Biomedical subjects

Yasuhiro Kojima

Publications and source records attributed to Yasuhiro Kojima.

12 recordsLinked to original sources

PubMed2026

scSurv: a deep generative model for single-cell survival analysis.

MOTIVATION: Single-cell omics analysis has unveiled the heterogeneity of various cell types within tumors. However, no methodology currently reveals how this heterogeneity influences cancer patient survival at single-cell resolution. Here, we introduce scSurv, combining a Cox proportional hazards model with a deep generative model of single-cell transcriptome, to estimate individual cellular contributions to clinical outcomes. RESULTS: The accuracy of scSurv was validated using both simulated and real datasets. This method identifies cells associated with favorable or adverse prognoses and extracts genes correlated with their contribution levels. In melanoma, scSurv reproduces known prognostic macrophage classifications and facilitates hazard mapping through spatial transcriptomics in renal cell carcinoma. We also identified genes consistently associated with prognosis across multiple cancers and demonstrated the applicability of this method to infectious diseases. scSurv is a novel framework for quantifying the heterogeneity of individual cellular effects on clinical outcomes. AVAILABILITY: The implementation of scSurv is available on GitHub (https://github.com/3254c/scSurv) and Zenodo (https://doi.org/10.5281/zenodo.17793054).

Humans↗

PubMed2006

Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy.

STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.

Animals↗

PubMed2006

[Case presenting both clinical features of progressive supranuclear palsy and amyotrophic lateral sclerosis].

A 70-year-old Japanese male farmer, born and living in Kyoto prefecture, developed gait disturbance, with tendency to fall at age 68, and muscle atrophy and weakness of the right shoulder and arm a year and half later. All symptoms have been progressive ever since. The patient manifested marked dementia, parkinsonism associated with limitation of ocular movements in all directions with slow saccade, loss of startle reflex, asymmetric muscle atrophy and weakness in shoulder girdles and upper limbs with hyperreflexia, and positive Babinski reflexes. The needle electromyogram showed evidence of active denervation. Brain MRI showed cortical atrophy in the frontal and temporal lobes, and midbrain tegmentum. Cerebral blood flow image on SPECT suggested hypoperfusion in the frontal, temporal and parietal cortices and basal ganglia bilaterally. Thus, it is most likely that the present case suffered from clinical features of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy at the same time. Relation to the ALS/Parkinsonism/Dementia complex reported from Kii peninsula and Guam was discussed.

Aged↗

PubMed2004

Full stereochemical assignment and synthesis of the potent anthelmintic pyrrolobenzoxazine natural product CJ-12662.

The structure of the unusual anthelmintic pyrrolobenzoxazine terpenoid natural product CJ-12662 was established by X-ray crystallography and partial synthesis from 2-chloronitrobenzene. An unusual Meisenheimer-type rearrangement was used to provide the core pyrrolobenzoxazine heterocycle, and coupling of a tetracyclic pyrrolobenzoxazine lactone with the terpene alcohol was used to complete the synthesis of CJ-12662.

Anthelmintics↗

PubMed2003

Microsatellite instability and loss of heterozygosity in the nondysplastic colonic epithelium of ulcerative colitis.

Background. A major longterm risk for patients with ulcerative colitis (UC) is the development of colorectal dysplasia and cancer. Microsatellite instability (MI) has now been reported not only in colitic cancers but also in dysplasias, and even in nondysplastic inflamed mucosa. With the conventional microdissection technique, however, contamination by nonepithelial cells cannot be prevented and this could produce less reliable results than other methods. Therefore, we examined the condition of MI and loss of heterozygosity (LOH) of UC epithelium using a crypt isolation technique. Methods. One hundred and twenty-nine biopsy samples from 21 patients with UC were investigated for histology and microsatellite status, using nine microsatellite markers. A total of 1031 polymenase chain reaction (PCR) products were evaluated. Results. We found that no microsatellite markers displayed instability, but LOH at the 3p locus was detected in the nondysplastic epithelium of one patient with longstanding UC. Conclusions. Our study strongly suggests that MI does not contribute to the progression of the colitis-dysplasia sequence.

Adolescent↗

PubMed2002

Comparison of ACTH secretion in Cushing's adenoma and clinically silent corticotroph adenoma by cell immunoblot assay.

Immunocytochemical staining and cell immunoblot assay (CIBA) were performed in adenoma tissue from five patients with Cushing's disease and three patients with clinically silent corticotroph adenomas. All five patients with Cushing's disease showed hypersecretion of ACTH (130, 190, 331, 120, and 130 pg/ml), high levels of serum cortisol (26.6-44.0 micrograms/dl), and symptoms of Cushing's disease. All three patients with silent corticotroph adenoma showed hypersecretion of ACTH (110, 140, and 160 pg/ml) and normal levels of serum cortisol (11.4-26.8 micrograms/dl). The size of the pituitary adenoma on magnetic resonance imaging was smaller in patients with Cushing's disease (mean 8.2 mm) than in patients with silent corticotroph adenoma (mean 26.7 mm) (p = 0.001). Transsphenoidal surgery was performed to totally resect the adenoma tissue. Immunostaining for ACTH showed diffuse ACTH-immunopositive cells in all eight adenomas. CIBA technique showed a good correlation between percentage of ACTH-immunopositive cells and level of plasma ACTH in patients with Cushing's disease but no correlation between the two parameters in patients with silent corticotroph adenoma. The percentage of ACTH-secreting cells and the amount of hormone secreted by a single cell are too low in silent corticotroph adenomas to cause an increase in plasma ACTH level corresponding to the large tumor size.

Adenoma↗

PubMed2002

CJ-21,164, a new D-glucose-6-phosphate phosphohydrolase inhibitor produced by a fungus Chloridium sp.

A new D-glucose-6-phosphate phosphohydrolase (G6Pase) inhibitor, CJ-21,164 (1) was isolated from the fermentation broth of the fungus Chloridium sp. CL48903. The structure was elucidated to be a novel tetramer of the salicylic acid derivatives by spectroscopic analyses. Compound I inhibited G6Pase in rat liver microsomes with an IC50 of 1.6 microM. Glucose output from hepatocytes isolated from rat liver was inhibited when I was present in the incubation medium, consistent with the role of I as a G6Pase inhibitor.

Animals↗

PubMed2002

A novel antibiotic CJ-17,572 from a fungus, Pezicula sp.

A new antibiotic, CJ-17,572 (I) was isolated from the fermentation broth of a fungus Pezicula sp. CL11877. The structure of I was determined to be a new equisetin derivative by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant Staphylococcus aureus and Enterococcusfaecalis with IC50s of 10 and 20 microg/ml, respectively.

Acetylation↗

PubMed2002

CJ-21,058, a new SecA inhibitor isolated from a fungus.

A new equisetin derivative, CJ-21,058 (I) was isolated from the fermentation broth of an unidentified fungus CL47745. It shows antibacterial activity against Gram-positive multi-drug resistant bacteria by inhibiting ATP-dependent translocation of precursor proteins across a bacterial cell membrane.

Anti-Bacterial Agents↗

PubMed2002

CJ-15,696 and its analogs, new furopyridine antibiotics from the fungus Cladobotryum varium: fermentation, isolation, structural elucidation, biotransformation and antibacterial activities.

CJ-15,696 and 7 novel furopyridine antibiotics were isolated from the fungus Cladobotryum varium CL12284. Their structures were determined by X-ray crystallography and spectral analysis. Three biotransformed analogs were also prepared from CJ-15,696. CJ-15,696 showed moderate activity against various Gram-positive bacteria including some drug resistant strains such as methicillin resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗

PubMed2002

CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces serratus ATCC15502.

A novel kappa opioid receptor binding inhibitor CJ-15,208 (I) was isolated from the fermentation broth of a fungus, Ctenomyces serratus ATCC15502. The structure of I was determined to be a cyclic tetrapeptide consisting of one tryptophan, one D-proline, and two L-phenylalanine. Compound I was a selective binding inhibitor for the kappa opioid receptor: 47 nM (IC50) for kappa, 260 nM for mu, and 2,600 nM for delta. In the electrically-stimulated twitch response assay of rabbit vas deferens I recovered the suppression by a kappa agonist asimadoline with an ED50 of 1.3 microM, indicating that it is a kappa antagonist.

Animals↗

PubMed2002

Thielavins as glucose-6-phosphatase (G6Pase) inhibitors: producing strain, fermentation, isolation, structural elucidation and biological activities.

High-throughput screening of microbial extracts using rat hepatic microsomal glucose-6-phosphatase (G6Pase) led us to find thielavin B as a G6Pase inhibitor with inhibition of glucose output from glucagon-stimulated hepatocytes. Further searching for more potent analogs identified 11 new thielavins F-P in addition to the known thielavins A and B from a fungus Chaetomium carinthiacum ATCC 46463. Thielavin G showed the strongest activity as a G6Pase inhibitor (IC50=0.33 microM), while the IC50 of thielavin B was 5.5 microM. According to the structure-activity relationship, including authentic thielavins C, D and 3 partial hydrolysates from thielavins A and B, 3 benzoic acid-units and carboxylic acid functions are essential for G6Pase inhibition.

Animals↗