PBDX is the XG blood group gene.

We have identified the Xga antigen, encoded by the XG blood group gene, by employing rabbit polyclonal and mouse monoclonal antibodies raised against a peptide derived from the N-terminal domain of a candidate gene, referred to earlier as PBDX. In indirect haemagglutination assays, these anti-peptide antibodies react with Xg(a+) but not Xg(a-) erythrocytes. In antibody-specific immobilization of antigen (ASIA) and immunoblot assays, the anti-peptide antibodies react with the same molecule as does human anti-Xga. Therefore, by its identity with PBDX, Xga is identified as a cell-surface protein that is 48% homologous to CD99 (previously designated the 12E7 antigen), the product of MIC2 which is tightly linked to XG. PBDX is renamed here XG.

Pulsatile GnRH stimulates normal cyclic ovarian function in amenorrheic lactating postpartum women.

The postpartum period is characterized hormonally by elevated levels of PRL and low levels of gonadotropins and sex steroids. In breast feeding, this state of postpartum amenorrhea can persist for an extended period, even though PRL levels decrease slowly. Although the action of PRL on multiple target sites has frequently been suggested as the cause of this ovarian quiescence, a suckling-induced alteration in hypothalamic gonadotropin-releasing hormone (GnRH) production has also been hypothesized. To test this latter hypothesis, we provided a uniform pulsatile GnRH stimulus to eight exclusively breast-feeding women for an 8-week duration beginning at 4 weeks postpartum. Five women with functional hypothalamic amenorrhea served as a comparison group. All women received GnRH administered at a dose of 200 ng/kg every 90 min sc via a portable infusion pump. Serial blood sampling for LH, FSH, and PRL was performed weekly for 5 h at 10-min intervals beginning immediately before initiation of GnRH, during the period of GnRH, and 1 week after the cessation of GnRH. The women collected daily urine aliquots for estrone-3-glucuronide, pregnanediol-3-glucuronide, and LH determinations. Serial transvaginal sonography was used to monitor follicular development. Before GnRH treatment the urinary steroid and serum gonadotropin levels of the two groups were low and similar. As expected, PRL levels were higher in the postpartum women (87 micrograms/mL vs. 4.25 micrograms/L, P < 0.05). After initiation of pulsatile GnRH, LH values increased and FSH values decreased in both groups. The LH increase with GnRH was significantly greater in the breast-feeding group than in the hypothalamic amenorrhea group (19.75 mIU/mL vs. 12.34 mIU/mL, P < 0.05). Analysis of pulse frequency and amplitude revealed a nearly complete 1:1 induction of LH pulses by the exogenous GnRH in both groups, with the breast-feeding group showing a greater amplitude (12.26 mIU/mL vs. 5.34 mIU/mL, P < 0.05). The cycle lengths, urinary steroids, and vaginal ultrasonography demonstrated a more rapid initial ovarian responsiveness in the breast-feeding group, as determined by the length of the first follicular phase. The breast-feeding group also showed a brisker ovarian response, as evidenced by a greater number of follicles that were 12 mm or greater (2.3 vs. 1.2, P < 0.05), and a greater luteal phase peak and integrated pregnanediol excretion, respectively (3.02 micrograms/L creatinine and 39.87 micrograms/L creatinine/cycle vs. 1.89 micrograms/L creatinine and 7.69 micrograms/L creatinine/cycle, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Chromosomal mapping of the blood group genes.

The assignment of blood group loci proceeds more slowly than that of biochemical markers, since it depends largely on pedigree analysis and these studies take longer to achieve significance than some of the rapid modern methods. However, seven structural blood group loci ABO, MNSs, Rh, Fy, Sc, Xg, and Ch--Rg are confidently assigned, and four more provisionally or tentatively sited. Other loci are recognized as part of linkage groups that will help in the eventual assignment to their chromosomes. There is little linkage information, and no assignments, for other independent loci involved in the expression of the ABO, Pl, Rh, and Lu loci.

Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine.

The kinetics of the disposition of intravenous and oral clonidine in five normotensive subjects have been determined. It is proposed that a two-compartment model adequately describes the disposition of the drug. The drug is rapidly distributed (t1/2alpha = 10.8 +/- 4.7 min) but slowly elimainated (t1/2beta = 8.5 +/- 0.9 hr). The bioavailability of oral clonidine in the tablets tested averaged 75.2% and 40 to 50% of the bioavailable dose is excreted unchanged in urine. Renal clearance of the drug showed considerable intersubject variation (1.82 +/- 0.34 ml/min/kg) and exceed the calculated glomerular filtration rate in some subjects. Oral and intravenous clonidine induced significant falls in blood pressure (greater than 20/15 mm Hg) in our normotensive subjects and consistently caused marked sedation and dryness of the mouth. Sedation and salivary flow correlated with plasma clonidine concentration over the range 0 to 4 ng/ml. Falls in blood pressure were related to plasma concentration to 1.5 to 2 ng/ml but at higher concentrations the hypotensive effect was attenuated.

Regulator genes affecting red cell antigens.

Several mechanisms may be involved to explain the action of genes that regulate the expression of red cell antigens. When carbohydrate antigens are involved, lack of an enzyme in the biochemical pathway prevents formation of the precursor for the next and following steps of that path, or, alternatively, addition of an extra sugar to the immuno-dominant sugar may produce a new structure in which the expression of the expected antigen is masked. Thinking of genetic rather than biochemical interference, a regulator gene may "switch-off" the action of a structural gene, and this mechanism could involve the upset of repressor and/or derepressor genes. The mechanisms for the regulator genes described in this article are unknown. The effect of XGR is limited to red cells: the expression of 12E7 antigen on other tissues and cells, other than red cells, is invariable. The reported effects of XOr and XQ are for red cells, but it is unlikely that other cells and tissues have been studied intensively; propositi with these regulator genes are much rarer than people informative for XGR and In(Lu). The effects of In(Lu) are not limited to red cells but have been shown to regulate the expression of p80 on some white cells. Most of the abnormalities in Rhnull cells appear to be associated with the lack of the Rh antigens and lack of Rh proteins. The hypothesis of a functional complex involving Rh, lack of which affects incorporation of apparently unrelated proteins into the red cell membrane, is an attractive idea. Studies of the similar phenotype, Rhmod, suggest that some Rh specificities can be present in cells that appear to be as abnormal, serologically and morphologically, as Rhnull cells. Perhaps some polypeptides are functionally more important than others and perhaps all polypeptides required for the functional efficiency of the Rh complex have not yet been identified. Lack of Lutheran antigens is not always accompanied by modification of other red cell antigens. As suggested by Telen and green, if In(Lu) acts via a single mechanism, then that mechanism differs from that of XS2. Certainly the mechanisms of In(Lu) and XS2 differ in their action on the expression of CD44 or p80 antigens. The red cell surface is well charted territory, familiar to serologists, immunologists, biochemists, and geneticists. It still provides an excellent model for study of cell surface antigens and for the regulator genes described above that modify expression of some red cell antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of urinary metabolites of sodium dipropylacetate in man; potential sources of interference in organic acid screening procedures.

Organic acid screening of urine samples from two children with neurological disease demonstrated the presence of two unknown metabolites. The children were receiving an antiepileptic drug, sodium dipropylacetate. The major abnormal compound has been shown by gas chromatography-mass spectrometry to be 3-oxodipropylacetic acid, a previously unidentified metabolite of dipropylacetate in man, while the minor metabolite was indentified as 2-(n-propyl)-glutaric acid.

A new sulfur amino acid, named hawkinsin, identified in a baby with transient tyrosinemia and her mother.

An unknown compound present in the urine of a girl with prolonged transient tyrosinemia and her mother was isolated and identified as (2-L-cystein-S-yl-1,4-dihydroxycyclohex-5-en-1-yl)-acetic acid (IVa). The new amino acid was named hawkinsin (Haw) and characterized by gas chromatography-mass spectrometry (GC-MS) of its penta-trimethylsilyl (TMS) derivative and of its desulfuration components. Haw was compared with the synthetic reference compound using GC-MS, IR, TLC, PC, ion-exchange chromatogrpahy and high-voltage electrophoresis. IVa and (2,6-bis-L-cystein-S-yl-1,4-dihydroxycyclohexyl-1)-acetic acid were synthesized from 4-quinolacetic acid, the latter was prepared in two different ways. It is postulated that Haw originates from an intermediate in the 4-hydroxy-phenylpuruvate hydroxylase reaction (EC 1.14.2.2), and that mother and child are heterozygous for an inborn error of metabolism characterized by a defect in this hydroxylase system, which is unable to rearrange the intermediate to homogentisic acid.

A comparison of dopamine and homovanillic acid excretion, as prognostic indicators in malignant phaeochromocytoma.

The urinary excretion of dopamine and its metabolite homovanillic acid (HVA) were compared in 15 patients with malignant phaeochromocytoma. Six patients with increased dopamine and HVA excretion had disseminated malignancy and the poorest prognosis. Four patients with increased urinary dopamine levels but normal HVA excretion also had widespread metastases and poor prognosis. The best prognosis was for 5 patients who had normal excretion of dopamine and HVA, and minimal disease. When dopamine and HVA excretion were considered separately, it was found that duration of survival was significantly better for patients with normal dopamine excretion than those with increased dopamine excretion (p less than 0.003). There was no significant difference in survival time between patients with normal and increased HVA excretion. In this study dopamine excretion appeared to be a more discriminating biochemical index of malignancy, prognosis and disease progression than HVA excretion.

Creatine kinase activity in the detection of carriers of Duchenne muscular dystrophy: comparison of two methods.

Serum creatine kinase activity was estimated in 48 control women and 22 female carriers of Duchenne muscular dystrophy by two different methods. One method is based on the colorimetric determination of creatine liberated from creatine phosphate; the other, an N-acetyl cysteine activated UV system, was used in an automated mode. The two methods were equally efficient in carrier detection, and results were closely correlated over the range of values encountered in controls and carriers. Log creatine kinase values appeared to be normally distributed in controls, but the distribution in carriers appeared skewed towards its upper end. If both distributions are assumed to be Normal, the probability, together with its standard error, that a consultand is a carrier, can be calculated from her creatine kinase value, and if the latter is expressed in standard deviation units of the control log creatine kinase distribution, probability estimates can be compared between laboratories.

Capillary gas chromatographic drug screen for use in forensic toxicology.

A screening method is presented involving the use of capillary gas chromatography using a BP-5 column and nitrogen-phosphorous detection. This method is a quick yet reliable procedure for a large range of neutral and basic drugs and uses 1 mL or less of blood. Running standards that contain a number of commonly observed drugs with each batch of cases allows for more accurate tentative identifications of likely drugs in unknown cases and also provides a measure of quality assurance. This method is suitable for postmortem and clinical blood samples as well as plasma and serum.

Auberger red cell antigens are not part of the Kell, Colton, or Dornbrock blood group systems.

Since 1981, red cell samples from families were tested with anti-Aua and, since 1986, with both anti-Aua and anti-Aub in an attempt to elevate Auberger to a blood group system status. The results show that Auberger is not pan of the Kell (five families), Colton (three Families), or Dombrock (two families) blood group systems. Exclusion from four more systems (Di, Yt, LW, Ch:Rg) is required before system status may be claimed.

Rhmod phenotype: a parentage problem solved by denaturing gradient gel electorphoresis of genomic DNA.

Initial Rh phenotyping of a man with hemolytic anemia, his wife, and son appeared to exclude paternity. No exclusion was found in other blood groups or in the human leukocyte antigen (HLA) system; excluding Rh, the paternity index was 98.58 percent. Samples from these three family members, and two other family members, were tested with additional Rh antisera. The results indicated that the propositus has an Rhmod phenotype with expression of c, weak e, and very weak D, E, and G antigens. To support this hypothesis, DNA analysis of the RHD and RHCE genes was performed on the five family members. Polymerase chain reaction (PCR) products from exons 2 and 5 were analyzed by denaturing gradient gel electrophoresis (DGGE). The DNA results corroborated the serologic findings and refuted the exclusion of paternity.

Glycophorin A-deficient red cells may have a weak expression of C4-bound Ch and Rg antigens.

The blood group antigens Ch and Rg are polymorphisms of C4d. Antigen-positive red blood cells (RBCs) treated with proteases type as Ch-, Rg-. Although RBCs treated with sialidase may type Ch+ Rg+, they cannot be coated with C4 by the 10 percent sucrose method. Since studies of complement binding have shown that glycophorin A (GPA) is an important component for the uptake of C4 by RBCs, we tested all available GPA-deficient RBCs for their Ch and Rg status. Using eluates of human anti-Ch and anti-Rg, and monoclonal anti-Rg, we found that the Ch antigen was only weakly expressed on these RBCs, while Rg expression was variable. Our results imply that in the absence of GPA, C4 binds in vivo to a component or components other than GPA on RBCs.