 patients by organ and diseases involving the rib, diaphragm, or mediastinum may be classified as T4. CONCLUSION: The new staging system predicts patient outcome fairly well and the modification is well grounded. It appears, however, to be appropriate to subdivide T3 tumors by invaded organs and T3N2M0 disease may be better classified as stage IIIB. The classification of pulmonary metastasis appears to require further improvement.

Surface functional group dependence on apatite formation on self-assembled monolayers in a simulated body fluid.

Self-assembled monolayers (SAMs) of alkanethiols having CH3, PO4H2, COOH, CONH2, OH, and NH2 terminal groups formed on a gold surface via sulfur attachment were soaked in a simulated body fluid (SBF), whose ion concentrations were nearly equal to those of human blood plasma, at 37 degrees C for up to 40 days. The effect of their terminal functional groups on apatite formation was assessed using X-ray photo-electron spectroscopic (XPS) measurement and a quartz crystal microbalance (QCM) technique. The Ca and P atoms were detected, of which element intensities increased with time, on SAMs except for the alkanethiol having the methyl terminal group. The Ca/P atomic ratios of the apatites formed on the SAMs ranged from around 1.0 to around 1.3. The most potent inducer for apatite formation, judged from the growth rate (micrometers per day) calculated from the weight change during QCM measurement, was the SAM of the alkanethiol with the PO4H2 group, followed by that of the alkanethiol with the COOH group. The SAMs of the alkanethiols with the CONH2, OH, and NH2 groups possessed much weaker inducing powers than the former two SAMs. Little weight change was observed for the methyl-group-terminated alkanethiol SAM. The growth rates increased with time, irrespective of the terminal group species among apatite formation-inducing groups. During the experimental observation period, the following relationship held. The growth rate decreased in the order PO4H2 > COOH >> CONH2 approximately equal to OH > NH2 >> CH3 approximately equal to 0. Some negatively charged groups strongly induced apatite formation but the positively charged group did not, it can be said that the apatite formation initiated via calcium ion-absorption upon complexation with a negative surface-charged group may be dominant in biomaterial calcification where ionic species directly contact the biomaterial surface in body fluids.

Quantitative assessment of apatite formation via a biomimetic method using quartz crystal microbalance.

Quantitative assessment of hydroxyapatite formation on a gold surface via the biomimetic method, composed of a nucleation step in a simulated body fluid (SBF) containing glass powders and a subsequent apatite growth step in glass powder-free SBF, was made using a quartz crystal microbalance (QCM) technique. The frequency change of the QCM linearly increased with increasing soaking time, and largely depended on the nucleation period. The growth rates, defined as daily increase in thickness, increased monotonicly with an increasing nucleation period of up to 96 h, thereafter being constant at 2.0 microns/day. The growth rate of the apatite layer increased with increasing temperature of the SBF: 0.9, 2.0, and 3.8 microns/day at 25, 37, and 50 degrees C, respectively. The Arrhenius-type activation energy for the growth of apatite was 47.3 kJ/mol. The QCM method was found to be a very powerful tool for quantitative, in situ measurement of precipitation and growth of apatite in real time.

Activation of osteoclast-mediated bone resorption by the supernatant from a rabbit synovial cell line in response to polyethylene particles.

It is unknown whether the soluble factors produced from cells activated by wear particles in the fibrous tissue around failed joint prostheses really activate osteoclastic bone resorption. In this study, the activation of osteoclast-mediated bone resorption by the products from a rabbit synovial cell line (HIG-82) stimulated by various particles was investigated using rabbit unfractionated bone cells cultured on a dentin slice. The HIG cells were challenged with the following laboratory-made particles: high-density polyethylene (PE), cobalt alloy (Co-Cr), titanium alloy (Ti6Al4V), pure titanium (Ti), and sintered hydroxyapatite (HA). The size of each particle was < 2 microns. The supernatants from HIG cells cultured with the appropriate concentration of wear particles were added to unfractionated bone cells on a dentin slice, and then resorbed areas were determined for each particle. Interestingly, resorbed areas significantly increased only when the culture medium from HIG cells with PE particles was added to unfractionated bone cells. This study demonstrates that PE particles stimulate the rabbit synovial cells to produce soluble factors that induce osteoclast-mediated bone resorption. Moreover, this experimental model is a useful method sensitively to evaluate the effects of soluble factors from the cells stimulated by particulate biomaterials from joint prostheses on osteoclastic bone resorption.