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Biomedical subjects

J Humphries

Publications and source records attributed to J Humphries.

At least 37 records · Page 2Linked to original sources

Electrophoretic techniques for the analysis of synthetic amyloid beta-A4-related peptides.

Two electrophoretic techniques have been developed for the analysis of synthetic beta-A4 related peptides. The first is an acetic acid--urea--polyacrylamide gel electrophoresis denaturing system while the second employs capillary zone electrophoresis at pH 7. Both methods were calibrated to identify the state (monomeric or aggregate) of the longer amyloid fragments beta-A4(1-40) and beta-A4(1-43) during analysis.

Acetates↗

Chemical methods of protein synthesis and modification.

Chemical and recombinant methods have continued to complement one another in the synthesis of protein analogues. Chemical methods remain particularly valuable when non-coded modifications are to be introduced, although it has been accepted since the commercialization of semisynthetic human insulin that they can also be used effectively for coded changes, in certain cases. The main objective of all such operations is not methodological, but is the production of molecules for practical use and further study. This goal has been reached frequently by chemical means during the past year.

Base Sequence↗

"Bread and a pennyworth of treacle": excess female mortality in England in the 1840s.

The author analyzes excess female mortality in nineteenth-century England. She concludes that such mortality was affected by the economic environment and that "much literary evidence points to unequal access to food and a resulting susceptibility to epidemic and respiratory diseases as the transmission mechanism converting dependence and discrimination into relatively high death rates." Women were also adversely affected by harsh labor conditions, in addition to the heavy duties involved in motherhood and housework.

Demography↗

Evaluation of an outpatient culture device in continuous ambulatory peritoneal dialysis.

From August 1983 through August 1986, we used a dipstick culture device for outpatient dialysate cultures among patients undergoing continuous ambulatory peritoneal dialysis. The device was used in 42% of 531 peritonitis episodes. In 21% of the peritonitis episodes, patients elected to be hospitalized for treatment and, therefore, did not obtain a dialysate culture. The frequency of noncompliance was 18%. All samples were received within four days of mailing. Forty percent of isolates were gram-positive organisms, 30% were gram-negative, 3% were fungal organisms, and 27% of the cultures failed to yield a growth. Aside from a greater incidence of failure to define a bacterial growth responsible for peritonitis, the spectrum of organisms was similar to culture results obtained from the patients who elected, during this same period, to be hospitalized. We believe the dipstick device may be used effectively for outpatient dialysate cultures.

Ambulatory Care↗

Beta-cell tropin: synthesis and biological activity.

The structure of beta-cell tropin, an insulin secretagogue released by the neuro-intermediate lobe of the obese (ob/ob) mouse, has recently been determined as the 22-39 moiety of ACTH. A method for the preparation of this octadecapeptide using mild solid-phase procedures followed by preparative high pressure liquid chromatography is described. The molecular weight of the synthetic peptide has been confirmed by Fast Atom Bombardment mass spectrometry. Synthetic beta-cell tropin is indistinguishable in its chromatographic, antigenic and biological properties from natural beta-cell tropin.

Adrenocorticotropic Hormone↗

Peritonitis in continuous ambulatory peritoneal dialysis patients.

Peritonitis is the most important complication of continuous ambulatory peritoneal dialysis (CAPD). We reviewed our experience with peritonitis over a 2 1/2-year period. Our patients spent 4% of their total time on dialysis in hospital due to peritonitis. Thirty-eight percent of the episodes of peritonitis were treated without hospitalization. We evaluated the dialysate bag change technique as commonly performed with currently available devices (extension tubing and titanium Luerlock Tenckhoff catheter adapter). The aseptic techniques described for dialysis extension tubing changes appear adequate (with no increased incidence of peritonitis demonstrated shortly after an extension tubing set change). Long-term sterility is maintained at the dialysate bag puncture port and at the orifice of the dialysis catheter adapter (no positive cultures from the bag port and orifice of the titanium adapter). Etiologic diagnosis of uremia was not a risk factor predisposing to peritonitis. The incidence of peritonitis was greater among patients with less formal education and lower income. Out data suggest that patients with less formal education and of lower economic status be carefully evaluated before commencing CAPD.

Bicarbonates↗

Antibiotic activity in peritoneal dialysate.

There are few studies investigating whether antibiotics added to 30% glucose concentrate preserve their activity in the delivered dialysate. Using a Drake-Willock proportioning system, samples were obtained from the "to" patient path at ten minutes after starting and at four hours. Samples were tested for minimal inhibitory dilution (MID) against Escherichia coli and Staphylococcus aureus. Antibiotics evaluated included amikacin, tobramycin, gentamicin, cephalothin, cefamandole, moxalactam, ampicillin, penicillin, carbenicillin, and vancomycin. In all antibiotics studied, similar MIDs were obtained at the ten-minute and four-hour samples. Compared to saline, dialysate significantly impaired the antibiotic activity (a difference of two or more tube dilutions) of all antimicrobial agents except amikacin and vancomycin.

Anti-Bacterial Agents↗

Inhibition of preovulatory gonadotropin secretion in the rhesus monkey by [(<Glu-Pro)1,D-Phe2,D-Trp3,6]-LHRH.

We report the first example of a complete inhibition of preovulatory gonadotropin secretion resulting from administration of a luteinizing hormone releasing hormone antagonist during a spontaneous menstrual cycle. The antagonist, [(<Glu-Pro)1,D-Phe2,D-Trp3,6]-LHRH, was administered to a rhesus monkey beginning on Day 9 of the menstrual cycle; ovulation did not occur and preovulatory peaks of LH and FSH were not observed despite elevations in serum estradiol-17 beta of sufficient strength and duration to elicit gonadotropin surges. Midcycle gonadotropin surges had already commenced in another monkey, however the antagonist did partially inhibit LH and FSH secretion although ovulation and luteinization were not prevented. Normal hormone secretion patterns and luteal function were observed in another monkey when the antagonist was given after the midcycle FSH and LH peaks had already occurred. These data emphasize the importance of beginning treatment with LHRH antagonists early in the follicular phase of the menstrual cycle.

Animals↗

The socio-economic determinants of recourse to legal abortion.

"This study of the determinants of legal abortion examines the interconnections between human reproduction and social organization. The hypothesis is that in the context of liberalized abortion laws, the incidence of abortion is determined by the socio-economic circumstances of women. A simple model of this relationship is tested using international data drawn from a sample of countries." The policy implications for welfare and birth control planning are considered, as well as the implications for feminist action.

Abortion, Induced↗

On the inhibitory effects of luteinizing hormone-releasing hormone analogs.

A detailed study of the activity of LHRH analog antagonists has been made in four assay systems which measure inhibition of the action of LHRH on isolated rat pituitaries in vitro, inhibition of the release of the LH induced by LHRH in vivo in adult male rats and adult male chimpanzees, and inhibition of spontaneous ovulation in cycling female rats. Only a partial correlation was observed between the in vitro and in vivo assays. Currently, the most potent LHRH analog antagonists in the present study were based on a 1,2,3,6-tetra-substituted LHRH sequence. The analogs [D less than Glu1,DPhe2,DTrp3,DTrp6]-LHRH, Ac-[Pro1,DPhe2,DTrp3,DTrp6]LHRH and [(Glu-Pro)1, dphe2,DTrp3,DTrp6]LHRH completely inhibited spontaneous ovulation in cycling rats at a dosage of 200 microgram/rat, sc. The most potent inhibitors of ovulation were always very potent in vitro, but other analogs having identical in vitro activities had little or no antiovulatory activity even at substantially higher dosages. The analogs inhibited the action of LHRH in the rat more easily than in the chimpanzee. Twelve of 13 analogs at the analog to LHRH ratio of 100:1 significantly inhibited the LH response, while only 5 of 9 of these same analogs inhibited the LH response in the chimpanzee at the analog to LHRH ratio of 333:1. Only 1 of 8 analogs at a high dosage inhibited the binding of labeled LH to the gonadal LH receptor in vitro. The inability of the less polar (cyclopentane carboxylic acid) analogs to inhibit ovulation could be explained, at least partially, in terms of impaired absorption sc. Although the cyclopentane carboxylic acid analogs effectively inhibited the action of LHRH in vitro and, when given iv in vivo, they were not effective in blocking the LHRH-stimulated LH response in adult male rats when given sc, which is the mode of administration of the antiovulatory assay, suggesting the importance of the route of administration.

Animals↗

Structural requirements in positions 1, 2, 3, and 6 of the luteinizing hormone-releasing hormone (LH-RH) for antiovulatory activity.

Sixteen analogues of the luteinizing hormone-releasing hormone (LH-RH) were synthesized by the solid-phase method. In new and surprising relationships, it was found that the substitution of D-Trp into position 3 of [D- less than Glu1,D-Phe2,amino acid3,D-Phe6]-LH-RH significantly enhanced the antiovulatory potency, but substitution by Pro, N-Me-Phe,N-Me-Leu, or L-Trp reduced antiovulatory activity. The substitution of L- less than Glu in position 1 of [D-Phe2,Pro3,D-Phe6]-LH-RH by cyclohexylcarbonyl (Chc), benzoyl (Bz), Ac, Hyp, Ac-Met, hydrogen, Pro, and D- less than Glu residues, and the substitution of D-Phe in position 2 by D-Trp, D-His, D-Phg, and L-Phe residues resulted in analogues with no antiovulatory activity at 750 microgram/rat. Structural requirements for the design of inhibitors of higher potency have been discussed.

Amino Acid Sequence↗

Inhibitory analogues of the luteinizing hormone-releasing hormone having D-aromatic residues in positions 2 and 6 and variation in position 3.

A single sc injection of 750 microgram/rat of [D-Phe2,Pro3,D-Phe6]-LH-RH on proestrus completely inhibited ovulation in 4-day cycling rats. Ovulation was inhibited partially at 375 microgram/rat. At the 720 microgram/rat dosage, analogues of LH-RH with D-Phe in positions 2 and 6, and with Sar, Arg, or Hyp in position 3, resulted in partial inhibitors and an inactive analogue with Thr substitution. In the same assay, analogues with D-Phe in position 2 and D-Trp in position 6 were partial inhibitors when D-Phe, Met, or Val were in position 3 and inactive with Ile substitution.

Animals↗

Inhibition of the activity of the luteinizing hormone-releasing hormone (LH-RH) by analogues with variations at positions 2, 3, and 6 and the carboxyl terminus.

In the isolated rat pituitary assay, [Thr2,Leu3]-LH-RH, [Leu2,Ala3,D-Ala6]-LH-RH, and des-Gly10-[Abu2,Ala3,D-Ala6]-LH-RH ethylamide inhibited the LH release due to 0.3 ng/mL of added LH-RH at a 10 microgram/mL dosage. Under these same assay conditions, des-Gly10-[Ile2,Ala3,D-Ala6]-LH-RH ethylamide was about one-tenth as active, and no inhibition was observed by [Leu2,Ser3]-LH-RH or [Leu2,Asn3]-LH-RH at a 100 microgram/mL dosage. The corresponding results from FSH inhibition assays, in vitro, are also reported.

Animals↗