Comparison of risk factors for SARS-CoV-2 infection among healthcare workers during Omicron and Delta dominance periods in Japan.

BACKGROUND: The risk factors for coronavirus disease (COVID-19) among healthcare workers (HCWs) might have changed since the emergence of the highly immune evasive Omicron variant. AIM: To compare the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs during the Delta- and Omicron-predominant periods. METHODS: Using data from repeated serosurveys among the staff of a medical research centre in Tokyo, two cohorts were established: Delta period cohort (N = 858) and Omicron period cohort (N = 652). The potential risk factors were assessed using a questionnaire. Acute/current or past SARS-CoV-2 infection was identified by polymerase chain reaction or anti-nucleocapsid antibody tests, respectively. Poisson regression was used to calculate the risk ratio (RR) of infection risk. FINDINGS: The risk of SARS-CoV-2 infection during the early Omicron-predominant period was 3.4-fold higher than during the Delta-predominant period. Neither working in a COVID-19-related department nor having a higher degree of occupational exposure to SARS-CoV-2 was associated with an increased infection risk during both periods. During the Omicron-predominant period, infection risk was higher among those who spent ≥30 min in closed spaces, crowded spaces, and close-contact settings without wearing mask (≥3 times versus never: RR: 6.62; 95% confidence interval: 3.01-14.58), whereas no such association was found during the Delta period. CONCLUSION: Occupational exposure to COVID-19-related work was not associated with the risk of SARS-CoV-2 infection in the Delta or Omicron period, whereas high-risk behaviours were associated with an increased infection risk during the Omicron period.

Colonoscopic features and malignant potential of sessile serrated adenomas: comparison with other serrated lesions and conventional adenomas.

AIM: Sessile serrated adenomas/polyps (SSA/Ps) have been proposed as precursors of colorectal cancer. The aims of this investigation were to compare the endoscopic findings of SSA/Ps with those of other serrated lesions and to compare the histological findings of SSA/Ps with those of conventional adenomas. METHOD: We retrospectively reviewed colonoscopy records at our institution from 1984 to 2013 and identified cases of endoscopically or surgically resected conventional adenomas and serrated lesions, including SSA/Ps, hyperplastic polyps (HPs) and traditional serrated adenomas (TSAs). The colonoscopic findings of SSA/Ps were compared with those of the other two serrated lesions and histological findings were compared among all groups of lesions. RESULTS: There were 79 HPs in 68 patients, 77 SSA/Ps in 63 patients, 167 TSAs in 145 patients and 6324 conventional adenomas in 4129 patients. The inverted type and flat-elevated type were more frequent among SSA/Ps than among the other two types of serrated lesions. Magnifying colonoscopy revealed that a round and open pit pattern, expanded crypt openings and varicose microvascular vessels were more frequently observed among SSA/Ps than among the other types. The incidence of high-grade dysplasia or carcinoma among SSA/Ps (13.0%) was significantly higher than that among HPs (0%, P < 0.001) and equivalent to that among conventional adenomas (12.3%). CONCLUSION: SSA/Ps have colonoscopic features distinct from those of HPs and TSAs. The malignant potential of SSA/Ps seems to be equal to that of conventional adenomas.

Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy. Technical considerations based on experience at a single institution.

BACKGROUND AND PURPOSE: Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue. The goal of the study was to evaluate the efficacy and feasibility of reirradiation for patients with recurrent malignant brain tumors. PATIENTS AND METHODS: The subjects comprised 26 patients with recurrent malignant brain tumors treated with conventional radiotherapy (RT, n = 8), stereotactic radiotherapy (SRT, n = 10), and proton beam therapy (PBT, n = 8) at our institute. Fifteen patients had glioblastoma, 6 had WHO grade 3 glioma, and 5 had other tumors. The dose of initial radiotherapy was 34.5-94.4 Gy. Different radiation schedules were compared using the equivalent dose in 2-Gy fractions. RESULTS: Reirradiation was completed in all patients without a severe acute reaction. The reirradiation doses were 30-60 Gy (median, 42.3 Gy) and the total doses for the initial and second treatments were 64.5-150.4 Gy (median, 100.0 Gy). Currently, 11 patients are alive (median follow-up period, 19.4 months) and 15 are dead. The median survival and local control periods after reirradiation of the 26 patients were 18.3 and 9.3 months, respectively. For the 15 patients with glioblastoma, these periods were 13.1 and 11.0 months, respectively. Two patients showed radiation necrosis that was treated by surgery or conservative therapy. CONCLUSION: Reirradiation for recurrent malignant brain tumor using conventional RT, SRT, or PBT was feasible and effective in selected cases. Further investigation is needed for treatment optimization for a given patient and tumor condition.

A Japanese multicenter study of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroid in renal transplantation (the fourth report).

We examined the efficacy and safety of 4-drug combination therapy using high-dose mizoribine (MZR) (8 mg/kg/d), cyclosporine (CsA), basiliximab (BXM), and steroid (STR) in 39 renal transplant recipients. Acute rejection episodes (ARE), which occurred in 9 (23.1%) patients, correlated with lower blood levels of MZR (trough levels ≥ 2 µg/mL). In addition, lower MZR concentrations tended to be associated with a higher incidence of rejection episodes in children aged ≤ 10 years than in those aged ≥ 11 years. The area under the received operating characteristics (ROC) curve of MZR trough level to pred ARE was 0.825 (95% confidence interval, 0.690-0.962; P = .002). Based on the ROC analysis, are MZR cut-off of 1.6 µg/mL showed a sensitivity of 81.8% and a specificity of 75.0%. Adverse events were observed in 23 patients, including infections in 11 (7 patients positive for cytomegalovirus [CMV] antigen and 4 treated with anti-CMV drugs). The MZR trough levels seemed to be higher among patients with adverse events than in those free of them, but it was no significant. All patients experienced successful engraftment except 1 who died of unknown cause with a functioning graft. In conclusion, our study showed that low MZR trough levels correlated with the incidence of ARE. No serious adverse effects were encountered with this therapy.

Prognostic relevance of the lymph node ratio in surgical patients with extrahepatic cholangiocarcinoma.

AIM: Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma. PATIENTS AND METHODS: We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients. RESULTS: The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484). CONCLUSION: LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis.

BACKGROUND: Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. OBJECTIVES: To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). METHODS: Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. RESULTS: We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. CONCLUSIONS: Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity.

Repetitive scratching and noxious heat do not inhibit histamine-induced itch in atopic dermatitis.

BACKGROUND: Repetitive scratching is the most common behavioural response to itch in atopic dermatitis (AD). Patients with chronic itch often report that very hot showers inhibit itch. We recently reported that scratching and noxious heat stimuli inhibit histamine-induced itch in healthy subjects. However, no psychophysical studies have been performed in AD to assess the effects of repetitive heat pain stimuli and scratching on histamine-induced itch. OBJECTIVES: To examine the effects of repetitive noxious heat and scratching on itch intensity in patients with AD using quantitative sensory testing devices. METHODS: Itch was induced with histamine iontophoresis in 16 patients with AD in both lesional and nonlesional skin as well as in 10 healthy subjects. Repetitive noxious heat and scratching were applied 3 cm distal to the area of histamine iontophoresis. Subjects rated their perceived intensity of histamine-induced itch with a computerized visual analogue scale. RESULTS: Our results demonstrate that repetitive noxious heat and scratching do not inhibit itch intensity in lesional and nonlesional AD skin but do so in healthy skin. Of note, both these stimuli increase itch intensity in lesional AD skin. CONCLUSIONS: Our results strongly suggest that scratching and noxious thermal stimuli have a different effect upon histamine-induced itch perception in patients with AD when compared with healthy controls. This difference may be associated with both peripheral and central sensitization of nerve fibres in AD.

Even distribution of BK polyomavirus subtypes and subgroups in the Japanese Archipelago.

BK polyomavirus (BKV) is ubiquitous among humans, infecting children asymptomatically and then persisting in renal tissue. BKV has four subtypes (I-IV) that can be identified by serological and genotyping methods. Subtypes I and IV are most prevalent in all countries examined to date. Based on nucleotide sequence variation, subtype I is further classified into four subgroups (Ia, Ib-1, Ib-2 and Ic), each of which have a close relationship to a particular human population. To clarify the relationships between BKV and human populations, we investigated the distribution patterns of BKV subtypes and subgroups in the modern Japanese population, which was formed from two distinct ethnic groups. Urine samples were collected from immunocompetent elderly patients in six regions along the Japanese Archipelago. The 287-bp VP1 region of the viral genome from these samples was amplified using the polymerase chain reaction. The amplified VP1 regions were sequenced and a neighbor-joining phylogenetic tree was reconstructed to classify the BKV isolates. We observed a similar pattern of subtype distribution throughout the Japanese Archipelago, with subtype I always detected at high rates (67-75%), followed by subtype IV (19-31%), with rare or no detection of subtypes II and III. Based on phylogenetic and single nucleotide polymorphism analyses, the subtype I isolates were divided into subgroups; the percentage of the Ic subgroup was high in all geographic regions (88-100%). These results suggest that BKV subtypes and subgroups are evenly distributed in the Japanese Archipelago. We discuss the implications of these findings for the relationships between BKV and human populations.

Diagnostic utility of brain-natriuretic peptide for left ventricular diastolic dysfunction in asymptomatic type 2 diabetic patients.

AIM: Left ventricular (LV) diastolic dysfunction has been reported to be prevalent in diabetic subjects, but this recognition could often be missed. We evaluated prevalence of LV diastolic dysfunction and diagnostic utility of brain-natriuretic peptide (BNP) in asymptomatic patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Plasma BNP levels and LV geometry and diastolic filling indices, including the ratio of peak early transmitral Doppler flow (E) over flow propagation velocity (Vp) measured by colour M-mode Doppler echocardiography, were analysed in 98 consecutive asymptomatic patients with type 2 diabetes mellitus and 51 age-matched controls. RESULTS: The LV mass index and relative wall thickness were higher in diabetic groups than controls without any differences in LV systolic function. The frequency of diastolic dysfunction defined as E/Vp > or = 1.5 were 31% in diabetic groups and 15% in controls (chi(2) = 4.364, p = 0.037). By receiver-operating characteristic (ROC) curve analysis, a BNP cutoff value of 19.2 pg/ml in controls had a 53.1% positive predictive value (53.1%) and a high negative predictive value (94.4%) for E/Vp >/= 1.5, whereas a BNP cutoff value of 18.1 pg/ml in diabetic groups had a 61.8% positive and 97.3% negative predictive values. CONCLUSIONS: The frequency of E/Vp > or = 1.5 was higher in asymptomatic diabetic patients, suggesting that LV diastolic dysfunction was prevalent. The plasma concentration of BNP could be used to depict LV diastolic dysfunction in such population.

Vitamin B6 deficiency augments endogenous oxalogenesis after intravenous L-hydroxyproline loading in rats.

The effects of an intravenous hydroxyproline load on endogenous oxalogenesis were compared in rats fed a standard diet or a vitamin B6-deficient diet. Twelve male Wistar rats were randomized to two groups and were fed either a standard diet (control group) or a vitamin B6-deficient diet for 3 weeks. Then the animals were intravenously administered 100 mg (762.6 micromol)/ml hydroxyproline. In the control group, infusion of hydroxyproline increased the 5-h urinary oxalate and glycolate excretion above baseline to 0.27% (2.02 +/- 1.11 micromol) and 0.32% (2.43 +/- 1.60 micromol) of the administered dose (mol/mol), while it was respectively 2.01% (15.24 +/- 2.13 micromol) and 0.00% (-0.02 +/- 0.19 micromol) of the dose in the vitamin B6-deficient group. Therefore, vitamin B6 deficiency augmented endogenous synthesis of oxalate from hydroxyproline by 7.56-fold (15.24/2.02) compared with that in the control group. Urinary citrate excretion was significantly lower at baseline and all other times in the vitamin B6-deficient group compared with the control group. In conclusions, L-hydroxyproline loading augmented endogenous oxalogenesis in the vitamin B6-deficient group without causing hyperglycolic aciduria, and also led to significant hypocitraturia. These findings suggest that hydroxyproline is not metabolized to oxalate via glycolate, but rather via the 4-hydroxyglutamate to glyoxylate pathway (usually requiring vitamin B6-dependent enzymes) even in the presence of vitamin B6 deficiency.

Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan.

AIMS: To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe. METHODS AND RESULTS: Forty-five (11.3%) of 400 B-cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real-time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B-cell ML cases. CONCLUSIONS: The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.

Changes in Helicobacter pylori status in patients with rheumatoid arthritis under non-steroidal anti-inflammatory drugs.

BACKGROUND: The role of Helicobacter pylori infection in rheumatoid arthritis (RA) patients during treatment with non-steroidal anti-inflammatory drugs (NSAID) is still unclear. METHODS: By means of endoscopy and biopsy, gastroduodenal lesions and H. pylori status were repeatedly examined in 88 RA patients at intervals ranging from 26 to 49 months. Histology and culture were applied to determine H. pylori status. Serial changes in gastroduodenal lesions and histologic score for mucosal atrophy were compared among groups classified by initial and second H. pylori status. RESULTS: There were 28 patients with continuously positive H. pylori infection (CP group), 33 patients with continuously negative H. pylori infection (CN group), 7 patients in whom H. pylori status became negative (PN group), and 20 patients in whom H. pylori status could not be determined (UD group). Age, duration and species of NSAID, disease activity of RA, gastroprotective drugs applied and the prevalence of gastroduodenal mucosal lesions were not different among the groups at either the initial or the second examination. In the PN group, the score for mucosal atrophy at the second examination was significantly lower than at the initial examination, whereas no difference was found for the CP, CN and UD groups. Overall, histologic score for mucosal atrophy was higher in H. pylori-positive patients than in H. pylori-negative patients at both initial and second examination. CONCLUSIONS: In RA patients using NSAIDs, H. pylori infection may not affect the course of gastroduodenal lesions and activity of RA, but the infection contributes to mucosal atrophy.

Renal cell carcinoma with rhabdoid features: an aggressive neoplasm.

AIMS: Only a few reports on renal cell carcinoma with rhabdoid features have been published. This study was performed to investigate the clinicopathological characteristics of renal cell carcinomas with rhabdoid features. METHODS AND RESULTS: Among 253 cases of renal cell carcinoma in adults, eight cases with rhabdoid features were detected. Rhabdoid areas ranged from 10% to 90% of each of the cases. Seven of the eight cases were TNM stage III or IV, and four of the eight cases died within 8 months of surgery. Immunohistochemically, the rhabdoid areas were positive for CAM 5.2 (4/8), AE1/AE3 (6/8), epithelial membrane antigen (6/8) and vimentin (8/8), and negative for myogenetic markers (0/8). The mean MIB-1 labelling index in the rhabdoid areas was higher than that in the definite carcinomatous areas. Ultrastructurally, perinuclear whorls of intermediate filaments were demonstrated in three of the eight cases using paraffin-embedded blocks. CONCLUSIONS: The rhabdoid areas in renal cell carcinoma have histological, immunohistochemical and ultrastructural similarities to malignant rhabdoid tumours. Renal cell carcinoma with rhabdoid features is a highly aggressive neoplasm and its malignant behaviour may be due to the high cell-proliferative activity of the rhabdoid areas. Rhabdoid features in renal cell carcinoma may represent the endpoint of clonal evolution of renal cell carcinoma (especially in clear cell type cases).

Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial leiomyosarcoma.

To evaluate smooth muscle differentiation, myogenic markers [desmin, alpha-smooth muscle actin (SMA), and muscle-specific actin (HHF35)] have been widely used. Calponin and h-caldesmon, which are cytoskeleton-associated actin-binding proteins, have been reported to be more specific myogenic markers, especially since myofibroblasts express a small amount of h-caldesmon. Atypical fibroxanthoma (AFX) occurs in the sun-exposed skin of the elderly and follows a benign clinical course. Histologically, AFX, which is a pleomorphic spindle cell tumor and considered to be a superficial variant of malignant fibrous histiocytoma, also mimics leiomyosarcoma. AFX has been thought to differentiate along pathways with fibrohistiocytic and myofibroblastic phenotypes. AFX ( n=10), superficial leiomyosarcoma (S-LMS) ( n=17) and benign fibrous histiocytoma (BFH) ( n=17) were analyzed for myofibroblastic and smooth muscle differentiation immunohistochemically from the viewpoint of comparison. AFX and BFH showed immunoreactivities respectively for calponin (3/10, 11/17), desmin (3/10, 1/17), SMA (3/10, 13/17), and HHF35 (1/10, 5/17), but failed to express h-caldesmon (0/10, 0/17). S-LMS had a high immunoreactive rate of calponin (17/17), desmin (13/17), SMA (16/17), and HHF35 (16/17), while also expressing caldesmon (11/17). The results reveal that AFX and BFH have immunoreactivities for several myogenic markers, with myofibroblastic differentiation (calponin: +/-, h-caldesmon: -), but without the smooth muscle differentiation seen in S-LMS (calponin:+, h-caldesmon: +/-). In addition, calponin and h-caldesmon are considered to be useful markers for distinguishing AFX from S-LMS.

Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis.

AIMS: Prognostic factors affecting survival in cases of leiomyosarcoma of soft parts were investigated in this study. METHODS AND RESULTS: A retrospective study of 267 patients was carried out. This group comprised 142 females (53%) and 125 males (47%), whose ages ranged from 7 to 95 years (median 58 years). One hundred and five cases were superficially situated (arising from the skin or subcutis), while the remaining 162 cases were deeply situated (subfacial). Nineteen were cases of pleomorphic leiomyosarcoma where the diagnosis had been amended from malignant fibrous histiocytoma to leiomyosarcoma whilst under review. Of the 167 patients with follow-up data, 83 died of leiomyosarcoma. In univariate analysis, depth, tumour size (>or=50 mm), mitotic rate of >20 per 10 high-power fields (HPF), tumour necrosis of >50% and a high stage according to the most recent American Joint Committee on Cancer (AJCC) staging for soft tissue sarcoma were found to lessen significantly the rate of survival (log rank test; P < 0.05). However, in multivariate analysis (Cox's proportional hazards model), tumour size and high AJCC stage were the only factors that were correlated independently with decreased survival. CONCLUSIONS: This study indicates that the most reliable prognostic parameters are tumour size and AJCC stage in leiomyosarcoma.

H-, K-, and N-ras gene mutation in atypical fibroxanthoma and malignant fibrous histiocytoma.

Atypical fibroxanthoma (AFX) which is histologically similar to malignant fibrous histiocytoma (MFH), occurs in the sun-exposed skin. The presence of mutations at codons 12 and 13 of the H- and K-ras genes and in exons 1 and 2, which include codons 12, 13, and 61, of the N-ras gene was studied in 8 cases of AFX and 8 cases of storiform-pleomorphic-type MFH using polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-single-conformation polymorphism. Two of the 8 cases of MFH showed ras mutations in the H-ras gene at codon 12 (GGC-AGC) and in the K-ras gene at codon 13 (GGC-GAC). H- and K-ras gene mutations were not seen in any of the cases of AFX (0 of 8). N-ras gene mutation was not detected in either the AFX (0 of 8) or MFH (0 of 8) cases. In conclusion, although the number of cases in this study was small, H- and K-ras genes were present in some of the MFH cases and accordingly may play an important role in the pathogenesis of MFH. In addition, the finding that H-, K-, and N-ras gene mutations are not present in AFX may indicate why AFX has a more favorable behavior than MFH.

Immunoexpression of neurofibromin, S-100 protein, and leu-7 and mutation analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia.

The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related domain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spindle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegregations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene product (neurofibromin) and so-called Schwann cell markers (S-100 protein, Leu-7) in 17 cases of OFD immunohistochemically. Ten cases of fibrous dysplasia (FD) were also used for the purpose of comparison. Five OFD and 7 FD cases were analyzed for NF1 gene mutation at codon 1423, which is a GAP-related domain, by single-strand conformation polymorphism. Fibroblast-like cells of OFD showed the expression of neurofibromin (5 of 17), S-100 protein (9 of 17), and Leu-7 (5 of 17), and those of FD did not show these expressions, with the exception of 1 case that showed Leu-7 expression. Regarding the OFD cases, significant correspondence was found between cases showing expression of neurofibromin and S-100 protein, between cases showing expression of neurofibromin and Leu-7, and between cases showing expression of S-100 protein and Leu-7 (P < .01). NF1 gene mutation at codon 1423 was not detected in either the OFD (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OFD, which is associated with the expression of Schwann cell markers (S-100 protein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not seem to be related to OFD.