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PubMed1982

The development and characterization of a homologous radioimmunoassay for mouse placental lactogen.

A highly specific and sensitive homologous radioimmunoassay (RIA) has been developed for mouse placental lactogen(mPL). Mouse pregnancy serum and placental extracts showed parallel dilution-response curves, and no significant cross-reaction was seen with either mouse growth hormone or mouse prolactin. The sensitivity of the assay ranged from 0.5 to 1.0 ng/ml, and the intra- and inter-assay coefficients of variation were 5 and 11%, respectively. By RIA, mPL levels were detectable on day 9 of pregnancy (1 ng/ml) and increased until day 14 (100-150 ng/ml) in both C3H and BALB/c strains. On days 14-18 of pregnancy, mPL levels were maintained (95-125 ng/ml) in C3H mice, while they continued to increase (greater than 250 ng/ml) in BALB/c mice. In both strains, a midpregnancy peak in prolactin-like activity was detected by a radioreceptor assay but not by the mPL RIA.

Animals↗

PubMed1982

Insulin-stimulated tyrosine phosphorylation of the insulin receptor in detergent extracts of human placental membranes. Comparison to epidermal growth factor-stimulated phosphorylation.

Addition of insulin to Triton-solubilized extracts of human placental membranes selectively stimulates the incorporation of 32P from [gamma-32P]ATP into an endogenous 95,000-dalton protein, which is identified as a component of the insulin receptor by immunoprecipitation. The insulin-stimulated increment in 32P is recovered largely in [32P]tyrosine after acid hydrolysis. E Epidermal growth factor (EGF) stimulates the phosphorylation of a 150,000-dalton protein in these detergent extracts. This reaction differs in several respects from the insulin-stimulated phosphorylation of the 95,000-dalton protein. Insulin-stimulated phosphorylation exhibits an absolute requirement for Mn2+ as the sole divalent cation, whereas EGF-stimulated phosphorylation is supported by Mg2+ and Co2+ as well as Mn2+. In the presence of Mn2+, insulin-stimulated phosphorylation is not detected at less than 50 microM ATP, whereas EGF-stimulated phosphorylation is well expressed at 5 microM ATP. Thus, in detergent-solubilized membrane extracts, insulin stimulates the phosphorylation of its own receptor on tyrosine residues. This reaction has enzymatic properties distinct from those of the EGF-stimulated phosphorylation in these same extracts. The role of this insulin-stimulated phosphorylation reaction in the initiation of insulin's many biologic actions merits further study.

Adenosine Triphosphate↗

PubMed1986

Purification and partial characterization of hamster placental lactogen.

A radioreceptor assay for PRL-like activity was used to monitor the purification of a lactogenic protein, hamster placental lactogen (haPL), from late pregnant hamster placentae. Investigations of the PRL-like activity in placental extracts demonstrated that haPL is subject to disulfide-related aggregation phenomena that are not observed for mouse PL. By inclusion of 2-mercaptoethanol in the buffers used for purification, monomeric haPL was obtained. A 750-fold purification was achieved by ammonium sulfate precipitation and chromatography on phenyl-Sepharose, TSK diethylaminoethyl-650S, hydroxylapatite, and Sephadex G-100. This procedure yielded 6.2 mg (by dry wt) of purified haPL from 286 g 15-day pregnant hamster placentae, with an overall yield of 20%. The purified haPL has a mol wt of 25,200 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point of 8.8. haPL is lactogenic as judged by its ability to compete for lactogen binding sites on rabbit mammary gland membranes and to stimulate secretion of alpha-lactalbumin by cultured mouse mammary gland epithelial cells.

Animals↗

PubMed1989

Mouse placental lactogen-I: RIA and gestational profile in maternal serum.

A RIA for mouse placental lactogen-I (mPL-I) was developed using recombinant mPL-I as the standard, radioligand, and antigen for antiserum production. Displacement curves for dilutions of serum and placental extracts from pregnant mice were parallel to the recombinant mPL-I standard curve. Serum from male and nonpregnant female mice and high concentrations of mouse PRL, GH, PL-II, proliferin, and proliferin-related protein did not cross-react in the assay. mPL-I appeared in maternal serum on day 6 of pregnancy. Its concentration remained low until day 8 and them increased to a very large peak on days 9-11 (maximum concentration, approximately 8 micrograms/ml). The mPL-I concentration declined after day 11, but the hormone could be detected at low concentration in maternal serum until the end of pregnancy. On day 10 of pregnancy, the mPL-I concentration of maternal serum was correlated with litter size. Fractionation of serum from 10-day pregnant mice by size exclusion chromatography indicated the absence of high mol wt forms of mPL-I in the circulation.

Animals↗

PubMed1992

Radioimmunoassay of a bovine pregnancy-associated glycoprotein in serum: its application for pregnancy diagnosis.

A sensitive and specific double-antibody RIA for a bovine pregnancy-associated glycoprotein (bPAG) is described. The limit of detection was 0.2 ng/ml. The assay was specific for bPAG in that pituitary and placental gonadotropic hormones and other placental or serum proteins assayed in serial dilutions did not cross-react. The RIA allowed measurement of bPAG in placental extracts, fetal serum, fetal fluids, and serum or plasma of pregnant cows. About 20% of unbred heifers and nonpregnant cows had detectable levels ranging from 0.30 +/- 0.09 to 0.50 +/- 0.17 ng/ml (mean +/- SD), and 15% of bull sera showed higher concentrations (3.01 +/- 1.73 ng/ml) of bPAG or bPAG-like protein. Variations among animals was observed in fetal serum bPAG concentrations. Bovine PAG was detected in maternal peripheral blood at Day 22 of pregnancy (mean +/- SD, 0.38 +/- 0.13 ng/ml) in some animals and at Day 30 in all pregnant cows. Peripheral serum bPAG levels increased progressively to 3.60 +/- 1.73 ng/ml (mean +/- SD) at Day 30 of pregnancy, to 24.53 +/- 8.81 ng/ml at Day 120, and to 1551.91 +/- 589.68 ng/ml at Day 270. Peak concentration of bPAG was 2462.42 +/- 1017.88 ng/ml and it occurred 1-5 days prior to parturition. After delivery, bPAG concentrations decreased steadily to 499.63 +/- 267.20 ng/ml at Day 14 postpartum (pp), 10.12 +/- 7.84 ng/ml at Day 60 pp, and 1.44 +/- 1.08 ng/ml at Day 90 pp. The undetectable concentration (less than 0.20 ng/ml) was reached by Day 100 +/- 20 pp. An investigation undertaken in Holstein heifers, Holstein cows, and Hereford cows used as recipients for purebred Holstein embryos supplied evidence of the influence of breed of recipient and sex of fetuses on peripheral concentrations of bPAG. A herd of 430 Holstein-Friesian heifers that had received transferred embryos were bled at Day 35 postestrus (pe) for measurement of bPAG. The bPAG was detected in 287 of 430 serum samples analyzed. By rectal palpation performed at Day 45 pe, 267 heifers with detectable levels of bPAG at Day 35 pe were confirmed to be pregnant as were 3 of 143 heifers previously diagnosed as not pregnant by RIA. These results suggest that detection of this placental-specific antigen in the serum could be used as a specific serological method for early pregnancy diagnosis in cattle from 28 days after breeding.

Animals↗

PubMed1989

High molecular weight forms of placental lactogen: evidence for lactogen-macroglobulin complexes in rodents and humans.

Gel filtration chromatography of maternal plasma from late pregnant hamsters demonstrated that approximately 90% of hamster placental lactogen-II (PL-II) is present as high mol wt (Mr) forms. A major peak of immunoactive hamster PL-II with a Mr of 600,000 and a smaller peak (Mr, 210,000) were observed. The major high Mr form of hamster PL-II in plasma had a Mr of 360,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). High Mr forms also predominate in placental extracts, but differ from the plasma forms. 125I-Labeled monomeric hamster PL-II (Mr, 22,000) formed a disulfide-bonded complex (Mr, 720,000 by gel filtration and 360,000 by SDS-PAGE) when incubated in vitro with serum of male, nonpregnant female, or pregnant hamsters. The in vitro complex was also formed with unlabeled hamster PL-II. Similar high Mr complexes were formed, but to a lesser extent, when 125I-labeled mouse PL-II and human PL were incubated with the homologous late pregnant serum. High Mr complexes (Mr, 360,000 by SDS-PAGE) were also formed when the three 125I-labeled PLs were incubated with purified human alpha 2-macroglobulin. The most prominent circulating high Mr form of hamster PL-II had a Mr similar to that of alpha 2-macroglobulin by both gel filtration and SDS-PAGE. In addition, it had a mobility similar to that of alpha 2-macroglobulin on nondenaturing polyacrylamide gels, and it was about 10% asparagine-linked carbohydrate by weight, as is alpha 2-macroglobulin. These similarities and the ability of hamster PL-II to form a disulfide-bonded complex with alpha 2-macroglobulin in vitro suggest that the major circulating form of PL-II in the hamster may be a disulfide-bonded complex of one or more PL monomers with alpha 2-macroglobulin or a related plasma protein. Similar complexed forms of PL may be present in mice and humans.

Animals↗

PubMed1997

Developmental regulation of tissue transglutaminase during human placentation and expression in neoplastic trophoblast.

The expression of tissue transglutaminase (tTG) was studied during the formation of the normal human placenta and in molar pregnancies and choriocarcinoma, in order to correlate its expression with the functional characteristics of the recognized trophoblast cell types. tTG expression was found to be developmentally regulated. Before 6-7 weeks' gestation, only the chorionic villous cytotrophoblast expresses tTG. Thereafter the overlying syncytiotrophoblast becomes positive. tTG expression is gradually downregulated in the intermediate trophoblast cells emerging from the tips of the chorionic villi invading the uterine tissue. In the decidual wall, the intermediate trophoblast does not express tTG, whereas scattered syncytial cells, the placental bed giant cells, express tTG. Villi from complete hydatidiform mole (CHM) show tTG expression in both the cyto- and the syncytiotrophoblast. The intermediate trophoblast cells from CHM show heterogeneous tTG expression, with a majority of negative cells, whereas extravillous syncytia always express tTG. In choriocarcinoma, the tumour cells show heterogeneous tTG expression, with a majority of positive cells. Analysis of tTG protein and mRNA in placental extracts by Western and Northern blotting did not provide evidence for expression of the truncated form of tTG found in some cell types. The regulated expression of tTG in the normal placenta suggests that the enzyme is involved in important trophoblastic functions and may participate in the control of invasion.

Blotting, Northern↗

PubMed2000

Respiratory pacemaker cells responsive to CO(2) in the upper medulla: dose response and effects of mediators.

We previously reported on the presence of respiratory pacemaker cells that are highly sensitive to CO(2), in a region of the medulla oblongata in the fetal rat, 2 mm rostral to the obex. We now report on the CO(2) dose responses of these cells, as well as their responsiveness to certain chemical agents known to affect breathing in the fetus. Twenty-day-old fetal Sprague Dawley rats were block-dissected, and the cells of target areas were dissociated as previously described. Neuronal cells were plated on a medullary background and placed in the incubator with 10% CO(2) for 2-3 weeks. Cells were then studied using patch-clamp techniques. Pacemaker cells with single or bursting potentials showed responsiveness to CO(2) starting with pulses of 10 msec. Irregular beating or silent cells had poor or absent responsiveness to CO(2). Pacemaker cells responded to norepinephrine with increased firing potential; this action was blocked by metropolol. PGE(2) had no effect on pacemaker-cell activity, but indomethacin increased the spike frequency from 336+/-41 to 384+/- 65 spikes/min. Morphine stimulated the pacemaker cells from 205+/-25 to 272+/-29 spikes/min; this was blocked by naloxone. Finally, a placental extract, which inhibited breathing in the unanesthetized fetal sheep preparation, increased the activity of pacemaker cells from 301+/-35 to 452+/-52 spikes/min. In all of the above, irregular beating cells responded poorly and silent cells did not respond. The findings indicate that these pacemaker cells are uniquely designed to respond to CO(2) and have some properties which allow them to respond to certain chemical mediators in a manner similar to that of the whole respiratory system in vivo.

Animals↗

PubMed2002

Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis.

BACKGROUND: Chronic radiation cystitis occurs a minimum of three months after completion of pelvic radiotherapy and represents a range of clinical symptoms for which there is as yet no recommended standard management. OBJECTIVES: The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation cystitis and evaluate the evidence. SEARCH STRATEGY: Synonyms for radiation therapy and for the spectrum of radiation toxicity to the bladder in both text and MeSH terms were combined and applied to a range of databases without restriction of year of publication, methodology or language. SELECTION CRITERIA: The inclusion criteria included studies of interventions for the non-surgical management of all grades of late radiation cystitis. DATA COLLECTION AND ANALYSIS: Out of 80 relevant studies, there were no RCTs that met the inclusion criteria, but there were three prospective case series and two non-randomised studies which assessed different interventions and were not comparable. MAIN RESULTS: Sixty-three reports met the stated inclusion criteria. The majority were predominantly retrospective case series with the exception of two trials which were unrandomised and unblinded studies with a control group for comparison of effect. Although these two trials, Micic 1988, (intravesical placental extract) and Milani 1988, (flavoxate) provided the strongest evidence they were not randomised and were essentially isolated controlled studies. REVIEWER'S CONCLUSIONS: In such a relatively rare condition there are obvious difficulties in identifying sufficient patients to participate in a randomised controlled trial. The number of published reports is a reflection of the degree of medical interest that exists in providing therapeutic solutions for late radiation cystitis. However, in spite of the two studies of level IIA evidence, the absence of randomised controlled trials makes it impossible to draw any firm conclusions.

Chronic Disease↗

PubMed1993

Spatiotemporal expression of pregnancy-specific glycoprotein gene rnCGM1 in rat placenta.

As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1 transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Both antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells.

Amino Acid Sequence↗

PubMed2001

Small GTP-binding proteins in the nuclei of human placenta.

Mitochondria and crude nuclei containing fractions from human placenta have been shown to contain proteins which bind [alpha(32)P]-GTP. Prior to this study the number of GTP-binding proteins in placental nuclei and their nucleotide specificity was not known. Also unknown was the identity of any of the GTP-binding proteins in mitochondria of human placenta. Nuclei and mitochondria were purified from human placental extracts by sedimentation. Proteins were separated by electrophoresis and transferred to nitrocellulose membranes. Overlay blot with [alpha(32)P]-GTP identified two nuclei proteins with approximate molecular weights of 24 and 27 kDa. Binding of [alpha(32)P]-GTP to the 27 and 24 kDa proteins was significantly displaced by guanine nucleotides but not by adenine, thymine or cytosine nucleotides or deoxy (d) GTP. Western blot with a specific antibody to Ran identified a band at 27 kDa in nuclei and in mitochondrial fractions. These data indicate that both nuclei and mitochondria contain 24 and 27 kDa GTP-binding proteins. The GTP-binding proteins in nuclei display binding specificity for guanine nucleotides and the hydroxylated carbon 2 on the ribose ring of GTP appears essential for binding. It will be important in future studies to determine the functions of these small GTP-binding proteins in the development and physiology of the placenta.

Cell Nucleus↗

PubMed1990

Sarcolectin and interferon in the regulation of cell growth.

Sarcolectin is an endolectin present in a great variety of conjunctival tissues (muscles, cartilage, sarcomas), but also in brain or placental extracts of vertebrates, including primates. When purified to electrophoretical homogeneity as a 65-kd protein, it agglutinates cells and has an affinity for simple sugars. In addition, it is able to inhibit the synthesis of interferon (IFN)-dependent secondary proteins and to restore cells to their status ad primum. The biological effect of Poly(I).Poly(C)-induced feedback interferon is inhibited by the addition of sarcolectins, which also abolishes cellular refractoriness to repeated IFN induction. Similarly, sequential association of, first, Poly(I).Poly(C); 4-5 h later, sarcolectin restores the full capacity of both to promote cell growth, unrestrained by IFN. Indeed, the secondary proteins which are in the process of being synthesized are inhibited. In a great variety of animal cells, sarcolectin can also initiate growth after it has been blocked by IFN. This is not an all-or-none effect, but a balance may be struck by IFN and sarcolectin, depending on their respective concentrations and specific activity. We propose that the coordination of these cellular functions of Poly(I).Poly(C), IFN, and sarcolectin takes place in the form of a triangular growth-regulatory cycle and postulate that they thus maintain a balance during differentiated normal tissue development.

Animals↗

PubMed1976

Gallium-67 distribution in pregnant mammals.

Studies on the distribution of 67Ga in pregnant rabbits showed a marked concentration of the isotope in uterine tissue and flushings of 5-day pregnant rabbits 24 hours after isotope injection. The isotope no longer localized throughout the uterine tissues and flushings on injection of 7- to 8-day pregnant rabbits but was specifically associated with the blastocysts and sites of implantation. As the gestation time progressed 67Ga increasingly concentrated in placental and mammary tissue while the concentration in serum and thymus tissue decreased. The marked concentration in placental tissue was readily discernible on total-body scans of pregnant rabbits. Column chromatography of uterine washings and placental extracts from pregnant rabbits and thymus extracts from estrous rabbits showed most of the isotope associated with moieties greater than or equal to 200,000 MW whereas the isotope in "milk" and extracts of mammary tissue was bound to components of 25,000-35,000 MW. Extracts of thymus from pregnant rats showed a marked, selective loss of 67Ga binding in two peaks of approximately 50,000 and 120,000 MW compared to the chromatographic profile of extracts from normal rat thymus.

Animals↗

PubMed1999

A cellulose-binding domain-fused recombinant human T cell connective tissue-activating peptide-III manifests heparanase activity.

The chemokine connective tissue-activating peptide (CTAP)-III, which belongs to the leukocyte-derived growth factor family of mediators, was previously shown to be mitogenic for fibroblasts. However, it has recently been shown that CTAP-III, released from platelets, can act like a heparanase enzyme and degrade heparan sulfate. This suggests that CTAP-III may also function as a proinflammatory mediator. We have successfully cloned CTAP-III from a lambdagt11 cDNA library of PHA-activated human CD4(+) T cells and produced recombinant CTAP-III as a fusion protein with a cellulose-binding domain moiety. This recombinant CTAP-III exhibited heparanase activity and released degradation products from metabolically labeled, naturally produced extracellular matrix. We have also developed polyclonal and monoclonal antibodies, and these antibodies against the recombinant CTAP-III detected the CTAP-III molecule in human T cells, polymorphonuclear leukocytes, and placental extracts. Thus, our study provides tools to examine further immune cell behavior in inflamed sites rich with extracellular moieties and proinflammatory mediators.

Animals↗

PubMed1993

Visualization of lectin-like proteins in human placenta by means of anti-plant lectin antibodies.

Proteins antigenically cross-reactive with lectins were sought in the placenta by immunohistochemistry using polyclonal antibodies raised in rabbit against four well-known lectins: Concanavalin A, Wheat germ agglutinin, Ulex europaeus agglutinin, and Phaseolus vulgaris leukoagglutinin (PHA-L), as well as one antibody raised in goat against PHA-L. Even at high dilutions of the primary antibody, strong staining was obtained after short incubations, in patterns generally resembling those obtained for placental lectins by other means, such as those based on binding capacity for glycosylated probes. One of the immunohistochemical patterns distinguishes with great clarity between the trophoblast cell layers, thus relating to developmental and functional parameters; another localises PHA-L-immunoreactivity to the syncytiotrophoblast. These results underline the validity of the immunohistochemical screening as an approach in its own right. Both positive and negative controls were applied to the immunohistochemical methodology. These controls showed that the staining patterns obtained relate to the specificities of the primary antibodies employed; i.e. to lectins. The PHA-L-like cross-reactivity was analysed immunochemically. In electrophoretically separated and Western-blotted placental extracts there were found anti-PHA-L-binding fractions of apparent molecular weights 30 kDa, 58 kDa and 67 kDa. Control studies of the PHA-L antigen showed anti-PHA-L-binding fractions of approximate molecular weights 32 kDa and 60 kDa. The 30 kDa fraction from placenta and the 32 kDa fraction from PHA-L antigen bound lactosylated BSA but not fucosylated BSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

PubMed1994

Genetically polymorphic alpha-L-fucosidase (FUCA1) isozymes detected in blood plasma.

The main isozyme patterns of desialylated blood plasma or serum alpha-L-fucosidase (FUCA) were found to be almost identical to those of semen, urine, placental extracts, and leukocyte lysates, when detected by polyacrylamide gel isoelectric focusing, and activity staining using the fluorogenic substrate 4-methylumbelliferyl-alpha-L-fucopyranoside. Three phenotypes (1, 2-1, and 2) determined from plasma samples were identical to the phenotypes from urine and leukocyte lysates from the same individuals. A population study of plasma samples collected from 485 Japanese individuals indicated that the frequencies of the FUCA1*1 and FUCA1*2 alleles were 0.7505 and 0.2495, respectively. The mean plasma enzyme activities (+/- SD) of the three phenotypes were 318.8 +/- 116.7 nmol/ml per h for type 1, 268.0 +/- 108.3 nmol/ml per h for type 2-1, and 233.2 +/- 84.4 nmol/ml per h for type 2. The mean activities of types 1 and 2 suggest that, on average, the FUCA1*1 gene product in plasma has about 1.4 times the activity of FUCA1*2.

Adult↗

PubMed1981

Evidence for a placento-insular axis in the rat fetus.

Rat pups delivered by caesarian section one day before term, either remained attached to (experimental group) or were separated from their placenta (control group). Both groups were transferred into an incubator and their metabolic parameters studied. In the control group, plasma amino acid concentration fell from 11.2 to 6.9 mmol/1, plasma insulin fell from 151 to 45 mu U/ml and blood glucose fell from 3.5 to 2.6 mmol/1 during the first hour of extrauterine life. In the breathing feto-placental units, plasma amino acid concentration remained at its birth level, plasma insulin remained high (109 mu U/ml) causing rapid hypoglycaemia (1.63 mmol/1). An immediately postnatal glucagon and corticosterone surge was visible only in the experimental group. A partially purified placental extract (molecular weight 6000 to 30000) stimulated insulin secretion in vivo (fasted adult rats) and in vitro (isolated neonatal islets). It is concluded that the placenta maintains fetal hyperinsulinaemia by creating fetal hyperaminoacidaemia and, possibly, by secreting a beta cytotropic factor.

Amino Acids↗

PubMed1978

Malate dehydrogenase types in the Asian-Pacific area, and a description of new phenotypes.

A survey of more than 21 000 haemolysates from blood samples collected in various parts of south and southeast Asia, Australasia and the Western Pacific and examined in this laboratory has revealed several new alleles controlling variants of sMDH; in addition, further information has been provided on the distribution of sMDH3 in New Guinea. Two of the variant alleles, sMDH3 and sMDH6, achieve polymorphic frequency in various populations. sMDH3 is widely distributed in New Guinea, with highest frequencies in the Eastern Highlands. The pattern of its distribution suggests the mutant arose originally in a Papuan-speaking population. So far, sMDH6 has been detected only in Micronesians from a number of islands in the Carolines. A single example of another new variant, sMDH 5-1, and two examples of a slow variant, sMDH 7-1, were detected in samples from Iran and Singapore, respectively. No examples of mMDH variants were found in a total of 652 placental extracts from Papua New Guinea and Australia.

Australia↗