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Biomedical subjects

M Lynch

Publications and source records attributed to M Lynch.

At least 235 records · Page 13Linked to original sources
PubMed1989

Human polyomavirus: lack of relationship of viruria to prolonged or severe hemorrhagic cystitis after bone marrow transplant.

Urine cytology was studied prospectively for the presence of human polyomavirus (HPV) in 17 consecutive patients undergoing marrow transplantation and correlated with hematuria and hemorrhagic cystitis. Of the 15 evaluable patients, nine had cytologic findings consistent with HPV infection during the first month after transplantation. Of these nine patients, two had gross and seven had microscopic hematuria, all without symptoms of cystitis. Hematuria resolved within 30 days of onset, although three patients had persistent cytologic evidence of HPV until 100 days after transplantation. During the follow-up ranging from 8 to 14 months, none of the patients developed hemorrhagic cystitis. Our data do not support the relationship between HPV and prolonged or severe hemorrhagic cystitis previously suggested by others, nor did we see any late onset hemorrhagic cystitis.

Adult↗
PubMed1989

Escalating doses of etoposide with cyclophosphamide and fractionated total body irradiation or busulfan as conditioning for bone marrow transplantation.

In a phase I study 28 patients with lymphohematopoietic malignancies were treated with escalating doses of etoposide combined with cyclophosphamide 120 mg/kg and either fractionated total body irradiation (TBI) 1320 cGy in 11 fractions (n = 17) or busulfan 16 mg/kg (n = 11). Twenty transplants were allogeneic, seven autologous and one syngeneic. The maximally tolerated dose of etoposide in combination with TBI and cyclophosphamide was 60 mg/kg; at etoposide doses of 65 mg/kg three patients developed life-threatening or fatal mucosal toxicity. In combination with busulfan, the maximally tolerated dose of etoposide was 30 mg/kg. At an etoposide dose of 40 mg/kg two patients developed life-threatening or fatal toxicity (one mucosal, one hepatic). Mucositis requiring narcotic analgesics, hepatotoxicity, hematologic toxicity and interstitial pneumonitis were otherwise similar in TBI and busulfan-treated patients. Skin toxicity was observed significantly more often in the busulfan group. Five deaths occurred before day +30, two in the TBI group and three in the busulfan group. Eleven patients are surviving, ten in continuous complete remission, at a median of 9 (range 3-23) months following transplantation. Etoposide in combination with TBI and cyclophosphamide or busulfan and cyclophosphamide is associated with significant but acceptable toxicities. The maximally tolerated dose of etoposide is higher when combined with TBI than with busulfan. Promising response rates in this high risk group of hematologic malignancies warrant further evaluation of these etoposide containing conditioning regimens.

Adolescent↗
PubMed1989

Water availability and trachoma.

As part of an epidemiological survey of risk factors for trachoma in 20 villages in the United Republic of Tanzania, we investigated the relationship of village water pumps, distance to water source, and quantity of household water to the risk of inflammatory trachoma. We also evaluated whether there was an association between the cleanliness of children's faces and these water variables. No association was found between the presence of a village water supply and the prevalence of trachoma. However, the risk of trachoma in the household increased with the distance to a water source--although there was no association with the estimated daily amount of water brought into the house. Likewise, children were more likely to have unclean faces if they lived more than 30 minutes from a water source, but whether they had clean faces was not associated with the daily quantity of water brought into the household. The effect of the distance to water supply on trachoma may well reflect the value placed on water within the family, and this determines the priority for its use for hygiene purposes. The results of the study suggest that changing the access to water per se may be insufficient to alter the prevalence of trachoma without also a concomitant effort to change the perception of how water should be utilized in the home.

Child↗
PubMed1988

In vitro neurite extension by granule neurons is dependent upon astroglial-derived fibroblast growth factor.

When grown in the absence of astroglial cells, purified mouse cerebellar granule neurons survive less than 36 hr and do not extend neurites. Here we report that low concentrations of basic fibroblast growth factor (bFGF, 1-25 ng/ml) maintained the viability and promoted the differentiation of purified granule neurons. The effect of bFGF on granule cell neurite outgrowth was dose dependent. Neurite outgrowth was stimulated markedly in the presence of 1-25 ng/ml bFGF, but effects were not seen below 1 ng/ml or above 50 ng/ml. When affinity-purified antibodies against bFGF (1-5 micrograms/ml) were added either to purified granule cells or to co-cultures of neurons and astroglial cells, process extension by granule neurons was severely impaired. The inhibition of neurite outgrowth in the presence of anti-bFGF antibodies was reversed by the addition of 25 ng/ml of exogenous bFGF. In addition to neuronotrophic effects, bFGF influenced the rate of growth of the astroglial cells. This result depended on whether the astroglia were grown in isolation from neurons, where low doses of bFGF (10-25 ng) stimulated glial growth, or in coculture with neurons, where much higher doses of bFGF (100-250 ng/ml) were needed for glial mitogenesis. Immunoprecipitation of lysates from 35S-labeled cerebellar astroglial cells with anti-bFGF antibodies revealed a single band after SDS-PAGE at 18,000 Da, the molecular weight of bFGF. These results indicate that glial cells synthesize bFGF and are possibly an endogenous source of bFGF in cerebellar cultures. Thus, astroglial cells synthesize soluble factors needed for neuronal differentiation.

Animals↗
PubMed1988

Substrate analogue inhibitors of the IgA1 proteinases from Neisseria gonorrhoeae.

Substrate analogues based on the amino acid sequence of the hinge region of human IgA1 around the cleavage site of the IgA1 proteinases secreted by Neisseria gonorrhoeae are competitive inhibitors of these enzymes. The octapeptide Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser, which occurs between residues 233 and 240, has an IC50 value of 0.26 mM for the type 1 proteinase and 0.50 mM for the type 2 enzyme. Acetylation of the octapeptide N-terminal amino group lowers affinity for the type 1 proteinase sixfold but does not change binding to the type 2 enzyme. Amidation of the C-terminal carboxyl group does not change binding to the type 1 proteinase but improves IC50 for the type 2 enzyme. Simultaneous blockade of both the N- and C-termini drastically lowers affinity of the octapeptide for both proteinases. Sequential replacement of the hydroxy amino acids in the blocked octapeptide with cysteine yields a series of inhibitors that generally bind to the neisserial IgA1 proteinases as well as or better than the unblocked octapeptide. The most effective inhibitor contains a cysteine residue at position 6 (P3') and has an IC50 value for the type 2 IgA1 proteinase of 50 microM. Dimerization of the cysteine-containing octapeptides significantly diminishes inhibitory properties. The substrate analogues described here are the first synthetic inhibitors of the neisserial IgA1 proteinases to be reported.

Amino Acid Sequence↗
PubMed1988

Estimation of relatedness by DNA fingerprinting.

The recent discovery of hypervariable VNTR (variable number of tandem repeat) loci has led to much excitement among population biologists regarding the feasibility of deriving individual estimates of relatedness in field populations by DNA fingerprinting. It is shown that unbiased estimates of relatedness cannot be obtained at the individual level without knowledge of the allelic distributions in both the individuals of interest and the base population unless the proportion of shared marker alleles between unrelated individuals is essentially zero. Since the latter is usually on the order of 0.1-0.5 and since there are enormous practical difficulties in obtaining the former, only an approximate estimator for the relatedness can be given. The bias of this estimator is individual specific and inversely related to the number of marker loci and frequencies of marker alleles. Substantial sampling variance in estimates of relatedness arises from variation in identity by descent within and between loci and, with finite numbers of alleles, from variation in identity in state between genes that are not identical by descent. In the extreme case of 25 assayed loci, each with an effectively infinite number of alleles, the standard error of a relatedness estimate is no less than 14%, 20%, 35%, and 53% of the expectation for full sibs and second-, third-, and fourth-order relationships, respectively. Attempts to ascertain relatedness by means of DNA fingerprinting should proceed with caution.

Alleles↗
PubMed1988

Effect of an atrial natriuretic peptide, anaritide, on renal function in dogs on high- and low-sodium diets.

These studies examined the effects in dogs of dietary Na intake on plasma "ANF-like" immunoreactivity (PAI), and on the renal response to anaritide, a synthetic natriuretic peptide. There were no significant differences between high-Na (120 mEq/day) and low-Na (3 mEq/day) dogs in endogenous PAI, nor was PAI altered by oral or i.v. volume expansion with 0.9% saline. Renal arterial infusion of anaritide did not alter arterial pressure, renal blood flow or the frational excretion of lithium, but increased the fractional excretion of Na to similar degrees in both groups. The peptide increased GFR only in the low-Na group. Extremes of sodium balance do not seem to alter the renal response to anaritide, which apparently does not inhibit sodium reabsorption in the proximal tubule.

Animals↗
PubMed1987

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen.

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.

Binding, Competitive↗
PubMed1987

Evolution of intrafamilial interactions.

A theory for the evolution of behavioral interactions among relatives is developed that allows for genetic correlations between the types of behavior that are expressed in different social contexts. Both theoretical and empirical considerations indicate that such genetic constraints will almost certainly be common in natural populations. It is shown that when genetic correlations between elements of social behavior exist, Hamilton's rule inaccurately describes the conditions for evolution by way of kin selection. The direction in which social organization evolves is a delicate function of the genetic covariance structure among behaviors expressed as an offspring, sibling, parent, etc. A change in this covariance structure caused by random genetic drift or by a change in environment for a population exhibiting genotype-environment interaction can cause the population to suddenly cross a threshold into a new selective domain. Consequently, radical changes in social organization may arise between closely related species without any major shift in selective pressures external to the population.

Altruism↗
PubMed1987

External wear of the polyethylene socket in cemented total hip arthroplasty.

We examined 59 cemented high density polyethylene sockets removed at revision hip arthroplasty. Of these 19 showed areas of wear between the outside of the socket and the acetabular bone. This was associated with lack of acrylic cement in those areas and was also related to the depth of the wear on the articulating surface of the socket. It is suggested that, in some cases, changes at the bone-cement junction are secondary to socket loosening and abrasion against the bone of the acetabulum, rather than to particles migrating from the metal-polyethylene interface. It is therefore important that impingement of the neck of the femoral stem on the edge of the cup be avoided and that, when the socket is inserted, it is not in direct contact with the bone.

Acetabulum↗
PubMed1987

Deep infection in Charnley low-friction arthroplasty. Comparison of plain and gentamicin-loaded cement.

A retrospective review of 1542 Charnley low-friction arthroplasties was carried out to compare the incidence of deep infection arising after plain and gentamicin-containing acrylic cement. There was no significant difference between the two series in primary operations, the infection rate being 1.72% and 1.65% respectively. However, in secondary operations (conversions and revisions) the gentamicin-containing cement gave significantly better results--a 0.81% infection rate as compared with 3.46%. All operations were performed in a clean air enclosure using total-body exhaust suits. Radiological diagnosis of deep infection was possible within one year of operation in all cases. Late haematogenous infection occurred in one case and was related to a skin lesion.

Adult↗
PubMed1987

Invasive aspergillosis: an unusual cause of hemorrhagic pancreatitis.

Advances in chemotherapy have improved survival in patients with hematological malignancies, solid tumors, and have allowed for rapid progress in the field of organ transplantation. However, the frequency of opportunistic, specifically mycotic, infections has risen and provides a new challenge in the treatment of these patients. The following case report illustrates the need for early diagnosis and treatment and is the first known case reported of fatal hemorrhagic pancreatitis secondary to disseminated aspergillosis.

Aged↗
PubMed1986

Nucleotide sequence and analysis of the 58.3 to 65.5-kb early region of bacteriophage T4.

The complete 7.2-kb nucleotide sequence from the 58.3 to 65.5-kb early region of bacteriophage T4 has been determined by Maxam and Gilbert sequencing. Computer analysis revealed at least 20 open reading frames (ORFs) within this sequence. All major ORFs are transcribed from the left strand, suggesting that they are expressed early during infection. Among the ORFs, we have identified the ipIII, ipII, denV and tk genes. The ORFs are very tightly spaced, even overlapping in some instances, and when ORF interspacing occurs, promoter-like sequences can be implicated. Several of the sequences preceding the ORFs, in particular those at ipIII, ipII, denV, and orf61.9, can potentially form stable stem-loop structures.

Amino Acid Sequence↗