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At least 19 recordsLinked to original sources
PubMedDate not supplied

Genotypological method of analysis of individual responsiveness of an organism in experiment.

The principle of a genotypological method of analysis of individual responsiveness of an organism in experiment is formulated on the basis of data in the literature and the results of the author's own investigations. The main objective of a genotypological method is the determination of the constitutional typological features of responsiveness and their markers on the basis of similar or different norms of reaction and paratypical factors. It is proposed that individual responsiveness in a population be determined by way of disclosing in individuals the corresponding markers previously established in linear and non-linear animals in experiment, while observing a number of necessary conditions. These markers, capable of playing the role of indicators of a "constitutional typological reaction norm" and also of an individual reaction norm with respect to a concrete agent, are called genotypological markers.

Animals↗
PubMed1976

Predicting individual responses to drug treatment in schizophrenia: a test dose model.

The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research.

Antipsychotic Agents↗
PubMed2024

eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.

Humans↗
PubMed1976

Transcendental meditation in hypertension. Individual response patterns.

Seven selected hypertensive patients were stabilized on drugs at a research clinic. Subjects learned transcendental meditation (T.M.), were seen weekly, and took their own blood pressure several times daily. After 12 weeks of T.M. six subjects showed psychological changes and reduced anxiety scores. Six subjects also showed significant reductions in home and four in clinic blood-pressures. Six months later four subjects continued to derive psychological benefit and two showed significant blood-pressure reductions attributable to T.M. at home and clinic.

Adult↗
PubMed1977

Statistical detection of individual evoked responses: an evaluation of Woody's adaptive filter.

The practical performance of the adaptive filter developed by Woody (1967) and Harris and Woody (1969) is assessed in terms of its ability to distinguish evoked responses from the background EEG. It is concluded that selection of good initial template, in this case the Averaged ER, renders iterations beyond the first doubtful validity in the majority of subjects. It is stressed that where iterations are pursued care should be taken over the choice of a suitable statistic to index the process. Finally, given the efficacy of the cavariance function in detecting the grosser features of ER morphology in individual responses, a single trial approach to the analysis of ERs is recommended.

Computers↗
PubMed2026

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite↗
PubMed1979

Measurement of the responses of individuals to environmental stress and pollution: studies with bivalve molluscs.

Certain physiological differences between individuals in different populations of the mussel, Mytilus edulis, are described. In particular, the scope for growth differs in space and time and may be used to assess the animals' physiological condition. When the required measurements are made in the field, the rates of growth predicted from the physiological data agree well with observed rates of growth. An alternative approach utilizes mussels transplanted to various waters, with indices of condition then measured in then measured in the laboratory under standard conditions; an example of this approach is illustrated. Laboratory experiments are used to equate various levels of physiological condition with fecundity, in an attempt to equate physiological effects on the individual with likely population damage. A cytochemical index of stress is described, based on the latency of lysosomal enzymes; spatial variability in this index, and its relation with the scope for growth, are discussed. Finally, the results of some experiments on the effects of petroleum hydrocarbons on mussels are described and the presence of inducible activity of NADPH-dependent tetrazolium reductase in the blood cells is demonstrated. Certain considerations that apply in adopting similar measurements of biological effects of pollution in environmental monitoring programmes are discussed.

Animals↗
PubMedDate not supplied

[Immunology of Chagas' disease].

American trypanosoniasis or Chagas' Disease is a serious health problem in Latin America. Schizotrypanum (Trypanosome) cruzi infection produce an inmune response, cellular and humoral well identified in all mammals so far studied, including man. The initial parasistemic disease is brought promptly under control, maybe as result of such inmune response. Chronical disease result of individual responses, through inmune aberration as main pathogenic factor. There is not, and there is no probability to develop it in a short time, suitable inmunoprophylaxis for Chagas' disease.

Animals↗
PubMed1976

Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil.

Neither radiation alone (375 to 1500 rad) nor5-fluorouracil (FU) alone (50-250 mg/kg) is sufficient to prevent an increase in the volume of the solid tumour model hepatoma 3924A. However, as little as 750 rad with 100 mg/kg FU can reduce the tumour below the volume at the time of treatment for as long as 14 days. A series of combined FU and radiation doses given every 11 days should then result in successively smaller tumour volumes until the tumour is eradicated. Changes in tumour volume were analysed by two different methods: (1) tumours in each treatment mode were grouped together and the average response to treatment determined, and (2) tumour volume changes in individual tumours were analyzed utilizing the chi2 technique, which fits the logarithmic tumour volume change with time to polynomials. This two-directional method of analysis has the advantage of permitting both an overview of the main effects of treatment via the averages, and at the same time a detailed examination of the mechanism by which these effects occur through the analysis of individual response. The results suggest that, in addition to concentrating on the cellular response immediately after therapy, greater emphasis should be placed on the kinetic changes of the tumour 1-3 weeks after single or multiple modality therapy. These findings demonstrate how the sequencing of single and/or combined treatment modalities may be investigated in order to detemine how best to obtain maximum effects of treatment on different types of tumours following recovery of the host from the previous treatment series.

Animals↗
PubMed1979

Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells.

Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.

Acetylcholine↗
PubMed1975

Analysis of response properties of deefferented mammalian spindle receptors based on frequency response.

Sinusoidal responses of primary and secondary endings in deefferented spindles of anesthetized cats were studied over the low-frequency range 0.001-0.1 Hz. Stretch amplitudes were chosen conservatively small (25-100 mum peak-to-peak) so as to lie within the linear region. 1. At 0.1 Hz average sensitivity was 350 pps/mm for primary endings and 80 pps/mm for secondary endings. Sensitivity fell to lower values at lower frequencies, but even at 0.001 Hz, corresponding to 17 min/cycle, sensitivity remained elevated above static values determined with large stretches. Phase lead varied from 5 to 50 degrees and, in the case of primary endings, tended to be greater at lower frequencies. 2. Except for the different scaling factors, the only apparent difference between the frequency responses of primary and secondary endings was a tendency for primary endings to show a greater phase lead over the range 0.001-0.01 Hz. 3. Dynamic responsiveness was assessed theoretically from frequency-response data by calculating responses to ramps at various velocities. Over most of the velocity range dynamic responses were not proportional to velocity. The greater dynamic responsiveness of primary endings during large (6 mm) ramp stretches might be related to frequency response below 0.01 Hz. 4. Certain aspects of dynamic responsiveness to large ramps (6 mm) were accounted for by assuming all phases of responses were attenuated by 25 dB in the case of primary endings and 20 dB in the case of secondary endings. The nonlinearity responsible for attenuation appears to occur at an early stage in the sensory process. 5. Comparison of individual responses to slow ramps with predictions based on linear theory indicated the presence of abrupt departures from linearity for both primary and secondary endings.

Animals↗
PubMed2025

Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma.

BACKGROUND: Treatment for metastatic renal cell carcinoma (mRCC) has shifted from tyrosine kinase inhibitor (TKI) therapy to immune checkpoint inhibitor (ICI)-based therapy, improving outcomes but with variable individual responses. This study investigated the prognostic implications of pretreatment low skeletal muscle mass (LSMM) and myosteatosis in patients with mRCC undergoing first-line ICI-based therapies, comparing outcomes between PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor and PD-1 inhibitor&#x2009;+&#x2009;TKI, incorporating single-cell RNA sequencing. METHODS: A retrospective analysis was performed on 90 patients with mRCC treated with ICI-based therapies between November 2019 and March 2023. Patients were grouped based on whether they received PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor or PD-1 inhibitor&#x2009;+&#x2009;TKI combinations. LSMM was defined as skeletal muscle index below 40.8&#x2009;cm2/m2 for men and 34.9&#x2009;cm2/m2 for women. Myosteatosis was defined using skeletal muscle density, with cut-off values <&#x2009;41&#x2009;HU for BMI&#x2009;<&#x2009;25&#x2009;kg/m2 and <&#x2009;33&#x2009;HU for BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m2. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier curves and multivariable models. Single-cell RNA sequencing was performed on pretreatment samples to compare the immune microenvironment between patients with and without myosteatosis. RESULTS: The study cohort (26.7% female; median age: 60.5&#x2009;years) included 59 patients (65.6%) treated with PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor and 31 patients (34.4%) treated with PD-1 inhibitor&#x2009;+&#x2009;TKI. LSMM was present in 18.9% of patients, and myosteatosis in 41.1%, with comparable proportions across groups. During follow-up, 29 patients (32.2%) died: 16 in the PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor group and 13 in the PD-1 inhibitor&#x2009;+&#x2009;TKI group. The overall 1-year mortality rate was 22.2%, and PFS rate was 53.3%. Myosteatosis predicted poor OS (HR, 5.389; p&#x2009;=&#x2009;0.008) and PFS (HR, 2.930; p&#x2009;=&#x2009;0.022) in the PD-1 inhibitor&#x2009;+&#x2009;TKI group but was protective for PFS (HR, 0.461; p&#x2009;=&#x2009;0.049) in the PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor group. LSMM did not significantly affect outcomes in either group. Single-cell RNA sequencing revealed higher CTLA-4 expression in regulatory T cells and more effector memory CD8+ T cells in patients with myosteatosis, whereas patients without myosteatosis had more anti-tumoural non-classical monocytes. CONCLUSIONS: Myosteatosis negatively impacts OS and PFS in patients with mRCC treated with PD-1 inhibitor&#x2009;+&#x2009;TKI therapy but is protective for PFS in those treated with PD-1 inhibitor&#x2009;+&#x2009;CTLA-4 inhibitor therapy. Altered checkpoint expression and immune cell composition associated with myosteatosis may contribute to these differential responses.

Humans↗
PubMed1978

Comparison of fixed doses of chenodeoxycholic acid for gallstone dissolution.

96 patients with gallstones have been treated for up to four years with chenodeoxycholic acid in daily doses of 500, 750, or 1000 mg. None of the patients started on 500 mg daily showed complete gallstone dissolution. 8 out of 41 patients on 750 mg daily had complete dissolution of their radiolucent gallbladder stones after six or more months, and a further 4 showed partial dissolution. 5 out of 28 patients on 1000 mg daily had complete dissolution of their radiolucent gallbladder stones after at least six months, and a further 9 showed partial gallstone dissolution. The mean duration of therapy was greater on 750 mg than on 1000 mg/day (1.27 vs. 0.58 years), and when results were analysed after the first six months' therapy the total response-rate was significantly greater for the 1000 mg dose (12 out of 28) than for the 750 mg dose (9 out of 41). The individual response of radiolucent gallabladder stones to therapy could not be predicted from stone size, weight of patient, dosage/kg, orchange in biliary lipids. Treatment of radiolucent gallstones with chenodeoxycholic acid should start at 1000 mg daily.

Bile↗
PubMed2026

Urinary clusterin as a biomarker of human kidney disease progression and response to the endothelin receptor antagonist atrasentan: An exploratory analysis from the SONAR trial.

The endothelin receptor antagonist atrasentan improved kidney outcomes in the SONAR trial for type 2 diabetes and chronic kidney disease (NCT01858532), though individual responses varied. To identify molecular biomarkers of atrasentan response and outcome, we conducted a nested case-control proteomics study (N&#x2009;=&#x2009;180) within the SONAR trial population and identified urinary clusterin (uCLU) as the top candidate. Transcriptomic analyses of human kidney biopsies at tissue and single cell level from independent cohorts revealed higher CLU mRNA levels associated with worse kidney function and outcomes. An endothelin signaling activation score derived from pathway genes was reduced by atrasentan in mice with diabetic kidney disease. In the SONAR trial (N&#x2009;=&#x2009;3,060) population, higher uCLU predicted worse outcomes, while atrasentan reduced uCLU by 42.6% over six weeks. Early uCLU changes independently predict improved kidney outcomes. In summary, uCLU is associated with kidney disease progression and response to atrasentan treatment, supporting its potential as a pharmacodynamic biomarker to target therapy.

Humans↗
PubMed1977

The action of antacids on serum gastrin concentrations in man.

The effects of two doses of NaCl and NaHCO3 as well as of Al(OH3) and AlCl3 respectively, on serum gastrin concentrations and intragastric pH were compared in duodenal ulcer patients. Also the effect of one dose of an AlPO4 containing commercial antacid on serum gastrin concentration and intragastric pH was studied in duodenal ulcer patients and in a control group. Care was taken to induce swallowing at the times the substances were given through an orogastric tube. The study showed that antacids elicited significantly greater gastrin responses than their non-buffering chloride compounds and that the rise of gastrin after a single dose of antacid was small but significant in duodenal ulcer patients and insignificant in non-ulcer controls. Several factors as rising intragastric pH, individual responsiveness, duodenal ulcer state, vagal influences, the participating ions and their amount contribute to the rise of gastrin after antacids.

Aluminum↗