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At least 19 recordsLinked to original sources
PubMed1976

Antigenic relationships among five reovirus-like (RVL) agents by complement fixation (CF) and development of new substitute CF antigens for the human RVL agent of infantile gastroenteritis.

The human reovirus-like (HRVL) agent, Nebraska calf diarrhea virus (NCDV), epizootic diarrhea of infant mice (EDIM) virus, simian agent (SA)-11, and the "O" (offal) agent were found to be similar, if not identical, in reciprocal complement fixation (CF) tests employing hyperimmune animal sera. In addition, in CF tests with paired sera from 35 diarrhea patients who shed the HRVL agent, 74% developed serologic evidence of infection with the HRVL antigen, 43% with NCDV, 51% with EDIM virus, 57% with SA-11, and 71% with the "O" agent. Thus, in addition to the NCDV, which had previously been described as a suitable substitute CF antigen for the HRVL agent, the SA-11, "O", and EDIM viruses may also be utilized as substitute antigens for the HRVL agent. However, the "O" agent appears to be the most efficient of the four substitute CF antigens and thus should be used preferentially when the HRVL agent is not available. The "O" agent was about as efficient as the HRVL agent and significantly more efficient than the NCDV for detecting seroresponses. The greatest efficiency for detecting infection with the HRVL agent resulted when sera were tested with both the HRVL and "O" agents as 31 (89%) of the patients developed serologic evidence of infection with one or both antigens. The finding of additional substitute CF antigens for the HRVL agent may have implications in the immunoprophylaxis against human disease.

Animals↗
PubMed1979

Augmentation of the in vitro humoral immune response by pharmacologic agents. II: comparison of the effects of antiproliferative agents with DBcAMP.

We have compared the stimulatory activity of DBcAMP with various antiproliferative agents on the induction of the humoral immune response. When they are present only during an early stage of immune induction, DBcAMP, colcemid, cytosine-arabinoside, hydroxy urea, and high specific activity 3H-thymidine can all enhance the primary 19s antibody response to SRBC. In contrast, each of these agents inhibits the PFC response, when they are incubated with the cells during late stages of induction of humoral immunity. Because all of these agents can inhibit proliferation of cultured cells, the results suggested that DBcAMP and other agents that elevate cAMP could augment humoral immunity via their effects on cellular proliferation. However, we also found that although each agent could modulate induction of the immune response to SRBC, only DBcAMP produced a dose- and time-dependent augmentation of the response to DLF. We conclude that although antiproliferative effects of drugs may contribute to augmentation of some humoral antibody responses, this effect alone is insufficient to account for the mechanism by which agents that elevate intracellular levels of cAMP produce enhancement of humoral immunity.

Animals↗
PubMed1978

Effect of two cancer chemotherapeutic agents on the antibacterial activity of three antimicrobial agents.

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside.

Amikacin↗
PubMed1979

Infectious bursal agent vaccination of chicks from infectious bursal agent-vaccinated dams.

Chicks from infectious bursal agent-vaccinated broiler breeders were vaccinated with a commercial infectious bursal agent vaccine at intervals after hatching. Bursas from some of these chicks were examined for infectious bursal agent-specific fluorescence four days after vaccination and bursas from others were examined for histological lesions of infectious bursal disease 21 days after vaccination. Serological studies were conducted to determine if active immunity to infectious bursal agent followed vaccination. Chicks failed to develop immunity if their levels of maternally-derived serum neutralizing antibody were in excess of approximately log(2) 7 at the time of vaccination. When antibody titres fell below this level, vaccination usually resulted in infectious bursal agent virus replication in the bursa and consequential bursal damage but was followed by development of active immunity.

Animals↗
PubMed1978

Double-blind crossover comparison between a beta-adrenergic agent and a new anticholinergic agent by metered dose inhaler.

The recently developed anticholinergic agent Oxitropium bromide (OTB) by metered dose inhaler is compared in a double-blind crossover study with the beta-adrenergic agent Fenoterol (FEN). Total airway resistance and forced expiratory volume served as evaluation criteria for the bronchodilating effect. The maximum effect is reached more quickly with FEN, but the effect of OTB lasts longer. On the whole the results show that the intensity of action of the anticholinergic agent coincides to a large extent with that of the beta-adrenergic agent.

Adult↗
PubMed1978

[Inhibition and psychotropic agents. Therapeutic disinhibitory agents].

The concept of disinhibitory agent is heterogeneous. If the disinhibitory property refers to inhibition in its clinical meaning, all psychotropic drugs can answer the denomination of disinhibitory agent when they are prescribed in some pathological entities. Traditionally this denomination refers to a few major tranquillizers, the antipsychotic action of which is linked to the improvement of the affective indifference and of the decrease of the psychomotor activity. However the pharmacokinetic data reveal that some potent sedative neuroleptics can become disinhibitors at high doses and some disinhibitory agents can become sedative substances at higher doses.

Antidepressive Agents↗
PubMed1979

Augmentation of the in vitro humoral immune response by pharmacologic agents. I: An explanation for the differential enhancement of humoral immunity via agents that elevate cAMP.

Agents that elevate intracellular concentrations of cAMP in cultured spleen cells can augment the in vitro 19s humoral immune response to SRBC. DBcAMP and 8BrcAMP were more effective than MIX, CT, PGE1, or ISO in producing the enhanced PFC response, when they were present only during an early stage of immune induction. The thesis is presented that the differential ability of these agents to augment humoral immunity results from their relative ability to maintain elevated concentrations of intracellular cAMP. Studies on the cellular mechanism by which cAMP elevation produces immune enhancement reveal that DBcAMP effects are on a T-cell-deficient population of murine spleen cells (predominantly B cells and macrophages). In addition, we showed that DBcAMP cannot replace the need for helper T cells in the induction of the PFC response to SRBC. Taken collectively, these results suggest that cAMP may be an important immunoregulatory signal, and that a variety of pharmacologic agents that modulate the induction of the humoral immune response may operate via this as a final common biochemical pathway.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture.

A previous paper (Kimberlin & Walker, 1977) described an experimental model of scrapie in hamsters in which the incubation period decreased progressively over the first 4 passages before becoming stable at the 5th and subsequent passes. Studies have been made of some of the agent strains present in brains taken from the 2nd, 3rd, 4th and 6th hamster passes. The results indicate the presence of at least two strains of agent at the 3rd passage level. One of these (431K) is highly pathogenic for mice and the other (263K) has an extremely low pathogenicity for mice. However only one of these strains (263K) is present in hamster brain after the 6th serial passage. It is suggested that the 'adaptation' of scrapie to hamsters may involve the selection, from a mixture, of a single strain which is highly pathogenic for hamsters. The possibility of modification of the properties of agent strains on passage discussed.

Animals↗
PubMed1976

Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery.

In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented.

Adrenergic alpha-Agonists↗
PubMed2026

Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI↗
PubMed2026

ELISA (Embedding-Linked Interactive Single-cell Agent): an interpretable hybrid generative Artificial Intelligence agent for expression-grounded discovery in single-cell genomics.

Translating single-cell RNA sequencing (scRNA-seq) data into mechanistic biological hypotheses remains a critical bottleneck, as agentic AI systems lack direct access to transcriptomic representations while expression foundation models remain opaque to natural language. Here, we introduce ELISA (Embedding-Linked Interactive Single-cell Agent), an interpretable framework that unifies single-cell generative pretrained transformer expression embeddings with biomedical bidirectional encoder representations from transformers-based semantic retrieval and large-language model (LLM)-mediated interpretation for interactive single-cell discovery. An automatic query classifier routes inputs to gene marker scoring, semantic matching, or reciprocal rank fusion pipelines depending on whether the query is a gene signature, natural language concept, or mixture of both. Integrated analytical modules perform pathway activity scoring across 60+ gene sets, ligand-receptor interaction prediction using 280+ curated pairs, condition-aware comparative analysis, and cell-type proportion estimation, all operating directly on embedded data without access to the original count matrix. Benchmarked across six diverse scRNA-seq datasets spanning inflammatory lung disease, pediatric and adult cancers, organoid models, healthy tissue, and neurodevelopment, ELISA significantly outperforms CellWhisperer, a classical lexical retriever (BM25), and a random baseline in cell type retrieval (combined permutation test, $p < 2\times 10^{-5}$ for each), with particularly large gains on gene-signature queries (Cohen's $d = 5.98$ for mean reciprocal rank). ELISA replicates published biological findings (mean composite score 0.88), and generates candidate hypotheses through grounded LLM reasoning, bridging the gap between transcriptomic data exploration and biological discovery.

Generative Artificial Intelligence↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. I. Tentative hypothesis for the induction of antigen-specific suppression by antigen-immunosuppressive-agent conjugates].

The most important mechanisms for the specific depression of immune reactions--immuno-tolerance, enhancement, transfer of antibodies, drug induced tolerance, immunological suicide, application of antibody-toxin-complexes--are discussed with regard to their possible application in the clinical practice. A tentative hypothesis for induction of antigen specific suppression is proposed, basing on the use of antigen-immunosuppressive agent-conjugates (AIC). Antigen binding lymphocytes are supposed to bind the AIC and to pick them up through endocytosis. After breakdown of the AIC in the lymphoid cells the free immunosuppressive agent can become effective causing damage to the specific cell clones.

Animals↗
PubMed1977

Methods for the study of antidiarrheal agents. Study of commonly used protective and adsorbent agents.

Several agents were employed to induce diarrhea in squirrel monkeys: (1) diarrhaogenic diets, (2) various doses of cholera toxin, (3) prostaglandin derivatives, (4) bile, (5) lactulose, (6) phenolphthalein, (7) castor oil. Kaolin, pectin, Kaopectate and placebo were used as antidiarrheal treatment. Evaluation was based on (a) frequency, (b) consistency, (c) total and dry weight of the stools, and (d) electrolyte loss. The spectrum of procedures employed appeared to be suitable for the evaluation of antidiarrheal agents of the protective and adsorbent class.

Animals↗
PubMed1979

Vocalization response to close-arterial injection of bradykinin and other algesic agents in guinea pigs and its application to quantitative assessment of analgesic agents.

A method for determining the vocalization response to algesic agents in conscious guinea pigs is described. Retrograde injection of small amounts of algesic agents into the femoral artery caused transient but obvious vocalization response in a dose-dependent manner. The vocal sound was converted into electrical signals and the envelope of the sound obtained by a peak detector circuit was recorded on an ink-writing oscillograph. The area of the vocalization response circumscribed by a base line and the envelope tracing of the vocal sound was also recorded. Bradykinin, kallidin, acetylcholine (ACh) and nicotine caused the vocalization response, while substance P, histamine, bethanechol, methacholine, serotonin, kallikrein and prostaglandins E1 and E2 caused no or little response. No detectable tachyphylaxis to bradykinin, ACh and nicotine was observed. The pretreatment with hexamethonium abolished the response induced by ACh or nicotine but not the response induced by bradykinin. These results suggest that the paravascular pain receptor of the femoral artery excited by ACh is nicotinic in character. Subcutaneous injection of morphine, pentazocine, diclofenac and aminopyrine inhibited the vocalization response induced by bradykinin in a dose-dependent manner.

Acetylcholine↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. II. Immunogenicity of antigen-immunosuppressive-agent conjugates].

The maintenance of specific immunogenicity of carrier proteins is a necessary condition for the successful use of antigen-immunosuppressive agent-conjugates (AIC) for an antigen specific suppression of the immune response. The experimental results indicate that, in spite of the binding of 6-mercaptopurine (6-MP) and toluyl (T) to bovine gamma globulin (BGG) and human serum albumin (HSA), the carrier specific immunogenicity is not significantly altered. The intradermal application of 6-MP-BGG and T-BGG emulsified with complete Freund's adjuvant in guinea pigs results, in all cases, in a well detectable anti BGG hemagglutination and precipitation titer. This kind of immunization leads also to a formation of anti 6-mercaptopurine and anti new antigen determinants (NAD's) antibodies.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. IV. Studies on the specific suppression of humoral immune response in guinea pigs by antigen-immunosuppressive-agent conjugates].

Bovine gamma globulin (BGG) antigens were modified by the binding of 6-mercaptopurine and toluyl residues, and their influence on the humoral immune response in guinea pigs was investigated. The antigen-immunosuppressive agent-conjugates (AIC) were different, depending on the method used for their preparation and the number of coupled residues per one molecule of BGG. Conjugates denoted as MPI-n-BGG were prepared by special chemical binding of corresponding thioisocyanates. MPII-n-BGG were synthetized by acetylation, and MPIII-n-BGG conjugates, by reductive alkylation. Pretreatment of guinea pigs with MPIII-19-BGG, MPII-16-BGG resulted in a stimulatory effect on the subsequent humoral immune response induced by BGG application. A significant suppressive influence was detectable if the animals had been pretreated with MPII-6-BGG and MPI-26-BGG. MPI-13-BGG and MPI-36-BGG had no effect on the later induced anti-BGG antibody formation. The immune response against a second antigen (human serum albumin) was not influenced by this kind of pretreatment of the animals. Therefore it seems justified to conclude that both stimulatory and suppressive effects seen here were antigen specific and that both the method for chemical modification and the number of coupled 6-MP residues are very important for their effectivity.

Agglutination↗
PubMed1978

Immunological response to infection with human reovirus-like agent: measurement of anti-human reovirus-like agent immunoglobulin G and M levels by the method of enzyme-linked immunosorbent assay.

The report describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against the human reovirus-like agent of infantile gastroenteritis (HRVLA). This ELISA system proved to be four times as sensitive as the standard anti-HRVLA fluorescent-antibody assay and ten times as sensitive as the standard anti-HRVLA complement fixation assay. In addition, the ELISA was capable of determining immunoglobulin G (IgG) and IgM subclasses of anti-HRVLA antibody using a single dilution os serum. With this assay, it was discovered that 11 of 21 infected children had anti-HRVLA IgM in their acute sera before the appearance of anti-HRVLA IgG. ELISA is a useful tool in the evaluation of immunological response to HRVLA infection.

Adult↗