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Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

As near-infrared radiation (NIR), which is a composition of sunlight with an 780-1400 nm wavelength, is associated with skin aging such as wrinkles and slacks, the biological actions of NIR with high dermal penetration remains unclear. In the present study, we found that NIR irradiation (40 J/cm 2 ) at different levels of irradiance (95-190 mW/cm 2 ) using a laboratory device with a xenon flash lamp (780-1700 nm) caused sebaceous gland enlargement concomitantly with skin thickening in the auricle skin of hamsters. The sebaceous gland enlargement resulted from the proliferation of sebocytes due to an increase in the number of proliferating cell nuclear antigen (PCNA)- and lamin B1-positive cells in vivo. In addition, NIR irradiation transcriptionally augmented the production of epidermal growth factor receptor (EGFR) accompanied with an increase in the reactive oxygen species (ROS) level in hamster sebocytes in vitro. Furthermore, the administration of hydrogen peroxide increased the level of EGFR mRNA in the sebocytes. Therefore, these results provide novel evidence that NIR irradiation causes the hyperplasia of sebaceous glands in hamsters by mechanisms in which EGFR production is transcriptionally augmented through ROS-dependent pathways in sebocytes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.

Direct proton-knockout reactions of ^{55}Sc at ∼220  MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

Background: The 8th edition American Joint Committee on Cancer (AJCC) proposed a prognostic stage (PS), which included not only anatomical factors, but also biological factors. We aimed to investigate the clinicopathological significance of the PS and to compare PS and anatomical stage (AS) that has been established by the Union for International Cancer Control (UICC)., Methods: Between 2002 and 2017, 800 patients were included in the study. Patients were classified using pathological UICC AS and pathological AJCC PS. The usefulness of PS in comparison with AS was validated using the Akaike information criterion (AIC) and Harrell concordance index (C-index)., Results: A total of 401 (50.1%) patients had pathological AS I, 324 (40.5%) had AS II, and 75 (9.4%) had AS III. Meanwhile, 535 (66.8%) had pathological PS I, 163 (20.4%) had PS II, and 102 (12.8%) had PS III. The number of AS II cases was 1.99-fold higher than that of PS II cases. For each stage, these survival curves were almost similar between AS and PS classification. Therefore, many patients to be classified into stage I and stage III were included in AS II group, while many patients to be classified into stage II were included in AS I group. To trichotomize the survival groups, PS appeared to be more specific than AS, and AIC and C-index confirmed the speculation., Conclusion: For the prognostication of primary breast cancer patients, AJCC PS appeared to be able to stratify the cases more appropriately than UICC AS.

Mesothelin is expressed in various types of malignant tumors. The present study immunohistochemically investigated mesothelin expression and its clinicopathological significance in each subtype of breast cancer, with special reference to its cellular localization, in particular, membrane mesothelin expression. Using tissue specimens from 482 patients with breast cancer, immunohistochemistry was used to study mesothelin expression and help classify its localization as membrane or cytoplasmic expression. Mesothelin expression was detected in 77 (16.0%) cases and was the highest in triple-negative breast cancer (31/75; 41.3%), followed by human epithelial growth factor receptor type 2 type (6/33, 18.2%) and luminal type (36/374; 9.6%). Among the 482 cases, membrane mesothelin expression was detected in 73 cases and was significantly associated with a negative hormone receptor status, higher Ki-67 labeling index, nuclear grade 3 and a lower relapse-free survival rate. Cytoplasmic mesothelin expression was not significantly associated with a lower relapse-free survival rate (P=0.058). In the 343 cases of luminal type, the membrane mesothelin expression-positive group had significantly worse prognosis than the membrane mesothelin-expression-negative group (P=0.042). There was no significant difference in the relapse-free survival rate according to the membrane mesothelin expression status in the triple-negative type and other types. It was suggested that membrane mesothelin expression in luminal type breast cancer is associated with a lower rate of relapse-free survival., (Copyright: © Suzuki et al.)

Purpose: 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging ( 18 F-FDG PET/CT) is an important diagnostic tool in breast cancer. The utility of maximum standardized uptake values (SUVmax) of primary tumors has been evaluated to predict sentinel node (SN) and non-SN metastasis in clinically node-negative (cN0) patients., Patients and Methods: 18 F-FDG PET/CT was performed on 414 cN0 patients. The following parameters were evaluated: SUVmax at 60 min (SUVmax1), SUVmax at 120 min (SUVmax2), percent change between SUVmax1 and SUVmax2 (ΔSUVmax%), SN metastasis foci maximum size (SN meta size), and ratio of metastatic SNs to total SNs or SN ratio (SNR). It was assessed whether these were risk factors for SN metastasis. The relationship between these parameters and the status of SN and/or non-SN metastasis was retrospectively explored to predict non-SN metastasis., Results: All SUV parameters significantly correlated with pathological T factor (pT), nuclear grade, lymphatic invasion (Ly), and Ki-67 labeling index. On multivariate analysis, pT and Ly were independent predictive factors for SN metastasis. In SN meta-positive cases, SN meta size, SNR, and ΔSUVmax% were predictors for non-SN metastasis on univariate analyses, and the former two were independent predictors on multivariate analysis. The combination of SUVmax2 and ΔSUVmax% was an independent predictor of non-SN metastasis (P = 0.0312) and was associated with prediction of non-SN metastasis negative status with high probability (92.3%)., Conclusions: In patients with cN0 breast cancer, SUV parameters of the primary tumor were correlated with pathological features. The combination of SUVmax2 and ΔSUVmax% may be useful for predicting non-SN metastasis.

Sebaceous gland cells (sebocytes) differentiate to intracellularly accumulate lipid droplets - a phenomenon similar to that found in adipocytes. In the present study, we examined whether the regulation of lipogenesis in sebocytes is the same as that in preadipocytes. When sebocytes and preadipocytes, prepared from auricle and subcutaneous adipose tissues from the inguinal region of hamsters, respectively, were treated with a common differentiation inducer, insulin, intracellular lipid-droplet formation and triacyglycerol (TG) production were dose- and time-dependently augmented in both. Insulin increased the production of perilipin, a differentiation marker in both sebocytes and adipocytes. Insulin-like growth factor 1 (IGF-1) augmented the intracellular level of TG in sebocytes and preadipocytes. In addition, the action of 1α,25-dihydroxyvitamin D 3 [1,25(OH 2 )D 3 ] on TG production was the opposite between sebocytes and preadipocytes. Furthermore, 5α-dihydrotestosterone (5α-DHT) augmented the TG level in sebocytes, whereas it did not alter TG production in preadipocytes. Moreover, insulin-augmented TG production in sebocytes was enhanced by IGF-1 and 5α-DHT, while diminished by 1,25(OH 2 )D 3 . In preadipocytes, the insulin-augmented production of TG was decreased by IGF-1, 1,25(OH 2 )D 3 , and 5α-DHT. These results suggest that sebocytic lipogenesis is partially similar to but substantially different from adipocyte lipogenesis due to the forementioned hormones and growth factors in the skin under physiological conditions., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Background: To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUV max ) at 60 min (SUV max 1) and SUV max at 120 min (SUV max 2) (ΔSUV max %) using dual time point 18 F-fluorodeoxyglucose emission tomography/computed tomography ( 18 F-FDG PET/CT) in breast cancer., Methods: Four hundred and sixty-four patients with primary breast cancer underwent 18 F-FDG PET/CT for preoperative staging. ΔSUV max % was defined as (SUV max 2 - SUV max 1) / SUV max 1 × 100. We explored the optimal cutoff value of SUV max parameters (SUV max 1 and ΔSUV max %) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUV max 1 and ΔSUV max % were analyzed by Cox's univariate and multivariate analyses., Results: The optimal cutoff values of SUV max 1 and ΔSUV max % were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUV max 1 groups (P = 0.0003) and also between high and low ΔSUV max % groups (P = 0.0151). In Cox multivariate analysis for RFS, SUV max 1 was an independent prognostic factor (P = 0.0267) but ΔSUV max % was not (P = 0.152). There was a weak correlation between SUV max 1 and ΔSUV max % (P < 0.0001, R 2  = 0.166). On combining SUV max 1 and ΔSUV max %, the subgroups of high SUV max 1 and high ΔSUV max % showed significantly worse prognosis than the other groups in terms of RFS (P = 0.0002)., Conclusion: Dual time point 18 F-FDG PET/CT evaluation can be a useful method for predicting relapse in patients with breast cancer. The combination of SUV max 1 and ΔSUV max % was able to identify subgroups with worse prognosis more accurately than SUV max 1 alone.

Exclusive cross sections and momentum distributions have been measured for quasifree one-neutron knockout reactions from a ^{54}Ca beam striking on a liquid hydrogen target at ∼200  MeV/u. A significantly larger cross section to the p&#95;{3/2} state compared to the f&#95;{5/2} state observed in the excitation of ^{53}Ca provides direct evidence for the nature of the N=34 shell closure. This finding corroborates the arising of a new shell closure in neutron-rich calcium isotopes. The distorted-wave impulse approximation reaction formalism with shell model calculations using the effective GXPF1Bs interaction and ab initio calculations concur our experimental findings. Obtained transverse and parallel momentum distributions demonstrate the sensitivity of quasifree one-neutron knockout in inverse kinematics on a thick liquid hydrogen target with the reaction vertex reconstructed to final state spin-parity assignments.

The present study reports a case of metachronous bilateral breast cancer associated with neurofibromatosis type 1 (NF1). A 67-year-old female, who had undergone a radical mastectomy of the left breast 34 years ago due to breast cancer, presented with a tumor of the right breast. The clinical stage of the original breast cancer was T2N0M0 stage IIA and adjuvant chemotherapy had not been not administered. With regard to the right-sided breast tumor, on physical examination, multiple neurofibromas and café-au-lait spots were found to be scattered over the skin. A 2-cm tumor was palpable. The preoperative histopathological diagnosis of the right-sided breast tumor was invasive ductal carcinoma, T2N0M0 stage IIA, with negative results for hormone receptors and human epidermal growth factor receptor 2. The patient underwent a modified radical mastectomy and axillary node dissection, and received adjuvant chemotherapy. The bilateral tumors were similar in histology and immunophenotype, each being histological grade 3, triple-negative and with a basal-like subtype. Based on a literature review of 90 breast cancers in 84 patients with NF1 (84 patients, 90 breasts), younger age onset, advanced clinical stage and hormone receptor negativity were characteristic features. Bilateral cancer occurred in 8.3% of patients and was characterized by ER negativity, earlier stage and younger age compared with patients with unilateral cancer.

The first γ-ray spectroscopy of ^{52}Ar, with the neutron number N=34, was measured using the ^{53}K(p,2p) one-proton removal reaction at ∼210  MeV/u at the RIBF facility. The 2&#95;{1}^{+} excitation energy is found at 1656(18) keV, the highest among the Ar isotopes with N>20. This result is the first experimental signature of the persistence of the N=34 subshell closure beyond ^{54}Ca, i.e., below the magic proton number Z=20. Shell-model calculations with phenomenological and chiral-effective-field-theory interactions both reproduce the measured 2&#95;{1}^{+} systematics of neutron-rich Ar isotopes, and support a N=34 subshell closure in ^{52}Ar.

We have earlier prepared a pancreatic cancer-associated mucin, whose altered carbohydrate structure was recognized by Vicia villosa (VVA), Bauhinia purpurea (BPA), and peanut (PNA) lectins and which was found preferentially in the sera of patients with pancreatic or gastric cancer. Cancer-associated structures of the sugar chain on serum antigen may reflect those occurring in malignant tissues. Accordingly, we investigated the tissue distribution of carbohydrate structures reactive to these lectins by using lectin histochemistry in pancreatic cancer, gastric cancer, and colonic cancer tissue specimens and in their normal counterparts. VVA showed a higher affinity for pancreatic cancer (77.5%), gastric cancer (89%), and colonic cancer (87%) cells than for the cells of their normal counterparts, whose affinity was 0%, 41.7%, and 36.4%, respectively. PNA showed a higher affinity for pancreatic (70%) and colonic cancer cells (86.5%). BPA failed to show significant binding differences between neoplastic and normal cells in any of the pancreatic, gastric, or colonic tissue specimens. It did, however, bind to intraductal contents in most of the pancreatic cancer tissues but bound to intraductal contents in only a few chronic pancreatitis and normal pancreatic tissues. VVA and PNA did not bind to intraductal contents in any of the normal, chronic pancreatitis, or pancreatic cancer tissues. These results imply that, among the lectins used so far, VVA has the highest affinity for neoplastic cells, and it may provide a supplement for use in the pathologic diagnosis of malignant diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Temocapril is a novel ACE inhibitor that is cleared via dual excretion routes in humans. Borderline or mildly hypertensive patients with normal renal function [group 1, creatinine clearance (CLCR) > 70 ml/min (4.2 L/h), n = 12], moderate renal impairment [group 2, CLCR 30 to 70 ml/min (1.8 to 4.2 L/h), n = 12] or severe renal impairment [group 3, CLCR < 30 ml/min (1.8 L/h), n = 12] received a single oral dose of either temocapril 1 mg (n = 6, each group) or enalapril 5mg (n = 6, each group). These 2 drugs gave similar values for the area under the plasma concentration-time curve (AUC) of the active diacids. The maximum plasma concentration of enalapril diacid was increased 2- and 6-fold in moderate and severe renal impairment, respectively, whereas that of temocapril diacid was not altered. The AUC of enalapril diacid increased 13-fold at CLCR values < 30 ml/min, but that of temocapril diacid increased only 2-fold. The duration of plasma ACE inhibition due to enalapril was greatly prolonged by the impairment of renal function, whereas that due to temocapril was affected very little. Urinary recovery of temocapril diacid was decreased markedly in patients with severe renal dysfunction, most probably because the diacid was excreted through the biliary route. On the other hand, urinary recovery of enalapril diacid remained fairly high even in patients with severe renal impairment, because of extremely high plasma diacid concentrations resulting from the lack of biliary excretion. These observations suggest that temocapril is beneficial in the treatment of hypertension in patients with severely impaired renal function.

We have previously described the purification and partial characterization of a new pancreatic cancer-associated antigen, a pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This study describes the clinical evaluation of various assay systems for this antigen which depend on measuring respective serum levels. Elevated levels of antigen were detected in the sera from both patients with malignant and non-malignant diseases. However, elevated serum levels of CA19-9 and Lewisa and Lewisb epitopes on moieties were restricted to pancreatic and biliary tract cancers, although adequate sensitivity was not attained. Coordinate evaluation of these three markers improved the sensitivity to some extent without loss of specificity for the diagnosis of pancreatic and biliary tract cancers, because of the heterogeneity of the coexpression of these epitopes. We developed additional assay systems with a combination of this antigen and two lectins (Bauhinia purpurea (BPA) and Vicia villosa (VVA)). Elevated levels of BPA- and VVA-reactive antigens were detected in 41% and 31%, respectively, of pancreatic cancer sera samples. Few patients with chronic pancreatitis had an elevated serum level of either antigen, and higher elevated levels of these markers were restricted to the sera of patients with malignancies. Our results suggest that this antigen is found in the sera of patients with various conditions and in the sera of normal subjects but that antigens bearing CA19-9 or Lewisa or Lewisb epitopes and an altered carbohydrate structure recognized by BPA and VVA lectins are preferentially present in the sera of patients with pancreatic and other malignancies.

We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)-serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat. Large pharmacological doses of cerulein induced acute pancreatitis in the rat. Ketanserin reduced the cerulein-induced increase in serum amylase concentration in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly improved cerulein-induced pancreatitis and was associated with a significant reduction of the increase in serum amylase concentration. In addition, a very specific serotonin S 2 antagonist, ritanserin which has no antihypertensive effect, also reduced the cerulein-induced increase in the serum amylase concentration. These results suggest that S 2 (5-HT 2) may play a role in pathophysiology of cerulein-induced pancreatitis in the rat.

To determine the effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure (IARF), that disorder was induced in male Wistar rats. After the animals were anesthetized with sodium pentobarbital (50 mg/kg, i.p.), the right kidney was removed and the left renal pedicle was clamped for 60 min. DBcAMP (5 mg/kg, i.p.) was given each 30 min before and after the renal pedicle clamping in half the dose each. Twenty-four hours after surgery, the levels of serum creatinine, BUN, serum potassium, and FENa% were significantly less elevated; and the total urine volume was significantly less decreased for 24 h in the group of IARF given DBcAMP than in the group of IARF alone. The elevation in Ca2+ content of the renal cortex was also significantly lower in the group of IARF given DBcAMP than in the group of IARF alone. These data indicate that DBcAMP can produce a beneficial effect on experimentally induced IARF. Since the intracellular accumulation of Ca2+ has been reported to be a potentially harmful factor in the development of IARF, it is suggested that the effect of DBcAMP on IARF can be in part due to an inhibition of the intracellular accumulation of Ca2+ in the kidney.

In our previous study, two antigens associated with pancreatic cancer were prepared from ascites of the patients by using a newly developed affinity chromatography technique; one expressed CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This report describes the other part of the antigens, which was scarcely found in normal sera. This antigen was a glycoprotein with a high molecular weight of 1,000,000 in its native state, estimated by size exclusion chromatography on Sephacryl S400. After sodium dodecyl sulfate polyacrylamide gel electrophoresis and blotting analysis, the antigenic activity was observed on the 200-Kd band, and monoclonal antibody of CA50 showed intense reactivity to it. By means of an enzyme immunoassay, CA19-9 determinant was also recognized on it to a lesser extent, although sialyl SSEA-1 and Dupan-2 determinants were scarcely observed. From these observations, the present antigen was considered to be a serum glycoprotein carrying type-1 polylactosamine determinant and differs from previously reported glycoprotein carrying CA19-9 in its insolubility in perchloric acid solution because of its lesser degree of glycosilation. Serum levels of the antigen measured by enzyme-linked immunosorbent assay demonstrated that highly positive rates were observed in 78% of pancreatic cancers, 82% of biliary tract cancers, and 96% of hepatocellular carcinomas.

Experimental tubulointerstitial nephritis (TIN) was induced in guinea pigs by immunization with homologous Tamm-Horsfall protein (THP). This disease was characterized by focal interstitial mononuclear cell infiltration around the distal nephron segments with degeneration of renal tubular cells. Although concomitant granular immunoglobulin deposition on the tubular basement membrane and a rise of serum anti-THP antibodies were recognized, they were related to the severity of the lesion. Lymphocytes from lymph nodes of animals with TIN showed blast transformation in the presence of THP in vitro. Following the transfer of lymphocytes and spleen cells from guinea pigs with THP-induced TIN to nonimmunized animals, the recipient animals developed TIN 7 days later. These observations suggest that TIN induced in guinea pigs by challenge with homologous THP may, at least in part, be related to a cell-mediated immune response.

In order to elucidate the role of oxygen-derived free radicals in acute pancreatitis, scavengers and an inhibitor of production of these free radicals were administered to rats with experimentally-induced acute pancreatitis. Acute reflux pancreatitis was produced by the occlusion of the common bile duct (OCD). Catalase and superoxide dismutase (SOD) were used as scavengers, and allopurinol was used as an inhibitor of production of free radicals. Six h after surgery, serum amylase, lipase, and thiobarbituric acid (TBA) reactant levels were elevated significantly, and histological changes in the pancreas, consisting of edema, inflammatory cell infiltration, and necrosis, partially around the intralobular and interlobular ducts, developed in the control rats receiving no agent. However, serum lipase and amylase levels in the rats given each agent were significantly lower (p less than 0.05) than in the controls. The histological changes in the pancreas were less marked in agent-treated rats than in untreated rats. These results suggest that oxygen-derived free radicals participate in the development of acute pancreatitis.