Assessing age-related change in Japanese mental foramen opening direction using multidetector computed tomography.

OBJECTIVE: The purpose of this study was to investigate how the opening direction of the mental foramen (MF) changes with age in a Japanese population using multi-detector computed tomography (MDCT). METHODS: Post-mortem MDCT scans of 121 Japanese subjects (66 males and 55 females) were carried out where all subjects possessed at least twenty teeth, including molar teeth, in the upper and lower jaws. Two angles of the mental foramen opening were measured, namely the superior-inferior angle in the coronal plane and anterior-posterior angle in the transverse plane, on the CT reconstructed images. The associations between age and these two angles were evaluated using a multiple regression analysis. RESULTS: For male subjects, the relationship between the superior-inferior angle and age was a quadratic curve (p < 0.001). This angle increased until the subject reached their early 50s and then the angle decreased with age. In the transverse plane, there was a linear relation between the anterior-posterior angle and age (p=0.002).It was noted also that the angle decreased with age. By contrast, however, no significant associations between the two angles and age for either measurement were noted for female subjects. This study demonstrated that the opening direction of the mental foramen changes with age in Japanese male subjects. By contrast this change in the opening direction of the mental foramen was not demonstrated in Japanese female subjects. In male subjects, the opening direction moves superiorly until the individual reaches their early 50s, and then moves inferiorly with advancing age. It also shifts from a posterior to an anterior position with age. CONCLUSION: These observed change differ from the results of previous studies. The findings could be useful for forensic science as they demonstrate a change in the position of mental foramen in a sample of contemporaneous male Japanese subjects.

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies.

Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.

Electromyogram biofeedback training for daytime clenching and its effect on sleep bruxism.

Bruxism contributes to the development of temporomandibular disorders as well as causes dental problems. Although it is an important issue in clinical dentistry, no treatment approaches have been proven effective. This study aimed to use electromyogram (EMG) biofeedback (BF) training to improve awake bruxism (AB) and examine its effect on sleep bruxism (SB). Twelve male participants (mean age, 26·8 ± 2·5 years) with subjective symptoms of AB or a diagnosis of SB were randomly divided into BF (n = 7) and control (CO, n = 5) groups to undergo 5-h daytime and night-time EMG measurements for three consecutive weeks. EMG electrodes were placed over the temporalis muscle on the habitual masticatory side. Those in the BF group underwent BF training to remind them of the occurrence of undesirable clenching activity when excessive EMG activity of certain burst duration was generated in week 2. Then, EMGs were recorded at week 3 as the post-BF test. Those in the CO group underwent EMG measurement without any EMG BF training throughout the study period. Although the number of tonic EMG events did not show statistically significant differences among weeks 1-3 in the CO group, events in weeks 2 and 3 decreased significantly compared with those in week 1, both daytime and night-time, in the BF group (P < 0·05, Scheffé's test). This study results suggest that EMG BF to improve AB tonic EMG events can also provide an effective approach to regulate SB tonic EMG events.

Development of a simple and efficient method for transformation of buckwheat plants (Fagopyrum esculentum) using Agrobacterium tumefaciens.

Apical meristems of seedlings of buckwheat (Fagopyrum esculentum var. Shinano No. 1) were pricked with a needle and inoculated with Agrobacterium tumefaciens (LBA4404, pBI121). The inoculated seedlings were grown to maturation and allowed to pollinate randomly to set the seeds (T1 plants). The transformation efficiency of the T1 plants was estimated by germination in the presence of geneticin (20 microg/ml) and by detection of beta-glucuronidase (GUS) gene with PCR, indicating that 36% and 70% of the T1 plants were transformed, respectively. Four plants taking on a mutated morphology were selected from T1 plants which were transformed with the method using A. tumefaciens harboring a modified pBI121 for plasmid rescue. Southern blot analysis of plasmids rescued from the 4 T1 plants demonstrated that each plasmid contained a different flanking DNA of the buckwheat genome, an evidence that T-DNA was integrated in different sites of the genomic DNA among the 4 T1 plants.

Lichen planus with involvement of all twenty nails and the oral mucous membrane.

A 57-year-old man had had deformities of all ten fingernails for one and a half years before presentation and deformities of all ten toenails for the previous six months. The surfaces of the nails were rough, with excessive longitudinal striations. The bases of the nails were slightly hypertrophic, and the tips were atrophic and itchy. A longitudinal nail biopsy including the nail matrix revealed the typical histology of lichen planus. Reticulated pigmentation, maceration, and erosion on the buccal mucous membrane were also discovered. Histological analysis of the buccal mucous membrane revealed lichen planus intermingled with eosinophils. Immunological blood analysis revealed elevated CD4+ T cells and CD4/CD8 ratio. He worked as a tinsmith and had dental metal. The metal series patch test revealed positive reactions to chromate and tin. Treatment with systemic steroids was quite effective in treating the nail lesions.

[Effects of fudosteine, a new cysteine derivative, on airway secretion in rabbits and rats].

We examined the effects of fudosteine [(-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid], a new cysteine derivative, on airway secretion in rabbits and rats. Indirect measurement of airway secretion in rabbits, which was expressed by the amount of dye excreted into the respiratory tract, was carried out according to the Sakuno's method, with some modifications. Fudosteine (500 mg/kg, p.o.) significantly increased the amount of dye excreted into the respiratory tract. As a direct method of measurement of airway secretion, the modified Perry and Boyd's method was used to collect respiratory tract fluid (RTF) in rabbits. Fudosteine (500 mg/kg, p.o.) significantly augmented the output volume of RTF, but there was no difference from the control in protein and phosphatidylcholine (PC) contents into RTF. On the other hand, fudosteine increased chloride ion concentration in broncho-alveolar lavage of rats. Fudosteine did not stimulate PC secretion in a primary culture of rat type II pneumocytes, and it did not have a mucolytic effect against gastric mucin in vitro. From the results described above, it was concluded that fudosteine may be a new cysteine derivative which offers a serous secretion.

Histopathological characterization of spontaneously developing osteoarthropathy in the BCBC/Y mouse established newly from B6C3F1 mice.

A new breed of mouse showing cinnamon-color of hair and osteoarthropathy was born from mouse of the B6C3F1 strain, and was named the BCBC/Y mouse. The incidence and severity of the articular lesions increased with aging, and by 10 to 22 months of age, many mice showed moderate-severe motor paresis with ankylotic changes of the limb joints. Abnormal radiographic changes were observed at many joints with increasing age. There was bone and joint deformity, followed by progressive osteoarthritic changes and ankylosis of the limb joints. Histopathologically, degenerative changes, followed by loosening, fissuring and erosion of the articular cartilage were observed at early stage of articular lesions. Unilateral progressive changes, characterized by joint fusion with abnormal osteophytes, were observed at late stage of articular lesions with aging. For successive breeding to establish a homogeneous strain, generation mice retained the symptoms of the primary mice. Thus, these BCBC/Y mice may be a useful as mode to elucidate the hereditary background and hyperplastic changes of the osteochondrocytes for pathogenesis of the osteoarthropathy.

Impact of the 1970 legal BAC 0.05 mg% limit legislation on drunk-driver-involved traffic fatalities, accidents, and DWI in Japan.

Official statistics of motor vehicle fatality data have indicated that alcohol involvement in fatal crashes has declined substantially in Japan since 1970. The national campaign against drunken driving in Japan provides a natural experiment in which to test the predictions of deterrence theory. Utilizing official data over the 1960-1995 period, we report conclusive evidence that 1970s legislation is having a measurable and long-term effect on alcohol-related motor vehicle fatalities. Enactment of the lower legal blood alcohol limit with a combination of other severe sanctions has been more desirable in the prevention of alcohol-related fatalities in the long term as shown in this study. Further extensive research is necessary to investigate performance at the lower legal limit in other societies in order to inspire a strong "international lobby" to support the reduced legal blood alcohol limit for drivers all over the world, as there is no doubt that a reduction in alcohol-impaired driving will result in a substantial savings of human lives and resource worldwide.

Spontaneous osteoarthritic lesions in a new mutant strain of the mouse.

In our laboratory, mice showing signs of osteoarthritic lesions with cinnamon colored (yellowish-brown) hair were discovered in a colony of B6C3F1 mice. This mouse is characterized by tiptoe walking and swelling and ankylotic changes in the ankle joint. As to radiographic findings, osteoarthritic changes, such as erosion and/or fusion of the bone tissue, were evident in the ankle joints. Histopathological characteristics included irregularity of articular surfaces caused by fissuring and/or erosion with degeneration of articular cartilage, as well as osteophytes with abnormal proliferation of chondrocytes in joint margin regions. Subsequently, ankylotic changes in the ankle joints were completed in the formation of a cartilaginous bridge and fusion of articular cavity with abnormal proliferation of cartilaginous or bone tissues. This mouse strain may provide an additional animal model that is valuable in the study of human osteoarthritis (OA).

Substrate specificity of 2-deoxy-scyllo-inosose synthase, the starter enzyme for 2-deoxystreptamine biosynthesis, toward deoxyglucose-6-phosphates and proposed mechanism.

A crucial enzyme in the biosynthesis of the 2-deoxystreptamine aglycon of clinically important aminocyclitol antibiotics is 2-deoxy-scyllo-inosose synthase (DOIS), which is responsible for the initial carbocycle formation of 2-deoxy-scyllo-inosose (1) from D-glucose-6-phosphate (G-6-P) (2). To get more insight into the mechanism and substrate specificity, deoxy-D-glucose-6-phosphates (deoxy-G-6-P) were chemically synthesized and subjected to the reaction with DOIS. The enzyme appeared to use 2-deoxy- and 3-deoxy-G-6-P as substrates, both of which were converted into the corresponding dideoxy-scyllo-inosose products, but 4-deoxy-G-6-P failed in cyclization by DOIS. These results clearly support the proposed reaction mechanism involving the initial oxidation at C-4 of the G-6-P substrate. Another implication is the potential use of DOIS for the preparation of useful dideoxyinososes.

Signature current of SO2-induced bronchitis in rabbit.

To investigate abnormalities of airway epithelial ion transport underlying chronic inflammatory airway diseases, we performed electrophysiological, histological, and molecular biological experiments using rabbits exposed to SO2 as a model of bronchitis. By comparison with control, the SO2-exposed trachea exhibited decreased short circuit current (Isc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by diphenylamine 2-carboxylate or Cl--free bath solution. A significant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sustained Isc increase in SO2-exposed, but not in normal, tracheas. The Northern blot analysis showed a strong expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.

ATP-induced Cl- secretion with suppressed Na+ absorption in rabbit tracheal epithelium.

The effect of extracellular ATP on ion transport of rabbit tracheal epithelium was examined using an Ussing chamber. Isoproterenol (10(-8)-10(-5) M) did not alter the electrophysiological properties across the tracheal epithelium. Apically applied ATP induced an initial transient increase in short circuit current (SCC) followed by a decline to below the prior baseline. The initial increase by ATP (10(-4) M) was significantly inhibited by a Cl(-) -channel inhibitor diphenylamine-2-carboxylate (DPC, 5 x 10(-4) M) and Cl(-) -substitution with gluconate in the bath solution, while a cystic fibrosis transmembrane regulator (CFTR) Cl(-) -channel inhibitor glibenclamide (10(-4) M), a Na(+)-channel inhibitor amiloride (10(-4) M) and a K(+) -channel inhibitor quinidine (10(-4) M) all failed to alter it. The decline in SCC by ATP was abolished by amiloride, while DPC or Cl-substitution with gluconate in the bath solution did not alter it. Ca(2+)-removal from the bath solutions did not significantly alter the initial increase nor the decline by ATP. Ionomycin (10(-5) M) induced an initial transient increase in SCC, to a degree similar to that by ATP alone. A calmodulin antagonist W-7 reduced the SCC baseline and abolished SCC increase by ATP. These findings indicate that ATP activates Ca(2+)-dependent Cl(-) -channels with an inhibition of Na -channel activity or absorption in rabbit tracheal epithelium.

Detection of DNA bending in a DNA-PAP1 protein complex by fluorescence resonance energy transfer.

The structure of DNA in a DNA-protein complex was studied by means of fluorescence resonance energy transfer (FRET) method. Oligonucleotide phosphorothioates were labeled with fluorescein and eosin to obtain a donor- and acceptor-labeled DNA. The formation of a complex of the DNA with PAP1(70), which is a DNA binding site fragment derived from transcription regulatory protein, PAP1, of fission yeast, was confirmed by gel retardation analysis and fluorescence measurements. FRET of the donor- and acceptor-labeled DNA with and without PAP1(70) indicated that the DNA in the complex was bent about 26 degrees toward the protein-binding surface.

Rectal submucosal tumor-like lesion originating from intestinal tuberculosis.

We present the case of a 55-year-old man who underwent transsacral local excision for a rectal submucosal tumor-like lesion suspected to originate from tuberculosis. The lesion, 2 cm in size, was found incidentally in the posterior wall of the lower rectum during anal fistulectomy. The lesion was apart from the primary crypt of the anal fistula. Barium enema and colonoscopy revealed a protuberant submucosal growth with a shallow depression of the overlying mucosa. Although computed tomography and magnetic resonance imaging showed a well defined round mass within the rectal wall, digital rectal examination suggested extramural origin. Since repeated endoscopic biopsies were negative, we selected the transsacral approach for excisional biopsy to achieve histological diagnosis. The lesion was confined to the rectal wall and the full-thickness rectal wall was excised. Histologically, a foreign-body granuloma with acute inflammation was the main component of the lesion. Caseating granulomas and Langhans' giant cells, consistent with tuberculosis, were also found.

Are lower legal blood alcohol limits and a combination of sanctions desirable in reducing drunken driver-involved traffic fatalities and traffic accidents?

In 1970 and 1978, a set of strict new countermeasures against drunk driving went in to effect in Japan. Analysis of official statistics of motor vehicle fatality data have indicated that alcohol involvement in fatal crashes has declined substantially in Japan since 1970. From the beginning of 1970 to the late 1980s and 1990s, public awareness of and tolerance for the problem of alcohol-impaired driving changed dramatically, as shown in this study. Further it seems that attitudes in Japan on drink driving have improved over the last 20 years or so, instep with a major program of government action. As well as being part of a long running campaign to reduce alcohol related road deaths and injuries, these accident savings are an important part of a national strategy which began in 1970, comprising a well structured legislative program introducing a lower legal limit, progressive penalties for those above the legal limit, over and above Police enforcement strategies underpinning the law and reinforcing the publicity massage. Enactment of the lower legal blood alcohol level with a combination of other severe sanctions is desirable for prevention of alcohol-related traffic casualties, DWI, and accidents, which is shown in this study. Finally, much of the current reduction in alcohol-related fatalities and morbidity reflects that Japanese society has largely endorsed alcohol impaired driving as a socially undesirable behavior. However, this study suggests that it is necessary for policy makers to understand that the DUI problem in Japan must be handled with diverse approaches, rather than relying exclusively on the deterrence based laws.

[A case report of multiple pseudoaneurysms of the left ventricle following acute myocardial infarction].

Multiple pseudoaneurysms of the left ventricle following acute myocardial infarction were successfully repaired in a 50-year-old man. Three days after onset of acute myocardial infarction, we electively performed PTCA on the right coronary artery which was completely occluded at the proximal segment. One month after PTCA, the left ventriculogram revealed multiple pseudoaneurysms of the left ventricle. Primary closure of orifices of the pseudoaneurysms was performed using pledgeted mattress sutures under cardiopulmonary bypass. Histology of aneurysm confirmed the diagnosis of pseudoaneurysm.

[Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography].

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.

Effects of repetitive airway obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs.

We examined the effects of multiple repetitive airway obstruction (RAO) on arterial oxygen saturation (SaO2) and pulmonary and systemic arterial pressure in eight anesthetized spontaneously breathing dogs. SaO2 was monitored at the tongue with a pulse oximeter. RAO created by an electrical valve that was attached to a tracheal cannula was alternated with seven consecutive spontaneous breaths until the nadir SaO2 (nSaO2) became constant or decreased to less than 35%. Tracheal occlusion durations of 15, 30, 45 and 60 s were chosen arbitrarily. In each animal nSaO2 decreased with every trial number in an exponential fashion, and the rate of nSaO2 fall was greater for the longer occlusion duration. In each animal the increases in pulmonary arterial pressure (PAP) and systemic arterial pressure (SAP) were inversely related to the nSaO2 values, and the relationship between nSaO2 and PAP or SAP was identical for all occlusion durations. Moreover, when the animals breathed pure oxygen and SaO2 did not decrease, there were no significant increases in the PAP and SAP at similar levels of pleural pressure (Ppl). In another six dogs, the effects of RAO on PAP and SAP were compared with those of intermittent hypoxic exposure without apnea, which was achieved by the inhalation of hypoxic gas (4 to 6% O2, 5% CO2 in N2) instead of RAO, to examine the effects of interruption of ventilation. The relationships between nSaO2 and both pressures did not differ significantly from those during RAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin E2 inhalation increases the sensation of dyspnea during exercise.

To clarify the role of vagal afferents from the lung in the sensation of dyspnea, we examined the effects of prostaglandin E2 (PGE2) inhalation on the sensation of dyspnea during exercise in eight normal male subjects. This intervention was chosen because inhaled PGE2 is known to stimulate vagal afferent receptors in the lung, in particular C-fiber endings, without a significant increase in airway resistance. After either physiologic saline or PGE2 aerosol (100 micrograms/ml) inhalation through a Bird nebulizer for 2 min, exercise tests were performed on a bicycle ergometer. The tests consisted of 3 min at rest followed by graded work loads (zero to 150 watts, 50-watt increments). Minute ventilation (VE) and respiratory rate were monitored from an expiratory line through a face mask. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated from samples of mixed expired gas. The sensation of difficulty in breathing (dyspnea) was measured on a modified Borg scale at rest and at the end of each work load. We found that although airway resistance and lung volume did not change significantly between saline and PGE2 inhalations, inhaled PGE2 significantly increased the magnitude of the dyspneic sensation when compared with inhaled saline at the same levels of work load, ventilation, and oxygen consumption. These results suggest that in addition to probable roles of motor command and chemical drive, afferent vagal activity from the lung also contributes to the sensation of dyspnea during exercise.