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S Higgins

Publications and source records attributed to S Higgins.

At least 55 records · Page 3Linked to original sources

Standardization for four protein analytes with the Behring Nephelometer.

Owing to the generally higher values observed in the initial establishment of immunoglobulins (Ig) G, A, and M assays with the Behring Nephelometer, we elected to verify five commercial protein calibrators. This initial verification was performed by standardizing the Behring Nephelometer with the World Health Organization (WHO) International Reference Preparation for Human Serum Immunoglobulins G, A, and M. The instrument was also standardized for immunoglobulins and transferrin with use of the Reference Preparation for Serum Proteins (RPSP II). Analytical recoveries of the commercial calibrators varied. Also, assigned protein concentrations in both the WHO and RPSP II preparations made them unacceptable to us as benchmark calibrators for the Behring Nephelometer. Individual proteins (IgG, IgA, IgM, and transferrin) were obtained and primary standards prepared. Both transferrin and IgG were successfully standardized. However, IgA and IgM primary standards lacked 100% antigenicity, requiring removal of nonreactive IgA and IgM or reassignment of the correct value. The problem remains to find appropriate purified materials for IgA and IgM standardization.

Blood Proteins↗

High-dose corticosteroids in patients with the adult respiratory distress syndrome.

Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.

Clinical Trials as Topic↗

Folate sensitive site at 10q23 and its expression as a deletion.

A patient is reported for whom initial chromosome analysis indicated 45,X/46,XX/46,XX,10q- mosaicism. The clinical findings included hypothyroidism and a low red cell folate estimation. The deleted chromosome 10 was subsequently shown to be an extreme expression of the folate sensitive heritable fragile site at 10q23, and a possible association between this and the in vivo folate status of the patient is suggested.

Chromosome Deletion↗

Sequence organisation of rat seminal vesicle F gene: location of transcriptional start point and sequence comparison with six other androgen-regulated genes.

Seminal vesicle F gene, encoding an androgen-regulated serine-rich structural protein of the rat copulatory plug, has been sequenced together with 5' and 3' flanking regions. The intron/exon arrangement of the gene deduced from restriction maps was confirmed. The major and possible minor transcriptional start points were located by primer extension analysis and S1 nuclease mapping. A published nucleotide sequence for seminal vesicle S gene which also encodes an androgen-regulated protein of the copulatory plug has been extended to allow comparison of F and S genes. The considerable sequence homology between the two genes confirms their evolutionary relatedness. Homology is especially high in their promoter regions and their transcriptional start points are identical. They share several regions of dyad symmetry including one just upstream of the promoter. The upstream regions of F and S genes were compared with those of five other androgen-responsive rodent genes in an attempt to identify common sequence motifs that might be involved in hormonal regulation of gene expression.

Animals↗

Isolation and characterisation of genomic and cDNA clones for an androgen-regulated secretory protein of rat seminal vesicles.

Testosterone controls the synthesis of seminal vesicle protein F in male rats by regulating the cellular concentration of its mRNA (mRNAF). Phage lambda recombinants have been isolated containing the complete F gene. In addition plasmids have been constructed containing cDNAF sequences some of which are probably full-length (approximately 700 bp). Detailed restriction mapping shows that the F gene is 1.7 kbp long and contains approximately 1.0 kbp of intervening sequence arranged in at least two introns (420 bp and 600 bp). Part of cDNAF has been sequenced showing that the terminal 125 bp of the 3' untranslated region of mRNAF has substantial (greater than 70%) sequence homology with the 3' end of the mRNA coding for another androgen-dependent seminal vesicle protein (protein S). The cloned F gene has been detected in liver and seminal vesicle DNA along with an homologous but structurally different gene. The hormonal control of mRNAF was examined with cDNAF. A pronounced (approximately 3000-fold) differential response to testosterone was observed.

Androgen-Binding Protein↗

Isolation and characterisation of genes for androgen-responsive secretory proteins of rat seminal vesicles.

Under the influence of testosterone, rat seminal vesicles synthesise large amounts of a tissue specific protein, S. Recombinant lambda clones have been isolated containing overlapping sequences covering a 27.5 kilo base region of the rat genome within which the gene for protein S is located. Recombinant plasmids bearing cDNA sequences for protein S were constructed in pBR328. One (pcS2) contains a 690 nucleotide insert and is probably full length. Detailed restriction maps of the S-gene are presented and the structure was confirmed by analysis of R-loops and heteroduplexes. The S-gene covers a 2 kbp region of the genome and consists of a 5' intron (490 bp) separating a leading exon (120 bp) containing the 5' untranslated region from a central exon (310 bp) containing most of the coding sequence and part of the 3' untranslated region. A larger intron (1100 bp) lies within the 3' untranslated region. The cloned gene is representative of the native gene but the S gene may be heterogeneous. Using pcS2, the hormonal control of S-specific mRNA was examined and a pronounced differential response to testosterone was observed.

Animals↗

The Xenopus oocyte as a surrogate secretory system. The specificity of protein export.

Combining messenger RNA from one kind of secretory cell with the cytoplasm of another such cell can reveal the nature and specificity of protein export mechanisms. We show that messenger RNAs from secretory cells of chickens, rats, mice, frogs, guinea-pigs, locusts and barley plants, when injected into Xenopus oocytes, direct the synthesis and export of proteins. Chicken ovalbumin, Xenopus albumin, mouse thyroid-stimulating hormone, locust vitellin and guinea-pig milk proteins were identified using specific antibodies, whilst chicken lysozyme and ovomucoid, rat albumin, Xenopus vitellogenin and rat seminal vesicle basic proteins were identified provisionally from their molecular weights. Certain endogenous proteins are sequestered and secreted although most oocyte proteins are not exported. Similarly the major polyoma viral protein and the simian virus 40 and polyoma tumour antigens are retained within the oocyte. Radioactive proteins exported by oocytes programmed with chicken oviduct or Xenopus liver RNA are not re-exported in detectable amounts when injected into fresh oocytes, nor is there secretion of chicken oviduct or guinea-pig mammary gland primary translation products prepared using wheat germ extracts. Thus the export of secretory proteins from oocytes cannot be explained by leakage and may require a cotranslational event. The secretory system of the oocyte is neither cell-type nor species-specific yet is highly selective. We suggest that the oocyte can be used as a general surrogate system for the study of gene expression, from transcription through translation to the final subcellular or extracellular destination of the processed protein.

Animals↗

Propranolol as an antihypertensive agent in children.

The antihypertensive effect of oral propranolol was studied in 9 children with hypertension. After treatment with propranolol, systolic blood pressure fell by an average of 26 mmHg (P less than 0.01). Diastolic pressure decreased by 20 mmHg on average (P less than 0.01). The mean propranolol dose was 2.5 mg/kg per day. Side effects included bradycardia and anorexia. There was no correlation between pretreatment plasma renin activity and fall in blood pressure. Propranolol is an effective and well tolerated antihypertensive agent in children.

Adolescent↗

A case of early-stage epithelial ovarian cancer in pregnancy.

There are few reports in the literature of platinum-based chemotherapy administered in pregnancy. We present a case of serous adenocarcinoma of the ovary complicating pregnancy. Following laparotomy at 16 weeks of gestation, four cycles of cisplatin were administered prior to confinement at 32 weeks. There were no neonatal sequelae. We believe there is increasing evidence for the safe use of cisplatin in pregnancy.

Adult↗