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In this randomized, observer-blinded, phase 2/3 study, S-268019-b (n = 101), a recombinant spike protein vaccine, was analyzed for noninferiority versus BNT162b2 (n = 103), when given as a booster ≥6 months after 2-dose BNT162b2 regimen in Japanese adults without prior SARS-CoV-2 infection. Interim results showed noninferiority of S-268019-b versus BNT162b2 in co-primary endpoints for neutralizing antibodies on day 29: geometric mean titer (GMT) (124.97 versus 109.70; adjusted-GMT ratio [95% CI], 1.14 [0.94-1.39]; noninferiority P-value,0.0001) and seroresponse rate (both 100%; noninferiority P-value, 0.0004). Both vaccines elicited anti-spike-protein immunoglobulin G antibodies, and produced T-cell response (n = 29/group) and neutralizing antibodies against Delta and Omicron pseudovirus and live virus variants (n = 24/group) in subgroups. Most participants reported low-grade reactogenicity on days 1-2, the most frequent being fatigue, fever, myalgia, and injection-site pain. No serious adverse events were reported. In conclusion, S-268019-b was safe and showed robust immunogenicity as a booster, supporting its use as COVID-19 booster vaccine.

BACKGROUND: Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy. OBJECTIVE: To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC. MATERIALS AND METHODS: This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks. RESULTS: The CTL induction rate in the S-588410 group was 93.3% (p

In early 2020, developing vaccines was an urgent need for preventing COVID-19 from a contingency perspective.S-268019-a is a recombinant protein-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising a modified recombinant spike protein antigen adjuvanted with agatolimod sodium, a Toll-like receptor-9 agonist. In the preclinical phase, it was administered intramuscularly twice at a 2-week interval in 7-week-old mice. Immunogenicity was assessed, and the mice were challenged intranasally with mouse-adapted SARS-CoV-2 at 2 and 8 weeks, respectively, after the second immunization. After confirming the preclinical effect, a Phase 1/2, randomized, parallel-group clinical study was conducted in healthy adults (aged 20-64 years). All participants received 2 intramuscular injections at various combinations of the antigen and the adjuvant (S-910823/agatolimod sodium, in μg: 12.5/250, 25/250, 50/250, 25/500, 50/500, 100/500, 10/500, 100/100, 200/1000) or placebo (saline) in an equivalent volume at a 3-week interval and were followed up until Day 50 in this interim analysis.In the preclinical studies, S-268019-a was safe and elicited robust immunoglobulin G (IgG) and neutralizing antibody responses in mice. When challenged with SARS-CoV-2, all S-268019-a-treated mice survived and maintained weight until 10 days, whereas all placebo- or adjuvant-treated (without antigen) mice died within 6 days. In the Phase 1/2 trial, although S-268019-a was well tolerated in adult participants, was safe up to Day 50, and elicited robust anti-spike protein IgG antibodies, it did not elicit sufficient neutralizing antibody levels.The S-268019-a vaccine was not sufficiently immunogenic in Japanese adults despite robust immunogenicity and efficacy in mice. Our results exemplify the innate challenges in translating preclinical data in animals to clinical trials, and highlight the need for continued research to overcome such barriers. (jRCT2051200092).

In this randomized, observer-blinded, phase 2/3 study, S-268019-b (n=101), a recombinant spike protein vaccine, was analyzed for noninferiority versus tozinameran (n=103), when given as a booster ≥6 months after 2-dose tozinameran regimen in Japanese adults without prior COVID-19 infection. Interim results showed noninferiority of S-268019-b versus tozinameran in co-primary endpoints for neutralizing antibodies on day 29: geometric mean titer (GMT) (124.97 versus 109.70; adjusted-GMT ratio [95% CI], 1.14 [0.94-1.39]; noninferiority P-value, P-value, 0.0004). Both vaccines elicited anti-spike-protein immunoglobulin G antibodies, and produced T-cell response (n=29/group) and neutralizing antibodies against Delta and Omicron pseudovirus and live virus variants (n=24/group) in subgroups. Most participants reported low-grade reactogenicity on days 1-2, the most frequent being fatigue, fever, myalgia, and injection-site pain. No serious adverse events were reported. In conclusion, S-268019-b was safe and showed robust immunogenicity as a booster, supporting its use as COVID-19 booster vaccine.JRCT IDjRCT2031210470HighlightsThird COVID-19 vaccine dose (booster) enhances immune responseInterim phase 2/3 data for booster ≥6 months after the 2nd dose in Japan are shownS-268019-b was noninferior to tozinameran in inducing neutralizing antibodiesSera boosted with either vaccines neutralized Delta and Omicron virus variantsS-268019-b was safe, and results support its use as a booster in vaccinated adults

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.

440 Background: S-588410 is a cancer peptide vaccine composed of 5 human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from 5 cancer-testis antigens: DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1; all of which are highly expressed in urothelial carcinoma. This study aimed to evaluate the effect of S-588410 maintenance therapy on peptide-specific cytotoxic T-lymphocyte (CTL) induction in patients with advanced or metastatic urothelial carcinoma after first-line platinum-based chemotherapy. Methods: An open-label, multicenter phase II trial was performed across 62 sites in Japan, the United Kingdom, France and Bulgaria (EudraCT 2013-005274-22). Eligible patients had completed ≥4 cycles of first-line platinum-based chemotherapy without disease progression. HLA-A*24:02-positive patients received S-588410 (1 mg of each of 5 peptides mixed with Montanide ISA 51 VG) subcutaneously weekly for 12 weeks, then every 2 weeks for up to 2 years. HLA-A*24:02-negative patients were enrolled in an observation group and did not receive study drug. The primary endpoint for the S-588410 group was the CTL induction rate at 12 weeks, defined as the proportion of patients who showed increased CTL activity for ≥1 peptide. Secondary endpoints included CTL induction rate after 1 year, antitumor effect defined by immune-related response criteria, progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 81 patients with platinum-sensitive advanced or metastatic urothelial carcinoma were enrolled (S-588410 group, n=45; observation group, n=36) between April 2014 and November 2017. Most patients were male and Asian with a mean age of 67 years. CTLs were induced in 42 (93.3%) patients who received S-588410 for 12 weeks (P

Background: Although the application of methotrexate (MTX) and the development of interventional radiology has made uterine preservation possible for cervical ectopic pregnancy in most cas...

Since some murine cells expressing human CD4 fail to internalize HIV-1, another block was thought to be located at the level of viral entry in addition to CD4. Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry. Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains. In contrast, the same cells were not infected with chimeric clones constructed by substitution of monocyte- or macrophage-tropic strain-derived env region or V3 region into T cell line-tropic HIV-1, indicating V3 loop of envelope protein is required for murine CXCR4mediated HIV-1 entry. We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.

Background: Few studies have examined the response of the fetus under stress, such as with maternal infection. Recent work has indicated that nitric oxide (NO) modulates corticotropin-releasing hormone (CRH) secretion by the hypothalamus, but details of the action of NO on the fetus remain unclear. Therefore, we investigated the expression of inducible nitric oxide synthase (iNOS) mRNA and the response pattern following lipopolysaccharide (LPS) loading using a rat model of fetal infection. Methods: Fetuses were delivered by cesarean section on day 20 of gestation and immediately placed in a chamber maintained at 37°C and 100% relative humidity. The LPS group (n=12) was given 400 μg of LPS/100 g body weight, and the physiologic saline group (n=12) was given physiologic saline. Fetuses were then incubated for a further 3 hours. Fetuses were decapitated, the trunk blood was collected immediately after cesarean section or after 3 hours of incubation, and the fetal brains were fixed in formaldehyde and cryopreserved. Coronal cryosections of the brains were prepared, and a 35S-uridine triphosphate-labeled antisense RNA probe for iNOS was then prepared. In situ hybridization was performed, and iNOS expression was evaluated semiquantitatively on the basis of optical density. In both groups, plasma corticosterone levels were determined with radioimmunoassay. Results: Expression of iNOS mRNA was not noted in the physiologic saline group (3 hours postpartum). In the LPS group, iNOS mRNA expression was observed in the subfornical organ, but not in the paraventricular nucleus. Plasma corticosterone levels were significantly elevated in the LPS group. Conclusions: In 20-day-old rat fetuses, the hypothalamic-pituitary-adrenal axis was already mobilized in response to LPS-induced stress. These results suggest that iNOS is not involved in the acute response of the hypothalamic-pituitary-adrenal axis to LPS challenge in 20-day-old rat fetuses.

Aim: The aim of this study is to report the feasibility of a newly developed intra‑ abdominal fan retractor system for use in gynecologic laparoscopic surgery. Methods: Five hundred women undergoing gasless laparoscopic surgery using the abdominal wall lifting device were included in the study. The intraoperative and postoperative courses and complications were examined. Results: The intra‑abdominal retractor system provided adequate exposure in all cases except for one patient with morbid obesity. Neither the presence of the intra‑abdominal retractor blades nor the mechanical arm interfered with the placement of instruments during surgery. No complications related to the use of gasless laparoscopy were encountered in this study period. Conclusion: The new intra‑abdominal fan retractor system is feasible in gynecologic laparoscopic surgery. (J Nippon Med Sch 2005; 72: 213―216)

The purpose of this study is to develop an x-ray detector system for multislice CTs with 0.5 slice thickness and 0.5- second revolution, and to evaluate clinical advantages. The detector adopts a newly developed ceramic scintillator having a high light-output efficiency as well as a high light-transmittance. By employing high precision machining technology to fabricate the detector, it is not necessary to mask the gap from incident x-ray in the longitudinal direction between neighboring cells. The scintillator properties and the geometry of the detector provide a high x-ray-to-light conversion efficiency, and realize a good low-contrast detectability for CTs. The detector structure allows 0.5 mm slice thickness. The afterglow intensity of the scintaillator is less than 0.1 percent at 3 ms, facilitating 1800 views per second for 0.5-second revolution. This detector improves the performance of CT scanners.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Real-time 3D CT is a high-speed cone-beam CT (4D-CT) with good low-contrast detectability. In a single rotation, a voxel data set with higher spatial resolution over a wide z- axis range can be obtained. Using continuous rotation, temporarily continuous voxel data sets and 3D dynamic images can be acquired. We have developed a large area 2D detector for 4D-CT, and we have got the first 4D-CT test images.

We present here a case of massive subchorionic hematoma complicated by intrauterine growth retardation and oligohydramnios diagnosed at 22 weeks' gestation. The patient was managed with the following medications: (1) tocolysis with ritodrine infusion, (2) 10%maltose infusion therapy (1500mL/day), (3) antibiotic infusion (cefotaxim sodium, 2 g/dayx7) and (4) kampo therapy with Sairei-to until delivery. At 33 weeks and 0 days' gestation, a female baby weighing 1,342 g was delivered without complication by caesarean section. During surgery, an escape of about 500~600 g of dark brown blood with no clots was noted from the subchorionic space of the placenta. Examination of the placenta showed a large fibrosis with well-defined margins on the fetal surface.

Search for proteases responsible for an altered processing of APP which generates intermediates containing β A4 peptide is preceding to understand the formation of β amyloid deposits characteristic of Alzheimer's disease, since many studies reveal that APP is ordinarily processed so as not to generate β amyloid. Here, we have examined the action of thrombin, a serine protease in the blood clotting, in APP processing. Thrombin cleaved the mouse recombinant APP 695 in vitro , resulting in the accumulation of 28 kDa fragment. The immunoblot analysis showed that the fragment is derived from the carboxy-terminal side of the recombinant APP 695 . Further, amino acid sequencing exhibited that the fragment is generated by the cleavage at Arg 510 - lle 511 and therefore includes entire β A4 peptide. We consider that the 28 kDa fragment is a possible intermediate for β A4 peptide. Thus thrombin may be involved in the altered processing of APP.

Ninety-five cases (154 tendons) with the digital flexor tendon laceration were treated in our clinic from 1979 to 1984. Among these cases, there were 4 cases (4 tendons) of rupture after repairing of the tendon. All cases were adult. All tendons (one was in zone I, two in zone II, and one in zone III), were lacerated sharply and were repaired by the Tsuge's method (using a looped nylon suture) within 2 days after injury.Two tendons were ruptured during the period of the early motion therapy by the Kleinert's method, one during immobilization, and one after immobilization. Active flexion of the finger during the period of immobilization (2 cases), accidental powerful grasping (1 case), and passive extension of the finger (1 case), were the proximate causes of rupture.Loss of cooperation for the therapy on the side of the patient, and unadjustable cast were also to be considered as a cause, especially in the cases of early motion therapy.

Open surgery for reconstruction of anterior cruciate ligament (ACL) such as Insall method required large incision and long period of post-operative immobilization. Arthroscopic surgery has many advantages in comparison with open surgery such as small incision, minimmum scar formation, preventing muscle damage and so on.Our technique for ACL reconstruction under X-ray control is reported. Initially, arthroscopic meniscectomy and/or meniscal suture are done. Then 3cm skin incisions are made on lateral femoral condyle and anterior of the tibia. After exposure of the cortex, 1.5mm Kirshner wires are inserted under X-ray image.The isometric points for ACL reconstruction are just posterior and superior region of the femoral attachment and anterior medial site of the tibial attachment.Following these Kirshner wires, stepped bone tunnels are made using 5mm and 8mm reamers. Then the Leeds-Keio's artificial ligament is passed carefully and fixed with bone plugs and staples.If necessary, extra-articular reconstruction is done. After a week of immobilization, the device of continuous passive motion is applied and three weeks later, partial weight bearing is permitted using the Lenox-Hill brace. Although the follow-up period is short as long as 4 months, range of motion and stability are better with our present method than our previous open method.

Sixteen cases of arthroscopic ACL reconstruction were reviewed, Nine cases were followed for more than 6 months postoperatively.Loss of range of knee motion was none or minimal except for one case. Instability was found in 8 of 9 cases, which was so high in frequency that authors reviewed postoperative roentgenograms of those cases and discussed on ligament placements.

The purpose of this paper is to describe comparison of the human and rabbits spinal nerve roots. Rabbits have been selected in several spine studies as they are easier to obtain and keep. However, an appreciation of difference in structurel is essential for the correct extrapolation of results in the human stuation.Six rabbits weighing 3.0-3.5kg. were used. Microangiography was done, and vascularity of their spinal cord and nerve roots were examined macroscopically, histologically and radiographycally.The main results found in this study were as follows:1) Segmental artery supplies 3 main spinal branches, i. e. radicular artery, spinal dorsal rami artery and spinal ventral rami artery. There are one anterior spinal artery and two posterior spinal arteries in spinal cord. Ventral radicular artery anasomoses to anterior spinal artery and dorsal radicular artery anastomoses to posterior spinal artery. These are essentially same in the human and rabbits.2) The difference is the number of artery in spinal nerve roots. Rabbits have few arteries in their nerve roots. This suggests that nutrition of spinal nerve roots in rabbits depends on cerebrospinal fluid more than blood supply compared with the human.

We determine the size of the dural sac of the lumbar spine by measuring the sectional area. The area of lumbar canal stenosis is below 90mm2. According to this indicator, eighteen cases of lumbar canal stenosis (LCS) and eleven cases of spondylosis (OAS) are investigated. The average ages are sixty-one in LCS and seventy-four in OAS. Other morphological investigations by CT revealed no difference between LCS and OAS.We conclude that the symptoms of LCS mainly depends on the dynamic factors and spinal instability.

The patients with lumbar disorders were studied by colour thermography of the lower extremities. In the lumbar disc herniation 15 (71.4%) of the 21 patients had the cold area at the affected extremities. Thirteen (86.7%) of the cold area positive group had muscle atrophy at the affected extremities or buttocks. And the positive group had longer duration from onset and were older.Significant difference in the extent of pain was not found between the two groups.In the other disorders, some patients had positive findings and the others had normal thermogram. This study showed, in general, the tendency that the patients without neurological deficit had normal thermogram.

Electrophysiological evaluation of the cauda equina or nerve roots has been recently applied in diagnosis of lumbar disorders.The monopolar catheter electrode was inserted into the epidural space at the levels of L3-4, L4-5, and L5-S. The recordings were made on stimulating the tibial and the peroneal nerves at the bilateral popliteal fossae.The cauda equina action potentials (CEAP) were recorded in 42 cases with various kinds of lumbar disorders, including lumbar disc herniation, lumbar canal stenosis, chronic low back pain and the control was taken in case with cervical or thoracic spine without lumbar problem.The nerve action potentials (NRAP) was recorded intraoperatively at the nerve roots by monopolar catheter electode in 10 cases with either lumbar disc hernation or lumbar canal stenosis.In eight cases of eleven of disc herniation. the voltage decreased more than 30% at the affected level. In six of seven roots in disc herniation, NRAPs demonstrated polyphasic.The results suggests that CEAP and NRAP are useful for diagnosis of the affected nerve roots, and that further research will be necessary to obtain more accurate evaluation more.