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PubMed2006

Does genotype and equol-production status affect response to isoflavones? Data from a pan-European study on the effects of isoflavones on cardiovascular risk markers in post-menopausal women.

The increase in CVD incidence following the menopause is associated with oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their oestrogenic and oestrogen receptor-independent effects, but evidence to support this role is scarce. Individual variation in response to diet may be considerable and can obscure potential beneficial effects in a sample population; in particular, the response to isoflavone treatment may vary according to genotype and equol-production status. The effects of isoflavone supplementation (50 mg/d) on a range of established and novel biomarkers of CVD, including markers of lipid and glucose metabolism and inflammatory biomarkers, have been investigated in a placebo-controlled 2 x 8-week randomised cross-over study in 117 healthy post-menopausal women. Responsiveness to isoflavone supplementation according to (1) single nucleotide polymorphisms in a range of key CVD genes, including oestrogen receptor (ER) alpha and beta and (2) equol-production status has been examined. Isoflavones supplementation was found to have no effect on markers of lipids and glucose metabolism. Isoflavones improve C-reactive protein concentrations but do not affect other plasma inflammatory markers. There are no differences in response to isoflavones according to equol-production status. However, differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to isoflavones v. placebo are evident with specific ERbeta genotypes. In conclusion, isoflavones have beneficial effects on C-reactive protein, but not other cardiovascular risk markers. However, specific ERbeta gene polymorphic subgroups may benefit from isoflavone supplementation.

Biomarkers↗
PubMed2005

A comparative analysis of temporomandibular joint morphology in the African apes.

A number of researchers have suggested a functional relationship between dietary variation and temporomandibular joint (TMJ) morphology, yet few studies have evaluated TMJ form in the African apes. In this study, I compare TMJ morphology in adults and during ontogeny in Gorilla (G.g. beringei, G.g. graueri, and G.g. gorilla) and Pan (P. paniscus, P. troglodytes troglodytes, P.t. schweinfurthii, and P.t. verus). I test two hypotheses: first, compared to all other African apes, G.g. beringei exhibits TMJ morphologies that would be predicted for a primate that consumes a diet comprised primarily of moderately to very tough, leafy vegetation; and second, all gorillas exhibit the same predicted morphologies compared to Pan. Compared to all adult African apes, G.g. beringei has higher rami and condyles positioned further above the occlusal plane of the mandible, relative to jaw length. Thus, mountain gorillas have the potential to generate relatively more muscle force, more evenly distribute occlusal forces along the postcanine teeth, and generate relatively greater jaw adductor moment. G.g. beringei also exhibits relatively wider mandibular condyles, suggesting these folivorous apes are able to resist relatively greater compressive loads along the lateral and/or medial aspect of the condyle. All gorillas likewise exhibit these same shape differences compared to Pan. These morphological responses are the predicted consequences of intensification of folivory and, as such, provide support for functional hypotheses linking these TMJ morphologies to degree of folivory. The African apes to not, however, demonstrate a systematic pattern of divergence in relative condylar area as a function of intensification of folivory. The ontogenetic trajectories for gorillas are significantly elevated above those of Pan, and to a lesser but still significant degree, mountain gorillas similarly deviate from lowland gorillas (G.g. gorilla and G.g. graueri). Thus, adult shape differences in ramal and condylar heights do not result from the simple extrapolation of common growth allometries relative to jaw length. As such, they are suggestive of an adaptive shift towards a tougher, more folivorous diet. However, the allometric patterning for condylar area and condylar width does not systematically conform to predictions based on dietary specialization. Thus, while differences in condylar shapes may confer functional advantages both during growth and as adults, there is no evidence to suggest selection for altered condylar proportions, independent of the effects of changes in jaw size.

Africa↗
PubMed1996

ERG measurements of the spectral sensitivity of common chimpanzee (Pan troglodytes).

The spectral sensitivity of the common chimpanzee (Pan troglodytes) was measured with electroretinogram (ERG) flicker photometry. Chromatic adaptation conditions were used to establish the presence of S-, M- and L-cone pigments. Each of 26 chimpanzees showed substantial and approximately equivalent adaptational changes over the middle and long wavelengths implying an absence of any significant polymorphic variations in the M- and L-cone pigments. As inferred from ERG measurements, the S-cone pigment of the chimpanzee has a spectral peak of about 430 nm. Chimpanzee spectral sensitivity measurements were compared to those obtained from equivalently tested normal human trichromats. The spectral sensitivity of the two species is very similar, chimpanzees being slightly more sensitive to short wavelength lights and slightly less sensitive to long wavelength lights than human subjects. Curve-fitting analyses suggest that spectral filtering may be lower in the chimpanzee lens than it is in the human lens, and that the L/M cone ratio is lower in the chimpanzee.

Adaptation, Ocular↗
PubMed2001

Enamel hypoplasia in the deciduous teeth of great apes: variation in prevalence and timing of defects.

The prevalence of enamel hypoplasia in the deciduous teeth of great apes has the potential to reveal episodes of physiological stress in early stages of ontogenetic development. However, little is known about enamel defects of deciduous teeth in great apes. Unresolved questions addressed in this study are: Do hypoplastic enamel defects occur with equal frequency in different groups of great apes? Are enamel hypoplasias more prevalent in the deciduous teeth of male or female apes? During what phase of dental development do enamel defects tend to form? And, what part of the dental crown is most commonly affected? To answer these questions, infant and juvenile skulls of two sympatric genera of great apes (Gorilla and Pan) were examined for dental enamel hypoplasias. Specimens from the Powell-Cotton Museum (Quex Park, UK; n = 107) are reported here, and compared with prior findings based on my examination of juvenile apes at the Cleveland Museum of Natural History (Hamman-Todd Collection; n = 100) and Smithsonian Institution (National Museum of Natural History; n = 36). All deciduous teeth were examined by the author with a x10 hand lens, in oblique incandescent light. Defects were classified using Fédération Dentaire International (FDI)/Defects of Dental Enamel (DDE) standards; defect size and location on the tooth crown were measured and marked on dental outline charts. Enamel defects of ape deciduous teeth are most common on the labial surface of canine teeth. While deciduous incisor and molar teeth consistently exhibit similar defects with prevalences of approximately 10%, canines average between 70-75%. Position of enamel defects on the canine crown was analyzed by dividing it into three zones (apical, middle, and cervical) and calculating defect prevalence by zone. Among gorillas, enamel hypoplasia prevalence increases progressively from the apical zone (low) to the middle zone to the cervical zone (highest), in both maxillary and mandibular canine teeth. Results from all three study collections reveal that among the great apes, gorillas (87-92%) and orangutans (91%) have a significantly higher prevalence of canine enamel defects than chimpanzees (22-48%). Sex differences in canine enamel hypoplasia are small and not statistically significant in any great ape. Factors influencing intergroup variation in prevalence of enamel defects and their distribution on the canine crown, including physiological stress and interspecific dento-gnathic morphological variation, are evaluated.

Age Factors↗
PubMed2000

Differential distribution in rat brain of mu opioid receptor carboxy terminal splice variants MOR-1C-like and MOR-1-like immunoreactivity: evidence for region-specific processing.

The present study examined immunohistochemically the regional distribution of the mu opioid receptor splice variant MOR-1C by using a rabbit antisera generated against the C-terminal peptide sequences and compared it with MOR-1. Overall, the distribution of MOR-1C-like immunoreactivity (-LI) differed from MOR-1-LI. Both MOR-1C-LI and MOR-1-LI were prominent in a few central nervous system regions, including the lateral parabrachial nucleus, the periaqueductal gray, and laminae I-II of the spinal trigeminal nuclei and the spinal cord. In the striatum, hippocampal formation, presubiculum and parasubiculum, amygdaloid nuclei, thalamic nuclei, locus coeruleus, and nucleus ambiguous MOR-1-LI predominated, whereas MOR-1C-LI was absent or sparse. Conversely, MOR-1C-LI exceeded MOR-1-LI in the lateral septum, the deep laminae of the spinal cord, and most hypothalamic nuclei such as the median eminence, periventricular, suprachiasmatic, supraoptic, arcuate, paraventricular, ventromedial, and dorsomedial nuclei. Double-labeling studies showed colocalization of the two receptors in neurons of the lateral septum, but not in the median eminence or in the arcuate nucleus, even though both MOR-1 isoforms were expressed. Because both MOR-1 and MOR-1C are derived from the same gene, these differences in regional distribution represent region-specific mRNA processing. The regional distributions reported in this study involve the epitope seen by the combinations of exons 7, 8, and 9. However, if other MOR-1 variants containing exons 7, 8, and 9 exist, the antisera would not distinguish between them and MOR-1C.

Alternative Splicing↗
PubMed2005

Proteomic analysis of organ-specific post-translational lysine-acetylation and -methylation in mice by use of anti-acetyllysine and -methyllysine mouse monoclonal antibodies.

Post-translational lysine-acetylation and -methylation are two major PTMs of lysine residues in proteins. Recently, we established pan-reactive anti-acetyllysine mouse mAbs, which can bind to Nepsilon-acetylated lysine residues in various contexts of amino acid sequences. In the present study, we established pan-reactive anti-methyllysine mouse mAbs comparable to the anti-acetyllysine ones. By using these anti-acetyllysine and -methyllysine antibodies, we found that the pattern of lysine-acetylated and -methylated proteins in mouse organs showed extreme variation from organ to organ. We selected brain and skeletal muscle as model cases to be further analyzed by 2-DE followed by Western blotting. In brain, alpha-tubulin at its basal level was found to be extremely acetylated; and alpha-enolase was shown to be a newly recognized possibly acetylated protein. NF-L protein, Hsc70, alpha-tubulin fragments, beta-actin, and brain-type creatine kinase were identified as putative lysine-methylated proteins in mouse brain. In skeletal muscle, lysine-methylation of alpha-actin and both lysine-acetylation and -methylation of muscle-type creatine kinase were found as novel putative lysine-modified proteins. The approach presented here might be useful to find novel disease markers and/or drug target molecules that would not be noticed by use of the traditional proteomic approach only.

Acetylation↗
PubMed1993

A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody.

Hepatitis C virus persists in most infected hosts, and causes chronic hepatitis, liver cirrhosis, and/or hepatocellular carcinoma in humans. During the infection the RNA genome of hepatitis C virus undergoes frequent missense mutations at one or two "hypervariable" regions within a presumptive envelope gene (Okamoto et al., 1992, Virology 190, 894-899; Ogata et al., 1991, Proc. Natl. Acad. Sci. USA 88, 3392-3396). In the present study, we analyzed three cases of hepatitis C virus infection, two in chimpanzees and one in humans, for the antigenicity of peptides predicted from the hypervariable region of viral RNA obtained during the follow-up. Our results showed a successive appearance of hepatitis C virus mutants with antigenically distinct amino acid sequence within the domain; and the amino acid replacement was associated with an alteration of predicted local secondary structure of the epitope region. Hence, the hypervariable domain of the hepatitis C virus envelope appeared to be structurally flexible and antigenically variable, providing the virus a way to escape from host immunity.

Amino Acid Sequence↗
PubMed1998

Preponderance of slightly deleterious polymorphism in mitochondrial DNA: nonsynonymous/synonymous rate ratio is much higher within species than between species.

We estimated synonymous (dN) and nonsynonymous (dS) substitution rates for protein-coding genes of the mitochondrial genome from two individuals each of the species human, chimpanzee, and gorilla. The genes were analyzed both separately and in a combined data set. Pairwise sequence comparisons suggest that the dN/dS rate ratios are about 5-10 times higher in within-species comparisons than in between-species comparisons. This result is confirmed by a more rigorous likelihood ratio test, which rejected the null hypothesis that the dN/dS rate ratios are identical within and between species. The likelihood models account for the genetic code structure, transition/transversion rate ratio, and codon usage bias and are expected to produce more reliable results than the commonly used contingency test. Separate analyses of different genes show that the dN/dS rate ratios are higher within species than between species for all 13 mitochondrial genes, with the difference being statistically significant for all except three small or slowly evolving genes. Furthermore, in conserved genes, nonsynonymous rates within species tend to be higher than the between-species rates by a greater proportion than in fast-changing genes. Our findings confirm and extend earlier results obtained from smaller data sets and suggest the operation of slightly deleterious mutations throughout the mitochondrial genome in the hominoids. Implications of the results for evolutionary studies and, in particular, for studies of the origin of modern humans, are discussed.

Adenosine Triphosphatases↗
PubMed2003

Dynamic plantar pressure distribution during terrestrial locomotion of bonobos (Pan paniscus).

We collected high-resolution plantar pressure distributions of seven bonobos during terrestrial bipedal and quadrupedal locomotion (N = 146). Functional foot length, degree of hallux abduction, and total contact time were determined, and plots, showing pressure as a function of time for six different foot regions, were generated. We also studied five adult humans for comparison (N = 13). Both locomotion types of the bonobo show a large variation in plantar pressure distributions, which could be due to the interference of instantaneous behavior with locomotion and differences in walking speed and body dimensions. The heel and the lateral midfoot typically touch down simultaneously at initial ground contact in bipedal and quadrupedal walking of bonobos, in contrast with the typical heel-strike of human bipedalism. The center of pressure follows a curved course during quadrupedalism, as a consequence of the medial weight transfer during mid-stance. Bipedal locomotion of bonobos is characterized by a more plantar positioning of the feet and by a shorter contact time than during quadrupedal walking, according to a smaller stride and step length at a higher frequency. We observed a varus position of the foot with an abducted hallux, which likely possesses an important sustaining and stabilizing function during terrestrial locomotion.

Animals↗
PubMed2005

Are the differences between Stw 431 (Australopithecus africanus) and A.L. 288-1 (A. afarensis) significant?

Recent studies of early hominin body proportions paint a complex evolutionary picture, with multiple instances of reversal in body shape. These interpretations rest heavily upon the inferred limb joint proportions of Australopithecus africanus. For example, the partial skeleton Stw 431 has been suggested to show ape-like joint proportions compared to the A. afarensis specimen A.L. 288-1. This suggests an evolutionary reversal in the more recent A. africanus. However, no study has examined the probability of sampling the differences between Stw 431 and A.L. 288-1 from a single extant hominoid species. The present study compares elbow/hip and elbow/lumbosacral joint size ratios between Stw 431 and A.L. 288-1 using exact randomization, based on chimpanzee and human models of variation. Results indicate that differences in elbow/hip proportions between Stw 431 and A.L. 288-1 can be sampled from a single species. In contrast, differences in elbow/lumbosacral proportions between Stw 431 and A.L. 288-1 show a significantly low probability of being sampled from a single species. Thus, Stw 431 and A.L. 288-1 are not significantly different from each with regard to limb joint proportions, but Stw 431 has a significantly smaller lumbosacral joint. This pattern does not conform to previous interpretations of limb proportions in A. africanus. Low statistical power in the present study may account for the discrepancy. Further research is needed to illuminate the functional implications of variation in relative lumbosacral joint size in early hominins.

Animals↗
PubMed1998

Phenotypic variation in strength among eleven inbred strains of rats.

As a first step toward the long-range goal of identifying the genes that determine strength, we subjected 11 inbred strains of rats to three tests of muscular strength. The tests consisted of measuring (1) the force exerted by the rat as it was pulled by the base of the tail off a grid on the pan of a top-loading electronic balance (scale test); (2) the length of time the rat hung from a 2.5-mm-diameter U-shaped wire (wire-hanging test); and (3) the length of time the rat hung from a vertically oriented grid consisting of 4-mm-diameter rods (grid-hanging test). Six rats of each gender from each strain were tested at 12 weeks of age, once/day for 5 consecutive days. For the two tests that required use of all four limbs (the scale and grid-hanging tests), one strain performed best (DA). In contrast, on the test that required primarily the use of the front limbs (wire-hanging test), the DA was the lowest performing strain and the F344 rats the best. This differential ranking suggests that the tests selected for variance in the morphological distribution of strength among the strains. There was a 1.5- to 5.2-fold divergence observed between the males of the highest and lowest strains on the scale test and grid hanging tests. This large divergence provides the opportunity to search for intermediate phenotypes and quantitative trait loci that contribute to the different performances of the strains on these strength tests.

Animals↗
PubMed2002

An adult patient with acute hepatitis type B which was protracted and complicated by polyarteritis nodosa: a case report.

Polyarteritis nodosa (PAN), an extra-hepatic complication of hepatitis type B, is usually treated with a combination of immunosuppressive and antiviral drugs. Less commonly, interferon (IFN) has been used alone. A 57-year-old man was admitted to our hospital with epididymitis and acute hepatitis with genotype A, hepatitis B virus (HBV). He became a carrier with complicating PAN. The administration of interferon alpha2b (IFNalpha2b) at a dose of 6 MU/day for 4 weeks alleviated abdominal and neuronal symptoms related to PAN, although HBV replication was not eliminated. This is the first case of PAN with HBV of genotype A and which was treated with IFN alone. This case indicates the possibility that IFN is efficacious for extra-hepatic complications of hepatitis type B and suggests that differences in genotype may be associated with variation in the likelihood of progression to persistent infection and the incidence of extra-hepatic complications in Japan.

Journal Article↗
PubMed2025

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation.

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the K. pneumoniae species complex (n = 7,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (n = 1,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of K. pneumoniae and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.

Klebsiella pneumoniae↗
PubMed2025

ves1α genes expression is the major determinant of Babesia bovis-infected erythrocytes cytoadhesion to endothelial cells.

Babesia bovis causes the most pathogenic form of babesiosis in cattle, resulting in high mortality in naive adults. This parasite invades red blood cells (RBCs) within the bovine hosts where they multiply and produce clinical disease. Babesia bovis exports numerous proteins into invaded RBCs changing its properties. Thus, the infected RBCs (iRBCs) are capable to cytoadhere in the microvasculature of internal organs and brain, leading to respiratory distress, neurologic signs, and mortality. Variant Erythrocyte Surface Antigen 1 (VESA1) is one of those exported proteins by B. bovis which represents a major virulence factor due to its central role in immune evasion by antigenic variation and intravascular parasite sequestration. VESA1 is a heterodimer protein encoded by ves1α and ves1β multigene family and localized on the ridges, the focal point for cytoadhesion. To gain further insights into the molecular mechanisms of cytoadhesion of B. bovis, we panned the parasites with bovine brain microvasculature endothelial cells, which resulted in obtaining several clones with different cytoadherence abilities. The transcriptome analysis of 2 high and 2 low cytoadherent clones revealed that ves1α sequences were diversified, likely resulting from genomic recombination. On the other hand, ves1β sequences were almost identical among these 4 clones. Insertion and expression of ves1α of a clone with high binding into ef-1α locus of a low binding clone increased cytoadherence confirming the role of ves1α suggested by our transcriptome data. Whole genome sequencing of cytoadherent clones revealed active locus of ves1 on chromosome 2. These results suggest that VESA1a proteins encoded by ves1α genes determine the cytoadherence strength of B. bovis and they are in the active site for recombination.

Animals↗
PubMed2007

Validation of plaster endocast morphology through 3D CT image analysis.

A crucial component of research on brain evolution has been the comparison of fossil endocranial surfaces with modern human and primate endocrania. The latter have generally been obtained by creating endocasts out of rubber latex shells filled with plaster. The extent to which the method of production introduces errors in endocast replicas is unknown. We demonstrate a powerful method of comparing complex shapes in 3-dimensions (3D) that is broadly applicable to a wide range of paleoanthropological questions. Pairs of virtual endocasts (VEs) created from high-resolution CT scans of corresponding latex/plaster endocasts and their associated crania were rigidly registered (aligned) in 3D space for two Homo sapiens and two Pan troglodytes specimens. Distances between each cranial VE and its corresponding latex/plaster VE were then mapped on a voxel-by-voxel basis. The results show that between 79.7% and 91.0% of the voxels in the four latex/plaster VEs are within 2 mm of their corresponding cranial VEs surfaces. The average error is relatively small, and variation in the pattern of error across the surfaces appears to be generally random overall. However, inferior areas around the cranial base and the temporal poles were somewhat overestimated in both human and chimpanzee specimens, and the area overlaying Broca's area in humans was somewhat underestimated. This study gives an idea of the size of possible error inherent in latex/plaster endocasts, indicating the level of confidence we can have with studies relying on comparisons between them and, e.g., hominid fossil endocasts.

Animals↗
PubMed2003

A longitudinal study on hand and wrist skeletal maturation in chimpanzees ( Pan troglodytes), with emphasis on growth in linear dimensions.

Skeletal maturation in the chimpanzee hand and wrist (the RUS system; radius, ulna, and short bones) was studied both longitudinally and cross-sectionally. Maturity states were evaluated in each of the 13 bones of the RUS system based on the TW2 method (Tanner and Whitehouse method), and the RUS score was calculated by the summation of scores for these bones. Individual variation was examined by means of residual curves and pseudo-velocity curves of RUS score and anterior trunk length (ATL). Norms of the age change pattern in RUS skeletal maturation and the growth of ATL were determined for each sex, and the relationships among ATL growth and skeletal and reproductive maturation were examined. We found a fairly good relationship between ATL growth and RUS skeletal maturation. Comparison of growth and development between humans and chimpanzees showed that growth characteristics are coupled with each other at puberty in male chimpanzees and in both sexes of humans. Although nutritional condition influenced ATL growth in infancy, it had no effect on the RUS maturational process. Social relationships appeared to influence both ATL growth and RUS maturation. Analyses on relationships between RUS skeletal maturation, ATL growth, and reproductive maturation, showed that RUS skeletal maturation is a good indicator of "physiological age".

Age Determination by Skeleton↗
PubMed2000

Human variant glucose-6-phosphate transporter is active in microsomal transport.

Glycogen storage disease type lb (GSD-lb) is caused by deficiencies in the glucose-6-phosphate transporter (G6PT), which works together with glucose-6-phosphatase to maintain glucose homeostasis. In humans, there are two alternatively spliced transcripts, G6PT and variant G6PT (vG6PT), differing by the inclusion of a 66-bp exon-7 sequence in vG6PT. We have previously shown that the G6PT protein functions as a microsomal glucose-6-phosphate (G6P) transporter, which is anchored to the endoplasmic reticulum by ten transmembrane helices. Here, we demonstrate that vG6PT is also active in microsomal G6P transport. The additional 22 amino acids in vG6PT is predicted to constitute a part of the luminal loop 4. Our data indicate that this loop plays no vital role in microsomal G6P transport. Further, we show that G6PT mRNA is expressed in all organs and tissues examined, but that the vG6PT transcript is expressed exclusively in the brain, heart, and skeletal muscle. These results raise the possibility that mutations in exon-7 of the G6PT gene, which would not perturb glucose homeostasis, might have other deleterious effects.

Alternative Splicing↗
PubMed1991

Photoacoustic study of iron-deficiency anaemia.

A photoacoustic spectrum of a smear of whole blood clearly shows all of the details of the haem absorption in an optical spectrum and good optical absorption data without a data extraction procedure. There are three peaks; gamma (420 nm), beta (550 nm), and alpha (585 nm) in the band 350-700 nm. For iron-deficiency anaemia the peak/peak ratios, ratios of the value of peak gamma to that of the peak beta and peak alpha, and the integral/integral ratios, ratios of the value of the integral under the peak gamma to that under the peak beta, peak alpha, peak beta and peak alpha are closely related to the variation of haemoglobin concentration. Linear relationships among the ratios and the Hb concentration are found. These ratios could be a good index of haem synthesis disturbance.

Anemia, Hypochromic↗