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Sebaceous lipogenesis in human skin. Variability with age and with severity of acne.

Lipogenesis from [14C] glucose was measured in skin biopsies from the shoulder-blade region of forty-two male subjects. In the acne age range, dermal lipogenesis showed an upward trend with increasing severity of acne; a similar trend was found in forehead sebum excretion rate, but no correlation was obvious between dermal lipogenesis (back) and sebum secretion rate (forehead) in the same subject. In older subjects, dermal lipogenesis was significantly increased in those with a past history of severe acne. At high rates of dermal lipogenesis there was a small but significant increase in wax ester labelling relative to triglyceride and squalene. No increase was found in squalene labelling relative to other lipids, either with increasing lipogenic rate or in severe acne. Dermal and epidermal lipogenesis rates showed no correlation with age. In dermis, however, there was a decrease in wax ester labelling relative to triglyceride, and a marked decrease in squalene labelling relative to both triglyceride and wax esters, with increasing age.

Acne Vulgaris

Structure and variability of human chromosomes analyzed by recent techniques.

Besides the AT-specific fluorochromes, GC-specific fluorescent antibiotics are now available for chromosomal analysis. Chromosomal bands represent large accumulation of DNA sequences with similar AT:GC ratio. These uniform differences from the mean AT:GC ratio in the bands can be explained only by at least partial repetition of short DNA sequences in these regions. By comparison of various staining techniques more information also on the constitutive heterochromatin in man becomes available. The human NOR region exhibits a complex organization when studied by various base-specific fluorochromes and silver staining. The DNA-specific fluorochromes are also useful tools in cytophotometric DNA measurements.

Adenine

Variability in β-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75&#x2009;&#xb1;&#x2009;4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p&#x2009;<&#x2009;0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans

Immunoglobulin diversity: correlation of non-allelic antigenic markers with the basic sequences of the variable region of human lambda chains.

Three forms of the amino terminal half (variable region) of human pathological lambda light chains of immunolglobulins were identified antigenically. By study of all completely sequenced Bence Jones proteins hitherto analyzed and a greater number of proteins subjected to automated sequence determination as well as normal light chains three distinct isotypic basic sequences were identified. The basic sequences are shown to be associated with characteristic antigenic markers representing three V region genes encoding the variable half of lambda chains of immunoglobulins.

Alleles

Restriction of human immune antibodies to heavy-chain variable subgroups.

Human immune antibodies such as anti-Rh and anti-Kell antibodies were tested in hemagglutination and hemagglutination inhibition experiments for VH subgroup composition. A striking VH subgroup restriction was found in several of these groups of antibodies. In the majority of cases there was a restriction to one particular VH subgroup for a single antibody specificity in a given individual. In some cases there was also an overall restriction to one particular subgroup for antibodies with the same antibody specificity. This was particularly pronounced for anti-D antibodies, which was primarily restricted to VHII, and for the anti-Kell, which was particularly related to VHIII. Subgroup-specific antigens for all the main VH subgroups were blocked on combination of the antibody molecule with antigen. No relation was found between VH restriction and restriction to IgG subclass, or genetic markers or chi and lambda light-chain type.

Antibodies

Ovulation induction with human menopausal gonadotrophins: an evaluation of a variable daily dosage regimen.

Human menopausal gonadotrophins (HMG) were used together with human chorionic gonadotrophin (HCG) in 19 women and 39 treatment cycles in an attempt to induce ovulation. Daily 24 hours urinary total estrogen excretion rates were measured and HMG daily dosage was varied according to levels obtained. HCG injections were timed to coincide with an estimated urinary total estrogen excretion rate of 100-150 g per 24 hours. Thirty-one ovulatory cycles occurred (79%) and there were nine pregnancies (23%) of which five were multiple. Eleven cycles were complicated by hyperstimulation (25.6%) of which six were severe. The variable HMG dosage regimen was found to offer no advantages when compared with our standard daily dosage regimen. A rapid rise of estrogen excretion occurred in over 80% of hyperstimulation cycles, including all severe ones, and it was found that this rise could occur after the last dosage of HMG had been given. Because of this, it is proposed that HCG injections be delayed until 48 hours after the last injection of HMG. The finding of a value for the last available 24 hour urinary total estrogen excretion of less than 150 microgram can be taken as an indicator that hyperstimulation is unlikely to occur, and that HCG can safely be given. No indication was found that such a procedure would diminish ovulation or pregnancy rates.

Chorionic Gonadotropin

[The primary structure of the Bence-Jones protein Kue. The amino acid sequence of the variable part of a human L-chain of the kappa-type (author's transl)].

The complete primary structure of the variable region of Bence-Jones protein Kue was elucitated with the aid of a few tryptic peptides, as well as one chymotryptic and one BNPS-scatol fragment. As a consequence of the evident homologies to other proteins this protein belongs to subgroup k/I. Protein Kue has some amino acid exchanges in certain positions in common with other proteins, probably giving rise to a new sub-subgroup. The constant region shows no amino acid exchanges in comparison with other human kappa L-chains. With valine covering position 191, protein Kue should be grouped per definition as an allotype Km (3).

Amino Acid Sequence

Amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob.

The amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob has been determined. This protein has previously been shown to have a deletion in the hinge region [Lopes, A. D., & Steiner, L. A. (1973) Fed. Proc., Fed. Am. Soc. Exp. Biol. 32, 1003; Steiner, L. A., & Lopes, A. D. (1979) Biochemistry (preceding paper in this issue)]. The complete sequence was established by analysis, in the automated sequenator, of the intact Fd' piece and of three large overlapping fragments prepared from Fd' by digestion with cyanogen bromide, by tryptic digestion of the citraconylated Fd', and by cleavage with hydroxylamine. Portions of the sequence were confirmed by examination of the amino acid composition and the partial sequence of a variety of small peptides obtained by enzymatic degradation. The Dob heavy-chain variable region appears to belong to the VHIII subgroup, but there are several unusual substitutions. Residue 45 in the Dob sequence is proline, although all other known heavy-chain sequences in man, mouse, rabbit, and guinea pig have leucine at this position. Positions 10 (aspartic acid), 68 (alanine), and 82 (leucine) in the Dob sequence are also atypical. There is no deleted segment in the variable region of the Dob heavy chain nor any abnormality in the variable-constant joining region. The hinge-region deletion appears to be the only gross structural anomaly in the Dob heavy chain.

Amino Acid Sequence

The human Y chromosome: its routine identification and variability.

Different criteria for identifying the human Y chromosome using only conventional staining techniques were evaluated and a procedure based on three of them was developed. It leads to correct identification in 93% of cells even without resorting to differences in size between the Y and the other G chromosomes. The variability in size of the human Y chromosome was assessed in a random group of White men. It was found to be significantly greater than that of all other chromosomes in the karyotype when the comparisons were made in such a way as to avoid the size-dependent component of variation.

Analysis of Variance

Variable adherence to normal human urinary-tract epithelial cells of Escherichia coli strains associated with various forms of urinary-tract infection.

The ability to become attached to normal epithelial cells from the urinary tract was much greater in Escherichia coli bacteria isolated from the urine of patients with acute symptomatic pyelonephritis or cystitis than in those isolated from the urine of patients with asymptomatic bacteriuria. Attachment of the bacteria could be prevented by incubation in urine containing antibodies against the strain tested. The ability to attach to uroepithelial cells might be a virulence factor for E. coli strains which cause symptomatic urinary-tract infection.

Acute Disease

[Antigenic determinants of human immunoglobulin light and heavy chain variable regions. Comparison with animal species].

An antigenic analysis of human heavy and light chain variable region subgroups has been done on different animal species, by means of heterologous specific antisera using a hemagglutination-inhibition procedure. Excepted in lemur sera, where Vkappa III and Vlambda III are the only variable antigenic determinants found, all VL antigenic determinants tested were shown to be present in primates. In other mammals (carnivores, some rodents, some artiodactyls) several VL antigenic subgroup determinant were detected while others were not. No VL antigenic determinant was found in other classes studied. The VH III subgroup antigenic determinant was found among all primates, some mammals and avains. The results suggest that there has been more preservation in the variable region of immunoglobulin chains, and particularly VH III chain, than in the constant region of immuoglobulin molecule.

Animals

Heavy and light chain variable region subgroups: antigenic analysis among human monoclonal immunoglobulins.

An antigenic analysis of human heavy and light chain variable region subgroups has been possible by means of heterologous specific antisera using a hemagglutination-inhibition procedure. The specificity of antisera had been shown to be directed against antigenic determinants of VkappaI, VkappaII, VkappaIII, VlambdaI, VlambdaII, VlambdaIII and VHIII by means of chemically subgrouped proteins. A series of IgG, IgA, IgM and IgD were examined for the presence of a VHIII variable region subgroup antigenic determinant. The data showed that 50% IgG, 62% IgA, 55% IgM, 45% IgD were positive for VHIII antigenic determinant. NH2 terminus blocked monoclonal immunoglobulin belonging to the VHIII subgroup were found, increasing incidence of this subgroup among IgG. A preferential association of VHIII antigenic determinant with IgG1, IgG3 subclasses was observed among IgG myeloma proteins while the preferential association was only observed with IgG1 subclass when anti-Rh antibodies were considered. Among 53 IgG of kappa type 20 (37%) kappaI, 30 (56%) kappaII, 3 (5%) kappaIII subgroups were found and among 42 IgG of lambda type 13 (31%) lambdaI, 13 (31%) lambdaII and 16 (38%) lambdaIII were observed. Although numbers are limited in each group for conclusions a study of VHIII and non VHIII antigenic subgroup determinant with respect to the light chain subgroups is given. The non-allelic behaviour of this VHIII antigenic determinant was observed. Preliminary data on the presence of these human antigenic determinants among different animals species were given.

Animals

Temperature and acid-base status of human blood at constant and variable total CO2 content.

The influence of temperature on the acid-base status of normal human blood was studied in closed systems (constant CCO2) and open systems (variable CCO2). pH-T coefficients of true plasma and erythrocytes in closed systems were similar to coefficients for water (dpH/dT = -0.017 U/degrees C at 25 degrees C). Between 26 degrees C and 42 degrees C there was no significant variation in the relative alkalinities [OH-]/[H+], the charge state of proteins in plasma and erythrocytes or the proton Donnan ration. The equations established enabled calculation of the pH of true plasma and erythrocytes and of blood PCO2 and temperature, using only one of these four parameters. Under open-system conditions, temperature was shown to cause a rise in the apparent buffer power of whole blood non-bicarbonate systems (28.8 and 34.8 mM.l-1.u-1 at 26 degrees C and 42 degrees C respectively). These results show (1) that erythrocytes in closed systems seem very well able to maintain proton distribution regardless of temperature fluctuations and (2) when blood temperature rises, it cannot be excluded that vital organs are better protected against respiratory disturbances.

Acid-Base Equilibrium

Antigenic determinants of heavy chain variable regions: immumological typing of the human immunoglobulin VHIII subgroup.

An antigenic determinant of the VHIII variable region subgroup was defined by means of a heterologous specific antiserum using a hemagglutination inhibition procedure. The specificity of this antiserum was established in inhibition experiments with proteins either of known primary structure or belonging to a definite VH subgroup. A series of IgG, IgA, IgM and IgD monoclonal proteins was examined for the presence of this VHIII subgroup antigenic determinant. The data showed that 50% of the IgG, 62% of the IgA, 55% of the IgM and 41% of the IgD were VHIII-positive, and that certain "blocked" monoclonal immunoglobulins belonged to this subgroup. A preferential association of the VHIII antigenic determinant with the IgG1 and IgG3 subclasses was observed among IgG myeloma proteins while the preferential association was only observed with the IgG1 subclass when anti-Rh antibodies were studied. The VHIII subgroup exhibited nonallelic behavior.

Epitopes

Prematurity and perinatal mortality in the Rhesus (Macaca mulatta): relationship to birth weight and gestational age.

While the relative influence of birth weight and gestational age in determining perinatal mortality has not been definitively established, it has been assumed that birth weight makes the predominant contribution to perinatal mortality. The joint effects of birth weight and gestational age were examined by analyzing approximately 2,500 births from timed pregnancies in two rhesus (Macaca mulatta) breeding colonies. Perinatal events in the rhesus are described and shown to be similar to the human. The results demonstrate that gestational age is as important as birth weight in determining perinatal mortality. Since the degree of accuracy in the estimation of rhesus gestational age was much greater than is usually attained in human studies, the estimation of gestational age from the last menses may be too crude to determine the importance of this variable in human perinatal mortality.

Animals

Structural diversity and evolutionary constraints of oxidative phosphorylation.

The oxidative phosphorylation (OxPhos) system is central to metabolism. The more than 90 structural subunits are encoded by different chromosome categories (autosomal, X, and mtDNA). The system is envisioned as an invariant structure between cells and individuals. However, a comprehensive analysis of the 1,000 Genomes Project data reveals unexpected genetic intra-individual variability resulting from the heterozygosity of diploid autosomal genes, while diversity at the population level is generated by variability in mtDNA. We characterized the different levels of structural constriction at evolutionary and population levels for all OxPhos protein residues. To support this analysis, we developed ConScore, a conservation-based predictor of variant impact within OxPhos proteins (area under the receiver operating characteristic curve [ROC-AUC] = 0.97; area under the precision-recall curve [PR-AUC] = 0.94). Notably, for the nuclear-encoded subunits, we found mechanisms limiting individual variability as allelic imbalance or homozygosity bias. Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease.

Oxidative Phosphorylation