PubMed Health⌕ Search

Biomedical subjects

D M Joseph

Publications and source records attributed to D M Joseph.

16 recordsLinked to original sources
PubMed1998

Carcinoembryonic antigen in breast nipple aspirate fluid.

New diagnostic tools are needed to complement mammography and physical examinations for early detection of breast cancer, particularly among younger women. We evaluated the tumor biomarker, carcinoembryonic antigen (CEA), in 215 nipple aspirate fluid (NAF) samples collected from one or both breasts of 147 women, ages 27-87 years. Most subjects were recruited at the time of mammography examination. The 215 nipple fluid CEAs range from undetectable levels to 8400 ng/ml (median, 1100 ng/ml). Normal serum CEA levels are less than 6 ng/ml. There are no significant differences between the CEAs in fluid from normal breasts (112 samples) and breasts with various histories of tumors (total, 103 samples). Analyses for determinants of CEAs in fluids from normal breasts show higher levels among current smokers (P = 0.03) and marginal elevations among nulliparous women (P = 0.07). CEAs in these samples are not correlated with age, menopausal status, current hormone use, prior breastfeeding, or family history of breast cancer. Follow-up studies of these women and comparisons of CEAs in fluids from normal and cancer-containing breasts will help clarify whether this biomarker is useful for risk assessment or early cancer detection.

Adult↗
PubMed1997

Selective inhibitors of monoamine oxidase. 4. SAR of tricyclic N-methylcarboxamides and congeners binding at the tricyclics' hydrophilic binding site.

Linear [6.6.6] tricyclic moieties whose center ring is made of two atoms of differing size (here primarily thioxanth-9-ones and phenoxathiins) monosubstituted meta to the sulfur by C(O)NHMe include potent and selective inhibitors of monoamine oxidase A. Similarities with effects on SAR of acylamide and of diazapentacyclic substitution on such rings, including positional variables, the requirement for monomethylation (primary and dialkylated amides are inactive and higher monoalkylated amides show little or no potency), and that sulfur is optimally in sulfone form, suggest that binding to the enzyme occurs similarly in each series. No significantly greater rise in blood pressure was found in rats given sufficient 8 to inhibit most brain and liver MAO A and then followed by oral tyramine than was found on administration of tyramine to controls. This is in contrast to a large blood pressure rise in rats pretreated with phenelzine followed by tyramine, and in accord with the belief that an inhibitor selective for MAO A which is reversibly bound to the enzyme and therefore displaced by any ingested tyramine will not lead to the "cheese effect" (hypertension during treatment with MAO inhibitors usually caused by ingestion of foods containing tyramine).

Animals↗
PubMed1996

Comparison of primary charge separation in the photosystem II reaction center complex isolated from wild-type and D1-130 mutants of the cyanobacterium Synechocystis PCC 6803.

We compare primary charge separation in a photosystem II reaction center preparation isolated from a wild-type (WT) control strain of the cyanobacterium Synechocystis sp. PCC 6803 and from two site-directed mutants of Synechocystis in which residue 130 of the D1 polypeptide has been changed from a glutamine to either a glutamate (mutant D1-Gln130Glu), as in higher plant sequences, or a leucine residue (mutant D1-Gln130Leu). The D1-130 residue is thought to be close to the pheophytin electron acceptor. We show that, when P680 is photoselectively excited, the primary radical pair state P680+Ph- is formed with a time constant of 20-30 ps in the WT and both mutants; this time constant is very similar to that observed in Pisum sativum (a higher plant). We also show that a change in the residue at position D1-130 causes a shift in the peak of the pheophytin Qx-band. Nanosecond and picosecond transient absorption measurements indicate that the quantum yield of radical pair formation (phi RP), associated with the 20-30-ps component, is affected by the identify of the D1-130 residue. We find that, for the isolated photosystem II reaction center particle, phi RP higher plant > phi RP D1-Gln130Glu mutant > phi RP WT > phi RP D1-Gln130Leu mutant. Furthermore, the spectroscopic and quantum yield differences we observe between the WT Synechocystis and higher plant photosystem II, seem to be reversed by mutating the D1-130 ligand so that it is the same as in higher plants. This result is consistent with the previously observed natural regulation of quantum yield in Synechococcus PS II by particular changes in the D1 polypeptide amino acid sequence (Clark, A.K., Hurry, V. M., Gustafsson, P. and Oquist, G. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 11985-11989).

Cyanobacteria↗
PubMed1994

Does slow energy transfer limit the observed time constant for radical pair formation in photosystem II reaction centers?

We have used spectrally photoselective femtosecond transient absorption spectroscopy on photosystem II reaction centers to show that there are at least two pools of chlorin molecules/states which can transfer excitation energy to P680, the primary electron donor in photosystem II. It has previously been shown that one chlorin pool equilibrates with P680 in 100 fs [Durrant et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11632-11636], and we report here the observation of energy transfer from a second more weakly coupled chlorin pool. The effect of the weakly coupled pool is to increase the apparent time constant for radical pair formation from 21 ps when P680 is selectively excited to 27 ps when the accessory chlorins are excited. We conclude that it is possible to observe both radical pair formation somewhat slowed by an energy transfer step and radical pair formation not limited by this slow energy transfer, depending upon which chromophores are initially excited. These observations provide evidence that when using photoselective excitation of P680, the observed 21 ps time constant for radical pair formation is not limited by a slow energy transfer step.

Energy Transfer↗
PubMed1993

Rate of oxidation of P680 in isolated photosystem 2 reaction centers monitored by loss of chlorophyll stimulated emission.

We have continued our studies of the primary photochemistry of isolated photosystem 2 reaction centers using femtosecond transient absorption spectroscopy. Experiments were performed over a wide range of excitation and probe wavelengths, using several data collection time scales. This has enabled us to resolve five different lifetimes ranging between 100 fs and 200 ps plus a nanosecond component. We demonstrate here and elsewhere [e.g., Durrant, J.R., Hastings, G., Joseph, D. M., Barber, J., Porter, G., & Klug, D. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11632-11636] that the kinetic spectra associated with all but two of these lifetimes are clearly distinguishable. We have previously reported that a 21-ps lifetime is associated with pheophytin reduction [Hastings, G., Durrant, J. R., Hong, Q., Barber, J., Porter, G., & Klug, D. R. (1992) Biochemistry 31, 7638-7647]. In this paper, we show that it is possible to spectrally and temporally resolve stimulated emission from PS2 reaction centers with great accuracy and that this stimulated emission is largely unaffected by those kinetic components which are faster than 21 ps. The observation of a distinct stimulated emission band allows us to distinguish charge-separated states from chlorin singlet states. In this way, we are able to show that the proportion of charge-separated states prior to the 21-ps component is between 0% and 25%. We also show that the shape of the spectrum which we obtain for the state P680+Ph- is essentially invariant between 100 ps and 9 ns, and is the same as that previously reported for P680+Ph- by other researchers.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlorophyll↗
PubMed1992

Subpicosecond equilibration of excitation energy in isolated photosystem II reaction centers.

Photosystem II reaction centers have been studied by femtosecond transient absorption spectroscopy. We demonstrate that it is possible to achieve good photoselectivity between the primary electron donor P680 and the majority of the accessory chlorins. Energy transfer can be observed in both directions between P680 and these accessory chlorins depending on which is initially excited. After excitation of either P680 or the other chlorins, the excitation energy is observed to equilibrate between the majority of these pigments at a rate of 100 +/- 50 fs-1. This energy-transfer equilibration takes place before any electron-transfer reactions and must therefore be taken into account in studies of primary electron-transfer reactions in photosystem II. We also show further evidence that the initially excited P680 excited singlet state is delocalized over at least two chlorins and that this delocalization lasts for at least 200 fs.

Chloroplasts↗
PubMed1984

High tibial osteotomy for varus gonarthrosis. A long-term follow-up study.

We evaluated the results in eighty-three patients (ninety-five knees) who had had a high tibial osteotomy for either unicompartmental osteoarthritis or osteonecrosis. The operations were performed between 1965 and 1976. The mean length of follow-up was 8.9 years (range, five to fifteen years). The early results were promising: at two years 97 per cent and at five years 85 per cent of the knees had either an excellent or a good result. At subsequent follow-up, however, only sixty knees (63 per cent) had an excellent or good result, and in the remainder recurrent pain had developed. Twenty-two knees (23 per cent) had been revised to a total knee arthroplasty because of pain. The alignment obtained by the osteotomy was not as important in determining the long-term result as we had previously believed. Although recurrent varus deformity was observed in more than one-quarter of the knees, it was not necessarily associated with an unsatisfactory result. The passage of time was the most important factor in determining the result, as only fifteen (37 per cent) of the knees that had been followed for more than nine years were pain-free. We now believe that total knee arthroplasty is a more suitable operation for patients who are more than sixty years old and that high tibial osteotomy should be reserved for patients who have a strenuous occupation or who wish to continue to participate in sports activities.

Adult↗
PubMed1981

Bone-block iliotibial-band transfer for anterior cruciate insufficiency.

The anterior distal part of the iliotibial trace with attached bone block from Gerdy's tubercle was used as an intra-articular graft fixed by a screw to the tibia to control anterior instability (otherwise known as anterior, anteromedial, or anterolateral laxity) in twenty-four knees which were followed for two to four years. Concomitant single-plane 2+ to 4+ medial instability was present in eleven knees and was treated in five of them by simple immobilization, by imbrication of the medial collateral ligament, or by the Vigliani procedure. At follow-up, stability was improved and the result was rated good or excellent in twenty-one (88 per cent) of the twenty-four knees. The operation is applicable to the majority of chronic laxities of the knee and, because no immobilization is necessary, the postoperative care is much simplified and the rehabilitation time is much shorter. The procedure is contraindicated where there is posterior or single-plane lateral laxity.

Adolescent↗