Identification of semen from criminal materials by means of paper chromatography--a forensic-medical study

In the present experiments attempts were made to identify semen from various specimens such as the semen itself, spots of semen on clothes, putrefied semen or semen contaminated with blood, menstrual blood, vaginal fluid, according to the techniques of LEVONEN. As the result it has been clarified that in every instance it is possible to isolate and detect the spots of choline by spraying Dragehdorff's reagent.</p

A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer

Profound and durable responses to a single dose of pembrolizumab in lung cancer are rare. We encountered a non-small cell lung cancer patient showing a deep and durable response with a single dose of pembrolizumab. A 79-year-old man reported bloody sputum for several weeks and visited a general physician. A chest x-ray revealed a tumor shadow in the right middle lung field at that time, and the patient was referred to our hospital. He was diagnosed with adenocarcinoma of the lung by transbronchial biopsy. The expression of programmed death ligand 1 in tumor cells was 100% by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first-line therapy. Cancer cells had significantly shrunk at the end of the first cycle. The patient had grade-3 immune-related hepatitis at the end of the first cycle. Pembrolizumab treatment was stopped and prednisolone (80 mg/body) was initiated. Subsequently, liver function normalized, and prednisolone was tapered and discontinued. Since then, no tumor recurrence has been detected for 1.5 years without treatment. There have been few reports of profound and durable responses to a single dose of pembrolizumab in lung cancer. The results indicate that a single dose of pembrolizumab alone may be sufficient to cause durable response and serious immune-related adverse events in some cases

Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case: A 65-year-old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD-L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3-positive T cells and CD138-positive plasma cells. Second-line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion: Pembrolizumab may be used as a treatment option for pulmonary LCNEC

Dramatic response to immunochemotherapy followed by salvage surgery in an elderly lung cancer patient

Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment of lung cancer. Here, we encountered a case of inoperable locally advanced squamous cell carcinoma of the lung that became operable with pembrolizumab-based immunochemotherapy and achieved a pathological complete response. An 82-year-old man suspected of having lung cancer was referred to our hospital. The patient was clinically diagnosed with left upper lobe squamous cell carcinoma cT2aN3M0 c-stage IIIC. Immunostaining revealed the expression of programmed death-ligand 1 in 60% of tumor cells. The cancer cells disappeared after two cycles of chemotherapy with carboplatin and nanoparticle albumin-bound paclitaxel plus pembrolizumab. As the abnormal accumulation of 18F-fluorodeoxyglucose (FDG) on FDG-positron emission tomography/computed tomography before chemotherapy almost disappeared after pembrolizumab-based immunochemotherapy, left upper lobectomy and lymph node dissection were performed. No cancer cells were pathologically detected from the resected tissue. Therefore, ICIs combined with chemotherapy may enable inoperable advanced lung cancer patients to undergo surgery and achieve a complete response

Quantitative Study of Neurons with Intracytoplasmic Pigments in Dorsal Root Ganglia Atomic Bomb and Aging

Three females in their fifties and five males in their seventies, all of whom had been exposed to the Nagasaki atomic bomb explosion in 1945, were investigated concerning the aging of neurons of the dorsal root ganglia. Through this study dealing with the frequency of neurons with intracytoplasmic pigments, lipofuscin, neuromelanin, eosinophilic granules and neurons free of pigment, no significant difference in four kinds of neurons between the exposed persons and the nonexposed persons was detected in 50-59 year-old females. Contrariwise in the 70-79 year-old males, the frequency, as average but not as individual persons, was significantly higher in lipofuscin, lower in neuromelanin, and unchanged in eosinophilic granules and no pigment

Structure of MSPL–inhibitor complex

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19

Self-Contained Induction of Neurons from Human Embryonic Stem Cells

BACKGROUND: Neurons and glial cells can be efficiently induced from mouse embryonic stem (ES) cells in a conditioned medium collected from rat primary-cultured astrocytes (P-ACM). However, the use of rodent primary cells for clinical applications may be hampered by limited supply and risk of contamination with xeno-proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an alternative method for unimpeded production of human neurons under xeno-free conditions. Initially, neural stem cells in sphere-like clusters were induced from human ES (hES) cells after being cultured in P-ACM under free-floating conditions. The resultant neural stem cells could circumferentially proliferate under subsequent adhesive culture, and selectively differentiate into neurons or astrocytes by changing the medium to P-ACM or G5, respectively. These hES cell-derived neurons and astrocytes could procure functions similar to those of primary cells. Interestingly, a conditioned medium obtained from the hES cell-derived astrocytes (ES-ACM) could successfully be used to substitute P-ACM for induction of neurons. Neurons made by this method could survive in mice brain after xeno-transplantation. CONCLUSION/SIGNIFICANCE: By inducing astrocytes from hES cells in a chemically defined medium, we could produce human neurons without the use of P-ACM. This self-serving method provides an unlimited source of human neural cells and may facilitate clinical applications of hES cells for neurological diseases

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

Molecular Identification of t(w5): Vps52 Promotes Pluripotential Cell Differentiation Through Cell-Cell Interactions

After implantation, pluripotent epiblasts are converted to embryonic ectoderm through cell-cell interactions that significantly change the transcriptional and epigenetic networks. An entree to understanding this vital developmental transition is the t(w5) mutation of the mouse t complex. This mutation produces highly specific defects in the embryonic ectoderm before gastrulation, leading to death of the embryonic ectoderm. Using a positional cloning approach, we have now identified the mutated gene, completing a decades-long search. The gene, vacuolar protein sorting 52 (Vps52), is a mouse homolog of yeast VPS52 that is involved in the retrograde trafficking of endosomes. Our data suggest that Vps52 acts in extraembryonic tissues to support the growth and differentiation of embryonic ectoderm via cell-cell interactions. It is also required in the formation of embryonic structures at a later stage of development, revealing hitherto unknown functions of Vps52 in the development of a multicellular organism.NSFCellular and Molecular Biolog