Tongue-palatal contact changes in patients with skeletal mandibular prognathism after sagittal split ramus osteotomy: an electropalatography study.

The purpose of this study was to investigate the changes in tongue-palatal contact patterns using electropalatography (EPG) before and after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Nine clients who underwent SSRO for mandibular setback and seven control subjects were participated in this study. Tongue-palatal contact patterns for /t/, /s/ and /k/ production were investigated using EPG before surgery and 3 months after surgery. The mean value of whole total of palate contact (WT) in the maximum contact frame was examined before and after SSRO. The correlation quantity between the change of center of gravity (COG) value and the amount of mandibular setback was also evaluated. The mean value of WT for /t/ and /s/ significantly increased after SSRO, and the EPG pattern became normal. However, a remarkable change in WT for /k/ was not observed, and the mean value was significantly larger in the SSRO group before and after surgery than in the control group. A negative correlation between COG variation and the amount of mandibular setback for /t/ and positive correlation for /s/ was observed. This study demonstrated that tongue-palatal contact patterns for /t/ and /s/ articulation improved clearly after SSRO. There was a significant correlation between COG variation and the amount of mandibular setback. However, no significant change was detected through perceptual assessment before and after SSRO. Further investigation is needed to determine whether these results will change over time.

The effect of magnetic field during freezing and thawing of rat bone marrow-derived mesenchymal stem cells.

Previous studies showed that a programmed freezer with magnetic field can maintain a high survival rate of mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the influences of magnetic field during freezing and thawing on the survival of MSCs isolated from rat bone marrow. The cells were frozen by a normal programmed freezer or a programmed freezer with magnetic field (CAS-LAB1) and cryopreserved for 7 days at -150 °C. Then, the cells were thawed in the presence or absence of magnetic field. Immediately after thawing, the number of surviving or viable cells was counted. The cell proliferation was examined after 1-week culture. Cryopreserved MSCs which were frozen by a normal freezer or a CAS freezer were transplanted into bone defects artificially made in calvaria of 4-week-old rats. Non-cryopreserved MSCs were used as a control. The rats were sacrificed at 8, 16, or 24 weeks after transplantation and the bone regeneration area was measured. Proliferation rates of MSCs after 1 week were significantly higher in the CAS-freezing-thawing group than in the CAS-freezing group. The extent of new bone formation in the CAS-freezing-thawing group tended to be larger than in CAS-freezing group 24 weeks after transplantation. These results suggest that a magnetic field enhances cell survival during thawing as well as freezing.

Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.

BACKGROUND: The renin-angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. METHODS: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). RESULTS: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. CONCLUSIONS: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN.

DC-SIGN, a human C-type lectin, is expressed on the surface of dendritic cells (DC), while a closely related human gene, DC-SIGNR or L-SIGN, is found on sinusoidal endothelial cells of liver and lymph node. Both DC-SIGN and DC-SIGNR/L-SIGN can bind ICAM-3 and HIV gp120, and transmit HIV to susceptible cells in trans. Here, we report the cloning of five mouse genes homologous to human DC-SIGN and DC-SIGNR/L-SIGN. Only one gene, named mouse DC-SIGN, is highly expressed in DC, and is not found in a panel of mouse macrophage and lymphocyte cell lines. The other four genes, named mouse SIGNR1 (SIGN-Related gene 1), SIGNR2, SIGNR3 and SIGNR4, are expressed at lower levels in various cells according to RT-PCR and Northern blot analyses on RNA. All the genes of mouse DC-SIGN and SIGNRs map to adjacent regions of chromosome 8 A1.2-1.3. However, like human DC-SIGN, only the mouse DC-SIGN gene is closely juxtaposed to the CD23 gene, while the other four SIGNR genes are located close to each other in a neighboring region. mRNAs of mouse DC-SIGN and three SIGNR genes encode type II transmembrane proteins (DC-SIGN, 238 amino acids; SIGNR1, 325 amino acids; SIGNR3, 237 amino acids; SIGNR4, 208 amino acids), but the SIGNR2 gene only encodes a carbohydrate recognition domain (CRD) without a cytosolic domain and a transmembrane domain (SIGNR2, 178 amino acids). Amino acid sequence similarities between the CRD of human DC-SIGN and the mouse homologues are 67% for DC-SIGN, 69% for SIGNR1, 65% for SIGNR2, 68% for SIGNR3 and 70% for SIGNR4 respectively. However, the membrane proximal neck domains in the mouse genes are much shorter than their counterparts in human DC-SIGN and DC-SIGNR/L-SIGN. This family of mouse C-type lectins is therefore complex, but only one of the new genes, DC-SIGN, is juxtaposed to CD23 and is expressed at high levels in DC.

Analysis of sialo-N-glycans in glycoproteins as 1-phenyl-3-methyl-5-pyrazolone derivatives by capillary electrophoresis.

A method for the analysis of the sialo-N-glycans in glycoproteins was established by the electrokinetic chromatography mode of capillary electrophoresis (CE) in sodium dodecyl sulfate (SDS) micelles as 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives, using sialo-N-glycans in fetuin as a model. Six major and some minor peaks were observed for the N-glycans in fetuin, which were well separated from each other using 50 mM phosphate buffer, pH 6.0, containing SDS to a concentration of 30 mM in an uncoated fused-silica capillary, and these peaks were assigned to sialo-N-glycans having either of the biantennary or beta1-3/beta1-4 linked galactose-containing complex type triantennary N-glycans as the basic structures, by an indirect method based on the assignment of the peaks in high-performance liquid chromatography separated in parallel with CE and peak collation between these two separation methods. The attaching position of the sialic acid residue was determined using the linkage preference of neuraminidase isozymes. The established system is considered to be useful for routine analysis of microheterogeneity of the carbohydrate moiety of this model glycoprotein from the following reasons: (1) the derivatization with PMP proceeds quantitatively under mild conditions without causing release of the sialic acid residue, (2) the derivatives can be sensitively detected by UV absorption, (3) the procedure is simple, rapid and reproducible. Preliminary results of N-glycan analysis for several other glycoproteins under these conditions are also presented.

[Pharmacological profiles of mycophenolate mofetil (CellCept), a new immunosuppressive agent].

Mycophenolate mofetil (MMF, CellCept), a semisynthetic derivative of mycophenolic acid (MPA) produced by a fungus, is an inhibitor of the inosine monophosphate dehydrogenase (IMPDH) enzyme (IC50 = 25 nM) that catalyzes the synthesis of guanosine monophosphate (GMP) from inosine. GMP is an essential nucleoside for purine synthesis during cell division. As T and B-lymphocytes almost exclusively use the de novo pathway of purine synthesis, these cells are particularly sensitive to the inhibitory action of MMF. It has a mechanism of action distinct from cyclosporine and tacrolimus. Although MMF does not affect cytokine production, by inhibiting the rate-limiting enzyme IMPDH in the de novo synthesis of purines, it inhibits the proliferation of T and B-lymphocytes, the production of antibodies, and the generation of cytotoxic T lymphocytes. Reversal of acute allograft rejection and increased survival of kidney, heart and bone marrow cell allograft has been shown in several animal studies. Moreover, it was suggested that MMF combined with CsA prevented the acute rejection, and approximately half of the animals became long-term survivors. The Ministry of Health and Welfare approved MMF in 1999 for use for rejection treatment in renal transplantation based on several prospective, randomized and blind efficacy trials.

Echographia as a symptom of interictal state in an epileptic patient: a case report.

Echographia is a phenomenon in which a patient continuously translates verbal stimuli into writing. We encountered a patient with epilepsy who developed visual echographia during interictal periods. In this case, echographia was observed during two different periods, namely the period of disturbed consciousness after the epileptic seizure and the period of clear consciousness after suppression of the seizures. Disinhibition due to disturbance of the consciousness is considered to have been the cause of echographia in the former period. In the latter period, it is considered that echographia was caused by the release of lower function from suppression of upper function by brain dysfunction, as the after effect of status epilepticus. As echographia can be observed in epileptic patients, attention and careful observation by epileptologists is needed.

Case report: cheilitis granulomatosa with periodontitis.

We report a case of cheilitis granulomatosa with periodontitis in a 39-year-old Japanese man. Biopsy specimens from both areas showed noncaseating epithelioid cell granuloma. Dental examination revealed that the lower left first molar had periodontitis. The lower left first molar was removed, and antibiotics and anti-inflammatory drugs were administered. After 2 months of periodontitis therapy, the lips returned to normal size without recurrence and the swelling of the buccal mucosa regressed.

The ultrastructure of the sternal gills forming a striking contrast with the coxal gills in a fresh-water amphipod (Crustacea).

Sternomoera yezoensis has specialized sterna with 21 sternal gills in addition to six pairs of coxal gills. Despite a common high permeability to chloride ions, the epithelia of these two kinds of gills are diametrically opposed in the polarity of the cell membrane-mitochondria complex. The coxal gill epithelium (4-6 microm thick) is characterized by a well-developed AIS (apical infolding system) associated with a huge number of large mitochondria. The AIS exceeds two-thirds of the epithelial thickness and forms a highly sophisticated, subcuticular labyrinth. On the contrary, the sternal gill epithelium, an extension of the sternal epithelium proper, is extremely thick (10-15 microm) and is characterized by a very deep BIS (basolateral infolding system) associated with numerous slender mitochondria. The BIS reaches nine-tenths of the epithelial thickness and forms a giant, baso-lateral labyrinth. Shallower, less elaborate AIS and BIS without mitochondrial association originate from the opposite sides of these epithelia. Although AIS and BIS interpenetrate in the sternal gill epithelium, they never communicate. The results indicate that in addition to the coxal gills, the sterna with the sternal gills function as transporting as well as respiratory organs, though the functional difference between these two kinds of gills remains to be elucidated.

Differing cell surface distribution of human leukocyte antigen-DR molecules on epidermal Langerhans cells and eccrine duct cells.

Scanning electron microscopy (SEM) with immunogold labeling was employed to observe the undersurface of the human epidermis after it was split from dermal connective tissue, in an attempt to localize the molecules actually expressed on cell/tissue surfaces. We found that human leukocyte antigen-DR (HLA-DR) molecules were expressed on the surfaces of eccrine duct cells as well as those of epidermal Langerhans cells (LC) in normal skin. HLA-DR molecules, visualized by the deposition of gold particles, were distributed evenly on the LC surface but were present only along the interdigitating borders of the individual duct cells, thus producing a meshwork pattern on the duct surface. Transmission electron microscopy confirmed that the gold particles labeling cell surface HLA-DR molecules were seen only on the portions of duct cell membranes the interdigitated with neighboring duct cells. These findings suggest that the function of HLA-DR molecules may vary with their location and distribution. On the LC surface, the evenly distributed molecules seem to be well suited for promoting "accessory cell" functions. On duct cell surfaces, the HLA-DR molecules present along the intercellular spaces may be involved in trapping various peptide antigens that pass into the sweat gland filtrate and then are reabsorbed by the excretory duct, since these molecules have a highly permissive capacity for binding various peptides.

Melanocyte chemotactic factor produced by skin metastases of a breast carcinoma.

A 65-year-old woman underwent right modified radical mastectomy for a malignant lesion which had developed just below the right nipple. Two years after the operation, skin lesions composed of dark brown to black, pigmented, papular lesions developed in the precordia. A biopsy revealed this to be a cutaneous metastasis of the previous breast carcinoma. However numerous pigment blockade melanocytes were also found in the tumor nests, located in and/or beneath the epidermis. Although a black-colored breast carcinoma has been reported, the presence of pigment blockade melanocytes was not determined. Culture of the tumor nest recovered a population of melanocytes as well as the carcinoma cells. Boyden chamber analysis revealed the presence of a chemotactic factor for melanocytes in the culture medium. This seems to be the first documentation of melanocyte incorporation in breast carcinoma tissue.

Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease.

We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.

Lateral asymmetry of eye movements in temporal lobe epileptic patients with unilateral foci.

Eye movements in response to visual stimuli (Benton Visual Retention Test) were examined in 22 temporal lobe epileptics (TLEs), 10 primary generalized epileptics (PGEs), and 20 normal controls. In the normal controls, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, a tendency also found in the PGEs. In TLEs with right-sided foci, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, the direction of asymmetry found in the normal controls and PGEs. However, when calculated as laterality indices (the degree of asymmetry) TLEs with right-sided foci were significantly more negative than those of both the normal controls and PGEs. In TLEs with left sided foci, the percent fixation time on the right peripheral figure tended to be higher than that on the left peripheral figure, an asymmetry which differed significantly from the normal controls, PGEs and the TLEs with right-sided foci. The results here showed that TLEs with unilateral foci had distinct eye movements which varied with the laterality of the lesion in the direction of functional overactivation of the epileptogenic hemisphere.

Three cases of anomic aphasia after lesions in and/or around the basal ganglia.

The present paper reports 3 cases of aphasia with small lesions in the region of the basal ganglia to discuss whether neostrial dysfunction can cause aphasic symptoms. The Standard Language Tests of Aphasia (SLTA) was used to assess the type and degree of aphasia. Two patients with infarction either in the left putamen or in the head of the left caudate nucleus showed severe disturbance only in recalling words, especially nouns. The other patient showed the same symptom, in addition to writing disturbance that developed shortly after surgical extirpation of an arteriovenous malformation (AVM) in the left caudate nuclei. The symptoms common to the 3 patients corresponded well to the "anomic aphasia" proposed by Benson. The aphasic symptoms disappeared completely or largely within several months. This easy reversibility suggests that the aphasic disorder in the three patients was caused by damage not to the basal ganglia themselves, but to the affecting axons passing through or by the nuclei.

Neutrophil as a mediator of ischemic edema formation in the brain.

We investigated the contribution of neutrophils to brain edema formation using a transient focal ischemia model in rats. Rats were given anti-neutrophil monoclonal antibody (RP3) intraperitoneally to deplete circulating neutrophils. In RP3-treated rats, ischemic brain edema formation 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. We speculate that chemical mediators released by infiltrating neutrophils alter vascular permeability and play an important role in post-ischemic brain edema formation.

Laser-induced photoacoustic injury of skin: effect of inertial confinement.

Argon-fluoride (ArF) excimer laser-induced acoustic injury was confirmed by ablating the stratum corneum (s.c.) inertially confined by water in vivo. Hairless rats were irradiated through a quartz chamber with flowing distilled water or air and a 2.5 mm aperture. The laser was adjusted to deliver 150 mJ/cm2 at the skin surface for both conditions. Partial and complete ablation of the s.c. was achieved with 12 and 24 pulses, respectively. Immediate damage was assessed by the transmission electron microscopy. Partial ablation of the s.c. through air produced no damage, whereas partial ablation through water damaged skin to a mean depth of 114.5 +/- 8.8 microns (+/- SD). Full thickness ablation of the s.c. through air and water produced damage zones measuring 192.2 +/- 16.2 and 293.0 +/- 71.6 microns, respectively (P less than 0.05). The increased depth of damage in the presence of inertial confinement provided by the layer of water strongly supports a photoacoustic mechanism of damage. The damage induced by partial ablation of the s.c. provides evidence that photochemical injury is not a significant factor in the damage at a depth because the retained s.c. acts as a partial barrier to diffusion of photochemical products. Combined with our previous studies, these experiments demonstrate that pressure transients are responsible for the deep damage seen with 193 nm ablation and that photoacoustic effects must be considered when using short-pulse, high-peak power lasers.

Cell selectivity to laser-induced photoacoustic injury of skin.

Cell selectivity to photoacoustic injury induced by argon-fluoride excimer laser (193 nm) was studied. Rats were irradiated through air or water and a 2.5 mm aperture. The laser was adjusted to deliver 150 mJ/cm2 at the skin surface with 12 and 24 pulses. Immediate damage was assessed by transmission electron microscopy. Cell selectivity was observed in dermis and epidermis. Fibroblasts showed alteration of nuclear chromatin and cytoplasmic organelles, while some of the migratory cells adjacent to fibroblasts did not. Similar difference of damage was observed between keratinocytes and Langerhans cells in epidermis. Considering the relationship between cells and their microenvironment in tissue, this selectivity may be due to the difference of acoustical coupling of propagation of acoustic waves rather than to differential sensitivity of the cells to damage.

A new concept of basal cell epitheliomas based on the three-dimensional growth pattern of the superficial multicentric type.

Little is known about the growth characteristics of basal cell epitheliomas (BCEs), largely because of the difficulty in studying these tumors, both in situ and in vitro. In this study, the authors report that a scanning electron microscopic examination of 2 cases of superficial BCEs reveals that the tumor proliferates centrifugally as a monolayer beneath the epidermis as well as over the surfaces of hair follicles, while eroding and replacing the original basal architecture. Behind the leading edge of this monolayer, the cells split away from the epidermis to form a round border resembling a carpet being rolled up. This border then develops into a mass lesion, which represents the tumor cell foci seen in routine paraffin sections. These findings have led the authors to propose a fundamentally different explanation for the pathogenesis of these tumors: BCEs are conditioned neoplasms that require contact with the epidermal or hair follicular epithelium in order to grow. This hypothesis could explain the behavior of BCEs as well as the clinical and pathologic varieties observed in clinical practice.