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At least 55 records · Page 3Linked to original sources
PubMed1990

Lymphokine mRNA profile and functional analysis of a human CD4+ clone with unique antitumor specificity isolated from renal cell carcinoma ascitic fluid.

We here describe the isolation, characterization, profile of lymphokine expression and T-cell-receptor gene rearrangement pattern of 444P.3, a CD3+ CD4+ CD8- 4B4+ interleukin-2 (IL-2)-dependent clone derived from the malignant ascites of a patient with renal cell cancer. The 444P.3 clone exhibited unique antitumor specificity between days 45 and 84 in culture and then lost its lytic, but not its proliferative, capacity. To our knowledge this is the first description of a specific antitumor reaction in a patient with renal cell cancer against autologous tumor. IL-2-expanded 444P.3 cells, tested on day 104 in culture, expressed mRNA for tumor necrosis factor (TNF), IL-2 and tumor growth factor beta (TGF-beta) but not for IL-1, lymphotoxin or granulocyte/macrophage-colony stimulating factor (GM-CSF). The parental noncloned population expressed mRNA for TNF, lymphotoxin, GM-CSF and TGF-beta but not for IL-1 beta or IL-2. Analysis of established human T cell clones should include profiles of lymphokine secretion in addition to growth and proliferation patterns, antitumor activity and surface phenotype. Such characterization of clones may provide a better understanding of the immunoregulatory role and functional potential of various T cell subsets involved in human antitumor reactivity.

Ascites↗
PubMed2026

Genome-resolved analysis of colonization factor repertoires reveals ecological stratification in cervid gut microbiomes.

INTRODUCTION: Colonization factors (CFs) are important microbial traits associated with persistence and host adaptation in the gut, yet their large-scale organization in cervid gut microbiomes remains unclear. METHODS: A total of 3,311 non-redundant high-quality metagenome-assembled genomes (MAGs), derived from 688 cervid gut metagenomic samples across 15 publicly available projects and one in-house dataset, were analyzed. CF-associated genes were identified by comparison against the GHA CF database, and CF repertoires were characterized at genome, host-species, and gastrointestinal-segment levels. RESULTS: A total of 138,729 CF-associated genes spanning 71 CF families were identified. MAGs from Cervinae contained richer CF repertoires than those from Caprinae, and CF47 (Peptidase_C69), CF24_29 (QueH), and CF18 (Glycos_transf_2) were among the most prevalent families. CF repertoires were strongly structured by taxonomy, showed a moderate association with bacterial phylogenetic distance, and formed two recurrent genome-level configurations with distinct KEGG functional profiles. Integration of sample metadata further revealed differentiation of CF repertoires across host species and gastrointestinal segments, representing the major ecological dimensions examined in this study. Segment-associated CF variation was accompanied by redistribution of broader functional profiles, including enrichment of carbohydrate and lipid metabolism in the jejunum, membrane transport in the ileum, xenobiotics biodegradation in the cecum, and environmental adaptation in the rumen. DISCUSSION: These findings provide a genome-resolved view of CF repertoire organization in cervid gut microbiomes and demonstrate that colonization-associated functions are structured across microbial lineages and ecological contexts. This study highlights the importance of considering microbial taxonomy and host-associated environments when interpreting the distribution of CF repertoires in mammalian gut ecosystems.

Cervidae↗
PubMed1988

Hepatitis D virus infection in children with acute or chronic hepatitis B virus infection in Taiwan.

To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.

Acute Disease↗
PubMed1992

Comparison of two catheter withdrawal speeds during simultaneous urethral pressure profilometry in anesthetized bitches.

Maximal urethral closure pressure, functional profile length, and number of respiratory peaks on the resting urethral pressure profile, expressed as a percentage of those occurring on the bladder pressure recording, were compared at catheter withdrawal speeds of 1 and 3 mm/s in 30 anesthetized bitches. Significant (P less than 0.001) differences were found in maximal urethral closure pressure and percentage of transmission of respiratory peaks between the 2 speeds. Significant difference was not detected in functional profile length.

Animals↗
PubMed2025

Cross-species phenotypic profiling uncovers functional determinants of bacterial cold shock adaptation.

Temperature shifts impose broad physiological stress, requiring precise and dynamic regulatory programs to restore cellular homeostasis. While the heat shock response is well characterized, the mechanisms underlying cold shock response (CSR) remain less understood. To identify genes critical for cold adaptation, we applied transposon sequencing (Tn-seq) to monitor mutant fitness across the full course of CSR and sustained low-temperature growth in two mesophilic bacteria, Escherichia coli and Bacillus subtilis. In B. subtilis, phenotypic profiling revealed a temporally structured program: membrane fluidity and cell wall remodeling were most critical in the early stage of CSR, whereas post-transcriptional regulation became essential during late-stage recovery to reprogram gene expression and restore growth. Cross-species comparison uncovered both conserved and species-specific mechanisms, with RNA metabolism and ribosome/translation regulators playing broad roles. Specifically, we identified a conserved synergy between two ribosomal RNA methyltransferases, RsmA and RsmH, in promoting cold adaptation. In B. subtilis, mutants lacking these enzymes exhibited significant delay in translation recovery following cold-induced global inhibition. Together, these findings provide a comparative, systems-level view of bacterial cold adaptation and establish a framework for exploring stress responses in pathogens and extremophiles.

Cell envelope↗
PubMed1990

Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome.

TCR-gamma delta-bearing T cells have been reported to be increased in several immunodeficient patients. However, their functional role and phenotypic characterization have not yet been well documented. In this study we examined the surface phenotypes and functional properties of TCR-gamma delta+ cells from several patients with primary immunodeficiency syndrome. It was demonstrated that TCR-gamma delta+ cells detected by TCR-delta 1 mAb were increased in some of the patients, particularly in patients with Wiskott-Aldrich syndrome and severe combined immune deficiency. The TCR-gamma delta+ cells showed such a unique profile that more than 60% of the cells expressed delta-TCS1, which is normally present in a lesser amount, and that most of the cells lacked CD5 T lineage marker. TCR-gamma delta+ cells from the patients with primary immunodeficiency syndrome served as NK cells as observed in normal individuals, while displaying weak LAK and allogeneic cell-specific killer activities. The TCR-gamma delta+ cells were classified into several subpopulations according to their antigenic phenotype, then their NK activity of normal individuals and patients, lymphokine-activated killer and allo-specific killer activities of normal individuals were compared among the subpopulations. Delta-TCS1+ cells mediated almost the same killer activities as total TCR-gamma delta+ cells, whereas CD8+ TCR-gamma delta+ cells displayed stronger cytotoxic activities in both normal subjects and the patients with primary immunodeficiency syndrome.

Antibodies, Monoclonal↗
PubMed1991

Use of fine-wire electrodes for electromyographic evaluation of the external urethral sphincter during urethral pressure profilometry in male cats.

Evaluation of urethral pressure profilometry (UPP) with simultaneous fine-wire electromyography of the external urethral sphincter (EUS) was conducted in 11 healthy adult male cats sedated with xylazine and ketamine. A 3.5-F urethral catheter with a closed end and two 1-mm side-ports was infused with sterile 0.9% NaCl solution at a rate of 2 to 3 ml/min. A fine-wire electromyographic (EMG) electrode was placed percutaneously into or near the external urethral sphincter prior to the onset of the UPP. The maximal urethral pressure achieved and functional profile length were recorded from UPP. Setting both catheter withdrawal rate and paper speed at 5 mm/s enabled the measurement of actual urethral length directly from UPP. Sphincter EMG activity was rated as slight (+), moderate (+ +), or intense (+ + +). All recordings were replicated once during each trial for 8 cats and trials were replicated 5 to 7 days later in 4 cats. Before catheterization, EMG activity of the external urethral sphincter was rated slight (+), whereas intense (+ + +) activity accompanied insertion. The activity evoked by movement of the catheter subsided, but intense EMG activity of the external urethral sphincter was recorded from onset to completion of catheter withdrawal in all cats in both trials. The mean maximal urethral pressure was 93.1 +/- 13.29 cm H2O. The mean function urethral length was 8.1 +/- 0.93 cm. Maximal urethral pressure or function profile length did not differ significantly between recordings within trials or between trials. Simultaneous recording of EMG activity and UPP of the external urethral sphincter was shown to be a simple, noninvasive technique for assessing neuromuscular and anatomic urethral function.

Animals↗
PubMed1989

[Effects of prophylactic intraportal chemotherapy on liver function, blood profile and survival in patients with colo-rectal cancer].

Postoperative intraportal anti-cancer chemotherapy was used for 51 patients with curatively resected colorectal cancer who were selected in the randomized controlled study to evaluate its inhibitory effect on liver metastasis from colo-rectal cancer. In cases of intraportal chemotherapy, 30 mg of Mitomycin-C (in 3 doses) and 5 mg/kg (B.W.)/day (1985-1986) or 3 mg/kg/day (1987-1988) of 5-FU was injected through the catheter inserted into the portal vein during postoperative 14 days. In cases of the control group (58 patients), the same doses of the drugs were injected into the peripheral vein during the same term. Six patients with recurrences were observed in the intraportal chemotherapy group, and 3 of them had liver metastases. In the control group, more liver metastases were observed (5 of 7 recurrences were liver metastases). Intraportally injected 5 mg/kg/day of 5-FU slightly disturbed the liver function. The averages of the serum GOT, GPT and gamma-GTP level of these cases were higher than those of the control cases. Three mg/kg/day of intraportally injected 5-FU had no influence on the liver function. There were no differences in the incidence of leukocytopenia or thrombocytopenia between the two groups.

Aged↗
PubMed2026

Dietary Polyphenol Acteoside-Related Molecular Signatures in Clear Cell Renal Cell Carcinoma: Multi-Omics Profiling and Functional Validation of IMPDH1.

Clear cell renal cell carcinoma (ccRCC) is characterized by substantial metabolic and molecular heterogeneity, but the disease-relevant programs associated with acteoside, a dietary polyphenol, remain poorly understood. We integrated predicted acteoside targets with bulk, single-cell, and spatial transcriptomic data from ccRCC and combined molecular subtyping with cross-cohort machine-learning analysis. Acteoside-related signatures were preferentially enriched in malignant compartments and increased with tumor grade and stage. Consensus clustering identified two molecular subtypes with distinct biological and clinical features. C1 was associated with immune activation, metabolic activity, and more favorable survival, whereas C2 showed greater genomic instability, reduced renal epithelial differentiation, and poorer outcomes. We further benchmarked multiple machine-learning strategies and established a 10-gene prognostic model that retained predictive performance across independent cohorts, with IMPDH1 emerging as the strongest risk-associated feature. Functional experiments confirmed the biological relevance of IMPDH1: its knockdown suppressed ccRCC cell proliferation, DNA synthesis, colony formation, and migration, whereas overexpression produced the opposite effects. Together, these findings indicate that acteoside-related molecular signatures capture clinically relevant heterogeneity in ccRCC and provide a framework for linking dietary-polyphenol-related molecular space with tumor biology. The identification and functional validation of IMPDH1 further highlight its potential importance in ccRCC progression.

IMPDH1↗
PubMed1991

Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones.

Functional subsets of human T cells were delineated by analyzing patterns of lymphokines produced by clones from individuals with leprosy and by T cell clones of known function. CD4 clones from individuals with strong cell-mediated immunity produced predominantly interferon-gamma, whereas those clones that enhanced antibody formation produced interleukin-4. CD8 cytotoxic T cells secreted interferon-gamma. Interleukin-4 was produced by CD8 T suppressor clones from immunologically unresponsive individuals with leprosy and was found to be necessary for suppression in vitro. Both the classic reciprocal relation between antibody formation and cell-mediated immunity and resistance or susceptibility to certain infections may be explained by T cell subsets differing in patterns of lymphokine production.

Antibody Formation↗
PubMed1992

Phenotypic profile and functional characteristics of human gamma and delta T cells during acute toxoplasmosis.

Gamma and delta (gamma delta) T-cell receptor lymphocytes are increased during acute toxoplasmosis. These cells are BB3+ CD45RO+ CD8-. Purified gamma delta T cells failed to proliferate in response to Toxoplasma gondii antigen (stimulation index, 1.4 +/- 0.6) but were responsive to phytohemagglutinin stimulation (stimulation index, 20.8 +/- 1.9). Natural-killer-like cytotoxicity was strongly acquired only after in vitro culture of purified gamma delta T cells with recombinant interleukin 2 (40% +/- 7% specific lysis). Our data show that gamma delta T-cell receptor T cells with a peculiar phenotype are increased during human acute T. gondii infection.

Acute Disease↗
PubMedDate not supplied

Size, CD4 and CD8 marker profiles and functions of lymphocyte subpopulations in mucosal-associated lymph nodes.

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was lower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18). Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these nodes are activated and thus regulate regional immune responses via different pathways.

Animals↗
PubMed2026

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p&#x202f;<&#x202f;0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans↗