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Heat shock protein 90 (HSP90) facilitates diverse cellular processes by interacting process with more than 200 client proteins. Overexpression of HSP90 contributes to the pathogenesis of various malignant tumors, and HSP90 inhibitors attenuate the progression of malignant tumors in vitro/vivo. Numerous clinical trials have used HSP90 inhibitors to treat several cancers, and pimitespib (an HSP90 inhibitor) is covered by insurance for advanced gastrointestinal stromal tumor in Japan. In this study, we investigated the expression pattern of HSP90 and analyzed its clinical significance in extramammary Paget's disease (EMPD). All 77 EMPD tissues investigated were positive for HSP90 expression. The immunoreactivity of HSP90 in fetal cases due to EMPD tended to be highly stained. Although there was no significant difference in HSP90 mRNA levels between 24 paired lesional and nonlesional tissues, microRNA-inhibiting HSP90 levels in tumor tissues were significantly decreased compared with those in normal tissues. Thus, HSP90 may play an important role in the pathogenesis of EMPD and may be a novel therapeutic target for EMPD., (© 2023 Japanese Dermatological Association.)

Objective: To determine whether periodontal status is associated with oral function, including masticatory performance and occlusal force, among community-dwelling older adults., Background: Although a potential association between periodontal status and oral function has been reported, variations in the root surface area (RSA) of each tooth have not been considered., Methods: We used data from a population-based study involving community-dwelling older adults. The RSA with periodontal ligament (RSA-PL), which quantifies the RSA attached to the periodontal ligament and alveolar bone, was calculated based on full-mouth periodontal examination. Masticatory performance was assessed using spectrophotometric measurement of the color (a* value) of color-changing chewing gum. The bilateral maximal occlusal force (MOF) was measured using a pressure-sensitive sheet and dedicated software. The associations of the RSA-PL, a quantitative marker of periodontal tissue support, with the a* value and MOF were assessed using linear regression models., Results: The analyses included data from 250 adults [60.8% women; age, mean (standard deviation) 82.5 (5.0) years]. On average, the study participants had an RSA-PL of 26.3 cm 2 , a* value of 25.0, and an MOF value of 555.1 N. After adjustments for potential confounders, including dentition status, age, sex, dental visit regularity, smoking status, physical activity level, depressive symptoms, a history of stroke or diabetes mellitus, and body mass index, the RSA-PL was found to be associated with the a* value [coefficient (per 1 cm 2 increase): 0.16, 95% confidence interval (CI) 0.10-0.22)] and MOF (coefficient: 9.2, 95% CI 5.3-13.1)., Conclusion: This study demonstrated that greater amounts of remaining tooth-supporting structures, indicated by higher RSA-PL values, were associated with better masticatory performance and a higher occlusal force among community-dwelling older adults., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Some patients with coronavirus disease 2019 (COVID-19) develop skin manifestations. There may be regional and racial differences in the frequency and type of COVID-19-associated skin manifestations. There are, however, few reports on skin manifestations in COVID-19 patients in Asia, including Japan. We retrospectively investigated the frequency, type, and clinical course of skin manifestations in Japanese patients with COVID-19. From 22 February 2020 to 16 August 2021, 738 Japanese patients (median age 59 years, 55% male) with laboratory-confirmed COVID-19 on polymerase chain reaction or antigen tests were admitted to our hospital. We mainly admitted patients with mild to moderate severity who had symptoms such as cough, fever, and oxygen demand but did not require mechanical ventilation. A total of 2.8% (21/738) of the COVID-19 patients treated at our hospital were diagnosed with viral eruptions caused by COVID-19. Of the 21 patients, 19 developed erythematous papules, and two developed urticaria. There were no cases of pernio-like lesions, known as COVID toes. The median duration from the onset of other COVID-19 symptoms to the development of skin manifestations was 9 days. This study revealed that approximately 2-3% of Japanese patients with COVID-19 developed COVID-19-associated viral eruptions, most of which were erythematous papules., (© 2022 Japanese Dermatological Association.)

Although the prognosis of patients with extramammary Paget's disease (EMPD) treated with radical resection is good, the prognosis of EMPD with distant metastasis is very poor. PIK3CA mutations predict a good response to PIK3CA inhibitors. The aim of this study was to investigate the occurrence rate of PIK3CA mutations (including multiple mutations [MM]) related to the intertumor and intratumor heterogeneity in EMPD and to evaluate the correlation between these mutations and clinical parameters of EMPD. We performed droplet digital polymerase chain reaction to detect PIK3CA mutations (E542K, E545K, H1047R, and MM) in 68 patients with EMPD. In addition, we investigated the presence of PIK3CA mutations at multiple sites in 16 patients with PIK3CA mutations to assess the intratumor heterogeneity of PIK3CA mutations in EMPD. The frequency of one or more PIK3CA mutations in patients with EMPD was 30.8% (21/68). The frequency of E542K, E545K, H1047R, and MM were 10.2% (7/68), 13.2% (9/68), 11.7% (8/68), and 4.4% (3/68), respectively. No significant correlation was found between PIK3CA mutation patterns and clinical parameters. Of the 21 patients with PIK3CA mutations, 16 with tissue samples that could be analyzed at multiple sites were examined. The proportion of patients with the same PIK3CA mutations at all sites was 12.5% (2/16). The proportion of patients with the same PIK3CA mutations at least two or more sites, but not at all sites, was 31.2% (5/16). The proportion of patients with no PIK3CA mutations at other sites was 37.5% (6/16). The proportion of patients with other PIK3CA mutations at other sites was 18.7% (3/16). There is intertumor and intratumor heterogeneity of PIK3CA mutations. PIK3CA mutations in EMPD may be progressor mutations in EMPD., (© 2022 Japanese Dermatological Association.)

Objective: To investigate the potential association between periodontitis and arterial stiffness among the older Japanese population., Background: The prevalence of periodontitis is increasing in Japanese older adults. Arterial stiffness increases the risks of cardiovascular events and death, morbidity, and dementia., Methods: This secondary analysis of data from a cross-sectional study evaluated the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue that was estimated by a full-mouth periodontal examination. Severe periodontitis was defined per the parameters provided by the Centers for Disease Control/American Academy of Periodontology. The Cardio-Ankle Vascular Index (CAVI) was used for measuring the overall stiffness of the artery, and higher CAVI indicated increased arterial stiffness. An ordinal logistic regression model was used to evaluate the association between periodontitis and arterial stiffness., Results: The analysis included 185 Japanese adults [35% men; age, mean (standard deviation) 80.2 (4.4) years]. The average PISA and the prevalence of severe periodontitis were 64.4 mm 2 and 27.6%, respectively; 54 (29.2%), 56 (30.3%), and 75 (40.5%) participants were stratified to the CAVI < 9, 9 ≤ CAVI <10, and CAVI ≥ 10 groups, respectively. After adjusting for potential confounders, the odds ratio of the prevalence and severity of arterial stiffness evaluated using CAVI was 1.06 [95% confidence interval (CI) 1.01 to 1.10] for PISA per 10 mm 2 and 2.12 (95% CI 1.09 to 4.11) for severe periodontitis., Conclusion: Periodontitis was associated with arterial stiffness among Japanese older adults. Further studies are needed to investigate whether arterial stiffness is an intermediate factor in the pathway between periodontitis and systemic diseases, including cardiovascular disease and dementia., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In psoriasis, tumor necrosis factor (TNF)-α is a key pro-inflammatory cytokine that activates keratinocytes to produce other inflammatory mediators. In addition, increased serum or plasma TNF-α levels are considered to be biomarkers of psoriasis. Circulating cell-free DNA (cfDNA) originates from apoptotic or necrotic cells and reflects the severity of cellular damage. Although cfDNA has recently attracted attention as a marker in the diagnosis and prognosis of various disorders, there are few reports of its clinical implications in the field of dermatology including psoriasis. The aim of this study was to investigate whether the TNF-α gene is present in the cfDNA, and whether its levels can be utilized as a biomarker for patients with psoriasis. cfDNA was isolated from serum samples of 79 patients with psoriasis vulgaris and 29 with psoriatic arthritis. The levels of TNF-α in the cfDNA were assessed by droplet digital polymerase chain reaction. In this study, we made two novel findings. First, circulating TNF-α DNA levels in the cfDNA were significantly higher in patients with psoriasis than in healthy controls. In addition, the area under the curve was 0.91, suggesting that serum TNF-α DNA levels are effective as a diagnostic biomarker. Second, the levels of TNF-α DNA copies in the cfDNA were positively correlated with the Psoriasis Area and Severity Index (PASI) score in the group of patients with a PASI score higher than 10. Generally, a PASI score of more than 10 is defined as severe psoriasis; therefore, the levels of TNF-α DNA copies in the cfDNA could be a biomarker for severity in patients with severe psoriasis. Further studies are needed to establish serum TNF-α DNA levels as a novel biomarker of psoriasis., (© 2020 Japanese Dermatological Association.)

Background: Extramammary Paget's disease (EMPD) is a rare malignant skin cancer. One of the hallmarks of cancers, including EMPD, is an enhancement of aerobic glycolysis, which is also known as the Warburg effect. In the last step of glycolysis, the enzyme lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactic acid, the accumulation of which contributes to the creation of an acidic tumour microenvironment. This in turn results in immunosuppression in various types of cancers. However, the contribution of these pathways has not been well-studied in EMPD., Objective: To investigate the significance of the Warburg effect and its contribution to the tumour immune microenvironment in EMPD., Methods: The mRNA expression levels of molecules involved in glycolysis and immune-related cytokines were examined by ddPCR. The number of immune cells was assessed by immunohistochemistry (IHC)., Results: The levels of two glycolytic enzymes, HK2 and LDHA, in tumour tissues were significantly increased compared to those in paired-normal tissues. IHC analyses revealed increased numbers of PD-L1 + , PD-1 + , CD163 + M2 macrophages, Iba1 + macrophages and Foxp3 + Tregs that were associated with high LDHA levels in EMPD. ddPCR demonstrated that multiple cytokines including IL-4, IL-6, IL-10, TGF-β and CCL-2 were upregulated and associated with high LDHA levels in EMPD. Statistical analyses showed that IL-6 mRNA expression correlated with the number of CD163 + , Iba-1 + and Foxp3 + cells., Conclusion: The Warburg effect contributes to immunomodulation in the tumour microenvironment and further elucidation may lead to better understanding of the pathogenesis of EMPD., (© 2019 European Academy of Dermatology and Venereology.)

Background and Objectives: Identification of modifiable factors for mild cognitive impairment (MCI) is important since individuals with MCI are at a high risk of dementia and disability. Previous studies have suggested a potential association between periodontitis and cognitive impairment, but the results remain inconclusive. We designed a 5-year longitudinal study to explore the association between MCI and periodontitis and periodontal inflammation in older adults., Methods: This study included 179 community-dwelling dentate individuals (62 men and 117 women, average age: 80.1 years). A full-mouth periodontal examination at six sites per tooth was performed at baseline. Case definitions provided by the European Workshop in Periodontology Group C (EWP definition) and the Centers for Disease Control/American Academy of Periodontology (CDC/AAP definition) were used to define severe periodontitis. Additionally, the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue, was calculated using clinical periodontal parameters. Follow-up cognitive examinations for MCI diagnosis were performed by neurologists 1, 2, 3, and 5 years after baseline. Odds ratios (ORs) for MCI according to the presence of periodontitis and periodontal inflammation at baseline were calculated using multilevel mixed-effects logistic regression., Results: At baseline, 56.4% and 27.4% of the participants had severe periodontitis by the EWP and CDC/AAP definitions, respectively. After adjusting for follow-up period and other baseline health characteristics (age, sex, smoking status, educational level, physical activity level, obesity, depression, and diabetes), severe periodontitis by either definition was significantly associated with MCI (for the EWP definition: adjusted OR = 3.58, 95% confidence interval [CI] = 1.45-8.87; for the CDC/AAP definition: adjusted OR = 2.61, 95% CI = 1.08-6.28). Periodontal inflammation assessed by PISA was also significantly associated with a higher OR for MCI (adjusted OR = 1.05, 95% CI = 1.01-1.10, per 10-mm 2 increase in PISA)., Conclusion: Severe periodontitis and periodontal inflammation were associated with incident MCI among older community-dwelling men and women., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cyclin-dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6-cyclin D1 complex controls the cell cycle transition from G 1 phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression., (© 2019 Japanese Dermatological Association.)

Background and Objective: Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined the longitudinal relationship of periodontitis with cognitive decline in 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom data were available from comprehensive health examinations conducted in 2010 and 2013., Material and Methods: Based on a baseline full-mouth periodontal examination, severe periodontitis was defined using a Centers for Disease Control and Prevention/American Academy of Periodontology definition. Cognitive decline during the 3-year study period was defined using the results of the Mini-Mental State Examination (MMSE). Information on age, gender, education, depression, body mass index, smoking status, alcohol use, exercise, hypertension, diabetes, history of cardiovascular disease and stroke, and baseline MMSE scores were obtained and tested as potential confounders in the statistical models., Results: Among 85 study participants, 21 (24.7%) were defined as having severe periodontitis. Multivariable Poisson regression analyses revealed that severe periodontitis was significantly associated with an increased risk of cognitive decline [adjusted relative risk = 2.2; 95% confidence interval (95% CI): 1.1-4.5]. Furthermore, multivariable linear regression analyses revealed that participants with severe periodontitis had a 1.8-point greater decrease (95% CI: -3.3 to -0.2) in MMSE score than those without severe periodontitis., Conclusion: Within the limitations related to its small sample size, the findings of the present study suggest that severe periodontitis is significantly associated with future decline in cognitive function among community-dwelling older Japanese subjects., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the title compound, [Fe(C5H5)(C27H16NO)], designed and synthesized to explore a new electron-donor (D) and -acceptor (A) conjugated complex, the two cyclo-penta-dienyl rings adopt an eclipsed conformation. The anthracene tricycle is distorted towards a butterfly conformation and the mean planes of the outer benzene rings are inclined each to other at 22.7 (3)°. In the crystal, mol-ecules are paired into inversion dimers via π-π inter-actions. Weak inter-molecular C-H⋯π inter-actions link further these dimers into one-dimensional columns along the b axis, with the ferrocenylethynyl arms arranged between the stacks to fill the voids.

The title compound, [Fe2(C5H5)2(C40H22O2)] or 1,4-(FcPh)2Aq [where FcPh is 2-(4-ferrocenylphenyl)ethynyl and Aq is anthraquinone], was synthesized in an attempt to obtain a new solvent-incorporating porous material with a large void space. Thermodynamic data for 1,4-(FcPh)2Aq show a phase transition at approximately 430 K. The crystal structure of solvent-free 1,4-(FcPh)2Aq was determined at temperatures of 90, 300 and 500 K using synchrotron powder diffraction data. A direct-space method using a genetic algorithm was employed for structure solution. Charge densities calculated from observed structure factors by the maximum entropy method were employed for model improvement. The final models were obtained through multistage Rietveld refinements. In both phases, the structures of which differ only subtly, the planar Aq fragments are stacked alternately in opposite orientations, forming a one-dimensional column. The FcPh arms lie between the stacks and fill the remaining space, leaving no voids. C-H...π interactions between the Ph and Fc fragments mediate crystal packing and stabilization.

The title mol-ecule, C30H28O6, possesses crystallographically imposed twofold symmetry, with two central C atoms in the naphthalene unit lying on the rotation axis along [001]. The 4-eth-oxy-benzoyl groups at the peri positions of the naphthalene ring system are disordered over two sets of sites with occupancies of 0.769 (4) and 0.231 (4). They are directed in opposite directions from the naphthalene plane (anti orientation). For the major component, the dihedral angle between the aroyl benzene ring and the naphthalene ring system is 75.62 (13)° [minor component 75.5 (4)°], and that between the aroyl benzene rings is 32.58 (15)°. In the crystal, mol-ecules are linked via C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

The title molecule, C44H30O8, lies about a crystallographic inversion centre located at the centre of the central benzene ring. The benzene rings in the benzoyl and the terephthalate units make dihedral angles of 67.05 (7)° and 57.57 (7)°, respectively, with the naphthalene ring system. There is an intra-molecular C-H⋯O inter-action between the ketonic carbonyl O atom and an H atom on the naphthalene ring system. In the crystal, C-H⋯O inter-action of the benzene ring in the benzoyl group and weak C=O⋯π inter-action [O⋯centroid = 3.375 (2) Å] of the naphthalene ring with the O atom in the ketonic carbonyl group are observed. These inter-actions form layers parallel to the bc plane.

The mol-ecule of the title compound, C26H18F2O8S2, lies across a crystallographic twofold rotation axis. The benzene rings of the 4-fluorobenzoyl groups make dihedral angles of 78.93 (12)° with the naphthalene ring system. An intra-molecular C-H⋯π inter-action occurs. In the crystal, a number of C-H⋯O inter-actions link the mol-ecules, forming a three-dimensional structure.

In the mol-ecule of the title compound, C32H24O5, the benzoyl group and the 4-phenoxy substituted benzoyl group at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel. The two benzene rings make a dihedral angle of 21.18 (10)°, and are inclined to the naphthalene ring system by 86.53 (9) and 82.95 (8)°, respectively. In the crystal, C-H⋯O inter-actions are observed involving aromatic and meth-oxy H atoms with ketonic carbonyl O atoms, as well as C-H⋯π inter-actions between aromatic H atoms and the π-systems of naphthalene and benzene rings. These interactions form a three-dimensional architecture and afford a waved alignment of the naphthalene ring systems along the c axis.

In the mol-ecule of the title compound, C20H18O4, the dihedral angle between the naphthalene ring system and the benzene ring is 81.74 (5)°. An inter-molecular C-H⋯O inter-action is formed between an H atom at the 6-position of the naphthalene ring and the O atom of the meth-oxy group at the 7-position.

In the title mol-ecule, C25H20O4, the naphthalene and phen-oxy groups are oriented nearly perpendicular with respect to the benzene ring of the benzoyl group, with dihedral angles of 89.61 (5) and 86.13 (6)°, respectively. The crystal structure features C-H⋯O and C-H⋯π inter-actions.

In the title compound, C(31)H(20)O(5), the phenyl rings of the benzo-yloxy and benzoyl groups are twisted away from the naphthalene ring system by 64.27 (6), 73.62 (5) and 80.41 (6)°. In the crystal, C-H⋯O hydrogen bonds and C-H⋯π inter-actions link the mol-ecules, forming tubular chains parallel to the b axis. The chains are further connected into a three-dimensional network by C-H⋯π inter-actions and π-π stacking contacts [centroid-centroid distances = 3.622 (10)-3.866 (12) Å].

In the title compound, C28H24O6·CHCl3, the two 4-meth-oxy-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, the benzene rings making a dihedral angle of 25.76 (7)°. The naphthalene ring system makes dihedral angles of 72.51 (7) and 73.33 (7)° with the benzene rings. In the crystal, the naphthalene mol-ecules are linked by C-H⋯O inter-actions, forming a helical chain along the b-axis direction. A C-H⋯Cl inter-action is also observed between the aroylated naphthalene and chloro-form mol-ecules. The chloro-form mol-ecule is disordered over two positions with site occupancies of 0.478 (5) and 0.522 (5).

In the mol-ecule of the title compound, C34H36O4, the two 4-isobutyl-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, and the benzene rings make a dihedral angle of 21.59 (7)°. The dihedral angles between the benzene rings and the naphthalene ring system are 69.26 (6) and 64.29 (5)°. There are no classical hydrogen bonds in the structure, but inversion-related mol-ecules engage in π-π stacking, with an inter-planar spacing between related naphthalene groups of 3.4120 (16) Å.

In the title compound, C(38)H(24)O(6), the phenyl rings of the benzoyl and benzo-yloxy groups make dihedral angles of 67.12 (5), 85.15 (5), 76.41 (5) and 71.47 (5)° with the naphthal-ene ring system. In the crystal, C-H⋯O hydrogen bonds link mol-ecules into chains parallel to the b axis. The structure also features C-H⋯π and π-π stacking inter-actions, with centroid-centroid distances in the range 3.6441 (7)-3.9197 (8) Å.

In the title compound, C(32)H(32)O(4), the 4-propyl-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, and their benzene rings make a dihedral angle of 8.64 (10)°. The dihedral angles between the naphthalene ring system and the benzene rings are 69.37 (8) and 69.45 (8)°. In the crystal, C-H⋯O inter-actions link adjacent mol-ecules via their aroyl groups.

The metabolic process in red blood cells (RBCs) is anaerobic. The life-dependent adenosine triphosphate (ATP) for survival of cells is produced through glycolytic process. The aim of the study was to evaluate the effects of the glucose level on the mean corpuscular volume, mean corpuscular hemoglobin concentration, and hemolysis rate during hemolysis study by rotary blood pumps. The shear stress generated by rotary blood pumps may enhance glucose utilization by RBCs with depletion of glucose affecting ATP production and, consequently, cell size, shape, and morphology. The shear stress increases metabolism of RBCs consuming more energy ATP which is produced anaerobically from glycolytic process. Hence, in the closed circuit testing of rotary blood pumps, depletion of glucose might occur after prolonged pumping, which in turn affects metabolic process of RBCs by changing their size, shape, and morphology. It is thus suggested to monitor and control the glucose level of the fluid that suspends RBCs depending on the study duration.

In this study, mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) were measured to quantify RBC damage by rotary blood pumps. Six-hour hemolysis tests were conducted with a Bio-pump BPX-80, a Sarns 15200 roller pump, and a prototype mag-lev centrifugal pump (MedTech Heart) using fresh porcine blood circulated at 5 L/min against a 100 mm Hg head pressure. The temperature of the test and noncirculated control blood was maintained at 37 degrees C. The normalized index of hemolysis (NIH) of each pump was determined by measuring the plasma-free hemoglobin level. The MCV was measured with a Coulter counter, and MCHC was derived from total hemoglobin and hematocrit. MCH was derived from MCV and MCHC. A multivariance statistical analysis (ANOVA) revealed statistically significant differences (n = 15, P < 0.05) in MCV, MCHC, and MCH between the blood sheared by the rotary blood pumps and the nonsheared control blood. Normalized to the control blood, the Bio-pump BPX-80 showed an MCV of 1.04 +/- 0.03, an MCHC of 0.95 +/- 0.04, and an MCH of 0.98 +/- 0.02; the mag-lev MedTech Heart had an MCV of 1.02 +/- 0.02, an MCHC of 0.97 +/- 0.02, and an MCH of 0.99 +/- 0.01; and the roller pump exhibited an MCV of 1.03 +/- 0.03, an MCHC of 0.96 +/- 0.03, and an MCH of 0.99 +/- 0.01. Per 0.01 increase in NIH, the BPX-80 showed a normalized MCV change of +10.1% and a normalized MCHC change of -14.0%; the MedTech Heart demonstrated a +6.9% MCV and -9.5% MCHC change; and the roller pump had a +0.5% MCV and -0.6% MCHC change. Due to shear in the pump circuits, the RBC increased while the MCHC decreased. The likely mechanism is that older RBCs with smaller size and higher hemoglobin concentration were destroyed fast by the shear, leaving younger RBCs with larger size and lower hemoglobin concentration. Subhemolytic trauma caused the intracellular hemoglobin to decrease due to gradual hemoglobin leakage through the micropores formed in the thinned membrane. In conclusion, the rate of change in MCV and MCHC with respect to NIH change provides useful information relating to selective destruction of RBCs, while the MCH level reflects subhemolytic damage.

Leuprorelin acetate, a chemotherapeutic agent used to treat prostate cancer, is a synthetic luteinizing hormone-releasing hormone (LHRH) agonist. We report a 75-year-old man who presented with several large subcutaneous nodules at the site of leuprorelin acetate injections for his prostatic cancer. A biopsy of the nodules disclosed epithelioid granulomatous inflammation and resulted in a diagnosis of drug-induced granulomatous reaction to leuprorelin acetate.

We have treated two patients with extramammary Paget's disease/carcinoma (EMPD/C), a 62-year-old woman and a 78-year-old man. In both patients, lymph nodes in the areas of the bilateral inguinal, external iliac arteries, and abdominal aorta were affected. After surgery, they underwent 5 courses of systemic combination chemotherapy at 4-week intervals to residual or recurrent lymph node metastasis. Each course consisted of 3.5 mg mitomycin C and 50 mg epirubicin (day 1), 0.6 mg vincristine (days 1 and 7), 30 mg cisplatin (days 1, 2, and 3), and 350 mg 5-fluorouracil (days 3, 4, 5, 6, and 7). The affected lymph nodes in both patients subsided in response to the chemotherapy. Positron emission tomography (PET) scans confirmed the complete remission of lymph node metastasis in Case 1. In Case 2, they were reduced by more than 90% on computed tomography (CT) scans. Adverse effects included leukocytopenia, vomiting, hypesthesia, and constipation, all of which disappeared after the completion of chemotherapy. While surgery with wide local excision is the treatment of choice in patients with EMPD/C, there is currently no standardized treatment for advanced cases with metastasis. We describe two patients with EMPD/C whose metastatic lesions responded well to this combination of chemotherapy.

Small potent inhibitors of aggregation are eagerly demanded for preventing the inactivation of proteins. This paper shows that amino acid esters (AAEs) prevent heat-induced aggregation and inactivation of hen egg lysozyme. Lysozyme was completely inactivated (<1% original activity) during heat treatment at 98 degrees C for 30 min in a solution containing 0.2 mg/mL lysozyme in 50 mM Na-phosphate buffer (pH 6.5). The residual activities only slightly increased (<5%) in the presence of 100 mM commonly used additives such as arginine, guanidine, urea, and sugars. However, in the presence of 100 mM AAEs, the residual activities were >60% and no aggregates were observed during the heat treatment at 98 degrees C for 30 min. This fact provides new information on the scaffold for designing additives to prevent heat-induced aggregation.

Misfolding poses a serious problem in the biotechnological field in obtaining the active protein from inclusion bodies. Here we show that high temperature increases the refolding yield of reduced lyosyzme by a simple dilution method. The refolding yields at 98 degrees C were three times higher than those at 20 degrees C in the solutions tested, which is related to the fact that the thermally unfolded state of lysozyme is a more productive form for folding than the denaturant-induced fully unfolded state. The thermal-assisted refolding could be used for various reduced and denatured proteins as a result of its simplicity and low cost.