Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery.

BACKGROUND: Thrombus formation through the activation of tissue factor (TF) and factor (F) XI is a critical event in the onset of cardiovascular disease. TF expressed in atherosclerotic plaques and circulating blood is an important determinant of thrombogenicity that contributes to fibrin-rich thrombus formation after plaque disruption. However, the contribution of FXI to thrombus formation on disrupted plaques remains unclear. METHODS: A mouse monoclonal antibody against FXI and activated FXI (FXIa) (XI-5108) was generated by immunization with activated human FXI. Prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time, and ex vivo platelet aggregation in rabbits were measured before and after an intravenous bolus injection of XI-5108. We investigated the role of FXI upon arterial thrombus growth in the rabbit iliac artery in the presence of repeated balloon injury. RESULTS: The XI-5108 antibody reacted to the light chain of human and rabbit FXI/FXIa, and inhibited FXIa-initiated FXa and FXIa generation. Fibrin-rich thrombi developed on the injured neointima that was obviously immunopositive for glycoprotein IIb-IIIa, fibrin, TF, and FXI. Intravenous administration of XI-5108 (3.0 mg kg(-1)) remarkably reduced thrombus growth, and the APTT was significantly prolonged. However, PT, bleeding time and platelet aggregation were not affected. CONCLUSIONS: These results indicate that plasma FXI plays a potent role in thrombus growth on the injured neointima. Inhibition of plasma FXI activity might help to reduce thrombus growth on ruptured plaques without prolonging bleeding time.

Potential impact of global warming on deciduous oak dieback caused by ambrosia fungus Raffaelea sp. carried by ambrosia beetle Platypus quercivorus (Coleoptera: Platypodidae) in Japan.

Deciduous oak dieback in Japan has been known since the 1930s, but in the last ten years epidemics have intensified and spread to the island's western coastal areas. The symbiotic ambrosia fungus Raffaelea sp. is the causal agent of oak dieback, and is vectored by Platypus quercivorus (Murayama). This is the first example of an ambrosia beetle fungus that kills vigorous trees. Mortality of Quercus crispula was approximately 40% but much lower for associated species of Fagaceae, even though each species had a similar number of beetle attacks. It is likely that other oaks resistant to the fungus evolved under a stable relationship between the tree, fungus and beetle during a long evolutionary process. Quercus crispula was probably not part of this coevolution. This hypothesis was supported by the fact that P. quercivorus showed the least preference for Q. crispula yet exhibited highest reproductive success in this species. Therefore, P. quercivorus could spread more rapidly in stands with a high composition of Q. crispula. The present oak dieback epidemic in Japan probably resulted from the warmer climate that occurred from the late 1980s which made possible the fateful encounter of P. quercivorus with Q. cripsula by allowing the beetle to extend its distribution to more northerly latitudes and higher altitudes. Future global warming will possibly accelerate the overlapping of the distributions of P. quercivorus and Q. crispula with the result that oak dieback in Q. crispula will become more prevalent in Japan.

[Anterior chamber structural change in postural variation in pseudoexfoliation syndrome].

PURPOSE: The anterior chamber structure in the supine position and the prone position was investigated with ultrasound biomicroscopy (UBM) in pseudoexfoliation syndrome (PE). METHODS: We studied 12 eyes of 12 PE subjects. Patients were placed in the supine position for 30 minutes, after which UBM was performed. The UBM was repeated after 30 minutes in the prone position. Anterior chamber depth (ACD), angle opening distance 500 microns (AOD 500), and angle recess area (ARA) in 4 quadrants were measured. RESULTS: Following the postural change from the supine position to the prone position, ACD decreased significantly (p < 0.0001). AOD 500 and ARA decreased significantly in the superior (AOD 500: p < 0.05, ARA: p = 0.03) and temporal quadrants (AOD 500: p < 0.0001, ARA: p < 0.0001). CONCLUSIONS: The anterior chamber structural change was greater in the temporal and superior quadrants in the PE eyes. This corresponds with previous reports that zonular involvement by pseudoexfoliation material is more pronounced temporally and superiorly.

Anxiety and pain suppress the natural killer cell activity in oral surgery outpatients.

OBJECTIVE: Psychological stress has an influence on natural killer cell (NK) activity, which plays a central role in protection against microbial infection and cancer. Anxiety concerning cancer is a typical type of psychological stress observed in patients and is associated with various diseases. In this study, we examined whether anxiety about cancer reduces the NK activity or quality of life (QOL), or both, of outpatients. PATIENTS AND METHODS: NK activity was determined by means of a 4-hour 51 chromium-release assay, and a QOL questionnaire by the World Health Organization called QOL-BRIEF was also used. One hundred forty-four patients were asked a variety of questions about anxiety with respect to cancer and pain on their first visit to the outpatient clinic of our Department of Oral Surgery. RESULTS: The NK activity in patients with anxiety about cancer was significantly lower (P < .001) than that in those with no such anxiety. In contrast, NK activity was not influenced by any other factor tested, including differences in diseases and QOL scores. CONCLUSION: Anxiety about cancer may be one of the primary factors for suppression of NK activity in oral surgery outpatients.

Sugar-pendant diamines.

A set of 1,3-propanediamine derivatives connected to carbohydrates (5) has been prepared in four steps from peracetylated sugar and 1,3-dibromo-2-propanol in 60-73% yields. D-Glucose, D-mannose, D-galactose, D-xylose, D-ribose, and maltose are utilized as sugar molecules in this work. The diamine moiety was connected to the C1 carbon of the glycopyranose ring via an O-glycoside bond. All of the anomeric configurations and sugar puckering conformations, except in the D-maltose derivative, were determined by X-ray crystallography of the diazido or dibromo precursors. While glycosidation of peracetylated galactopyranose with 1,3-dibromo-2-propanol in the presence of boron trifluoride afforded both anomers, the neighboring group participation of the 2-acetoxy group yielded a single anomer for the other substrates. This method has been used to synthesize a library of sugar-pendant diamines including an OH-protected derivative (6), and an N,N'-diisopropyl-substituted derivative (7). A similar series of reactions using 2,3-dibromo-1-propanol gave ethylenediamine-type derivatives (11), and bis(bromomethyl)bis(hydroxymethyl)methane (12) gave bisglucose-pendant derivatives (16).

[Supraciliochoroidal fluid at an early stage after trabeculectomy].

PURPOSE: To examine the supraciliochoroidal fluid(SCF) by ultrasound biomicroscopy(UBM) at an early stage after trabeculectomy. SUBJECTS AND METHODS: Fifteen eyes without post-operative complications were examined by UBM before the operation and less than 2 weeks after trabeculectomy with mitomycin C. RESULTS: SCF was detected postoperatively in 6 eyes. One eye had choroidal detachment under indirect-ophthalmoscope and 5 eyes(33%) had SCF without choroidal detachment. The SCF in 4 eyes disappeared within 4 weeks after trabeculectomy. The intraocular pressure was 6.4 +/- 3.4 mmHg(mean +/- standard deviation) when SCF was detected and it rose to 13.2 +/- 7.2 mmHg when SCF disappeared. The intraocular pressure was 11.4 +/- 4.0 mmHg in the eyes without SCF, which was significantly higher than in the eyes with SCF. CONCLUSION: At an early stage after trabeculectomy, SCF was detected by UBM in some cases without ophthalmoscopic choroidal detachment. Compared with the reported frequency of SCF after 3 or 6 months, our study revealed that SCF was present more frequently at an early stage after trabeculectomy. Our results may indicate that the presence of SCF is related to early low intraocular pressure and that disappearance of SCF induces the elevation of intraocular pressure.

Effects of epinephrine and lactate on the increase in oxygen consumption of nonexercising skeletal muscle after aerobic exercise.

The purpose of this study was to measure O2 consumption of nonexercising skeletal muscles (VO2nonex) at rest and after aerobic exercise and to investigate the stimulant factors of O2 consumption. In experiment 1, we measured the resting metabolic rate of the finger flexor muscles in seven healthy males by 31P-magnetic resonance spectroscopy during a 15 min arterial occlusion. In experiment 2, the VO2nonex of the finger flexor muscles was measured using near infrared continuous wave spectroscopy at rest, immediate postexercise, and 3, 5, 10, 15, and 20 min following a cycling exercise at a workload corresponding to 50% of peak pulmonary O2 uptake for 20 min. We also monitored deep tissue temperature in the VO2nonex measurement area and determined catecholamines and lactate concentrations in the blood at rest and immediate postexercise. VO2nonex at rest was 1.1 +/- 0.1 microM O2/S (mean +/- standard error) and VO2nonex after exercise increased 59.6 +/- 7.2% (p < 0.001) from the resting values. There were significant correlations between the increase in VO2nonex and the increase in epinephrine concentration (p < 0.01), and between the increase in VO2nonex and the increase in lactate concentration (p < 0.05). These results suggest that epinephrine and lactate concentrations are important VO2nonex stimulant factors.

Iris and ciliary body melanomas: ultrasound biomicroscopy with histopathologic correlation.

OBJECTIVE: To correlate ultrasound biomicroscopic images of iris and ciliary body melanomas with their histopathologic features. METHODS: Ultrasound biomicroscopy was performed in 3 cases of iris melanoma and in 3 cases of ciliary body melanoma. Cross-sectional ultrasound biomicroscopic images were compared with findings from clinical examination and light microscopy to evaluate associations between their histopathologic, surface, and internal ultrasound characteristics. Unique images of intrastomal and obscured posterior tumor margins were visualized by ultrasound biomicroscopy. RESULTS: Results of this study revealed that ultrasound biomicroscopy offers an accurate method to evaluate tumor shape, reflectivity, and local invasion. Neoplastic tissue had only medium echogenicity. Enlarged vessels were correlated to echolucent spaces in the iris stroma. Anterior tumor margins were found within the iris stroma, within the anterior chamber angle, and on the endothelial surface of the cornea. Posterior tumor extension was noted to encroach onto the lens, into the sclera, and serous peripheral retinal detachments were associated with ciliary body tumors. CONCLUSION: Ultrasound biomicroscopic images correlated well with histopathologic features of anterior uveal melanomas including shape, reflectivity, and local extension. Arch Ophthalmol. 2000;118:1515-1521

A technique for performing ultrasound biomicroscopy in the sitting and prone positions.

To develop a reliable method for performing ultrasound biomicroscopy (UBM) in the sitting and prone positions. The probe suspended from an articulated arm was removed and reattached to the arm upside-down for use in the prone position and horizontally for use in the sitting position. A latex Tono-Pen tip cover was attached to the edge of the eyecup and was placed over the transducer through the small hole on the tip of the Tono-Pen tip cover. UBM was successfully performed in the prone and sitting positions with no loss of image quality. This method can expand the ability of the UBM to examine alterations in anatomic relationships among anterior segment structures between the supine, sitting, and prone positions.

Angle recess area decreases with age in normal Japanese.

PURPOSE: To investigate prospectively the relationships between anterior chamber angle configuration and refractive error, axial length, age, and body height in the Japanese. METHODS: We studied 65 eyes of 65 subjects (30 men, 35 women) who were either patients at the Ophthalmology Department of Mie University or volunteers. The 65 subjects underwent a complete eye examination, A-scan biometry, and ultrasound biomicroscopy. Images were exported to an IBM-compatible personal computer in PCX format. The angle recess area (ARA) was measured using a software program of our own design. RESULTS: The ARA decreased with age in all quadrants of all eyes. In older individuals, the angle in the superior quadrant was significantly narrower than in the other quadrants. The ARA correlated directly with anterior chamber depth (P < .001), axial length (P < .001), and body height (P = .003), and inversely with age (P < .001) and refractive error (P = .003) in pairwise analysis. Multivariate analysis revealed a significant association between ARA and anterior chamber depth (P < .001), axial length (P = .016), and younger age (P = .043). CONCLUSIONS: The anterior chamber area narrows with age, especially in the superior quadrant. Narrowing of the angle in Japanese is associated with older age, shorter axial length, and shallower anterior chamber depth. We hypothesize that because of the increasing prevalence of axial myopia in younger Japanese, angle-closure glaucoma could become less common in Japan in the future.

Differential diagnosis of anterior segment cysts by ultrasound biomicroscopy.

BACKGROUND: To describe the ultrasound biomicroscopic (UBM) features of anterior segment cysts. DESIGN: A retrospective case series. PARTICIPANTS: One hundred eighteen eyes with anterior segment cysts examined by UBM at The New York Eye and Ear Infirmary between August 1992 and November 1997 were included in this study. INTERVENTION: The authors reviewed demographic and diagnostic data from the medical record including ocular and medical history, age, race, gender, and intraocular pressure. Ultrasound data concerning the type, number, position, and acoustic characteristics of cysts were recorded. The authors then correlated the written, clinical, and UBM characteristics. RESULTS: One hundred eyes (92.6%) had neuroepithelial cysts. Ninety (83.3%) of these had primary neuroepithelial cysts, 10 (9.3%) had cysts associated with uveitis, 7 (6.5%) had implantation cysts, and 1 (0.9%) had a cavitated ciliary body tumor. Neuroepithelial cysts typically were round or ovoid, thin-walled, and echolucent. Of the 90 eyes with primary neuroepithelial cysts, 56 (62.2%) had 3 or fewer cysts; multiple cysts (>3 per eye) were found in 34 eyes (37.8%). The multiple cysts occupied more than 180 degrees in 12 patients (13.3%). Primary neuroepithelial cysts were located at the iridociliary junction (74.2%), pars plicata (14.0%), pars plana (6.8%), and iris (5.0%). Implantation cysts (seven eyes) tended to have thicker walls and two contained a copious, echogenic material. CONCLUSION: The UBM results provide important information regarding location and extent of anterior segment cystic lesions. Ultrasound characteristics may help differentiate between neuroepithelial, implantation, and neoplastic cysts.

A slit-lamp needling filtration procedure for uncontrolled glaucoma in pseudophakic and aphakic eyes.

In one aphakic and one pseudophakic patient without previous filtration surgery, a transconjunctival needling procedure similar to that used for failed filtration procedures was performed to create a filtering bleb. In both cases, intraocular pressure was successfully lowered for 6 months until the occurrence of bleb encapsulation, which was relieved by transconjunctival needling. There were no complications. In selected cases, this minimally invasive slit-lamp needling procedure provides successful filtration.

Iridolenticular contact decreases following laser iridotomy for pigment dispersion syndrome.

OBJECTIVE: To evaluate changes in anterior segment anatomy after laser iridotomy for pigment dispersion syndrome. METHODS: Ultrasound biomicroscopy was performed on 7 eyes of 7 untreated patients with reverse pupillary block and pigment dispersion syndrome. A radially oriented image with the probe perpendicular to the eye in the superior meridian was obtained before and at least 1 week after laser iridotomy in each eye. We assessed changes in angle recess area and iris-lens contact distance. RESULTS: Mean +/- SD patient age was 31.3 +/- 5.7 years and mean +/- SD refractive error was -5.0 +/- 3.9 diopters. Angle recess area (mean +/- SD, 0.78 +/- 0.28 vs 0.35 +/- 0.11 mm2; P=.001, paired t test) and iris-lens contact distance (2.05 +/- 0.28 vs 0.79 +/- 0.13 mm; P<.001) decreased following iridotomy. Central anterior chamber depth did not change. CONCLUSION: Flattening of the iris following laser iridotomy for pigment dispersion syndrome causes a decrease in iris-lens contact and angle width while lens position remains constant.

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension.

The redistribution of blood flow (BF) in the abdominal viscera during right-legged knee extension-flexion exercise at very low intensity [peak heart rate (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting, subjects performed a right-legged knee extension-flexion exercise every 6 s for 20 min. BF was measured in the upper abdominal aorta (Ao), right common femoral artery (RCFA), and left common femoral artery (LCFA). Visceral BF (BFVis) was determined by the equation [BFAo - (BFRCFA + BFLCFA)]. A comparison with the change in BF (DeltaBF) preexercise showed a greater increase in DeltaBFRCFA than in DeltaBFAo during exercise. This resulted in a reduction of BFVis to 56% of its preexercise value or a decrease in flow by 1,147 +/- 293 (+/-SE) ml/min at the peak workload. Oxygen consumption correlated positively with DeltaBFAo, DeltaBFRCFA, and DeltaBFLCFA but inversely with DeltaBFVis during exercise and recovery. Furthermore, BFVis (% of preexercise value) correlated inversely with both an increase in HR (r = -0.89), and percent peak oxygen consumption (r = -0.99). This study demonstrated that, even during very-low-intensity exercise (HR <90 beats/min), there was a significant shift in BF from the viscera to the exercising muscles.

Ultrasound biomicroscopy dark room provocative testing: a quantitative method for estimating anterior chamber angle width.

PURPOSE: To describe a quantitative method for measuring the iridocorneal angle recess area, and, using this, to evaluate factors associated with appositional angle-closure during dark room provocative testing using ultrasound biomicroscopy (UBM). METHODS: All patients (178 patients, 178 eyes) with clinically narrow angles referred for UBM dark room provocative testing between September 1996 and March 1998 were enrolled in this study. Images of the inferior quadrant of the angle taken under standardized dark and light conditions were analyzed. The angle recess area (ARA) was defined as the triangular area demarcated by the anterior iris surface, corneal endothelium, and a line perpendicular to the corneal endothelium drawn from a point 750 microm anterior to the scleral spur to the iris surface. ARA, and acceleration and gamma-intercept of the linear regression analysis of the ARA were calculated. In the linear regression formula, y = ax + b, the acceleration a describes the rate at which the angle widens from the scleral spur; the y-intercept b describes the distance from the scleral spur to the iris. RESULTS: Under dark conditions, the angles in 99 patients (55.6%) showed evidence of appositional angle-closure during testing. ARA (0.11 +/- 0.04 vs. 0.15 +/- 0.05 mm2, P < .0001, Student t-test), acceleration a (0.22 +/- 0.15 vs. 0.26 +/- 0.17, P = .068), and y-intercept b (66 +/- 46 vs. 92 +/- 47 microm, P = .0003) were smaller in eyes that were occluded. In the eyes that were not occluded, y-intercept b showed no significant difference between light and dark conditions (P = .1, paired t-test), while acceleration a did (P < .0001). In the eyes that were occluded, both decreased significantly under dark conditions (P < .0001). CONCLUSIONS The ARA linear regression formula provides useful quantitative information about angle recess anatomy. The more posterior the iris insertion on the ciliary face, the less likely the provocative test will be positive.

Anterior segment implantation cysts. Ultrasound biomicroscopy with histopathologic correlation.

OBJECTIVE: To correlate the clinical, histopathologic, and ultrasound biomicroscopic characteristics of anterior segment implantation cysts. METHODS: We performed a retrospective review of 7 cases of secondary anterior segment implantation cysts. We reviewed the clinical history, visual acuity, clinical findings, and ultrasound biomicroscopic characteristics in all cases. Histopathologic correlation was possible in 4 cases. RESULTS: Six eyes had been subjected to major trauma prior to cyst formation. Trauma was noted as blunt in 3 eyes and surgical in 3 eyes. The diagnosis was confirmed in 1 eye when conjunctival cells were aspirated on fine needle biopsy. Ultrasound biomicroscopy revealed large (mean +/- SD greatest diameter, 4.7 +/- 0.9 mm) cystic tumors. In 1 patient, a cyst-related indentation of the anterior lens surface was seen. Ultrasonographic evaluations of internal reflectivity revealed thick, moderately reflective cyst walls encapsulating a relatively hypoechoic core. In 3 cases, the cyst contents consisted of variably reflective material. The other 4 were completely sonolucent. Histopathologic correlation showed that the cyst walls were lined with stratified squamous epithelium. The moderately reflective cyst contents were found to be degenerated conjunctival cells with inflammatory foci and cholesterol crystals. The sonolucent regions correlated with inflammatory cells and fluid. CONCLUSIONS: This study demonstrates that implantation cysts are unilateral, large, and thick walled. They may be sonolucent or exhibit variable internal reflectivity. These findings as well as the extent of anterior segment involvement (particularly posterior extension) could be evaluated by ultrasound biomicroscopy prior to surgery.

[Clinical evaluation of chemiluminescence immunoassay PSA (ACS-PSA) for detection of prostate cancer].

Serum prostate specific antigen (PSA) levels were measured using an ACS-PSA kit in 147 systematic biopsy cases (61 with prostate cancer (PC)) and 96 transurethral resection of prostate (TUR-P) cases (2 with PC). In the 147 biopsy cases, the sensitivity for PSA using 3.0 and 10.0 ng/ml as cut-off values was 91.8 and 90.2%, while the specificity was 9.30 and 30.2%, respectively. The sensitivity for PSAD (A) (calculated by transabdominal ultrasound) using 0.25 and 0.5 ng/ml/cm3 as cut-off values was 91.8 and 90.2%, while the specificity was 22.1 and 50.0%, respectively. These data indicated that PSAD (A) provided better information for detecting PC than PSA alone. No statistical difference was found between PSAD (A) and PSAD (R) (calculated by transrectal ultrasound) in the utility of detecting PC. PSA below 15.0 ng/ml was seen in sixteen patients with PC. Five of these sixteen patients had a PSA level of < 3.0, and they underwent prostate biopsy based on the abnormality by digital rectal examination (DRE). The other eleven patients had PSAD (A) level of > 0.3 ng/ml/cm3. In all 243 cases, PC was not found in the 49 patients (PSA < 3.0 ng/ml) or 91 patients (PSAD (A) < 0.25 ng/ml/cm3) who had no abnormal findings by DRE and transabdominal ultrasonography. These results suggested a criterion in the use of the ACS-PSA kit for the indication of prostate biopsy and TUR-P.

Putative tumor suppressor gene region within 0.85 cM on chromosome 12 in radiation-induced murine lymphomas.

Analyses of genetic alterations in tumors from F1 hybrid mice produced by inter-subspecific crosses between genetically well-characterized inbred strains provide precise and comprehensive evidence for genetic abnormalities such as allelic loss. We performed loss of heterozygosity (LOH) analyses of 125 radiation-induced lymphomas of (BALB/cHeA x MSM/Ms)F1 hybrid mice by polymerase chain reaction (PCR) analysis of microsatellite DNA polymorphic markers. Very frequent LOH was found at a distal region on chromosome 12. To precisely define the most common region of LOH, we first determined the order of and distances between the available microsatellite loci around the region by using 586 (CXSD x MSM/Ms)F2 hybrid mice (1172 meiosis). The locus order and distances were [centromere]-D12Mit132-(0.34 cM)-D12Mit5O-(2.05 cM)-[D12Mit122, D12Mit53]-(0.85 cM)-D12Mit233-(0.43 cM)-D12Mit279-(O.17 cM)-D12Mit181-[telomere]. We then investigated the features of LOH at these loci. The highest frequency of LOH (83 of 125, 66%) was found at D12Mit233. The LOH patterns of individual lymphomas indicated that the most common region of LOH was within the 0.85 cM between D12Mit53 and D12Mit233, a region homologous to human chromosome 14q32.1. These results suggest that a putative novel tumor suppressor gene exists within this region.

Identification of tumor vascular antigens by monoclonal antibodies prepared from rat-tumor-derived endothelial cells.

We have reported the isolation and specific in vitro properties of tumor-derived endothelial cells (TEC) from rat KMT-17 fibrosarcomas transplanted into rats. To develop antibody-based tumor vascular targeting therapy for solid tumors, we have generated monoclonal antibodies (MAbs) using passive immunization of outside-out membrane vesicles of rat epididymal-fat-pad-derived capillary endothelial cells (FCEC) followed by active immunization of those of rat TEC. The MAbs produced were screened against TEC and FCEC. Of all cultured hybridomas, 75 (3.3%) of the secreted MAbs preferentially recognized TEC. We selected a total of 7 MAbs which detected antigens highly abundant in TEC, although 5 of the 7 MAbs were weakly positive for FCEC in cell-ELISA and FACS analyses. The antigens recognized by these MAbs, with the exception of MAb TES-7, were present on endothelial cells of tumor blood vessels in KMT-17 fibrosarcoma tissues, as shown by immunohistochemical analysis. Antigens of 40- and 80-kDa were recognized by MAbs TES-1, 7, 17, 21 and 26 and by MAbs TES-23 and 27 respectively. Although the function of these antigens, which are preferentially expressed on rat tumor-derived endothelial cells, is still unknown, we believe that future studies of such antigens will help elucidate the role of endothelial cells in tumor vasculature. Our results indicate that MAbs may provide a novel tool for the development of antibody-based therapy targeting tumor vasculature.

Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga mice.

The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.