Comparison of osseous healing after sagittal split ramus osteotomy and intraoral vertical ramus osteotomy.

The sagittal split ramus osteotomy (SSRO) is generally associated with greater postoperative stability than the intraoral vertical ramus osteotomy (IVRO); however, it entails a risk of inferior alveolar nerve damage. In contrast, IVRO has the disadvantages of slow postoperative osseous healing and projection of the antegonial notch, but inferior alveolar nerve damage is believed to be less likely. The purposes of this study were to compare the osseous healing processes associated with SSRO and IVRO and to investigate changes in mandibular width after IVRO in 29 patients undergoing mandibular setback. On computed tomography images, osseous healing was similar in patients undergoing SSRO and IVRO at 1year after surgery. Projection of the antegonial notch occurred after IVRO, but returned to the preoperative state within 1year. The results of the study indicate that IVRO is equivalent to SSRO with regard to both bone healing and morphological recovery of the mandible.

Mechanism of motor coordination of masseter and temporalis muscles for increased masticatory efficiency in mice.

The demand for the use of mice as animal models for elucidating the pathophysiologies and pathogeneses of oral motor disorders has been increasing in recent years, as more and more kinds of genetically modified mice that express functional disorders of the stomatognathic system become available. However, the fundamental characteristics of mouse jaw movements during mastication have yet to be fully elucidated. The purpose of this study was to investigate the roles of the masseter and temporalis muscles, and the mechanisms of motor coordination of these muscles for increasing masticatory efficiency in the closing phase in mice. Twenty-two male Jcl:ICR mice were divided into control (n = 8), masseter-hypofunction (n = 7) and temporalis-hypofunction groups (n = 7). Botulinum neurotoxin type A (BoNT/A) was used to induce muscle hypofunction. The masticatory movement path in the horizontal direction during the occlusal phase became unstable after BoNT/A injection into the masseter muscle. BoNT/A injection into the temporalis muscle decreased antero-posterior excursion of the late-closing phase corresponding to the power phase of the chewing cycle. These results suggest that the masseter plays an important role in stabilizing the grinding path, where the food bolus is ground by sliding the posterior teeth from back to front during the occlusal phase. The temporalis plays a major role in retracting the mandible more posteriorly in the early phase of closing, extending the grinding path. Masticatory efficiency is thus increased based on the coordination of activities by the masseter and temporalis muscles.

Therapeutic vaccination based on side population cells transduced by the granulocyte-macrophage colony-stimulating factor gene elicits potent antitumor immunity.

Among cancer immunotherapies, granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccine (GVAX) therapies appear promising and have been shown to be safe and effective in multiple clinical trials. However, the antitumor efficacies of GVAX therapy alone are in some cases limited. Here we showed that GVAX therapy targeting cancer stem cells (CSCs) substantially suppressed tumor development in syngeneic immunocompetent mice recapitulating normal immune systems. CSCs were isolated as side population (SP) cells from 4T1 murine breast carcinoma cell line and transduced with GM-CSF gene delivered by non-transmissible Sendai virus (4T1-SP/GM). Impaired tumorigenicity of subcutaneously injected 4T1-SP/GM depended on CD8+ T cells in concert with CD4+ T cells and natural killer cells. Mice therapeutically vaccinated with irradiated 4T1-SP/GM cells had markedly suppressed tumor development of subcutaneously transplanted 4T1-SP cells compared with those treated with irradiated cells of non-transduced 4T1-SP cells or non-SP (4T1-NSP/GM) cells. Tumor suppression was accompanied by the robust accumulation of mature dendritic cells at vaccination sites and T-helper type 1-skewed systemic cellular immunity. Our results suggested that CSC cell-based GVAX immunotherapy might be clinically useful for inducing potent tumor-specific antitumor immunity.

An anti-c-Fms antibody inhibits orthodontic tooth movement.

Orthodontic force induces osteoclastogenesis in vivo. It has recently been reported that administration of an antibody against the macrophage-colony-stimulating factor (M-CSF) receptor c-Fms blocks osteoclastogenesis and bone erosion induced by tumor necrosis factor-alpha (TNF-alpha) administration. This study aimed to examine the effect of an anti-c-Fms antibody on mechanical loading-induced osteoclastogenesis and osteolysis in an orthodontic tooth movement model in mice. Using TNF receptor 1- and 2-deficient mice, we showed that orthodontic tooth movement was mediated by TNF-alpha. We injected anti-c-Fms antibody daily into a local site, for 12 days, during mechanical loading. The anti-c-Fms antibody significantly inhibited orthodontic tooth movement, markedly reduced the number of osteoclasts in vivo, and inhibited TNF-alpha-induced osteoclastogenesis in vitro. These findings suggest that M-CSF plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption during orthodontic tooth movement mediated by TNF-alpha.

An uncommon cleft subtype of unilateral cleft lip and palate.

The finding that the vomer plays a crucial role in maxillary growth suggests that the bilateral cleft configuration of unilateral cleft lip and palate (UCLP), in which the vomer is detached from the non-cleft-side secondary hard palate, negatively influences palatal development, and this hypothesis was tested. Sixty persons with complete UCLP, including those with the vomer detached from (n = 30, b-UCLP) and attached to (n = 30, u-UCLP) the secondary hard palate, were analyzed morphologically, with the use of cast models taken at 10 days, 3 mos, and 12 mos of age. The anterio-posterior palatal length at 12 mos of age in those with b-UCLP was significantly shorter than that in those with u-UCLP, by 8.7% (p < 0.05). In addition, palatal width development in the first year in those with b-UCLP was also significantly retarded. These results suggest that the uncommon bilateral cleft subtype in UCLP should be included in the cleft classification.

Opioid receptor-like 1 (ORL1) receptor binding and the biological properties of Ac-Arg-Tyr-Tyr-Arg-Ile-Arg-NH2 and its analogs.

Hexapeptides such as Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) and Ac-Arg-Tyr-Tyr-Arg-Trp-Arg-NH(2) have been isolated from a combinatorial peptide library as small peptide ligands for the opioid peptide-like 1 (ORL1) receptor. To investigate the detailed structural requirements of hexapeptides, 25 analogs of these hexapeptides, based on the novel analog Ac-Arg-Tyr-Tyr-Arg-Ile-Arg-NH(2) (1), were synthesized and tested for their ORL1 receptor affinity and agonist/antagonist activity on mouse vas deferens (MVD) tissues. Analog 1 and its Cit(6)-analog (10) were found to possess high affinity to the ORL1 receptor, comparable to that of nociceptin/orphanin FQ, and exhibited potent antagonist activity (pA(2) values of 7.77 for 1 and 7.51 for 10, which are higher than that of [NPhe(1)]nociceptin(1-13)-NH(2) (6.90) on MVD assay. It was also found that the amino acid residue in position 5 plays a key role in agonist/antagonist activity, i.e. an L-configuration aliphatic amino acid is required for potent antagonist activity, while a nonchiral or D-configuration residue produces potent agonist activity. These lines of evidence may provide insight into the mechanisms controlling agonist/antagonist switching in the ORL1 receptor, and may also serve to help developing more potent ORL1 agonists and antagonists.

Communication about the ending of anticancer treatment and transition to palliative care.

BACKGROUND: Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. METHODS: A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). RESULTS: Thirty-nine percent of the bereaved family members reported that they were 'very distressed' in receiving information about the ending of anticancer treatment, and 19% reported 'considerable' or 'much' improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. CONCLUSIONS: In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Effects of short-term pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease.

Although the rehabilitation of patients with chronic obstructive pulmonary disease (COPD) improves both exercise capacity and quality of life, a standard protocol for COPD patients has not been established. To clarify whether physiologic and quality-of-life improvements can be achieved by an inpatient pulmonary rehabilitation program 5 days per week for 3 weeks, 18 patients with COPD were enrolled in a rehabilitation program. The physical exercise training regimen consisted of respiratory muscle stretch gymnastics and cycle ergometer exercise training. Pulmonary function tests, an incremental ergometer exercise test, a 6-min walking test, and a quality of life assessment by the Chronic Respiratory Questionnaire were administered before and after the program. The peak VO2, an indicator of maximal exercise capacity, did not increase, although the 6-min walking distance, an indicator of functional exercise capacity, increased significantly after rehabilitation. There was a significant improvement in the quality of life in terms of dyspnea, fatigue, and emotional state. These findings suggest that even a 3-week program may be beneficial for COPD patients. Increases in functional exercise capacity, even without an increase in maximal exercise capacity, are helpful for reducing dyspnea and improving quality of life parameters in patients with COPD.

Cardiorespiratory responses during cycle ergometer exercise with different ramp slope increments in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The ramp exercise test has been widely used to evaluate cardiopulmonary responses to an incremental exercise load. This study was performed to clarify whether different slopes of the ramp exercise test influence exercise tolerance, exercise limiting factors, and respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: We applied three different slopes (5 W/min, 10 W/min and 20 W/min) of the ramp exercise test in 9 patients with COPD and evaluated cardiopulmonary responses. RESULTS: There were no significant differences in peak oxygen uptake, anaerobic threshold (AT), minute ventilation, heart rate, arterial oxygen saturation, expired tidal volume, or respiratory rate at the maximal load among the three different ramp exercises tested. AT could be determined in six of nine patients (67%) at the slope of 5 W/min, in 8/9 (89%) at the slope of 10 W/min, and in 9/9 (100%) at the slope of 20 W/min. CONCLUSION: The findings suggest that the ramp slope does not affect exercise tolerance, exercise limiting factors, or respiratory patterns and each of these ramp slopes is useful for the evaluation of COPD. Ramp slopes of 10 W/ min or 20 W/min should be appropriate for the determination of AT.

Fast atom bombardment tandem mass spectrometric analysis of phospholipids in Drosophila melanogaster.

Direct determination of the phospholipid components in adult Drosophila melanogaster was carried out by using fast atom bombardment tandem mass spectrometry (FAB-MS/MS) of both the positive and negative ions. Approximately 50 molecular species were detected, including phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylinositol (PI). Eight PE, one PC and three PS molecular species were identified. Some variations with age and a few differences among the D. melanogaster strains in the PE and PC molecular species were found. There was a difference in the fatty acid structure of a 741 Da PE molecular species between the wild-types and a mutant strain (EthAR201) which requires a higher concentration of diethylether for anesthesia than the wild-types; in the mutant sn-1-oleoyl-2-linoleoyl (18:1/18:2) but in the wild-types sn-1-linoleoyl-2-oleoyl (18:2/18:1) were speculated. This suggests that this technique will be useful for the screening of phospholipid molecular species mutation.

Establishment of a drug sensitivity panel using human lung cancer cell lines.

We established a drug sensitivity panel consisting of 24 human lung cancer cell lines. Using this panel, we evaluated 26 anti-cancer agents: three alkylators, three platinum compounds, four antimetabolites, one topoisomerase I inhibitor, five topoisomerase II inhibitors, seven antimitotic agents and three tyrosine kinase inhibitors. This panel showed the following: a) Drug sensitivity patterns reflected their clinically-established patterns of action. For example, doxorubicin and etoposide were shown to be active against small cell lung cancer cell lines and mitomycin-C and 5-fluorouracil were active against non-small cell lung cancer cell lines, in agreement with clinical data. b) Correlation analysis of the mean graphs derived from the logarithm of IC50 values of the drugs gave insight into the mechanism of each drug's action. Thus, two drug combinations with reverse or no correlation, such as the combination of cisplatin and vinorelbine, might be good candidates for the ideal two drug combination in the treatment of lung cancer, as is being confirmed in clinical trials. c) Using cluster analysis of the cell lines in the panel with their drug sensitivity patterns, we could classify the cell lines into four groups depending on the drug sensitivity similarity. This classification will be useful to elucidate the cellular mechanism of action and drug resistance. Thus, our drug sensitivity panel will be helpful to explore new drugs or to develop a new combination of anti-cancer agents for the treatment of lung cancer.

[A resected case under thoracoscopic surgery of bilateral pulmonary metastases of renal cell carcinoma ten years after radical nephrectomy].

A 68-year-old male had received a left nephrectomy for renal cell carcinoma of the clear cell type in October, 1987. He had been given Interferon alpha (IFN alpha) for one year since then. He was referred to our hospital for bilateral abnormal shadows on the chest roentgenogram in December, 1997. He underwent a video-assisted thoracoscopic biopsy of bilateral lung in January, 1998, 11 years after his nephrectomy. The resected specimens contained a coin lesions measuring approximately 2 cm in diameter, and the lesions were microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence five months after the resection of the metastatic lesion.

Effect of docetaxel with cisplatin or vinorelbine on lung cancer cell lines.

Docetaxel shows substantial activity against lung cancer. To find the optimal drug combination for docetaxel, we evaluated the effects of cisplatin, etoposide, mitomycin C, irinotecan, vindesine, and vinorelbine using three human lung cancer cell lines, ABC-1, EBC-1, and SBC-3. Drug cytotoxicity was determined by MTT assay. Tumor cells were incubated for 96 hours in the presence of docetaxel and each of the test drugs stated above. The combined drug interaction was evaluated by median-effect plot analysis and improved IC50-isobologram analysis. Both methods showed strong antagonism (subadditive or protective effect) between docetaxel and etoposide when tested on ABC-1 and EBC-1 cells. Docetaxel and cisplatin displayed additive effects on all cell lines tested, when evaluated by improved IC50-isobologram analysis. The combination of docetaxel and vinorelbine exerted synergistic effect on the growth inhibition of SBC-3 cells, which showed a wide range of fractional cytotoxicity when analyzed by median-effect plot and supraadditive when analyzed by improved IC50-isobologram. These observations suggest a possibility that docetaxel can be used in combination with vinorelbine or cisplatin in the treatment of lung cancer.

Bronchial atresia with transient spontaneous disappearance of a mucocele.

We report the transient spontaneous disappearance of a mucocele due to bronchial atresia. Two years before presentation, a chest radiograph showed a hyperlucent right upper lung and a mucocele near the right hilum. A chest radiograph taken 1 year later showed that the mucocele had disappeared leaving an ovoid outline of a dilated bronchus. A chest radiograph obtained 3 months before presentation showed that the mucocele was present again. Atresia of the B3b bronchus of the right upper lobe was noted on thoracotomy. The "disappearance" of the mucocele probably was due to the clearance of mucoid material through collateral airways.

Changes of arterial oxygen saturation (SpO2) following push-back operation.

This study showed the influence of the push-back operation on the occurrence of sleep-related apnea in cleft-palate patients with an analysis of arterial oxygen saturation (SpO2) during sleep, polygraphic analysis of nasal air flow, and chest wall movements. The postoperative SpO2 was lower than that of the presurgical period in all cases, requiring from five to nine days to recover to presurgical levels. According to polygraphic analysis this depression of SpO2 was caused by peripheral obstructive apnea, while, in spite of the cessation of nasal airflow, chest wall movement continued.

High-dose etoposide treatment for CNS involvement in a patient with primary non-Hodgkin's lymphoma of the breast.

A 46-year-old man was referred to us for treatment of non-Hodgkin's lymphoma (NHL; diffuse large immunoblastic B cell type), which had initially developed in the breast. He was treated with five courses of chemotherapy with CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) and achieved a complete response. One year later, he noticed a gait disturbance. Magnetic resonance imaging (MRI) of the brain showed multiple nodules. A few abnormal cells were found in the cerebrospinal fluid (CSF). He was treated with high-dose etoposide (1,350 mg/ m2/course). After two courses, both the multiple nodular lesions in the brain and the abnormal cells in the CSF were resolved. High-dose etoposide is effective for CNS involvement by NHL.

Studies on the phosphorylation of a M(r) 25,000 protein, a putative protein phosphatase 2A modulator, by casein kinase I, and analysis of multiple endogenous phosphates.

A M(r) 25,000 protein, which was isolated from the cytosolic fraction of Xenopus laevis oocytes, is a newly identified substrate for casein kinase II and protein kinase C [Hashimoto et al. (1995) J. Biochem. 118, 453-460], and was recently shown to have the ability to modulate protein phosphatase 2A activity [Hashimoto et al. (1996) J. Biochem. 119, 626-632]. Acid phosphatase treatment of the protein shifted its electrophoretic mobility from 25 to 20 kDa on SDS-PAGE. The content of alkali-labile phosphate bound covalently to the protein was 53 mol per mol of M(r) 25,000 protein. Amino acid composition analysis revealed that there are 50 serine residues and 6 threonine residues per mol of this protein. Therefore, this M(r) 25,000 protein seems to be highly phosphorylated in vivo. The M(r) 25,000 protein, once partially dephosphorylated by acid phosphatase, served as an efficient substrate for casein kinase I and casein kinase II. When entirely dephosphorylated, the M(r) 25,000 protein was used as a substrate, the rate of phosphorylation with both casein kinases being decreased. This behavior of casein kinases toward the M(r) 25,000 protein reflects the possible mechanism of multisite phosphorylation in which the introduction of a phosphate group facilitates sequential phosphorylation.

Analysis of bile acids in urine specimens from healthy humans: determination of several bile acids with beta-hydroxyl and carbonyl groups.

Urinary bile acids of 39 healthy male undergraduates were analyzed by capillary gas chromatography and capillary gas chromatography-mass spectrometry. 3 alpha-Hydroxy-12-oxo-5 beta-cholanoic acid, 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic acid, 3 beta, 7 alpha-dihydroxy-5 beta-cholanoic acid, and 3 alpha, 7 alpha, 12 beta-trihydroxy-5 beta-cholanoic acid, in addition to known bile acids, were identified and then quantified. The major part of the urinary bile acids was occupied by secondary bile acids. Every 7 beta-hydroxylated bile acid species was found in more than 80% of the subjects. The bile acid detected in the largest amount was 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid. The metabolites of cholic acid were quantitatively more predominant than those of chenodeoxycholic acid. These results indicate that bile acids with beta-hydroxyl and carbonyl groups at the C-3,7 and/or 12 positions are usual bile acids usually found in the urine of healthy humans. It is concluded that the occurrence of these bile acids is an effect of the intestinal bacterial flora and living conditions.

Conjugation types of 7 beta-hydroxylated bile acids detected in healthy human urine.

Bile acids extracted from the urine of a healthy volunteer who excreted 7 beta-hydroxylated bile acids were fractionated to nonamidated, glycine-conjugated, taurine-conjugated, and sulfated bile acid fractions. The chemical conjugation types of the 7 beta-hydroxylated bile acids were then determined by treatment with several enzymes and by capillary column gas chromatography. Large amounts of 3 alpha,7 beta,12 alpha-trihydroxycholanoic acid were present as nonamidated and nonconjugated bile acids, while 3 beta,7 beta-dihydroxycholanoic acid formed nonamidated bile acid N-acetylglucosaminide. In addition, ursodeoxycholic acid formed both glycine-conjugated bile acid and glycine-conjugated bile acid N-acetylglucosaminide. Bile acid N-acetylglucosaminides were hydrolyzed by solvolysis.

Respiratory activities in relation to external glossal muscles.

In this study, the activities of the two external glossal muscles, Genioglossus (Gg) and Styloglossus (Sg), related to respiration were examined through the electromyography (EMG) in dog. During quiet breathing, no phasic respiratory activity were observed in either muscle. With hypercapnic condition induced by closed rebreathing respiratory system, both Sg and Gg showed phasic respiratory activities in respiration period. At first inspiratory EMG activity was observed from Sg (PaCO2 > 50 mmHg), then after a while from Gg (PaCO2 > 55 mmHg). NaCN injection bilaterally to the carotid body enhances the inspiratory ENG activities in both muscles. Sg was more sensitive than Gg to respiratory stimulation such as hypercapnia or NaCN injection.