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At least 19 recordsLinked to original sources

Parental longevity and polygenic longevity scores in relation to ageing-related factors in a population of 70-year-olds followed over six years: The Gothenburg H70 Birth Cohort Study.

As societies age, a deeper understanding of ageing-related factors that contribute to longevity is needed. We therefore investigated possible longevity factors (social, medical, and biological) in relation to parental longevity (PL) and polygenic longevity scores (PGLSs). We examined 1126 70-year-olds from the Swedish population-based Gothenburg H70 Birth Cohort study in 2014-2016 (response rate 72%), with follow-up in 2019-2022 (response rate 77.6%). Comprehensive examinations included self-reported information on parents' ages, socioeconomic factors, mental, cardiovascular, and neurological health, anthropometry, laboratory data, and genotyping to construct two continuous PGLSs variables (with and without the APOE locus). PL groups were categorised as high if both parents survived to age 85 (17.2%); medium if one parent had survived (43.3%), and low if neither parent had survived to age 85 (39.4%). Higher PL and higher PGLSs were related to less hypertension, higher educational level, better childhood, and current socioeconomic status. In addition, higher PL was associated with higher MMSE score, total cholesterol, HDL-cholesterol (HDL-c) and LDL-cholesterol (LDL-c), lower BMI, homocysteine and inflammatory markers (IL-6, CRP) levels, and less smoking, whereas higher PGLSs was related to less myocardial infarction. At follow-up, high-PL was associated with less increase in plasma pTau217. PGLSs were mainly related to socioeconomic and cardiovascular factors, while individuals with long-lived parents, in addition, had several other characteristics of longevity, such as less inflammation, homocysteine, and markers of dementia. PL may be a proxy for biological ageing and used as a screening for ageing-related disorders in the context of prevention.

APOE

Studies on factor VIII-related protein. I. Ultrastructural and electrophoretic heterogeneity of human factor VIII-related protein.

Human factor VIII-related protein precipitates with specific heterologous anti-bodies directed against purified factor VIII and supports ristocetin-induced aggregation of washed platelets. We purified human factor VIII from cryoprecipitate by subsequent gel filtration on crosslinked large-pore agarose. Factor VIII-related protein appeared as a large aggregate following electrophoresis on 3% polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS). The same material was separated into multiple bands (molecular weight in excess of several millions) following electrophoresis on SDS-1% agarose gels. After complete disulfide reduction of factor VIII-related protein and electrophoresis on SDS-5% polyacrylamide gels a single subunit chain (Mr approximately equal to 200 000) was revealed. Analysis of this protein, in its non-reduced state, by negative contrast electron microscopy showed filaments of markedly variable size. The calculated molecular weight of such filaments ranged from about 0.6.10(6) to 20.10(6). We conclude that size heterogeneity is an essential feature of human factor VIII-related protein.

Disulfides

Studies on the prevalence of renal disease and hypertension in relation to schistosomiasis. IV. Systemic blood pressure hypertension and related features.

Two comparable rural communities but with varying endemicity of urinary schistosomiasis in environs of Ibadan, Nigeria, have been studied by a total cross-sectional population survey. It has been found that:- (i) schistosomiasis does not predispose to raised blood pressure (ii) both diastolic and systolic blood pressure increase with age. (iii) prevalence of systemic hypertension is higher in females than males (iv) body weight and height are related to hypertension in both males and females (v) parity would seem to be related to hypertension in the females (vi) except in the younger female group (1--19 years) where polyuria, frontal headache, palpitations appear related to systolic hypertension, raised blood pressure would appear to have no symptoms. In particular headache in any part of the head bears no clear relationship. (vii) The majority of hypertensives would appear to belong to the primary variety but proteinuria among females has been found to be significantly related to hypertension.

Adolescent

Studies on bilharzial dysentery: the relation among the egg count, the number of bowel motion and the antibody titre and the relation between the schistosomal antibody titre as detected by indirect haemagglutination test and the size of the wheal area of the intradermal test.

The authors studied the relation among the egg count, the number of motions and the antibody titer in 185 patients suffering from bilharzial dysentery. They found that no significant relation between the level of antibody titre and the number of ova and also no relation between egg count and number of motions but a significant relation between the number of bowel motions and the level of antibody titre was recorded. An auto-immune mechanism in Schistosoma mansoni has also been shown in this work but it needs further proof. On the other hand two diagnostic tests were performed namely the intradermal test and the indirect haemagglutination test. The former gave 84% positivity while the latter gave 94% positivity. In comparing the wheal size of the intradermal test and the titre of haemagglutination, it has been found that the wheal increases in size with rise of the titre. Therefore the wheal size can roughly suggest the level of immunity of the patient.

Adult

Experience of father and later relations to men. A systematic study of women's relations to their father, their partner and their son.

Using data from a longitudinal, prospective study of 69 women, their partners and first-born children, the woman's description of her parents was compared with her report about her relationships to her partner and child. Information was independently collected from partner and child. The woman's way of relating both to her partner and to her son was more strongly connected with her report about her early paternal than with her report about her early maternal contact. The woman's experience of her father was related to her way of interacting with her child in the case of a son but not in the case of a daughter. Thus, the specific importance of a woman's image of her father for her way of relating to other significant males was emphasized.

Father-Child Relations

Discriminative stimulus properties of benzodiazepines, barbiturates and pharmacologically related drugs; relation to some intrinsic and anticonvulsant effects.

Using a food-reinforced two-lever operant method, rats (n = 12) were trained to discriminate chlordiazepoxide (5 mg/kg, p.o.) from solvent (p.o.). With rats trained thus as subjects, generalization experiments were done with various benzodiazepines, barbiturates and related compounds, and with two neuroleptic drugs. The ability of these drugs to induce a discriminative stimulus complex similar to that induced by chlordiazepoxide, was then compared with some intrinsic and anticonvulsant effects of the same drugs. It was found that the discriminative stimulus properties of benzodiazepines, barbiturates, and related compounds correlate with the ability of these drugs to induce ataxia, as well as with part of their anticonvulsant activity. However, the stimulus properties of these drugs, as defined by the procedure described, are based neither on their ataxia-inducing effect, nor on their general depressant or sedative action. It is concluded that these properties constitute a pharmacologically highly specific phenomenon.

Animals

Age-dependent relaxation of gene repression: increase of endogenous murine leukemia virus-related and globin-related RNA in brain and liver of mice.

A progressive loss in the ability of cells to maintain their normal specialized states of differentiation could be the common denominator underlying much of the physiology and pathology associated with the mammalian aging process. We investigated this possibility by searching for an age-dependent derepression of endogenous genes in tissues in which they are not normally expected to be expressed. Complementary DNA (cDNA) probes to globin genes and to the murine leukemia type C RNA virus (MuLV) genome were used to detect the presence of RNA complementary to these genes in RNA extracted from brain and liver in young and old mice. Significant amounts of globin RNA were found in brain nuclei and cytoplasm. No age difference was found in the globin RNA sequences present, but the number of globin RNA molecules increased from about 15 in 6-month to 34 in 27-month-old animals for nuclei and 280 in 6-month to 500 in 27-month-old animals for cytoplasm. Similar results were found for liver. RNA complementary to the MuLV cDNA probe was also found but, in contrast to globin, the different RNA sequences increased in both brain and liver nuclei from about 45% of the MuLV genome in 6-month to 72% in 27-month-old animals. The number of MuLV-related RNA molecules remained constant at about 22 and 38 per nuclei for brain and liver, respectively. Derepression of genes of this magnitude could result in a time-dependent increase in virus-related diseases and a general deterioration of the organism.

Aging

Burkitt's lymphoma: its clinical course in relation to immunologic reactivities to Epstein-Barr virus and tumor-related antigens.

In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen.

Antibodies, Viral

Measurement of unsaturated ""granulocyte-related'' (TC I and TC III) and ""liver-related'' (TC II) B12 binders by instant batch separation using a microfine precipitate of silica (QUSO G32).

A microfine precipitate of silica (Quso G32) almost instantly quantitatively adsorbs the polypeptide transcobalamin II from serum without adsorbing the glycoproteins transcobalamins I and III. This provides a simple, rapid, and reproducible method for the measurement of the granulocyte-related transcobalamins I and III and the liver-related transcobalamin II in serum, and is also applicable to their purification, and the separation and purification of other polypeptide-glycoprotein mixtures.

Blood Proteins

[The centric relation. IV. Variations in condylar positions according to the methods of measuring centric relation and to the patient's clinical type].

When recording and transferring centric relation onto an articulator errors can be minimized by proper use of dental materials. Remaining errors may be due to either the patient or the clinician. 3 recording techniques (Lucia, Dawson, Ramfjord) are being tested by 2 operators on 12 patients. In order to get a proper centric relation one must not rely upon a technique of taking it but rather on an adequate clinical evaluation of the TMJ at that moment. The role of inadequate intermaxillary relationship upon painful TMJ syndroms cannot be underestimate.

Adult

Carbon 13 magnetic resonance studies of DL-2-(alpha-hydroxyethyl) thiamin and related compounds. Relation of kinetic acidity to electronic factors in thiamin catalysis.

Carbon 13 NMR spectra have been obtained for aqueous solutions of DL-2-(alpha-hydroxyethyl)thiamin, DL-2-(alpha-hydroxybenzyl)thiamin, DL-2-(alpha-hydroxybenzyl)oxythiamin, and related N-3 methyl and N-3 benzyl analogs. The unusually large downfield shift of the 13C resonance of C-2 of hydroxyethylthiamin suggests that this carbon bears a partial positive charge. This result stands in contrast to results of x-ray crystallographic studies of hydroxyethylthiamin, which place a partial negative charge on C-2 (Pletcher, J., and Sax, M. (1974) J. Am. Chem. Soc. 96, 155-165). A partial positive charge on C-2 helps to explain the facility of carbanion formation at the alpha carbon both enzymatically and in model systems. The rates of proton-deuteron exchange of (C-alpha)-H with solvent deuterium, and of release of aldehyde to regenerate thiamin have been measured for hydroxyethylthiamin and analogs. The differences in kinetic acidity of (C-alpha)-H and of rates of aldehyde release are rationalized in terms of differing electron-withdrawing abilities of the substituents attached to N-3, and appear not to be related to intramolecular basic catalysis of these processes by the C-4' amino group.

Carbon Isotopes

The relation between stimulus frequency and the relative size of the components of the biphasic response of the vas deferens to electrical stimulation at different temperatures.

1. Electrical stimulation of the guinea-pig or rat vas deferens (pre- or post-ganglionically) at frequencies from 2-5 to 40 Hz with trains of stimuli of 30 sec duration induced a biphasic response. A rapid contraction (component A) was followed after a brief relaxation by a slower contraction (component B); the two phases were seen most clearly with stimulation frequencies of less than 10 Hz. 2. The responses to post-ganglionic stimulation were always larger than those to preganglionic stimulation. In general, at low frequencies component A exceeded component B whilst at high frequencies component B was the larger. Separation of the two components on the basis of their frequency response characteristics was better for rat than for guinea-pig vasa. 3. Log. frequency-response curves to transmural (post-ganglionic) electrical stimulation and log dose-response curves to noradrenaline were recorded for guinea-pig and rat vasa deferentia at 32 degrees, 22 degrees and 12 degrees C. For the guinea-pig reduction of bath temperature to 12 degrees C increased the amplitude of component A at 2-5 and 5 Hz; component B could not confidently be distinguished at this temperature. At 22 degrees C there was potentiation of B at lower frequencies and depression of B at higher frequencies. There was no response to noradrenaline at 12 degrees C. At 22 degrees C the response to noradrenaline was increased except to doses at or near the maximum to which the response was reduced. 4. For the rat was deferens component A was little changed by reduction of temperature. Component B at 12 degrees C was greatly depressed at higher frequencies. The response to noradreanaline was increased to lower doses and decreased to higher doses as the temperature was lowered. 5. The B component of the response of guinea-pig vasa at 22 degrees C and rat vasa at 32 degrees C was more sensitive than the A component to inhibition by thymoxamine. 6. Further analysis of the mechanisms underlying the A and B components of the biphasic response may be facilitated by relative isolation of each component by the appropriate selection of parameters of electrical stimulation and of temperature for the species being investigated. The contractions of the B component are similar to, if not identical with, those produced by exogenously applied noradrenaline.

Animals

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes.

OBJECTIVE: To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS: We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS: GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS: Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

Journal Article

Interference of time-related and unrelated cues with duration comparisons of young children: analysis of Piaget's formulation of the relation of time and speed.

The analysis of the relation of time and speed led Piaget to conclude that the time-speed confusion characterizing the intuitive stage undergoes development. He claimed that in the first stage, a child comparing the duration of two moving bodies attributes longer duration to the faster body, whereas in the second stage, he attributes longer duration to the slower body. It is proposed here that time-speed confusion is mediated simply by "more is more," and hence, as long as the child continues to confuse time with speed, he believes "faster" implies longer duration. Moreover, this confusion should not differ either in form or extent from the confusion of time and many other arbitrary quantitative dimensions (e.g., intensity of light). 72 children, 4-7 years old, compared duration differing either on speed or on intensity of light. As predicted, the tasks did not differ on performance level or on error types. Moreover, the performance on both tasks was consistent with the predictions of a facet model pertaining to analysis of time problems. Confusion dissipated with age and was similar for boys and girls.

Age Factors