Beyond Recycling Antibodies: Crovalimab's Molecular Design Enables Four-Weekly Subcutaneous Injections for PNH Treatment.

The advent of recycling antibodies, leveraging pH-dependent antigen binding and optimized FcRn interaction, has advanced the field of antibody therapies, enabling extended durability and reduced dosages. Eculizumab (Soliris) demonstrated the efficacy of C5 inhibitors for paroxysmal nocturnal hemoglobinuria (PNH), while its derivative, ravulizumab (Ultomiris), recognized as a recycling antibody, extended the dosing intervals. However, limitations including intravenous administration and inefficacy in patients with the R885H single-nucleotide polymorphism (SNP) in C5 could necessitate alternative solutions.

Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease.

In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4 T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.

Efficient production of bispecific antibody by FAST-Ig and its application to NXT007 for the treatment of hemophilia A.

Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A.

Isolation and structural elucidation of novel fusicoccan dehydroxypericonicin A from Roussoella sp.

A potent antifungal fusicoccane dehydroxypericonicin A (1) was isolated from Roussoella sp. along with known allantofuranone (2). The relative structure of 1 was fully elucidated by NMR spectroscopic manner.

Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment.

The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding.

Leiomyosarcoma after Total Laparoscopic Hysterectomy with Power Morcellation.

Introduction: Power morcellation is an effective and minimally invasive technique used to remove specimen tissues or the uterus in total laparoscopic hysterectomy (TLH). However, it has the risk of intraperitoneal dissemination of tissue and can cause a parasitic myoma. We report a case of leiomyosarcoma that occurred 4 years after TLH with power morcellation for fibroids.

Liquid chromatography-mass spectrometry with triazole-bonded stationary phase for N-methyl-D-aspartate receptor-related amino acids: development and application in microdialysis studies.

We aimed to monitor changes in the levels of amino acid neurotransmitters or neuromodulators simultaneously at the synaptic clefts of experimental animals. We developed a method for the simultaneous determination of the levels of amino acids, such as D-Ser, Gly, and L-Glu, which were involved in neurotransmission via the N-methyl-D-aspartate (NMDA) receptor, and other protein-constituted amino acids in a rat brain microdialysis (MD) sample. We used a liquid chromatography-mass spectrometry (LC-MS)/MS device equipped with a triazole-bonded column.

Small-scale screening method for low-viscosity antibody solutions using small-angle X-ray scattering.

In this study, we investigated the concentration range in which self-association starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore, on the basis of the results, we developed a practical method of screening for low-viscosity antibody solutions by using small-angle X-ray scattering (SAXS) measurements utilizing small quantities of samples. With lower-viscosity mAb3, self-association was not detected in the range of 1-80mg/mL.

The Optimal Duration of PTH(1-34) Infusion Is One Hour per Day to Increase Bone Mass in Rats.

Parathyroid hormone (PTH) is a potential medicine for osteoporosis, and subcutaneous (s.c.) PTH treatment enhances bone mass; however, continuous infusion of PTH elicits bone resorption and induces bone loss.

Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

Introduction: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma.

Case Presentation: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause.

A novel therapeutic strategy for chylous ascites after gynecological cancer surgery: a continuous low-pressure drainage system.

Purpose: Postoperative chylous ascites is an unusual complication following retroperitoneal surgery. A search of the English literature showed only 44 cases of chylous ascites following gynecological cancer surgery. The treatment is primarily conservative, but surgical treatment is considered in resistant cases.

Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization.

For many antibodies, each antigen-binding site binds to only one antigen molecule during the antibody's lifetime in plasma. To increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.

The s-wave of the multifocal electroretinogram in cats.

Purpose: To characterize the s-wave of the multifocal electroretinogram (mfERG) in cats, and to determine the contribution of the inner retina to the s-wave by examining the effects of tetrodotoxin (TTX) and N-methyl D: -aspartate (NMDA) injected into the vitreous cavity.

Methods: mfERGs were recorded from 15 eyes of 15 male cats under general anesthesia. The stimulus consisted of 37 elements, and the luminance of the bright and the black elements were 200 and 4 cd/m2, respectively.

[A pilot study of TS-1+CDDP therapy for highly advanced stage IV gastric cancer].

We performed a pilot study of combination chemotherapy with TS-1 and cisplatin for highly advanced gastric cancer. From June 2002, 12 patients with multiple liver metastases, carcinomatous lymphangitis or peritoneal dissemination, were enrolled in the study. TS-1 was administered at a daily dose on day 1-21 and an intermediate-dose of cisplatin (60 mg/m2) was administered on day 8.

A case of small cell carcinoma of the common bile duct.

Small cell carcinoma occasionally occurs in the gastrointestinal tract, but rarely in the biliary tract. We report a case of small cell carcinoma which occurred in the common bile duct. A 66-year-old female complained of epigastralgia and weight loss.

Immunohistochemical metallothionein expression in hepatocellular carcinoma: relation to tumor progression and chemoresistance to platinum agents.

Background: Metallothionein (MT), which is known to detoxify heavy metal ions, is considered to serve as a mechanism of resistance to platinum complex compounds. In the present study, MT expression in hepatocellular carcinoma (HCC) was immunohistologically investigated to clarify its relationship to clinical background factors and responsiveness to anticancer drugs.

Methods: Specimens from 117 patients with HCC were immunohistologically studied, using a monoclonal anti-MT antibody.

High sustained virologic response rate after interferon monotherapy in Japanese hepatitis C patients with a low HCV RNA titer and/or HCV genotype 2. A prospective study.

Objective: Hepatitis C virus (HCV) RNA titer and HCV genotype are considered to be major determinants of the outcome of interferon monotherapy. To clarify whether interferon monotherapy is really effective in patients with the appropriate viral parameters, we prospectively examined these parameters and treated the patients with interferon monotherapy.

Methods: Sixty-four patients with an HCV RNA titer <100 kIU/ml and/or HCV genotype 2 were enrolled in the study.

Amplitude of the s-wave of multifocal electroretinograms can indicate local retinal sensitivity in glaucomatous eyes.

Purpose: To determine whether the amplitude of the s-wave on a multifocal electroretinogram (mfERG) is correlated with the degree of visual field depression in eyes with glaucoma.

Methods: Twenty patients (20 eyes) with glaucoma,ages 46 to 69 years, were studied. Twenty healthy volunteers (20 eyes) with normal intraocular pressure and with no eye diseases served as controls.

Immunohistochemical study of transforming growth factor-beta 1, matrix metalloproteinase-2,9, tissue inhibitors of metalloproteinase-1,2, and basement membrane components at pancreatic ducts in chronic pancreatitis.

Little is known about the pathogenesis of fibrosis in chronic pancreatitis. To reach a better understanding of this problem, we investigated the immunolocalizations of type IV collagen (Col-IV) and laminin around pancreatic ducts, and those of matrix metalloproteinase-2,9 (MMP-2,9), tissue inhibitors of metalloproteinase-1,2), and transforming growth factor-beta 1 (TGF beta 1) at the ductal epithelia in chronic pancreatitis. This study included 20 surgical specimens of fibrotic pancreas from patients with chronic pancreatitis and five normal samples from autopsy cases.

Antiatherogenic effects of the antioxidant BO-653 in three different animal models.

Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo.

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.