Diagnostic performance of MR imaging of three major salivary glands for Sjögren's syndrome.

OBJECTIVE: We analyzed the diagnostic performance of the MR imaging findings of the parotid, submandibular, and sublingual glands to discriminate between patients with and without Sjögren's syndrome. METHODS: We retrospectively analyzed the correlation between the MR imaging and histopathological findings obtained from 69 patients with clinically suspected Sjögren's syndrome. We evaluated the heterogeneous signal intensity distribution on T1- and T2-weighted images, the multiple high-signal-intensity spots on MR sialograms, and the volume of the parotid, submandibular, and sublingual salivary glands. RESULTS: The multiple high-signal-intensity spots in the parotid gland showed the highest sensitivity and diagnostic accuracy (82% and 83%, respectively). In addition, the multiple high-signal-intensity spots and the heterogeneous signal intensity distribution in the submandibular gland showed high specificity (100% and 88%, respectively). The volume of the submandibular gland, but not that of the parotid or sublingual gland, was smaller in patients with Sjögren's syndrome. CONCLUSIONS: The presence of multiple high-signal-intensity spots on an MR sialogram in the parotid gland should be considered the best diagnostic indicator for Sjögren's syndrome. The presence of spots, heterogeneity, and the change to smaller volumes in the submandibular gland were also helpful because of their high specificity, particularly in advanced cases.

Expression of umami-taste-related genes in the tongue: a pilot study for genetic taste diagnosis.

OBJECTIVE: Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND METHODS: Tissue samples were collected from healthy volunteers by scraping the foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a taste-cell-specific G protein, and gene expression analysis by real-time polymerase chain reaction of ß-actin, gustducin (GNAT3) and umami receptors (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression following application of umami substances onto the tongue were analysed. RESULTS: Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of ß-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. CONCLUSION: Evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.

Toll-like receptors, NOD1, and NOD2 in oral epithelial cells.

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of beta-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.

Development of a compact ECR ion source for various ion production.

There is a desire that a carbon-ion radiotherapy facility will produce various ion species for fundamental research. Although the present Kei2-type ion sources are dedicated for the carbon-ion production, a future ion source is expected that could provide: (1) carbon-ion production for medical use, (2) various ions with a charge-to-mass ratio of 1/3 for the existing Linac injector, and (3) low cost for modification. A prototype compact electron cyclotron resonance (ECR) ion source, named Kei3, based on the Kei series has been developed to correspond to the Kei2 type and to produce these various ions at the National Institute of Radiological Sciences (NIRS). The Kei3 has an outer diameter of 280 mm and a length of 1120 mm. The magnetic field is formed by the same permanent magnet as Kei2. The movable extraction electrode has been installed in order to optimize the beam extraction with various current densities. The gas-injection side of the vacuum chamber has enough space for an oven system. We measured dependence of microwave frequency, extraction voltage, and puller position. Charge state distributions of helium, carbon, nitrogen, oxygen, and neon were also measured.

Arterial blood pressure regulation of pulpal blood flow as determined by laser Doppler.

Dynamic changes of pulpal blood flow (PBF) and gingival blood flow (GBF) induced by intra-venous injection of two kinds of vasoactive drugs were observed in dogs by means of Laser Doppler Velocimetry. Intra-venous injection of norepinephrine caused PBF to increase, corresponding to the blood pressure (BP) increase, while GBF decreased. Orciprenaline sulfate caused PBF to decrease parallel to the BP decrease, as compared with a GBF increase. The effects of these vasoactive drugs lasted longer on GBF than on PBF and BP. These results indicate that the regulation of blood flow in the dental pulp is more dependent on systemic blood pressure than on local vasoconstriction or vasodilation.

Axon reflex vasodilatation in cat dental pulp elicited by noxious stimulation of the gingiva.

Antidromic stimulation of sensory nerves has been shown to increase blood flow in the tissue they innervate. This study was designed to determine if antidromic vasomotor responses occur in feline dental pulp and if they are mediated by branched axons supplying both tooth pulp and gingiva. Dynamic changes in pulpal blood flow (PBF) elicited by electrical stimulation, pinching, heating, and capsaicin application to the gingivae were investigated in cat mandibular canine teeth by means of Laser Doppler Velocimetry. All inferior alveolar nerve bundles and the cervical sympathetic trunk had been previously sectioned to avoid the occurrence of brainstem reflexes, e.g., somato-autonomic vasomotor reflexes. Increases in PBF were observed in seven out of 12 cats when a restricted gingival area adjacent to the canine teeth was stimulated as described, but the increases were abolished after the sensitive gingival area was painted with lidocaine jelly, a surface anesthetic. These vasodilator responses, remarkably reduced following repeated application of 30 mM of capsaicin, are considered to be induced via antidromic activation of capsaicin-sensitive nociceptive nerve fibers, presumably by axon reflex mechanisms, suggesting that nerve terminals supplying the gingiva originate from parent axons which have collaterals that innervate the canine tooth pulp.

Absence of parasympathetic vasodilatation in cat dental pulp.

The existence and nature of parasympathetic nerve fibers in the dental pulp have long been a subject for discussion; indeed, vasodilator responses mediated by such nerve fibers have yet to be conclusively demonstrated in the dental pulp. This study was designed to determine whether parasympathetic vasodilator mechanisms do or do not exist in the cat dental pulp. Dynamic changes in pulpal blood flow (PBF), with mandibular lip blood flow (LBF) recorded as a control, were investigated in cat mandibular canine teeth by means of laser Doppler velocimetry. Peripheral trigeminal afferents (see below) were stimulated electrically to confirm that somato-parasympathetic reflex vasodilatation could be induced. The peripheral cut ends of the facial and glossopharyngeal nerve roots, which have been reported to contain parasympathetic nerve fibers to the oral tissues, were then stimulated intracranially. Electrical stimulation of trigeminal afferents (in the infraorbital nerve or the maxillary buccal gingiva) caused no change in PBF but did increase ipsilateral LBF. Neither facial nor glossopharyngeal nerve root stimulation caused a PBF increase, though both elicited increases in ipsilateral LBF. The vasodilator responses in the lip were sensitive to ganglion blockade (with hexamethonium), indicating vasodilatation via activation of parasympathetic vasodilator fibers. In contrast, intracranial stimulation of the trigeminal nerve root induced increases in both PBF and LBF which were reduced by pre-treatment with tripelennamine, indicating antidromic vasodilatation via the trigeminal sensory nerve. These results suggest that a parasympathetic vasodilator mechanism is not present in feline dental pulp.

Radiofrequency ablation of tachyarrhythmias in patients with Ebstein's anomaly.

We performed radiofrequency catheter ablation in five patients associated with Ebstein's anomaly to cure their refractory tachyarrhythmias. The presenting arrhythmias were four cases of orthodromic circus movement tachycardia using accessory pathways as a requisite limb, including one case of a Mahaim fiber and one of atrial flutter of common variety. All accessory pathways, including the Mahaim fiber, were ablated by RF energy delivered through the catheter placed at the AV annulus rather than the displaced anatomical AV groove. Interestingly, the antegrade or retrograde conduction interval over these accessory pathways was relatively longer than that of usual accessory pathways, and the accessory pathway potential was fractionated in some cases. The location of the atrioventricular node was displaced from the usual position to the postero-inferior area of Koch's triangle in one case. The configuration of the flutter wave was larger than usual in height as well as in width. All tachyarrhythmias were cured by RF catheter ablation. In the case of RF catheter ablation for patients with Ebstein's anomaly, close attention is indispensable in order to accomplish it safely and successfully, because of the anatomical and functional differences peculiar to Ebstein's anomaly.

Catheter ablation of idiopathic left ventricular tachycardia with multiple breakthrough sites guided by an electroanatomical mapping system.

Idiopathic ventricular tachycardia (VT) has been considered to be amenable to radiofrequency catheter ablation guided by Purkinje potentials. However, there appear to be various types of reentrant circuits associated with this VT deduced from the results of the successful radiofrequency catheter ablation cases. We describe in this report a patient with idiopathic left ventricular tachycardia which was electrically inducible and verapamil sensitive. Multiple earliest ventricular activation sites during tachycardia were detected with electroanatomical mapping using the CARTO system. Multiple applications at these sites failed to eliminate the VT. The earliest Purkinje potential was recorded at least 1.5 cm away from the earliest ventricular activation sites, and the radiofrequency current application at this site resulted in the complete abolition of this VT. The reentrant circuit of this tachycardia seemed to have multiple breakthrough sites to the ventricular myocardium, which were distant from the requisite part of the reentrant circuit of this VT involving the Purkinje fiber network conduction system.

A simple, yet accurate method for detecting and quantifying secretions from human minor salivary glands using the iodine-starch reaction.

The lack of published information about the minor salivary glands is due in part to the difficulties experienced in collecting and quantifying their secretions. In fact, no method exists for measuring their secretions that is both simple and accurate. This investigation examined the accuracy of our newly developed method (which simply employs the iodine-starch reaction) in 10 healthy non-medicated adults. A strip painted with a solution of iodine in absolute alcohol then with a fine starch powder mixed with castor oil was placed at a designated location on the lower-lip mucosa for 2 min to collect saliva. Black-stained spots of various sizes corresponding to the individual glands could be accurately visualized. After removal of the strip, the total stained area (mm2) was calculated by digitizing the spot areas using a computer system. The correlation coefficient (r) between known volumes of saliva and stain size was 0.995, indicating a close correlation. The correlation coefficient (r) between area values obtained in the first trial in each subject (Y) and the second (X; 10 min later) was 0.963, and the simple regression equation was close to Y=X, indicating good reproducibility. The mean flow rate microl/cm2 per min) obtained by converting mean total area to volume and thence to flow rate was 0.49+/-0.26, in good agreement with published values obtained by others. These results suggest that our newly developed method allows both the distribution and secretion rate of the minor salivary glands to be observed, and that it should be of practical value due to its simplicity, accuracy, and reproducibility.

Dependence of pulpal blood-flow responses on baseline blood-flow in the cat.

It has been shown earlier that electrical stimulation of the distal cut end of the inferior alveolar nerve (IAN) in the cat evokes three different patterns of pulpal blood-flow (PBF) response in the ipsilateral mandibular canine tooth (a decrease, a biphasic response, or an increase). The response to a given stimulus sometimes changed to another pattern even in one and the same experimental animal during the course of the experiment. It is known that the evoked decrease is due to activation of the sympathetics and that the increase is due to antidromic activation of sensory fibres; but, it is unknown why the response varies so much. It is hypothesised that the baseline blood-flow (BBF) modulates vasomotor responses in the dental pulp. To test this hypothesis, the effects of BBF on PBF responses elicited by the IAN stimulation mentioned above were investigated. Dynamic changes in PBF in cat mandibular canine teeth were elicited by electrical stimulation of the distal cut end of the IAN, at various BBF, with blood-flow monitored by laser Doppler flowmetry. The amplitude of the PBF vasodilator response increased as BBF was adjusted downwards (by cooling the tooth). In contrast, the amplitude of the PBF vasoconstrictor response increased as the BBF rose. Vasodilator responses could be transformed into vasoconstrictor responses, and vice versa, by alterations in the BBF. No systemic blood-pressure changes were elicited throughout the experiment. These results indicate that a consideration of baseline vascular tone is important, whenever the size of PBF responses to various stimuli is discussed or calculated.

Serious arrhythmias in patients with apical hypertrophic cardiomyopathy.

We report cases of serious arrhythmias associated with apical hypertrophic cardiomyopathy (AHCM). Thirty-one patients were referred to our institute to undergo further assessment of their AHCM from 1988 to 1999. Three patients with nonsustained ventricular tachycardia demonstrated an 123I-MIBG regional reduction in the tracer uptake. In two patients with ventricular fibrillation (VF), the findings from 123I-MIBG imaging revealed regional sympathetic denervation in the inferior and lateral regions. Electrophysiologic study demonstrated reproducible induction of VF in aborted sudden death and presyncopal patients, resulting in the need for an implantable defibrillator device and amiodarone in each patient. Patients with refractory atrial fibrillation with a rapid ventricular response suffered from serious congestive heart failure. A prudent assessment and strategy in patients with this disease would be indispensable in avoiding a disastrous outcome.

Experimental study of nystagmus induced by injecting various solutions into the middle ear cavity.

Injecting of various solutions into the middle ear cavity of cats and rabbits provoked certain characteristic types of nystagmus which resembled caloric nystagmus or clinical cases of peripheral vestibular disorders. Solutions with different degrees of specific gravity, osmotic effect and ion composition were used in this study. Direction-changing positional nystagmus, irritative nystagmus, and paralytic nystagmus were elicited according to the physical or chemical properties of each solution. Histological findings showed mild changes in the perilymphatic space and/or in the endolymphatic space in the period with some characteristic types of nystagmus. Infiltration of the substances into the inner ear fluids from the middle ear cavity via a round window membrane were probably responsible for these types of nystagmus.

Linearly and circularly polarized, 50 Hz magnetic fields did not alter intracellular calcium in rat immune cells.

This study was conducted to determine if exposure to 50 Hz magnetic field (MF) affects intracellular calcium ([Ca2+]i). We employed flow cytometry for real-time detection of possible changes in [Ca2+]i in a large number of cells. A solenoid coil for vertical MF exposure and a multiple-loop square-coil for horizontal MF were utilized. In the laboratory, background 50 Hz MF was less than 0.08 microT when all necessary equipment was powered. Rat thymocytes were exposed to 0.1 mT horizontal or vertical field, or to 0.14 mT circularly polarized field for 30 min; the effects of consecutive exposures to vertical and horizontal MFs, or vice versa, for 20 min each also were examined. In addition, intact thymocytes or lectin-activated thymocytes, splenocytes and peripheral blood lymphocytes were exposed to the 5 mT vertical field for 30 min. In all these experiments, no alteration in [Ca2+]i was evident. As a positive control, a calcium ionophore always was added to the medium following MF exposure to verify that the cells were capable of increasing [Ca2+]i and the system would record the response. The data indicate that MF exposure had no effect on [Ca2+]i under any of the conditions examined.

A case of delayed endolymphatic hydrops.

A 30-year-old male with delayed endolymphatic hydrops was given a sac operation. An intradural portion of the endolymphatic sac was resected and the epithelial surface was examined under a scanning electron microscope. The epithelium showed fibrous degeneration and disappearance of the epithelial cells. Pathogenesis of degeneration of the endolymphatic sac is discussed.

[Familial deafness showing hearing pattern of low-tone losses].

Clinical and electrocochleographic studies of low tone familial deafness were carried out in 19 patients of 10 families. These hearing impairments were characterized by an upward-sloping pure tone audiogram with 50dB to 60dB hearing threshold below 2000Hz and with normal or near-normal hearing threshold above this frequency. The type of inheritance in these families showed autosomal dominant mode and no associated malformation. In 7 patients, hearing tests were repeated, it was observed that hearing threshold was not elevated. The short increment sensitivity index (SISI) tests were positive suggesting a hair cell lesion in tested 7 patients. The caloric tests were normal in tested 3 patients. No abnormal internal ear configuration was found in both X-ray and high-resolution computed tomography. Twelve patients with these familial low tone deafness (FLTD), 19 patients with Ménière's disease, and 9 patients with low tone sudden deafness (LTSD) were studied using the transtympanic electrode technique of electrocochleography. All patients of FLTD showed normal negative summating potential (-SP) amplitude, and the cochlear microphonics (CM) showed a nearly same detection threshold as hearing level of the pure tone audiogram at 1 kHz and 0.5 kHz. The evidence suggested that the hearing impairment resulted from a localized abnormality of the cochlear apex, and without endolymphatic hydrops. On the other hand, patients with Ménière's disease and LTSD showed a high -SP amplitude and a satisfactory detection threshold of CM compared with hearing level of the pure tone audiogram. These findings suggest that both Ménière's disease and LTSD relate to endolymphatic hydrops.

Diagnostic value of capsule-like rim enhancement on magnetic resonance imaging for distinguishing malignant from benign parotid tumours.

The purpose of this study was to clarify the diagnostic value of capsule-like rim enhancement (CLRE) on magnetic resonance imaging (MRI) for distinguishing malignant from benign tumours of the parotid gland. We retrospectively evaluated contrast-enhanced T1-weighted images of 100 patients with malignant and benign parotid tumours for the presence, completeness, and irregularity of CLRE and its maximum thickness. We investigated any correlation of imaging and histopathological findings for 51 cases showing CLRE with available histology. The presence and completeness of CLRE did not differ significantly between benign and malignant tumours. Malignant tumours had more irregular CLRE than benign tumours (P<0.05). The mean CLRE thickness was significantly greater for malignant (2.4 mm) than benign tumours (1.4 mm) (P<0.0001). The two types of tumour were most accurately distinguished using a cut-off value of 1.5 mm thickness. Histopathology demonstrated the general correspondence of thick CLRE on MRI in malignant tumours with thick but sparse fibrous tissue and infiltration of tumour cells and lymphocytes, whereas thin CLRE in benign tumours typically represented dense fibrous tissue without infiltration of tumour cells. CLRE was more irregular and thicker in malignant tumours than in benign tumours, which may be of help in differentiating them.

FGF-2 stimulates periodontal regeneration: results of a multi-center randomized clinical trial.

The efficacy of the local application of recombinant human fibroblast growth factor-2 (FGF-2) in periodontal regeneration has been investigated. In this study, a randomized, double-blind, placebo-controlled clinical trial was conducted in 253 adult patients with periodontitis. Modified Widman periodontal surgery was performed, during which 200 µL of the investigational formulation containing 0% (vehicle alone), 0.2%, 0.3%, or 0.4% FGF-2 was administered to 2- or 3-walled vertical bone defects. Each dose of FGF-2 showed significant superiority over vehicle alone (p < 0.01) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the 0.3% FGF-2 group. No significant differences among groups were observed in clinical attachment regained, scoring approximately 2 mm. No clinical safety problems, including an abnormal increase in alveolar bone or ankylosis, were identified. These results strongly suggest that topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.