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Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care., (© 2023. The Author(s).)

A 19-year-old woman underwent prenatal ultrasonography, which confirmed the presence of an isolated cystic mass in the upper abdominal cavity of a fetus. A female infant weighing 3085 g was delivered at 36 weeks' gestation. Ultrasonography and computed tomography examination revealed a clear unilocular cyst and occupying the right side of the abdomen. The infant's respiratory status was unstable, and she fed poorly, owing to compression by the hepatic cyst. We performed ultrasound-guided aspiration of a hepatic cyst at 15 days old, but it rapidly re-grew. Therefore, we performed laparoscopic findings and fenestration of the hepatic cyst via an umbilical arc incision and the cyst wall was excised at 43 days old. The histopathological diagnosis was mesothelial cell-derived hepatic cyst. Three years after the operation, no recurrence has been observed. Hepatic cyst fenestration by umbilical incision can be performed safely in infants and it is a cosmetically superior method., (© Crown copyright 2022.)

Introduction: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests., Methods: Serum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS-CoV-2 S-RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851)., Results: The NAb (SARS-CoV-2 S-RBD IgG) titer peaked on day 90 after vaccination (30,808.0 μg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 μg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT-sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA)., Conclusions: Neutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT-sVNT is rapid and user-friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background/aim: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment., Patients and Methods: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history., Results: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients., Conclusion: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of our study was to evaluate the efficacy and safety of docetaxel plus ramucirumab with primary prophylactic pegylated (PEG)-granulocyte-colony stimulating factor (G-CSF) for pretreated non-small cell lung cancer (NSCLC)., Results: Sixty-one pretreated NSCLC patients underwent docetaxel plus ramucirumab. Primary prophylactic PEG-G-CSF was performed in 52 (85%) patients (prophylactic group). No febrile neutropenia (FN) (0%) was confirmed in 52 prophylactic group patients, whereas FN was observed in 3 (33%) of 9 non-prophylactic group patients. Among prophylactic group, median lines of prior therapy was 2 (range, 1-9). Median cycles of docetaxel plus ramucirumab was 3 (range, 1-25) (9 and 3 cases moved to ramucirumab and docetaxel monotherapies, respectively). Response rate and disease control rate were 30.8% and 73.1%, respectively. Median progression-free survival was 4.5 (95% confidence interval [CI], 3.0-6.6) months. Median overall survival was 11.4 (95% CI, 8.0-13.9) months. Six (11.5%) patients had grade 3/4 neutropenia. Observed grade 3 (incidence ≥10%) adverse event (AE) was oral mucositis (13.5%). There were no grade 4/5 non-hematological AEs., Conclusions: Our study demonstrated the efficacy and safety of docetaxel plus ramucirumab with PEG-G-CSF in clinical practice. Primary prophylactic PEG-G-CSF could markedly reduce incidence of FN., Methods: We retrospectively reviewed medical records of pretreated NSCLC cases who had received docetaxel plus ramucirumab in our departments., Competing Interests: CONFLICTS OF INTEREST Akito Hata received lecture fee from Chugai, Astra Zeneca, Boeringer Ingelheim, and Eli Lilly. Daijiro Harada has received lecture fees from Ono, Bristol-Myers Squibb, Yakult Honsha, Kyowa Hakko Kirin, AstraZeneca, Nippon Boehringer Ingelheim and Eli Lilly Japan. Toshiyuki Kozuki has received honoraria from Chugai, AstraZeneca, Eli Lilly Japan, Boehringer–Ingelheim, Ono, Bristol-Myers Squibb, Taiho, MSD, Pfizer and Kyowa Hakko Kirin, and research funding from Chugai, AstraZeneca, MSD, and Eli Lilly Japan. Naoyuki Nogami has received honoraria from Astellas, AstraZeneca, Ono, Taiho, Chugai, Eli Lilly, Boehringer Ingelheim and Pfizer. Nobuyuki Katakami received grants from Astra Zeneca, Eisai, Ono, Kyowa Kirin, Shionogi, Daiichi-Sankyo, Taiho, Chugai, Eli Lilly, Boeringer Ingelheim, and Merck Serono, and payment for lectures from Dainippon Sumitomo, Chugai, Boeringer Ingelheim, Astra Zeneca, Eli Lilly, Taiho, Janssen, Novartis, Pfizer, Ono, and Daiichi-Sankyo. The other authors declare no conflicts of interest.

By combination of differential scanning calorimetry (DSC) and fluorescence spectroscopy of 6-propionyl-2-(dimethylamino)naphthalene (Prodan), we elucidated the thermotropic phase behavior of hydrogenated soybean phosphatidylcholine (HSPC)-cholesterol binary liposome membrane which has similar lipid composition to Doxil®, the widely used liposome product in treatment of various tumors. We found that the characteristic points at cholesterol mole fraction (Xch)=0.023 and 0.077 correspond to the hexagonal lattice, in which cholesterol molecules are considered to be regularly distributed in all regions of HSPC lipid bilayer with 1 : 42 and 1 : 12 units, respectively, as static averaged structures. Apparent endothermic peak disappeared at Xch=0.40 in the DSC thermograms, indicating the existence of single liquid ordered phase at Xch>0.40. In addition, fluorescence measurements of Prodan and its lauroyl derivative in poly(ethylene glycol) (PEG)-modified liposomes indicated that PEG modification has a negligible effect on the phase behavior of HSPC-cholesterol binary liposome membrane. These results may provide useful information in developing novel liposome products whose stability and encapsulated drug release are controlled.

Purpose: We retrospectively investigated the radiographic findings in patients with atlanto-axial subluxation (AAS) due to rheumatoid arthritis, and clarified the effect of reduction of the atlanto-axial angle (AAA) on the cranio-cervical and subaxial angles., Methods: Forty-one patients, consisting of 29 females and 12 males, with AAS treated by surgery were reviewed. The average patient age at surgery was 61.0 years, and the average follow-up period was 4.0 years. We investigated the AAA at the neutral position in lateral cervical radiographs before surgery and at the last follow-up. In addition, we also investigated the clivo-axial angle (CAA) and the subaxial angle (SAA) at the neutral position before and after surgery., Results: Due to pre-operative AAA, the patients were classified into three groups as follows: (1) the kyphotic group (K group), (2) the neutral group (N group), and (3) the lordotic group (L group). The average AAA values at the neutral position in the K group before and after surgery were 6.0° and 18.1°, respectively (P < 0.001). In the N group 19.7° and 21.7°, respectively (P < 0.05), and in the L group 31.6° and 27.0°, respectively (P < 0.01). However, no significant differences in the average CAA values were found before and after surgery in all groups. Furthermore, no significant differences in the SAA values were seen before and after surgery in all groups., Conclusions: A proper reduction of the AAA did not affect the cranial angles or induce kyphotic malalignment of the subaxial region after atlanto-axial arthrodesis. However, if we can obtain a significant and large reduction of AAA in patients showing kyphosis before surgery, then this reduction will be offset in the atlanto-occipital joint and we should therefore pay special attention to its morphology after surgery.

Objective: Atlanto-axial subluxation (AAS) is caused by multiple conditions; however, idiopathic AAS patients without RA, upper-cervical spine anomalies or any other disorder are rarely encountered. This study retrospectively investigated the radiographic findings in idiopathic AAS patients, and clarified the differences between those AAS patients and those due to RA., Methods: Fifty-three patients with AAS treated by transarticular screw fixation were reviewed. The subjects included 8 idiopathic patients (ID group) and 45 RA patients (RA group). The study investigated the atlanto-dental interval (ADI) value and space available for spinal cord (SAC) at the neutral and maximal flexion position., Results: The average ADI value at the neutral position in the ID and RA groups before surgery was 7.8 and 7.2 mm, respectively (p > 0.74). The average ADI value at the flexion position in the two groups was 10.3 and 11.7 mm, respectively (p > 0.06). The average SAC value at the neutral position in the two groups was 12.0 and 17.1 mm, respectively (p < 0.01). Finally, the average SAC value at the flexion position in the two groups was 10.7 and 13.5 mm, respectively (p < 0.01)., Conclusions: The SAC value at both the neutral and flexion positions in idiopathic AAS patients was significantly smaller than those values in RA-AAS patients. This may be because the narrowing of the SAC in the idiopathic group easily induces cervical myelopathy. Furthermore, surgery was often recommended to RA patients, because of the neck pain induced by RA-related inflammation of the atlanto-axial joint, regardless of any underlying myelopathy.

This report presents a case of non-traumatic posterior atlanto-occipital dislocation. A 36-year-old female was referred with a history of numbness of the extremities, vertigo and neck pain for 1 year. The patient had no history of trauma. The axial rotation of range of motion of the cervical spine was severely restricted. A lateral cervical radiograph in the neutral position demonstrated a posterior atlanto-occipital dislocation. A coronal view on a computed tomography (CT) reconstruction image showed a loss of angle of the bilateral atlanto-occipital joint, and a sagittal reconstruction view of CT images also demonstrated flatness of atlanto-occipital joint. Instrumented occipito-cervical fusion was performed after reduction. A lateral cervical radiograph in the neutral position 1 year after surgery showed the reduction of atlanto-occipital joint, moreover, it was maintained even in an extended position. The patient had neurologic improvement after surgery. Flatness of the bilateral atlanto-occipital joint may have induced this instability. Occipital-cervical fusion was chosen in the present case since the patient showed restricted axial rotation of the neck before surgery. The surgery improved the preoperative symptoms including the function of cervical spine evaluated by JOACMEQ.

This report presents a case of atlanto-axial subluxation after treatment of pyogenic spondylitis of the atlanto-occipital joint. A 60-year-old male had 1-month history of neck pain with fever. Magnetic resonance imaging showed inflammation around the odontoid process. Intravenous antibiotic therapy was administrated immediately. After 6 weeks, CRP had returned almost to normal. After 4 months, laboratory data was still normal, but the patient experienced increasing neck pain. Lateral cervical radiography in the neutral position showed instability between C1 and C2. Computed tomography showed a bony union of the atlanto-occipital joint and severe destruction of the atlanto-axial joint on the left side. Transarticular screw fixation for the atlanto-axial joint was performed. A lateral cervical radiograph in the neutral position after surgery showed a solid bony union. Neck pain improved following surgery. We speculate that spondylitis of the atlanto-occipital joint induced a loosening of the transverse ligament and articulation of the atlanto-axial joint. A bony fusion of the atlanto-occipital joint after antibiotic treatment resolved the pyogenic inflammation concentrated stress to the damaged atlanto-axial joint, resulting in further damage. The atlanto-axial instability was finally managed by the insertion of a transarticular screw.

Simple one-pot methods for preparation of 2-oxazolines have been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Treatment of a mixture of carboxylic acids and 2-haloethylammonium salts with DMT-MM in methanol followed by refluxing in the presence of KOH gives oxazolines.

Objective: To evaluate the clinical significance of measuring the prostate-specific antigen-alpha(1)-antichymotrypsin (PSA-ACT) for differentiating prostate cancer from benign prostate hypertrophy (BPH) and for the staging of prostate cancer., Methods: Before treatment, total PSA (tPSA) and PSA-ACT were measured in 120 patients with prostate cancer and in 150 patients with BPH using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, the tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated., Results: tPSA, PSAD, PSA-ACT and ACTD levels in patients with prostate cancer paralleled the clinical stage and were significantly higher than those in patients with BPH. Furthermore, these four values were significantly higher in patients with pathologically extraprostatic disease than those with organ-confined disease. Receiver operating characteristics analysis among patients with PSA values of 4.1-10 ng/ml revealed that the areas under the curve for tPSA and ACTD were similar to those for PSA-ACT and ACTD, respectively and that no significant differences in the differentiation between prostate cancer and BPH were observed among these parameters., Conclusions: Measurement of PSA-ACT provides useful information for the clinical staging of prostate cancer and differential diagnosis between prostate cancer and BPH; however, compared with tPSA, PSA-ACT may not be significantly superior in the diagnosis and staging of prostate cancer.

Heat shock proteins 70 (hsp70) derived from tissues and cells can elicit cytotoxic T lymphocyte (CTL) responses against peptides bound to hsp70. However, peptides can markedly differ in their affinity for hsp, and this potentially limits the repertoire of peptides available to induce CTL by the hsp immunization. Hybrid peptides consisting of a high-affinity ligand for the peptide-binding site of hsp70 joined to T cell epitopes by a glycine-serine-glycine linker were constructed. Immunization with hybrid peptides complexed to mouse hsp70 effectively primed specific CTL responses in mice and were more potent than T cell peptide epitopes alone with hsp70. In vivo immunization with hsp70 and hybrid peptides led to rejection of tumors expressing antigen with greater efficacy than immunization with peptide epitope plus hsp70. Induction of CTL responses occurred independently of CD4(+) T cells, suggesting that immunization directly primed antigen-presenting cells to elicit CD8(+) cytotoxic T cell responses without T cell help. Both peptide/hsp70 complexes and mouse hsp70 alone were able to induce cultures of mouse bone marrow-derived dendritic cells (DC) to release cytokines, including DC from endotoxin-resistant C57BL/10Sc mice. Thus, hsp70/hybrid peptide complexes can activate DC for cytokine release, providing a potential adjuvant effect that could bypass T cell help.

Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) gamma-/- mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective tumor immunity in models of passive and active immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization with mAb against gp75 or active immunization against gp75 prevented the development of lung metastases. This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact in gamma-/- mice because IgG titers against gp75 develop normally in gamma-/- mice immunized with gp75. However, uncoupling of the Fc gamma R effector pathway from antibody recognition of tumor antigens resulted in a loss of protection against tumor challenge. These data demonstrate an unexpected and critical role for FcRs in mediating tumor cytotoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.

The melanosome is an organelle specialized for melanin synthesis that is derived from the endocytic pathway. Several melanosome membrane proteins have been identified, forming a family of proteins known as tyrosinase-related proteins. Two members of this family, tyrosinase and gp75, are well-characterized melanocyte differentiation antigens. Our previous studies have shown that gp75, the mouse brown locus protein, is sorted to melanosomes along the endocytic pathway, directed by a hexapeptide sorting signal located in the cytoplasmic tail. In this study, we report the unexpected finding that a portion of gp75 is secreted. Substantial levels of secretory gp75 were detected in melanocytic cells. Cell surface expression of gp75 was also detected, representing 2% of cellular gp75. Characterization of secretory gp75 cells showed that it is: (i) a truncated form that lacks the transmembrane region, the cytoplasmic tail where the endosomal sorting signal is located, and a small portion of the lumenal domain; (ii) more extensively glycosylated than endocytic/melanosomal gp75, containing trans-Golgi processed sugar residues; and (iii) generated post-translationally in an acid sensitive compartment after processing in the trans-Golgi, and secreted rapidly after generation. Thus, these endocytic/melanosomal membrane proteins can be processed to abundant secretory forms, probably in an endocytic compartment through a potentially novel secretory pathway.

DNA immunization has been shown to elicit both antibody and CTL responses against antigens expressed by infectious organisms. Because CTL responses have been implicated in rejection of cancer, we investigated whether DNA immunization by particle bombardment using a gene gun could induce CTL responses that were capable of rejecting tumors in mice. DNA immunization by particle bombardment using genes encoding beta-galactosidase and ovalbumin primed mice to generate CTLs in two genetic backgrounds (DBA/2 and C57BL/6 strains, respectively). DNA immunization was more potent in inducing CTLs than immunization with an optimized regimen of ovalbumin peptide plus immune adjuvant. Immunity induced by DNA immunization protected mice against s.c. challenge with tumors expressing the beta-galactosidase antigen. Tumors were rejected even when DNA immunization was started 3 or 7 days after tumor challenge as tumors were becoming established. Tumor rejection required CD8(+) T cells, confirming a role for CTLs in vivo. These studies show that DNA immunization by particle bombardment can efficiently induce CTL responses that are capable of rejecting even established tumors.

Recognition of self is emerging as a theme for the immune recognition of human cancer. One question is whether the immune system can actively respond to normal tissue autoantigens expressed by cancer cells. A second but related question is whether immune recognition of tissue autoantigens can actually induce tumor rejection. To address these issues, a mouse model was developed to investigate immune responses to a melanocyte differentiation antigen, tyrosinase-related protein 1 (or gp75), which is the product of the brown locus. In mice, immunization with purified syngeneic gp75 or syngeneic cells expressing gp75 failed to elicit antibody or cytotoxic T-cell responses to gp75, even when different immune adjuvants and cytokines were included. However, immunization with altered sources of gp75 antigen, in the form of either syngeneic gp75 expressed in insect cells or human gp75, elicited autoantibodies to gp75. Immunized mice rejected metastatic melanomas and developed patchy depigmentation in their coats. These studies support a model of tolerance maintained to a melanocyte differentiation antigen where tolerance can be broken by presenting sources of altered antigen (e.g., homologous xenogeneic protein or protein expressed in insect cells). Immune responses induced with these sources of altered antigen reacted with various processed forms of native, syngeneic protein and could induce both tumor rejection and autoimmunity.

Differentiation antigens on cancer cells are recognized by the immune system. A prototype set of these autoantigens in melanoma cells are the melanosomal glycoproteins, expressed in both melanomas and normal melanocytes. These are intracellular proteins that can be recognized by both antibodies and T lymphocytes. While one can understand how T cells can respond to intracellular proteins, based on cellular requirements for antigen processing and presentation, it is more difficult to understand how antibody responses to melanosomal proteins could lead to tumor rejection. We demonstrate that gp75 is expressed on the cell surface as well as intracellularly in human and mouse melanomas. The surface expression of gp75 can be augmented by IFN-gamma and during tumor growth in vivo. Surface expression of gp75 on mouse melanoma cells correlates with the ability of a monoclonal antibody (mAb) against gp75 to reject melanomas in syngeneic mice. Antibody-mediated rejection seems to require the Fc portion of the antibody, suggesting a role for Fc receptor-positive effector cells such as natural killer cells. However, although NK1.1(+) cells have been implicated in antibody-induced rejection in vivo, cell surface expression of gp75(+) on melanoma does not lead to susceptibility to antibody-dependent cellular cytotoxicity in vitro. The mAb to gp75 induced tumor rejection in mice carrying both scid and bg/bg traits, showing that neither thymus-dependent T cells nor natural killer cytotoxic activity was required in vivo. Long-term treatment of mice with mAb led to patchy depigmentation in the coat. In summary, an intracellular organellar protein can be expressed at the cell surface and provide an antigenic target for antibody therapy and autoimmunity.