A new approach for quantitative assessment of fetal general movements in the early second trimester of pregnancy using four-dimensional ultrasound.

PURPOSE: Complex fetal behavior involving multiple parts of the body, called general movement (GM), has been considered an essential predictor of neurological functional development because it directly reflects the integrity of the brain and central and peripheral nervous systems. We have developed a novel method for quantitative analysis of fetal behavior using four-dimensional ultrasound (4DUS) and conducted a pilot study for quantitative assessment of fetal GM in the early second trimester. METHODS: All subjects underwent 4DUS to depict the whole fetal body, and maximum velocity (MAXV), median velocity (MV), average velocity (AV), and mode velocity (MOV) were calculated by utilizing optical flow analysis. Receiver operating characteristic (ROC) curve analysis was performed to analyze the optimal speed parameters for detecting GM in the fetus. The Mann-Whitney U test was used to validate MAXV, AV, and MV ability to detect fetal GM. RESULTS: The presence of fetal GMs and the absence of fetal GMs were 226 and 107, respectively, based on optical flow analysis. Mann-Whitney U test revealed a significant difference in the presence or absence of fetal GM in MAXV, MV, AV, and MOV. ROC analysis showed that the area under the curve (AUC) of MAXV was 0.959; the threshold was 0.421, the sensitivity was 86%, and the specificity was 93%. In contrast, the AUC/threshold for AV and MV was 0.700/0.110 (sensitivity 71% and specificity 76%) and 0.521/0.119 (sensitivity 21% and specificity 90%), respectively. Spearman's rank correlation analysis also showed a weak negative correlation between GM and MAXV (r = - 0.235, P < 0.01) and AV (r = - 0.28, P < 0.01). CONCLUSION: In this study, we conducted a quantitative analysis of fetal behavior based on optical flow using 4DUS and demonstrated that it was highly accurate for detecting GMs and for evaluating developmental changes in GMs. The implementation of quantitative analysis of fetal GMs in the early second trimester has been very preliminary, and there is much debate on how it will be clinically applied to perinatal assessment.

A quantitative morphological analysis of three-dimensional CT coxal bone images of contemporary Japanese using homologous models for sex and age estimation.

Sexual dimorphisms and age-dependent morphological features of the human coxal bone were quantitatively analyzed using homologous models created from three-dimensional (3D) computed tomography images of the pelvis (male: 514 samples, female: 388 samples, age 16-100). Bilateral average coxal images of each sex and age decade were generated separately through principle component analyses (PCA). By measuring average point-to-point distances of 8472 corresponding points (average corresponding point differences [ACPDs]) between each homologous coxal image and the average images, the sex of more than 93% of the samples was correctly assigned. Some principal components (PCs) detected in PCA of the homologous models of the samples correlated fairly well with age and are affected by features of the curvature of the iliac crest, the arcuate line and the greater sciatic notch. Moreover, separate PCA using the average images of each age decade successfully detected the first PCs, which were strongly correlated with age. However, neither multiple regression analysis using PCs related to age nor comparison of ACPDs with the average images of each age decade could produce accurate results for age decade assignment of unknown (blind) samples. Therefore, more detailed analysis of age-dependent morphological features would be necessary for actual age estimation. In addition, some laterality or left and right shape difference of the coxal bone images was also elucidated, and was more significant in females. Analysis of 3D structures using homologous models and PCA appears to be a potential technique to detect subsistent morphological changes of bones.

Delay in the Provision of Medication by a Pharmacy Outside the Respiratory Outpatient Department.

Respiratory medicine physicians prescribe many different kinds of medications depending on patient's condition. To examine an outside pharmacy's ability to meet the demand of our respiratory prescription services, we developed a questionnaire for all the patients who came to our outpatient department from November 1, 2015 to January 31, 2016. A total of 298 of 330 patients answered the questionnaire. Overall, 169 patients mainly went to the pharmacy near our hospital, whereas 64 patients mainly went to another pharmacy. Specifically, 23 of 219 patients who answered the question "When you went to the pharmacy with prescription, have you ever been not immediately given medication?", were not immediately given medication by the pharmacy. The results show that the other pharmacy significantly delayed medication compared with the one near our hospital. Interestingly, there were many types of inhaler cases that were out of stock in both pharmacies. Also, we found that 9 of 11 patients who were not provided medication on the spot acquired the medication within 1 or 2 d. Further, 10 of 20 patients who were not provided medication on the spot were only able to obtain the medication once. We did not observe any changes in patients' physical condition due to the delay in medication.

Altered gene expression in gingival tissues and enhanced bone loss in rats with diabetes with experimental periodontitis.

BACKGROUND: Systemic hyperglycemia is clearly related to severity of periodontitis, meaning that periodontitis can be exacerbated by diabetes mellitus (DM). However, the biologic mechanisms responsible for this relationship remain unclear. Thus, in this study, the global gene expression in gingival tissue with periodontitis is profiled in Zucker diabetic fatty (ZDF) rats compared with Zucker normoglycemic littermates (Lean). METHODS: At age 8 weeks, ZDF and Lean rats received ligature placement around the maxillary right second molar. At 0, 14, 28, 42, and 56 days after ligature placement, the maxilla around the molar was analyzed using microcomputed tomography. Two and 7 days after ligature placement, total RNA in the gingival tissue was isolated, and gene expression analysis was conducted using a rat oligo array. To validate the microarray findings, the selected genes were analyzed using real-time quantitative polymerase chain reaction assays. RESULTS: There was a significant difference regarding the average amount of bone resorption between ZDF and Lean rats from days 14 to 56. On day 2, it was found that 113 genes were regulated (20 upregulated, 93 downregulated) in the presence of DM. Lipopolysaccharide binding protein (LBP) messenger RNA (mRNA) expression was significantly higher in gingival tissue with periodontitis from ZDF rats compared with that from Lean rats. On day 7, interleukin (IL)-10 and IL-24 mRNA levels were significantly lower, whereas IL-2 level was significantly elevated. CONCLUSION: The results of this study indicate that the role of DM in modulating bone breakdown related to periodontitis may involve an increased level of LBP and reduced levels of T-helper 2 cytokines.

Three dimensional surface analyses of pubic symphyseal faces of contemporary Japanese reconstructed with 3D digitized scanner.

Three dimensional pubic bone images were analyzed to quantify some age-dependent morphological changes of the symphyseal faces of contemporary Japanese residents. The images were synthesized from 145 bone specimens with 3D measuring device. Phases of Suchey-Brooks system were determined on the 3D pubic symphyseal images without discrepancy from those carried out on the real bones because of the high fidelity. Subsequently, mean curvatures of the pubic symphyseal faces to examine concavo-convex condition of the surfaces were analyzed on the 3D images. Average values of absolute mean curvatures of phase 1 and 2 groups were higher than those of phase 3-6 ones, whereas the values were approximately constant over phase 3 presumably reflecting the inactivation of pubic faces over phase 3. Ratio of the concave areas increased gradually with progressing phase or age classes, although convex areas were predominant in every phase.

Distribution of Aconitum alkaloids in autopsy cases of aconite poisoning.

Aconite is a well-known toxic-plant containing Aconitum alkaloids such as aconitines, benzoylaconines, and aconins. We describe here the distribution of Aconitum alkaloids detected by liquid chromatography-tandem mass spectrometry (LC/MS/MS) in three autopsy cases of suicide by aconite poisoning. Case 1: a male in his fifties had eaten aconite leaves. The concentrations of jesaconitine in cardiac blood, urine, and kidney were 12.1 ng/ml, 993.0 ng/ml, and 114.2 ng/g, respectively. Case 2: a female in her fifties had eaten aconite root. The aconite root in the stomach included a high level of mesaconitine. The concentrations of mesaconitine in cardiac blood, liver, and kidney were 69.1 ng/ml, 960.9 ng/g, and 776.9 ng/g, respectively. Case 3: a male in his sixties had drunk liquor in which aconite root had been soaked. The concentrations of mesaconitine and aconitine in cardiac blood were 259.5 and 228.5 ng/ml, respectively. The Aconitum alkaloid levels were very high in the liver. The absorption of ethanol and Aconitum alkaloids might have been increased because of his having undergone total gastrectomy. In all three cases, the Aconitum alkaloid levels were high in the liver and kidney and low in the heart and cerebrum. The level in the cerebrum was lower than that in blood. Data on the distribution of the Aconitum alkaloids in the body in cases of aconite poisoning is useful to elucidate various actions of aconite alkaloids.

[Efficacy and safety of sitafloxacin in patients with urinary tract infections].

Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.

Analyses of sexual dimorphism of reconstructed pelvic computed tomography images of contemporary Japanese using curvature of the greater sciatic notch, pubic arch and greater pelvis.

Three-dimensional pelvic images were reconstructed from multi-slice CT data of contemporary Japanese (males: 124; females: 104, 25-92 years old), and curvature analysis to examine sexual dimorphism was carried out in the great sciatic notch (GSN), the pubic arch and the greater pelvis in the images. Reconstructed pelvic CT images were visualized fairly well and anatomical landmarks were easily recognizable. When calculating the radii (curvature radii) of the best-fit circles for the spline curve lines set along the edges of the GSNs and of the pubic arches, sexes from these regions were correctly identified in 89.1% (males: 93.8%; females: 83.7%) and 94.7% (males: 97.3%; females: 91.8%) of cases, respectively, by setting an appropriate cut-off value. Furthermore, sexing was possible even in deeper regions of the GSN which are relatively resistant to postmortem damage. Curvature radii of the best-fit spheres of greater pelves showed no significant difference between sexes. However, curvature of the best-fit sphere for the left iliac fossa was significantly larger than that of the right one (p<10(-24)) in males, and the ratios were >1.0 in 88% of all male specimens analyzed. Meanwhile, no significant difference was observed among female samples. Although some left-sided dominancy has been reported in 2-dimensional measurements of the human pelvis, this 3-dimensional laterality in males was much more significant, and is a potential index of sex difference.

A fatal case of hemoperitoneum after ultrasound-guided liver biopsy in a patient with intravascular large B-cell lymphoma.

An autopsy case of fatal complication of percutaneous liver biopsy targeting a rare type of large B-cell lymphoma is presented. A 79 year-old man was referred to the hematology unit of a hospital because of anemia with thrombocytopenia and hepatosplenomegaly. Results of inguinal lymph node biopsy were inconclusive. To investigate a mass lesion in the liver visualized by ultrasonography, image-guided liver biopsy was performed following platelet infusion. The patient became unresponsive 6h post procedure because of hypotension due to intraperitoneal hemorrhage of undetermined origin. Autopsy revealed hemoperitoneum but failed to identify any macroscopic intra- or extrahepatic vascular injuries. Histopathological investigation disclosed infiltration of atypical lymphocytes into the systemic organs including the lymph nodes, spleen, liver, and lungs. Prominent hemophagocytosis was also noted. The lymphoma cells were exclusively accumulated within vascular and sinusoidal structures, and diagnosed with immunohistochemistry as Asian variant of intravascular large B-cell lymphoma. Massive blood extravasation was presumed to originate directly from the markedly dilated liver sinusoids filled with erythrocytes, macrophages and tumor cells, under the condition of impaired hemostasis. Although the biopsy was thought to have been correctly performed, this case would be instructive for evaluation of the indications and risks associated with liver biopsy.

[Study on the safety and efficacy of sitafloxacin--results of the use-results survey].

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was performed for 2 years from December 2008 to November 2010. In total, 3558 case cards were collected from 287 medical institutions and 3331 cases were subjected to a safety evaluation and 3225 were subjected to an efficacy evaluation. Incidence of adverse drug reactions (ADRs) was 4.44% (148/3331 cases). Major ADRs were diarrhea (55 cases) and hepatic function disorders (39 cases), and the incidences were 1.65% and 1.17%, respectively. Serious ADRs were observed in 5 cases (7 episodes); gastrointestinal haemorrhage, hepatic function abnormal, white blood cell count decreased, drug eruption, hypoglycemia, pneumonia, and superinfection in one case each. Efficacy rate was 92.9% (2997/3225 patients) in total with a range of 91.4 to 97.8% by type of infection such as respiratory tract and urinary tract. Eradication rate of indicated strains was 91.5% (808/883 strains) including Gram-positive bacteria at 92.3% (310/336 strains), Gram-negative bacteria at 90.7% (458/505 strains), anaerobes at 100.0% (28/28 strains) and atypical bacteria at 85.7% (12/14 strains). In conclusion, this use-results survey confirmed that STFX is a useful antibacterial agent with no serious problems in its safety profile and efficacy rates of over 90% against all infections.

A case of Takayasu arteritis complicated by right atrium perforation and injuries of the right common iliac artery and vein caused by cannulation for percutaneous cardiopulmonary support.

We describe an autopsy case of Takayasu arteritis with right atrium perforation and injuries of the right common iliac artery and vein caused by cannulation for percutaneous cardiopulmonary support (PCPS). The decedent was an 8-year-old girl admitted for examination in respect to chest pain and syncope. During catheter angiography, she suddenly went into cardiac arrest. PCPS was attempted, whereupon bleeding into the abdominal cavity and an injury to the common iliac vein were observed. She was pronounced dead 78 hours after the initiation of PCPS. Autopsy revealed thickening of the aortic wall from the ascending aorta to the abdominal aorta, with narrowing of the proximal branches. Hemopericardium induced by right atrium perforation, and an injury of the right common iliac artery, were also found. Microscopic examinations of the aorta disclosed thickening of each layer of the vessel wall and inflammatory cell infiltration, mainly into the outer layer of the media. It was speculated that manipulation of the catheter and the underlying Takayasu arteritis caused cardiac arrest. It is also considered that hypovolemia was induced by the injuries of the right common iliac artery and vein caused during the insertion of the PCPS venous cannula. In addition, the right atrium was injured by the edge of the PCPS cannula, leading to hemopericardium. In pediatric cases involving PCPS, or in cases where cannulation is difficult, regular examination of the pericardial and abdominal cavities by echocardiography would provide useful information to prevent such accidents.

Analyses of sexual dimorphism of contemporary Japanese using reconstructed three-dimensional CT images--curvature of the best-fit circle of the greater sciatic notch.

We examined various expression methods of sexual dimorphism of the greater sciatic notch (GSN) of the pelvis in contemporary Japanese residents by analyzing the three-dimensional (3D) images reconstructed by multi-slice computed tomography (CT) data, using image-processing and measurement software. Mean error of anthropological measurement values between two skeletonized pelves and their reconstructed 3D-CT images was 1.4%. A spline curve was set along the edge of the GSN of reconstructed pelvic 3D-CT images. Then a best-fit circle for subsets of the spline curve, 5-60mm in length and passing through the deepest point (inflection point) of the GSN, was created, and the radius of the circle (curvature radius) and its ratio to the maximum pelvic height (curvature quotient) were computed. In analysis of images reconstructed from CT data of 180 individuals (male: 91, female: 89), sexes were correctly identified in with 89.4% of specimens, with a spline curve length of 60mm. Because sexing was possible even in deeper regions of the GSN, which are relatively resistant to postmortem damage, the present method may be useful for practical forensic investigation.

An autopsy case of aortitis resulting in sudden death due to a rupture of aneurysm of the aortic sinus.

An autopsy case of spontaneous rupture of a clinically undiagnosed inflammatory aneurysm of the aortic sinus is presented. A 34-year-old man consulted a physician complaining of anterior chest pain and heartburn persisting for 2 days. Diagnoses of common cold and gastritis were made, but 3h later his condition deteriorated, leading to death. Autopsy revealed hemopericardium due to rupture of a saccular aneurysm of the aortic sinus. Histological examination of the aortic sinus disclosed aortitis characterized by fragmentation and loss of elastic tissues with fibrous thickening of the intima. Lymphocytes along with polymorphonuclear leucocytes and plasma cells infiltrated the adventitia and media at severely affected areas. These changes were limited to the aortic sinus, and other portions of the aorta and its main branches were essentially intact. An eccentric intimal thickening with medial degeneration was found within the anterior descending branch of the left coronary artery, and occasional collection of lymphocytes was noted in the epicardium. This case would be a rare and illustrative case for differentiation of aortitis, although we could not pinpoint the etiology of the aortitis because of non-specific histological findings and negative serological results for exogenous pathogens.

Lipopolysaccharide-mediated enhancement of bone metabolism in estrogen-deficient mice.

BACKGROUND: Osteoporosis may be a risk factor in periodontal disease. However, biologic mechanisms explaining the apparent interaction between these two diseases have not been defined. It is well known that lipopolysaccharide (LPS) increases the resorption of alveolar bone. We hypothesized that LPS and estrogen deficiency have synergistic effects on bone metabolism and may lead to enhanced bone resorption. METHODS: Eighty 8-week-old female ddY mice were divided into two groups and underwent a sham operation or bilateral ovariectomy. They were maintained for 4 weeks to assess estrogen-deficient bone loss. Osteoblasts and bone marrow cells (BMCs) were collected from ovariectomized (OVX) and sham-operated mice. Osteoclast differentiation in a coculture of osteoblasts and BMCs was investigated by tartrate-resistant acid phosphatase staining. Receptor activator of nuclear factor-kappa B ligand (RANKL) mRNA expression in LPS-treated osteoblasts was investigated using real-time polymerase chain reaction. Interferon-gamma (IFN-gamma) and interleukin (IL)-6 and -10 levels in the culture supernatants were evaluated by enzyme-linked immunosorbent assay. Group means were compared by analysis of variance followed by Tukey's honestly significant difference. RESULTS: There was a significant increase in the number of osteoclasts in LPS-treated cocultures from OVX mice compared to sham controls (P <0.05). RANKL mRNA expression in LPS-treated osteoblasts from OVX mice was greater than in sham mice (P <0.05). In contrast, the production of IFN-gamma in LPS-treated coculture from OVX mice was significantly lower than in sham mice (P <0.05). CONCLUSION: LPS-bearing Gram-negative organisms are abundant in periodontal disease, and the results supported the hypothesis that bone resorption is increased in estrogen-deficient patients.

Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis.

Phosphate and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene inactivated in numerous sporadic cancers, including melanomas. To analyze Pten functions in melanocytes, we used the Cre-loxP system to delete Pten specifically in murine pigment-producing cells and generated DctCrePten(flox/flox) mice. Half of DctCrePten(flox/flox) mice died shortly after birth with enlargements of the cerebral cortex and hippocampus. Melanocytes were increased in the dermis of perinatal DctCrePten(flox/flox) mice. When the mutants were subjected to repeated depilations, melanocyte stem cells in the bulge of the hair follicle resisted exhaustion and the mice were protected against hair graying. Although spontaneous melanomas did not form in DctCrePten(flox/flox) mice, large nevi and melanomas developed after carcinogen exposure. DctCrePten(flox/flox) melanocytes were increased in size and exhibited heightened activation of Akt and extracellular signal-regulated kinases, increased expression of Bcl-2, and decreased expression of p27(Kip1). Our results show that Pten is important for the maintenance of melanocyte stem cells and the suppression of melanomagenesis.

A study on mRNA expressions of interleukin 10 during fracture healing for wound age determination.

We investigated mRNA expressions of interleukin 10 (IL-10) during fracture healing for wound age determination. Macroscopically, calluses were formed at 144 h post-injury, and thickening of the fracture edge was observed at 240 h post-injury. Slight infiltration of neutrophils and macrophages was detected at 3 h post-injury, and moderate infiltration of T and B lymphocytes was detected at 72 h post-injury. In addition, osteoblasts proliferated at 24 h post-injury. IL-10 mRNA increased immediately after the intervention and peaked at 24 h, and the expressions were detected in osteocytes before and after injury, and in osteoblasts at 3 h post-injury. Although the intensity was stable in osteocytes, that in osteoblasts was strongest at 24 h post-injury. Among inflammatory cells, the expressions were exclusively detected in macrophages. These results indicated that examinations of macroscopic and microscopic changes in fracture edges, and mRNA expressions of IL-10, would be informative for fracture healing and dating.

Simultaneous detection of eight cytokines in human dermal wounds with a multiplex bead-based immunoassay for wound age estimation.

We performed quantification of IL 2, IL 4, IL 6, IL 8, IL 10, GM-CSF, IFN gamma, and TNF alpha in human dermal wounds for wound age estimation. The proliferation of dermal cells and infiltration of inflammatory cells were also analyzed. Neutrophils and macrophages were detected from 2 h post-injury, and strong infiltrations were seen at 33-49 h. T and B lymphocytes also infiltrated simultaneously from 71 h. Strong proliferation of fibroblasts were shown from 246 h, and thickening of the epidermis from 71 h. IL 10, GM-CSF, IFNgamma, and TNF alpha increased from the early phase of dermal wound healing, IL 6 exclusively in the middle phase, IL 2, IL 4, and IL 8 from the middle phase to the late phase. Among the cytokines analyzed in the present study, IL 6, IL 8, IFNgamma, and TNF alpha were strongly expressed. Results of the present study suggest that multiplex cytokine analysis at the wound site can be useful for wound age estimation. In addition, multiplex data obtained from the same sample with a single method would demonstrate more accurate interactions of cytokines during dermal wound healing. Although the present study was oriented to practical forensic pathology, the data obtained would be informative for various fields of medicine.

Simultaneous detections of 27 cytokines during cerebral wound healing by multiplexed bead-based immunoassay for wound age estimation.

Quantification of 27 cytokines following cerebral wounding was performed for wound age estimation. The cytokines evaluated included interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 p40, IL-12 p70, IL-15, IL-17, IL-18, basic fibroblast growth factor (bFGF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), Interferon-gamma (IFN-gamma), keratinocyte derived cytokine (KC), leukemia inhibitory factor (LIF), macrophage-colony stimulating factor (M-CSF), monokine inducible by interferon gamma (MIG), macrophage inflammatory protein (MIP)-1 alpha, MIP 2, platelet-derived growth factor BB (PDGF BB), regulated upon activation, normal T-cell expressed, and secreted (Rantes), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF). The proliferation of glial cells as well as the infiltration of inflammatory cells were also evaluated. Although astroglia proliferated from 72 hours post-injury, inflammatory cell dynamics were generally steady. Among cytokines analyzed in the present study, IL-1beta, IL-5, IL-6, IL-12 p40, G-CSF, IFN-gamma, KC, LIF, MIP2, and PDGF BB increased during the early phase of cerebral wound healing, and M-CSF increased during the middle phase, while IL-15, IL-18, and MIG increased during the late phase. In contrast, IL-1alpha, IL-10, IL-12 p70, and TNF-alpha were suppressed throughout the cerebral wound healing process. Based on our findings, quantitative cytokine analyses at the cerebral wound site may be a useful tool for wound age estimation. Further, this study suggests that multiplex data gained from the same sample using a single methodology demonstrates highly accurate cytokine interactions during the process of cerebral wound healing.

Alteration of mast cell proliferation/apoptosis and expression of stem cell factor in the regression of mastocytoma--report of a case and a serial immunohistochemical study.

BACKGROUND: Spontaneous regression of solitary mastocytoma is a well-described phenomenon, but its mechanism is unknown. METHODS: Serial-section immunohistochemical analyses were performed on biopsies of a mastocytoma from a Japanese child during the proliferation stage (PS, 7 months of age) and the regression stage (RS, 5 years old). RESULTS: Mast cell (MC) density in RS was markedly decreased (406 cells/mm2) compared to that in PS (3554 cells/mm2). MCs in RS were larger than those in PS. With proliferative cell nuclear antigen (PCNA) staining, 1.7% MCs were positive in PS, whereas no positive MCs were seen in RS. TUNEL-labeling index (LI) in RS (2.8%) increased 1.5-fold in PS (1.9%). With stem cell factor (SCF) staining, 57% of lesional MCs in RS revealed strong cytoplasmic immunoreactivity, whereas only 9% of MCs were positive in PS. Epidermal SCF reactivity was found as intracellular and intercellular patterns in both PS and RS. CONCLUSIONS: Loss of MC proliferating activity, an increase in apoptotic MCs, and increased expression of SCF in remaining MCs in RS may play a role in the involution of mastocytomas.