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.

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.

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.

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.

High serum levels of IGF-I contribute to promotion of endochondral ossification in mandibular condyle and cause its specific elongation in acromegaly-like rats.

Mandibular protrusion accompanies acromegaly or acrogigantism. To clarify the detailed mechanisms, we used an acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I). Human recombinant IGF-I (640 microg/day) continuously was infused subcutaneously to 10-week-old male rats (n=12) for four weeks. Control, sham-operated animals (n=12) were injected with saline alone. Twelve rats (six from each group) were killed immediately after ending administration at age 14 weeks. Another 12 rats (six from each group) were housed for an additional four weeks after treatment ended. Mandibular condylar length increased significantly in the IGF-I rats compared with the control rats, but no significant intergroup difference was found in the lengths of the coronoid and angular processes. Cartilaginous layer width, bone matrix volume, and the number of osteoblasts in the mandibular condyle increased significantly in the IGF-I group. These histopathological changes in the condyle disappeared after IGF-I administration was discontinued; however, the morphological change in condylar length remained. These findings suggest that mandibular protrusion in patients with acromegaly or acrogigantism may be evoked by superfluous elongation of the mandibular condyle and that such elongation can be induced by endochondral ossification caused by high IGF-I serum levels.

A case of masticatory disturbance incidental to trigeminal schwannoma: changes in occlusal force and masticatory sensation before and after radiosurgery.

We report here a case of masticatory disturbance evoked by trigeminal schwannoma, in which we have evaluated the changes in occlusal force and masticatory sensation before and after treatment for the tumour. The patient was a 43-year-old woman and her chief complaint was a loss of masticatory sensation on her left side. MR imaging revealed an enhanced tumour in the left cavernous sinus/Meckel's cave. The left masseter muscle function and occlusal force showed remarkable decreases before treatment; however, the sensory thresholds of her facial skin and dental pulp were not significantly different from the control side, indicating that her loss of masticatory sensation was not due to sensory disturbance but to occlusal force weakness. Gamma-knife radiosurgery resulted in a significant improvement in masticatory sensation following an increase in occlusal force.

Morphological and histopathological changes in tongues of experimentally developed acromegaly-like rats.

An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological tongue changes and clarify whether the changes were reversible. Human recombinant IGF-I (640 microg/day) was continuously subcutaneously infused into ten-week-old male rats for four weeks (IGF-I group; n = 6). Control sham-operated animals were injected saline alone (control group; n = 6). Rats were sacrificed immediately on ending administration at the age of fourteen weeks. Another 12 rats (6 from each group) were housed for an additional four weeks after administration ended. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. Tongue weights significantly increased with histopathological changes present (increases in the muscle-bundle width, spaces between muscle-bundles and epithelium thickness) in the IGF-I group compared to control rats. Tongue size returned to control levels after discontinuation of IGF-I administration. These findings suggest that the characteristic tongue enlargement was developed experimentally in our acromegaly-like rat model, and that such morphological and histopathological tongue changes are reversible on normalization of circulating IGF-I levels.

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.

Evaluation of the position, mobility, and morphology of the disc by MRI before and after four different treatments for temporomandibular joint disorders.

OBJECTIVES: The purpose of this study was to evaluate changes in disc position, mobility, and morphology in patients with temporomandibular joint disorders (TMD) in response to four different treatments, splint therapy, pumping manipulation, arthrocentesis, and arthroscopic surgery, using magnetic resonance imaging (MRI). METHODS: Eighty-five joints (85 patients) with unilateral internal derangement or osteoarthritis that were successfully treated were included in this study. The patients were divided into four groups as follows: splint therapy group, pumping manipulation group, arthrocentesis group, and arthroscopic surgery group. Changes in the disc position, mobility, and morphology before and after treatment were compared among the four groups using MRI. RESULTS: All discs showed anterior disc displacement (ADD) without reduction before treatment. Only 10% of the joints became ADD with reduction after treatment, and the other joints remained ADD without reduction in spite of treatment. Discs treated by arthroscopic surgery were located more anteriorly compared with pre-treatment. In pre-treatment MRI, the rate of stuck disc increased as the stage of the treatment advanced. In post-treatment MRI, all temporomandibular joints (TMJs) had mobile discs. The disc deformity advanced after arthrocentesis and arthroscopic surgery. CONCLUSIONS: Even though clinical signs and symptoms were alleviated by treatment, most discs remained ADD without reduction on MRI in spite of treatment. This suggests that the four treatments do not necessarily improve the position and deformity of the disc, and that arthroscopic surgery advances the deformity and anterior displacement of the disc. Disc mobility is important for improving clinical signs and symptoms.

Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via toll-like receptors, NOD1 and NOD2 in human oral epithelial cells.

Peptidoglycan recognition proteins (PGRPs), a novel family of pattern recognition molecules (PRMs) in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and are suggested to act as anti-bacterial factors. In humans, four kinds of PGRPs (PGRP-L, -Ialpha, -Ibeta and -S) have been cloned and all four human PGRPs bind PGN. In this study, we examined the possible regulation of the expression of PGRPs in oral epithelial cells upon stimulation with chemically synthesized pathogen-associated molecular patterns (PAMPs) in bacterial cell surface components: Escherichia coli-type tryacyl lipopeptide (Pam3CSSNA), E. coli-type lipid A (LA-15-PP), diaminopimelic acid containing desmuramyl peptide (gamma-D-glutamyl-meso-DAP; iE-DAP), and muramyldipeptide (MDP). These synthetic PAMPs markedly upregulated the mRNA expression of the four PGRPs and cell surface expression of PGRP-Ialpha and -Ibeta, but did not induce either mRNA expression or secretion of inflammatory cytokines, in oral epithelial cells. Suppression of the expression of Toll-like receptor (TLR)2, TLR4, nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the upregulation of PGRP mRNA expression induced by Pam3CSSNA, LA-15-PP, iE-DAP and MDP respectively. These PAMPs definitely activated nuclear factor (NF)-kappaB in the epithelial cells, and suppression of NF-kappaB activation clearly prevented the induction of PGRP mRNA expression induced by these PAMPs in the cells. These findings suggested that bacterial PAMPs induced the expression of PGRPs, but not proinflammatory cytokines, in oral epithelial cells, and the PGRPs might be involved in host defence against bacterial invasion without accompanying inflammatory responses.

Insulin-like growth factor-I stimulates acromegaly-like specific mandibular enlargement in rats.

To help us investigate the time course of mandibular enlargement in acromegaly or acrogiantism to determine the most suitable period for occlusal treatment in this disease, our aim was to develop a rat model of acromegaly (acrogiantism). In this study, prominent mandibular enlargement was induced by continuous subcutaneous infusion of human recombinant insulin-like growth factor-I (IGF-I) (640 microg/day) in 10-week-old male rats for 4 weeks (n = 6); the control sham-operated group was injected with saline alone (n = 6). Circulating human IGF-I was clearly detectable in the IGF-I group during the four-week administration period, while endogenous rat IGF-I levels decreased. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. The length of every bone examined (mandible, maxilla, and femur) showed a significant increase compared to control rats, especially the mandible. Although the mandible did not continue to grow after discontinuation of IGF-I administration, it did not return to control size, unlike the maxilla and femur, and disharmonious jaw size (between maxilla and mandible) persisted even after circulating IGF-I levels normalized. These findings in our rat model suggest that mandibular occlusal treatment should only be considered for acromegalic (acrogiantic) patients after serum IGF-I levels have normalized and bone growth has ceased.

Platelet responses and anaphylaxis-like shock induced in mice by intravenous injection of whole cells of oral streptococci.

Intravenous injection of lyophilized whole cells of various oral streptococcal strains into muramyldipeptide (MDP)-primed C3H/HeN mice induces rapid anaphylactoid shock. Here we examined the mechanism underlying this shock. In non-primed mice, Streptococcus intermedius K-213K (SiK213) and Streptococcus constellatus T21 (ScT21) produced little or no sign of shock. In MDP-primed mice, SiK213 caused lethal shock, while ScT21 only had a weak effect. SiK213 induced decreases in blood platelets and 5-hydroxytryptamine (5HT) preceding the shock, while the effects of ScT21 were weak. The SiK213-induced 5HT decrease and shock were reduced by a complement-C5 inhibitor. These results suggest that (i). streptococcal bacterial cells can induce rapid platelet responses, (ii). complement-dependent degradation of platelets may be involved in streptococcus-induced shock, (iii). the streptococcus-induced platelet degradation or degranulation may occur largely in the systemic circulation, and (iv). platelets may play a role not only in infectious diseases caused by gram-negative bacteria, but also in diseases caused by gram-positive bacteria.

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.

Centrally mediated reflex vasodilation in the gingiva induced by painful tooth-pulp stimulation in sympathectomized human subjects.

This study was designed to determine whether painful electrical stimulation of the tooth pulp induces centrally mediated reflex vasomotor changes in human gingiva and whether the sympathetic nervous system is involved in the vasomotor responses. Dynamic changes in maxillary gingival blood flow (GBF) following painful electrical stimulation of the mandibular lateral incisor were investigated, by means of laser-Doppler flowmetry, in both healthy volunteers and patients undergoing sympathetic blockade for hyperhidrosis. Increases in GBF were observed in both healthy volunteers and patients on the ipsilateral side without an increase in systemic blood pressure, but the evoked GBF increase disappeared when pain sensation was abolished by local anesthetization with 2% xylocaine solution. The vasodilator responses did not differ in amplitude between before and after the sympathectomy. These results suggest that painful tooth stimulation evokes centrally mediated reflex vasodilation, presumably via parasympathetic efferent fibers, in the human gingiva and that sympathetic vasomotor mechanisms are not involved in these responses.

Usefulness of heavily T(2) weighted magnetic resonance images for the differential diagnosis of parotid tumours.

OBJECTIVES: To evaluate the usefulness of heavily T(2) weighted (T2W) magnetic resonance (MR) images for the differential diagnosis of parotid tumours. METHODS: Conventional T2W and heavily T2W images obtained from 43 patients with parotid tumours were reviewed retrospectively. Tumours were classified pathologically into three types: pleomorphic adenoma (25 cases), Warthin's tumour (7 cases) and malignant tumour (11 cases). During interpretation of each MR image, special attention was paid to the homogeneity and signal intensity displayed by the solid portions of the tumours. RESULTS: Heavily T2W images could distinguish pleomorphic adenoma from Warthin's tumour and malignant tumours based on the homogeneity and signal intensity of the solid portions, whereas conventional T2W images could not. On conventional T2W images, neither homogeneity nor signal intensity differed significantly among these three tumour types. On heavily T2W images, malignant and Warthin's tumours appeared more homogeneous than pleomorphic adenoma (P<0.0061); signal intensity from pleomorphic adenoma was significantly different to signal intensity from malignant tumours (P<0.05) and Warthin's tumour (P<0.005). CONCLUSIONS: Heavily T2W MR images can be useful in distinguishing pleomorphic adenoma from Warthin's tumour and malignant tumours.

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.

Evaluation of pulse sequences used for magnetic resonance sialography.

OBJECTIVES: To determine the most appropriate sequences for the visualization of small parotid ducts in MR sialography. METHODS: MR images of a phantom consisting of distilled water in polyethylene tubes were obtained with turbo-spin echo (TSE), single-shot turbo-spin echo (SSTSE), half-fourier acquisition, single-shot turbo-spin echo (HASTE) and turbo gradient-spin echo (TGSE) pulse sequences and compared visually and quantitatively. MR sialograms obtained from healthy volunteers and patients with Sjögren's syndrome (SS) were obtained using the same four sequences. RESULTS: In the phantom, TSE images were best and the contrast-noise ratio (CNR) highest. In the volunteers, the main ducts were especially clearly visualized with TSE and in SSTSE; however, the majority of secondary and/or tertiary parotid ducts were not depicted by any of the sequences used. In SS patients, images of small main ducts and small pseudocysts were clearer using TSE. However, TSE could not depict the narrow main ducts or peripheral ducts or very small pseudocysts. CONCLUSIONS: TSE is considered the most suitable MR sequence for assessing small parotid gland ducts. However, further improvement is needed since it does not always visualize them sufficiently.

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.