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Biomedical subjects

D Lawrence

Publications and source records attributed to D Lawrence.

At least 91 records · Page 5Linked to original sources

Human immunodeficiency virus infection due to clotting factor concentrates: results of the Seroconversion Surveillance Project.

From 1987 to the present, the Seroconversion Surveillance Project has provided the means by which to monitor the risk of transmission of human immunodeficiency virus (HIV) by clotting factor concentrates. One hundred thirty-one hemophilia treatment centers in the United States are contacted regularly, and data on HIV testing of patients are collected. To date, 4366 (46.0%) of 9496 patients have been reported to be seropositive, and 37 new seroconversions have been identified. Nine of these have met the Centers for Disease Control criteria for seroconversion while the patient was taking factor concentrate. None of the nine seroconversions were due to concentrates that had been treated to inactivate viruses and made from plasma that had been tested for HIV antibody. These results indicate that there is a high prevalence of seropositivity in affected patient groups, but that the risk of HIV infection from currently available clotting factor concentrates is extremely low.

Blood Coagulation Disorders↗

Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin: difference of expression of cytokeratins in epidermal and dermal Merkel cells.

The origin of Merkel cells is uncertain, although current evidence by immunohistochemical keratin marker studies favors an epidermal derivation. We studied the expression of keratin species in Merkel cells of human fetus and adult using 19 anti-keratin antibodies. Epidermal and dermal Merkel cells contained not only simple epithelium-type but also some stratified epithelium-type keratins. Interestingly, expression of some keratins was different between epidermal and dermal Merkel cells, for example, AN3 (50, 58 kD) and CKB1 (50 kD) recognized epidermal Merkel cells, but not dermal Merkel cells. These results suggest that surrounding keratinocytes influence the expression of cytokeratins in Merkel cells or that dermal Merkel cells undergo a modification from keratin-producing epidermal Merkel cells to a more neural cell type by the association with nerve endings in the upper dermis. On the other hand, certain cytokeratin polypeptides recognizable with Ks19.1 (40 kD), CK5 (45 kD), and CAM5.2 (52.5 kD) were expressed in both epidermal and dermal Merkel cells. The expression of simple epithelium-type keratins in Merkel cells remained even after the epidermal basal cells gradually lost their expression.

Adult↗

Transforming growth factor beta stimulates mitogenically mouse NIH3T3 fibroblasts and those cells transformed by the EJ-H ras oncogene.

TGF-beta 1 stimulates thymidine incorporation and the growth rate of mouse NIH3T3 fibroblasts and of those cells transformed by the EJ-H-ras oncogene (TR15 cells), in the presence and the absence of serum. Thymidine incorporation, in serum-deprived cells, is stimulated to a higher degree by 0.1-1 ng/ml of TGF-beta in NIH3T3 than in TR15 cells, which have a 10-fold higher basal level of incorporation. In both cell types TGF-beta 1 is as active, or more active than other mitogens (TGF-alpha, PDGF-AB, bFGF) at the same concentration. The growth rate of NIH3T3 cells, in low serum or serum-free (S-) medium, is stimulated by only 10 picograms/ml of TGF-beta 1, and that of TR15 cells, in S- medium, by only 1 picogram/ml. In contrast, TGF-beta 1 inhibits mitogenically unestablished mouse embryo fibroblasts and these fibroblasts immortalized spontaneously and able to grow in S- medium. It also inhibits the anchorage-independent growth of TR15 cells. NIH3T3 and TR15 cells respond, similarly, to TGF-beta activated by acification of their culture medium. The kinetics of thymidine incorporation and of activation of the c-myc proto-oncogene, observed already after 1 hr, in treated NIH3T3 and TR15 cells, suggests a direct mitogenic stimulation. The level of activated c-myc RNA is 2-fold higher at 2 hr, and subsequently decreases relatively less in the TR15 cells.

3T3 Cells↗

Effect of atrial natriuretic hormone on metoclopramide-induced stimulation of aldosterone.

The effect of atrial natriuretic hormone (ANH) on metoclopramide-induced stimulation of aldosterone was studied in eight healthy young men after 3 days of controlled diet (150 mEq sodium, 100 mEq potassium). Baseline values were obtained after subjects had remained sitting for 1 hour. Subjects then received 2-hour infusions of placebo, dopamine (2 micrograms/kg/min), ANH (0.6 pmol/kg/min), and ANH plus dopamine. One hour after the beginning of each infusion, a 10 mg intravenous bolus of metoclopramide was given. Prolactin levels increased 10-fold after metoclopramide with placebo infusion, and about 50% of this stimulation was abolished by preinfusion with dopamine. ANH preinfusion did not suppress prolactin release. Urinary sodium excretion increased prominently during dopamine infusion. ANH at this dose had no effect on natriuresis. The dopamine dose given had almost no effect on metoclopramide-induced aldosterone secretion, whereas ANH infusions, which resulted in approximate doubling of plasma ANH levels, suppressed aldosterone. This study supports a role of ANH in aldosterone regulation, even at nonnatriuretic doses, and suggests that ANH is acting not only through the renin-angiotensin system but under certain conditions has significant physiologic action directly on glomerulosa cells.

Adrenocorticotropic Hormone↗

Hyperthyroidism associated with a thyroid adenoma in a dog.

Hyperthyroidism associated with thyroid adenoma was diagnosed in a dog. Typical clinical signs of hyperthyroidism were resolved with surgical excision of the adenoma. Hyperthyroidism in dogs usually is associated with thyroid carcinoma, which has a poor prognosis. This case emphasizes the importance of obtaining a histologic diagnosis of thyroid tumors in hyperthyroid dogs before giving a prognosis.

Adenoma↗

Purification and initial characterisation of koala immunoglobulins.

The production of koala immunoglobulins (Ig) was elicited by the immunisation of a koala (Phascolarctos cinereus) with bovine serum albumin. This Ig was then purified using the highly specific techniques of affinity chromatography. The purified protein was compared with a "potential" koala Ig protein which was subsequently purified by Protein G chromatography and both proteins were further characterised by agarose/SDS-PAGE and immunoelectrophoresis. Results indicate that koalas do produce Ig in response to antigen challenge, koala Ig has a higher net negative charge than that seen in most other mammals and possibly two subclasses of IgG and IgM are present in normal koala serum.

Animals↗

Early effects of lead on bone marrow cell responsiveness in mice challenged with Listeria monocytogenes.

Listeria monocytogenes challenge of lead-treated mice results in increased mortality. Since macrophage development constitutes the initial phase of the immune response to L. monocytogenes, bone marrow and spleens from Pb-treated mice that were infected with L. monocytogenes were analyzed for their ability to form colonies when exposed to the macrophage growth factor CSF-1. Serum colony-stimulating activity also was evaluated. Data obtained indicate the Pb exposure results in decreased responsiveness of bone marrow and spleen cells to CSF-1 while colony-stimulating activity in serum rises. This lack of bone marrow-derived macrophage development may contribute to the increased mortality observed with L. monocytogenes challenged. Pb-treated mice.

Animals↗

Technical report: an injection technique for repositioning subclavian catheters.

Malpositioned central venous catheters need to be repositioned so as to avoid local toxicity from chemotherapeutic and other agents and to prevent venous thrombosis. We describe a simple, safe and effective technique for repositioning silicone central venous catheters, by using a hand injection of sterile saline. It was successful in all nine patients in whom it was attempted, with no complications. Five catheters were single lumen and four were double lumen. We feel that this method should be attempted prior to the use of more invasive techniques.

Catheterization, Central Venous↗

Effect of varying potassium intake on atrial natriuretic hormone-induced suppression of aldosterone.

To further assess the mechanism of atrial natriuretic hormone (ANH) induced suppression of aldosterone, we infused 0.5 pmol/kg/min Ser-Tyr28 human ANH over 2 h under three dietary conditions: low salt (LS), low potassium (LK), and high potassium (HK). The diets were consumed for 3 days before each study day. After 3 days of LK diet, blood pressure was slightly higher than under the other conditions. Serum potassium on LK was significantly lower than on HK (3.8 +/- 0.1 v 4.3 +/- 0.2). The ANH infusion did not cause any changes in blood pressure or urinary sodium and potassium excretion. Urine volume increased with ANH infusion under all diet conditions. Plasma renin activity and plasma angiotensin II levels were significantly lower on LK than on LS or HK, probably reflecting sodium retention. Increase in plasma ANH levels of about 75% (well within normal range) suppressed all hormonal parameters on LS and HK diets, but had no significant effect on LK diet. The pattern of aldosterone changes closely followed the changes in the renin-angiotensin system. We conclude that under various physiologic conditions ANH suppresses aldosterone predominantly through suppression of renin.

Adult↗

Differentiation of Bacillus anthracis from Bacillus cereus by gas chromatographic whole-cell fatty acid analysis.

Three strains of Bacillus anthracis and seven strains of Bacillus cereus were grown on complex medium and on synthetic medium. Gas chromatographic analysis of whole-cell fatty acids of strains grown on complex medium gave nearly identical fatty acid patterns. Fatty acid patterns of strains grown on synthetic medium showed a high content of branched-chain fatty acids. Significant differences between the fatty acid patterns of the two species were found. Odd iso/anteiso fatty acid ratios were about equal in B. anthracis strains, whereas in B. cereus strains the fractions of iso acids were at least twice as high as the fractions of anteiso acids. The method described herein is used in our diagnostic laboratory to help differentiate between these two species.

Bacillus anthracis↗

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Adenosine Triphosphate↗

Erythrocyte insufflation-induced protection against oxygen toxicity: role of cytokines.

We studied the pulmonary response of adult rats to erythrocyte (RBC) and RBC lysate insufflation to define the mechanism of RBC insufflation-induced protection against oxygen toxicity. Tracheal insufflation of 1 ml RBC (75%) or RBC lysate induced an intense pulmonary inflammatory response. Within 24 h of oxygen exposure, greater than 95% of insufflated RBCs was hemolyzed. The cell-free fraction of alveolar lavage fluids from RBC- or RBC lysate-insufflated rats had similar capacity in protecting endothelial cells against H2O2 cytotoxicity. However, RBC insufflation but not RBC lysate insufflation, protected rats against oxygen toxicity. There was marked erythrophagocytosis by alveolar macrophages of RBC-insufflated rats. Insufflation of RBCs, but not RBC lysate, resulted in production of tumor necrosis factor and interleukin 1, which could be recovered by bronchoalveolar lavages. When rats were insufflated with a combination of RBC lysate and cytokines at dosages within the range of cytokine levels achievable in alveolar lavage fluids by RBC insufflation, they became tolerant to oxygen. These results suggest that endogenously produced tumor necrosis factor and interleukin-1 as a result of RBC insufflation may play an important role in RBC insufflation-induced oxygen tolerance.

Animals↗

Trisomy 13: a new recurring chromosome abnormality in acute leukemia.

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.

Acute Disease↗

Degradation of crystallins from a psoriatic patient undergoing PUVA therapy.

Comparative physico-chemical and spectroscopic analyses were carried out in human lens proteins obtained from extracts of normal, senile and PUVA cataracts. Mass recovery analysis reveals a large protein concentration loss in the PUVA cataract relative to the normal lens and senile cataract. This protein loss parallels an increase in the degraded polypeptide chains. However, the tryptophan content (2.1 mol/mol of 20 kDa protein subunit) and the apparent fluorescence quantum yield (phi f = 0.056) of the tryptophan residues which are believed to be involved in the development of UV-induced cataracts are unchanged after age-related alterations and/or in vivo photochemistry associated with psoralen (8MOP) photosensitized reactions.

Aging↗

Transforming growth factor type beta 1 modulates the effects of basic fibroblast growth factor on growth and phenotypic expression of rat astroblasts in vitro.

In a search of the growth factors possibly involved in brain ontogenesis we have examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the growth and phenotypic expression of rat astroblasts in primary culture. Along TGF-beta 1 elicited only a slight negative effect on the growth of these cells. However, this factor was found to modulate the mitogenic effects of other growth factors. On quiescent cells it potentiates the mitogenic effect of basic fibroblast growth factor (bFGF) but not that of other growth factors, namely, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and thrombin. TGF-beta 1 did not modulate significantly the stimulatory effect of these growth factors on the activity of the enzyme glutamine synthetase (GS); but kinetic studies showed that TGF-beta 1 delays the stimulation of GS activity. DNA synthesis monitored by the incorporation of [125I]iododeoxyuridine (125I-dUrd) was maximum after 24-30 h of treatment with bFGF. With bFGF plus TGF-beta 1 the maximum was shifted to 30-36 h. This shift is compatible with the idea that TGF-beta 1 induces responsiveness in some cells which are otherwise unresponsive to the mitogenic action of bFGF, and that this induction requires some time. This hypothesis is sustained by the observation that in cells treated for only 12 h with bFGF, the treatment with TGF-beta 1 for the same 12 h or for longer time did not stimulate significantly the cell growth. Stimulation occurred only when the bFGF treatment was continued after 12 h. Potentiation of the mitogenic effect of bFGF and shift of the maximum 125I-dUrd incorporation towards 24 h was seen with cells pretreated with TGF-beta 1. This potentiation effect decreased with increasing time between the two treatments. The potentiation effect of TGF-beta 1 is not mediated by an induction of new bFGF membrane receptors as seen by binding studies.

Animals↗

Blunted ACTH and cortisol response to afternoon tryptophan infusion in euthymic bipolar patients.

The serotonin precursor tryptophan was used to test neuroendocrine responses in remitted bipolar patients and controls. Tryptophan was administered in the afternoon when spontaneous cortisol secretion is lower than in the morning. Following pilot studies at various doses, 50 mg/kg L-tryptophan was given i.v. over 20 min to 11 patients and 14 controls. Controls demonstrated cortisol release, whereas the response curve for patients was indistinguishable from placebo. Differences between groups were significant at 15, 30, and 45 min. Changes in adrenocorticotropic hormone were consistent with those in cortisol. Prolactin and growth hormone levels increased in both patients and controls following tryptophan. Higher doses caused gastrointestinal upset in some subjects.

Adrenocorticotropic Hormone↗

Second annual meeting of the National Cooperative Vaccine Development Groups for AIDS. 15-18 October 1989; Fort Lauderdale, Florida.

In this short review of the three-day meeting on AIDS vaccine development where numerous scientific advances were described for the first time, it is nearly impossible to capture all of the highlights. Thus, areas such as advances in vaccine adjuvant development, standardized challenge pools for vaccine testing, novel approaches with retroviral vectors for construction of target cells for cellular immune assays, summaries from all of the international AIDS vaccine development programmes, and other topics which were covered at the meeting are not discussed above. In closing the meeting, W. Koff (NIAID) noted that 1989 represented the turning point for AIDS vaccine development, that pessimism had given way to cautious optimism, and that the fundamental focus had changed from 'if a vaccine could be developed' to 'when'. While several challenges still remain in the path toward development of a safe and effective vaccine, the meeting served both to focus the direction of the research agenda for the next year and to build new and stronger collaborations among the international network of scientists dedicated to the common goal of developing a safe and effective AIDS vaccine.

Acquired Immunodeficiency Syndrome↗