Associations among tooth loss, systemic inflammation and antibody titers to periodontal pathogens in Japanese patients with cardiovascular disease.

BACKGROUND AND OBJECTIVE: It is well known that there is a strong relationship between periodontitis and cardiovascular disease (CVD). Tooth loss reflects an end-stage condition of oral diseases, such as periodontitis. Infection with specific periodontal pathogens is known as a possible factor that influences development of CVD. The aim of this study was to assess the relationship between the number of residual teeth and systemic inflammatory conditions in patients with CVD. MATERIAL AND METHODS: We divided 364 patients with CVD into four groups, according to the number of residual teeth: (i) ≥20 teeth; (ii) 10-19 teeth; (iii) 1-9 teeth; and (iv) edentulous. We recorded medical history, blood data and periodontal conditions. Serum samples were obtained and their IgG titers against three major periodontal pathogens were measured. RESULTS: Smoking rate and the prevalence of diabetes mellitus were higher in edentulous patients and in subjects with a few teeth compared with patients with many teeth. The levels of C-reactive protein were higher in patients with 1-9 teeth than in those with 10-19 teeth and with ≥20 teeth. The level of Porphyromonas gingivalis IgG in the group with 10-19 teeth was statistically higher than that in the group with ≥20 teeth. The level of P. gingivalis IgG in the edentulous group tended to be lower than that in the other groups. CONCLUSION: The patients with 1-9 teeth had the highest level of C-reactive protein among the four groups, and the patients with 10-19 teeth had the highest level of IgG to periodontal bacteria. We conclude that the number of remaining teeth may be used to estimate the severity of systemic inflammation in patients with CVD.

Clarithromycin suppresses the periodontal bacteria-accelerated abdominal aortic aneurysms in mice.

BACKGROUND AND OBJECTIVE: Although clarithromycin (CAM) has many biological functions, including regulation of MMPs, little is known about its effect on abdominal aortic aneurysms. Periodontopathic bacteria have been reported to be associated with several kinds of circulatory diseases. The purpose of this study was therefore to clarify the effect of CAM on periodontopathic bacteria-accelerated abdominal aortic aneurysms. MATERIAL AND METHODS: Abdominal aortic aneurysm was produced in mice by the peri-aortic application of 0.25 m CaCl(2). The mice were inoculated once per week with live Porphyromonas gingivalis, which is one of the major periodontopathic bacteria. Test mice (n=8) were given a daily oral dose of CAM, while control mice (n=13) were not. RESULTS: Four weeks after the operation, the P. gingivalis-injected and CAM-treated mice showed a significant decrease in the aortic diameter in comparison with the mice only injected with P. gingivalis. Histopathologically, the samples obtained from the P. gingivalis-injected and CAM-treated mice showed less elastic degradation. Moreover, the plasma MMP-2 concentration of the CAM-treated mice decreased significantly. CONCLUSION: These findings suggest that CAM administration is useful to suppress periodontal bacteria-accelerated abdominal aortic aneurysms via MMP regulation.

Effects of the duration and inorganic nitrogen composition of a nutrient-rich patch on soil exploration by the roots of Lolium perenne in a heterogeneous environment.

We investigated the growth of and soil exploration by Lolium perenne under a heterogeneous environment before its roots reached a nutrient-rich patch. Temporal changes in the distribution of inorganic nitrogen, i.e., NO(3)(-)-N and NH(4)(+)-N, in the heterogeneous environment during the experimental period were also examined. The results showed that roots randomly explored soil, irrespective of the patchy distribution of inorganic nitrogen and differences in the chemical composition of inorganic nitrogen distribution between heterogeneous and homogeneous environments. We have also elucidated the potential effects of patch duration and inorganic nitrogen distribution on soil exploration by roots and thus on plant growth.

Expression of basic fibroblast growth factor and its receptor-1 in cardiac myxoma.

BACKGROUND: To clarify the significance of basic fibroblast growth factor (bFGF) in angiogenesis or proliferative activity in cardiac myxoma, the expression of bFGF and its receptor (FGFR-1) were immunohistochemically examined. METHODS: Formalin-embedded tissues of cardiac myxomas were obtained by surgical resection from 15 patients and analyzed by immunostaining of bFGF and FGFR-1. The microvessel density was measured in the 15 myxomas using platelet derived endothelial cell adhesion molecule-1. For evaluation of proliferative activity of the cardiac myxomas, proliferating cell nuclear antigen (PCNA) immunostaining was performed, and the PCNA labeling index was measured in each section. RESULTS: bFGF and FGFR-1 were observed in 73.3% and 67.7% of the myxomas, respectively. There was a close correlation between the expression of bFGF and FGFR-1. This co-expression was frequently observed in the myxoma cells around the microvessels appearing as a ring structure. Regarding possible relationships between the expression of bFGF or FGFR-1 and the clinicopathologic features, there were no parameters excluding the macroscopic type of myxoma. The microvessel density in the myxomas with bFGF or FGFR-1 expression was higher than that in myxomas without it. The PCNA labeling index in myxomas with bFGF expression was higher than that in myxomas without it, and the PCNA labeling index tended to be higher in myxomas with FGFR-1 expression than that in myxomas without it. CONCLUSIONS: bFGF and/or FGFR-1 was expressed in some of cardiac myxoma, and may be an important role for tumor angiogenesis and proliferative activity.

Hearing results after tympanoplasty in elderly patients with middle ear cholesteatoma.

Many reports about the effect of aging on hearing results after tympanoplasty have been published. However, they have not been evaluated comprehensively, i.e. by taking into consideration other aspects which also affect the outcome. In this study, the effect of aging on hearing results after canal wall reconstruction tympanoplasty was assessed in 236 consecutive ears of 213 patients > 20 years old with middle ear cholesteatoma. The elderly group (n = 34), defined as patients > or = 60 years old, was compared to the younger groups in terms of hearing results of postoperative hearing level, hearing gain, A-B gap and change in bone conduction hearing level at 4000 Hz after adjustment for age, gender, staged operation, preoperative hearing level and type of tympanoplasty, all of which affect hearing results, using the generalized linear regression method. Postoperative hearing level and hearing gain were found to be better amongst patients aged 20-29 and 30-39 years than in the elderly group, whilst A-B gap did not differ between all age categories. Within the elderly group, air conduction hearing level was shown to have improved after surgery. Changes in bone conduction hearing level at 4000 Hz were not significantly different between the age groups, suggesting that operative stress, i.e. mechanical stress or ossicular manipulation stress, does not aggravate sensorineural hearing loss in the elderly. We conclude that surgeons should be encouraged to perform tympanoplasty aimed not only at eradicating the lesion itself but also at improving hearing acuity in the elderly.

Inducible nitric oxide-mediated myocardial apoptosis contributes to graft failure during acute cardiac allograft rejection in mice.

The mechanism through which nitric oxide (NO) mediates cardiac myocyte death during acute cardiac rejection has not been fully delineated. We sought to determine whether NO promotes myocardial apoptosis and contributes to graft failure during acute cardiac rejection in a murine model. Heterotopic cardiac transplantation was performed from Balb/c (H-2d) to C3H/He mice (H-2k). Recipients were treated with aminoguanidine (AG) at 400 mg/kg every day after surgery. As references, we used isografts in Balb/c mice with and without AG treatment (400 mg/kg/day). Graft survival, histological changes and serum NO levels were assessed. Intra-graft apoptosis was evaluated using a DNA fragmentation detection assay (TUNEL method) and DNA laddering. Significant prolongation of graft survival was observed in allografts treated with AG in comparison with nontreated allografts. Serum NO levels, which peaked on day 7 in nontreated allografts, were significantly decreased in AG-treated allografts. AG treatment decreased the number of apoptotic cells and lowered the ratio of the apoptotic cardiac myocytes in contrast to that of the apoptotic infiltrating cells. DNA laddering was clearly detected in nontreated allografts but was suppressed in AG-treated allografts. Inhibition of NO production by AG prolonged murine cardiac allograft survival. The decrease in intra-graft apoptotic activity paralleled histological improvement. Cardiac myocyte death which occurs through an apoptotic process mediated by NO contributes to graft failure during acute cardiac rejection.

Immunostained cathepsins B and L correlate with depth of invasion and different metastatic pathways in early stage gastric carcinoma.

BACKGROUND: With the recent development of minimal treatment for early stage gastric carcinoma, identifying specific indicators of the metastatic potential of primary tumors has become more important. Cathepsin B and cathepsin L, both lysosomal cysteine proteases, degrade the extracellular matrix during tumor progression. Although many studies have shown their relation to human cancer progression, little is known about their roles in the early stage. The clinicopathologic significance of cathepsins was therefore studied in early stage gastric carcinoma. METHODS: Expression of both cathepsins was studied immunohistochemically in 51 tissue specimens from gastric carcinomas that invaded the submucosal layer or muscularis propria. The relation between their expression and clinicopathologic factors was analyzed. RESULTS: Both cathepsins were expressed at higher levels in tumors that invaded the muscularis propria than in those within the submucosa (P < 0.05). In addition, tumors with lymphatic invasion showed higher cathepsin B expression than those without it (P < 0.05), whereas tumors with venous invasion showed higher cathepsin L expression than those without it (P < 0.05). No other clinicopathologic factors correlated with expression of either cathepsin. CONCLUSIONS: Tumors with overexpression of cathepsins have powerful potential for invasiveness in the early stage of gastric carcinoma. Moreover, the authors hypothesize that cathepsins may be one of the determinants of the metastatic route. To the authors' knowledge, this is the first report on specific proteases concerning the mode of metastasis, and the results of this study suggest that therapeutic strategies for early stage gastric carcinoma might need to be changed according to the status of cathepsins.

Bile acids increase intracellular Ca(2+) concentration and nitric oxide production in vascular endothelial cells.

The effects of bile acids on intracellular Ca(2+) concentration [Ca(2+)](i) and nitric oxide production were investigated in vascular endothelial cells. Whole-cell patch clamp techniques and fluorescence measurements of [Ca(2+)](i) were applied in vascular endothelial cells obtained from human umbilical and calf aortic endothelial cells. Nitric oxide released was determined by measuring the concentration of NO(2)(-). Deoxycholic acid, chenodeoxycholic acid and the taurine conjugates increased [Ca(2+)](i) concentration-dependently, while cholic acid showed no significant effect. These effects resulted from the first mobilization of Ca(2+) from an inositol 1,4,5-triphosphate (IP(3))-sensitive store, which was released by ATP, then followed by Ca(2+) influx. Both bile acids and ATP induced the activation of Ca(2+)-dependent K(+) current. Oscillations of [Ca(2+)](i) were occasionally monitored with the Ca(2+)-dependent K(+) current in voltage-clamped cells and Ca(2+) measurements of single cells. The intracellular perfusion of heparin completely abolished the ATP effect, but failed to inhibit the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO(2)(-) production concentration-dependently, while cholic acid did not enhance it. The bile acids-induced nitric oxide production was suppressed by N(G)-nitro-L-arginine methyl ester, exclusion of extracellular Ca(2+) or N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium, calmodulin inhibitors. These results provide novel evidence showing that bile acids increase [Ca(2+)](i) and subsequently nitric oxide production in vascular endothelial cells. The nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in liver diseases including cirrhosis.

Temporal bone pathology findings due to drowning.

It has been reported that anoxia due to near-drowning or near-suffocation causes brain damage but not inner ear damage. On the other hand, it has been shown that brain death causes both brain damage and inner ear damage. However, studies of temporal bone pathology resulting from sudden death due to drowning are few. We studied temporal bone pathology in six cases of individuals who died of accidents due to drowning. In all temporal bones examined, we found extensive congestion petechiae and haemorrhage in the vessels in the mucosal layers of the middle ear and mastoid air cells, as well as in the vessels around the facial nerve and carotid canal. In the inner ear, there was no abnormality in Corti's organ or the vestibular organs, except in one case who died in the bath. Our findings suggest that petechiae haemorrhage or congestion in the vessels of the mucosal layer and the vessels themselves of the middle ear occurs upon acute death due to drowning.

Canal and otolith afferent activity underlying eye velocity responses to pitching while rotating.

Pitching the head while rotating (PWR) combines periodic activation of the semicircular canals and the otoliths to generate pitch and roll eye deviations and continuous horizontal nystagmus. Monkeys were tested after individual pairs of semicircular canals were plugged and single units were recorded in the vestibular nerve while the animals were sinusoidally pitched 20-40 deg about a spatial horizontal axis with 5- and 16-s periods and simultaneously rotated about a spatial vertical axis at 30-120 deg/s. As previously shown, the steady-state horizontal response disappeared after plugging the vertical semicircular canals, but was maintained when the lateral canals were plugged. When the left anterior and right posterior canal (LARP) pair was left intact, the steady-state response depended on the axis about which the pitching took place. When the axis was normal to the LARP plane, there was no steady-state response. When the pitching axis was perpendicular to the LARP normal, the response was maximal. Firing rates of otolith units were approximately in phase with pitch position, and the addition of rotation about a vertical axis did not change the response. Lateral canal units did not have a steady-state modulation during pitch or constant velocity rotation. During PWR, they oscillated at twice the pitch frequency. This corresponded to the frequency at which the canal was maximally activated as it aligned with the plane of rotation. The amplitude of modulation increased proportionally to rotational velocity, but the phase remained the same. These characteristics were unchanged during roll while rotating (RWR), which induces little continuous nystagmus. Anterior and posterior canal units were maximally excited near pitch-velocity maxima and minima, respectively, during pure pitching. During PWR, however, the phases of both components simultaneously shifted toward each other and toward being in phase with otolith units. The peak excitation tended toward a forward-pitch position when the rotation was to the ipsilateral side, and toward a backward pitch position when the rotation was to the contralateral side. With 120-deg/s rotation during a 16-s pitch period, the phase difference between anterior and posterior canal units was as small as 17 deg. These data support the postulate that the correlation between vertical canal and otolith units is the critical factor in generating continuous unidirectional horizontal nystagmus during PWR.

A novel autoantibody in paraneoplastic sensory-dominant neuropathy reacts with brain-type creatine kinase.

We have previously reported on a novel autoantibody in a patient with paraneoplastic sensory-dominant neuropathy. This autoantibody immunostains the rat primary sensory system and reacts with a 47 kDa protein on immunoblotting. Here, we report on the isolation from rat spinal cord of a molecule that is recognized by this autoantibody. By ammonium sulfate cut and gel filtration, affinity and ion exchange chromatographies, the immunoreactive protein was purified to homogeneity and identified as brain-type creatine kinase (B-CK). Our study revealed that the autoantibody of the patient reacted with B-CK in the primary sensory system.

Cochlear neuronal loss are determined by use of a neurofilament protein antibody in cases of bilateral profound deafness.

The temporal bones of two patients with profound bilateral deafness from infancy were studied immunohistochemically, using a neurofilament protein antibody to detect the cochlear neuronal elements. One patient exhibited Mondini dysplasia of the inner ear, with the organ of Corti almost completely deteriorated. The other patient is the first reported case involving complete aplasia of the organ of Corti in all turns. In both cases, the immunohistochemical staining clearly revealed a severe reduction in the number of afferent neurons, such as dendrites, spiral ganglion cells and cochlear axons. The number of efferent spiral bundles in the osseous spiral lamina and intraganglionic portion also decreased in parallel with the reduction in the number of cochlear afferent neurons. Our results are inconsistent with previously reported cases of presbycusis and acquired deafness induced by the measles virus, in which efferent neurons were preserved while afferent neurons degenerated. The loss of both the efferent and afferent neurons might be characteristics of congenital deafness.

ABR and temporal bone pathology in Hurler's disease.

This is believed to be the first report on estimating hearing loss in Hurler's disease, based on the correlation between ABR and temporal bone pathology. ABR findings revealed hearing loss to be about 70 dB or more as result of peripheral mixed impairment. A histological study of the temporal bones revealed almost all pathological findings in the conductive system, except for the hyperplastic arachnoid in the internal auditory canal. In the middle ear cavity, otitis media, residual mesenchyme and deformity of ossicles were found. We explain the conductive component to be due to otitis media and poor ossicular connection. However, the etiology of the sensorineural component remains speculative. In Hurler's disease, hearing loss with mental retardation is often found at infantile age. Therefore, assessing the extent of hearing loss exactly was difficult, for example, the severity. the etiology and incidence of sensorineural impairment. We emphasize the need for not only well-described pathological studies but also for more objective functional investigations, at least ABR.

Risk factors for recurrent and residual cholesteatoma in children determined by second stage operation.

OBJECTIVE: To clarify the risk factors for the development of recurrent and residual cholesteatoma in children. METHODS: We studied 84 ears of 83 children aged 10 years or younger who underwent a second stage operation 1 year after primary surgery with a canal wall reconstruction procedure, and analyzed the clinical risk factors for recurrent and residual cholesteatoma. RESULTS: Recurrent cholesteatoma was detected in 21 ears (25%) and residual cholesteatoma was noted in 35 (42%) of 84 ears. With respect to recurrent cholesteatoma, significant risk factors were determined to be male gender, pars flaccida type of cholesteatoma and the association of otitis media with effusion either in the side affected by cholesteatoma or on the opposite side. On the other hand, congenital type of cholesteatoma was a significant negative risk factor. With respect to residual cholesteatoma, the only risk factor was a posterosuperior type of cholesteatoma. Residual cholesteatoma was sometimes found even when the surgeon had declared complete removal of the cholesteatoma matrix at the time of primary surgery. CONCLUSIONS: High incidence of recurrent and residual cholesteatoma was noted at the second stage operation. Occurrence of recurrent cholesteatoma is closely related to eustachian tube dysfunction. Thin and highly proliferative cholesteatoma matrix in children may be responsible for high occurrence of residual cholesteatoma. Therefore, planned staged surgery is preferable to single stage surgery for the treatment of pediatric cholesteatoma.

Origin of auditory brainstem responses in cats: whole brainstem mapping, and a lesion and HRP study of the inferior colliculus.

In order to identify the origin of five waves of auditory brainstem responses (ABRs) in cats, we designed three experiments. In particular, we focused on the inferior colliculus (IC). Experiment 1: Evoked potential maps of the frontal sections of the brainstem from the level of the cochlear nuclei to the level of the ICs were constructed from the results of whole brainstem field-potential analysis comparing ABR peaks. Experiment 2: Both ICs were aspirated and the brainstem and midbrian were transected along the midline. Experiment 3: HRP was injected to the central nucleus of the IC to cause phase reversal of field potentials, and localization of brainstem auditory neurons projecting to the IC was studied. The results of these experiments suggest that each wave of the ABR is elicited from multiple sources of auditory brainstem nuclei and tracts only.

Role of the otolith organs in generation of horizontal nystagmus: effects of selective labyrinthine lesions.

Selective labyrinthine lesions were made to study the origin of excitation in the labyrinth during off-vertical axis rotation. Plugging the semicircular canals abolishes the response to rotation about a vertical axis, but optokinetic after-nystagmus (OKAN) and the sustained horizontal nystagmus induced by off-vertical axis rotation (OVAR) are maintained. After cutting the nerves of the lateral semicircular canals, neither horizontal OKAN nor the continuous horizontal nystagmus associated with off-axis rotation can be induced, although vertical OKN, OKAN and vestibular nystagmus are intact. This supports the theory that labyrinthine activity responsible for the nystagmus induced by OVAR arises in the otolith organs and couples to the oculomotor system through the velocity storage mechanism.

An organic and functional staging classification. A measurement of disability in otolaryngology.

The quantitative measurement of organic and functional problems is assessed by a staging classification that is a measurement of the severity of a patient's condition. The method separates a medical problem or disease into three stages. Stage 1 indicates disease with no complications or a problem of minimal severity. Stage 2 is disease with local complications or a problem of moderate severity. Stage 3 denotes disease with systemic complications or a problem of a serious nature. Eight examples in otorhinolaryngology are given to demonstrate the feasibility of developing scales that quantify organic and functional disability. The scale will be useful in evaluating diagnostic efficiency of physicians as well as to measure prognosis, therapeutic effectiveness, and medical care costs.