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Biomedical subjects

E Lawrence

Publications and source records attributed to E Lawrence.

14 recordsLinked to original sources

Isolation of 1001 new markers from human chromosome 11, excluding the region of 11p13-p15.5, and their sublocalization by a new series of radiation-reduced somatic cell hybrids.

The determination of the physical map of human chromosome 11 will require more clones than are currently available. We have isolated an additional 1001 new markers in a bacteriophage vector from a somatic cell hybrid cell line that contains most of chromosome 11, except the middle of the short arm. These markers were localized to five different regions, 11p15-pter, 11p12-cen, 11q11-q14, 11q14-q23, and 11q23-qter, by a panel of previously characterized somatic cell hybrids. The region 11q11-14 harbors genes that have been shown to be important in breast cancer, B-cell lymphomas, centrocytic lymphomas, asthma, and multiple endocrine neoplasia, type 1 (MEN1). To determine the positions of the recombinant clones located there, we developed a new series of radiation-reduced somatic cell hybrids. These hybrids, together with those previously characterized, allowed us to map the 11q11-q14 markers into 11 separate segregation groups.

Asthma

Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide.

1. The response of the cutaneous microvasculature to intradermal injection of the endothelins (ET-1, ET-2 and ET-3) and the modulatory effect of endogenously produced nitric oxide (NO) have been determined in the rat. 2. Intradermal injection of endothelins (0.1- 10 pmol/site) induced dose-dependent local reductions in blood flow, measured by 133xenon clearance, with the following potency order; ET-1 = ET-2 greater than ET-3. 3. Laser Doppler blood flowmetry established that ET-1 (10 pmol/site) significantly (P less than 0.05) reduced microvascular blood flow for 3 h after injection. Over a wide dose-range, the response to the endothelins did not include any vasodilatation or visible flare. 4. A possible modulatory role of locally-produced NO was investigated by the intradermal injection of the potent inhibitor of NO generation NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (100 nmol/site) injected alone induced a significant decrease in blood flow. The vasoconstriction induced by L-NAME was partially reversed by L-arginine (P less than 0.05) but not observed with NG-nitro-D-arginine methyl ester (D-NAME). 5. L-NAME significantly (P less than 0.05) enhanced the decrease in blood flow induced by submaximal doses of ET-1, ET-2 and ET-3 and vasopressin, although the results do not suggest that any of the vasoconstrictors stimulate NO release. The response to L-NAME was still observed 3.5 h after inducing a prolonged constriction with ET-1 (10 pmol/site).6. These results indicate that locally produced NO maintains a dilator tone in the cutaneous microvasculature of the rat and acts to modulate the effect of vasoconstrictors such as endothelins. Hence, it is suggested that in conditions where endogenous NO release is reduced, vasoconstrictor agents such as the endothelins could induce a dangerous decrease in blood flow possibly leading to ischaemia and tissue necrosis.

Animals

Altered microvascular reactivity to endothelin-1, endothelin-3 and NG-nitro-L-arginine methyl ester in streptozotocin-induced diabetes mellitus.

1 We have determined the dermal microvascular effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 nmol/site), endothelin-1 (ET-1, 0.1-10 pmol/site) and ET-3 (0.1-30 pmol/site) in rats with streptozotocin (STZ)-induced diabetes mellitus. Cutaneous blood flow changes as measured by a 133xenon (133Xe) clearance technique, were determined in diabetic rats four weeks after treatment with streptozotocin (STZ) and compared with responses measured in normal rats four weeks after treatment with saline. 2 Resting skin blood flow was similar in diabetic and in normal rats, as measured by 133Xe clearance and laser Doppler flowmetry. 3 Intradermal NG-nitro-L-arginine methyl ester (L-NAME) reduced skin blood flow in normal rats by 55.2 +/- 2.6% as measured by 133Xe clearance, (n = 9). L-NAME was significantly less effective in diabetic rats, inducing a 40.9 +/- 7.7% decrease in blood flow (n = 9, P less than 0.05). The enantiomer D-NAME had no effect in either group of rats. 4 Low doses of ET-1 and ET-3 injected intradermally induced dose-dependent decreases in blood flow, measured by 133Xe clearance, which were similar in both groups of rats. However, the responses to the highest doses of ET-1 (10 pmol/site) and ET-3 (10 and 30 pmol/site) were significantly reduced in the diabetic compared with the normal rats (P less than 0.05).In addition vasoconstriction to the highest doses of vasopressin (0.3 and 3 pmol/site) and vasodilatation to the neuropeptide calcitonin gene-related peptide (CGRP, 1O pmol/site) were similarly reduced in the diabetic rats (P <0.05).5. The decrease in blood flow induced by submaximal doses of ET-1 was enhanced by co-injection with L-NAME (100 nmol/site) in both diabetic and normal rats. However, this enhanced response was significantly reduced in the diabetic rats (P<0.05). A similar pattern of responses were observed to ET-3 in the presence and absence of L-NAME.6. These results indicate that the cutaneous microvasculature of rats with STZ-induced diabetes responds differently to intradermal ET-1 and ET-3 compared with normal rats; a similarly altered vascular reactivity was observed with vasopressin and CGRP. Hence, the diabetic microcirculation has impaired responses to several vasoconstrictors and a vasodilator. The effect of the nitric oxide synthase inhibitor L-NAME is also suppressed in the diabetics, suggesting that there may be decreased local production of, or response, to nitric oxide.

Animals

Electronic imaging in a teaching hospital intensive care unit: evaluation of the clinical review system.

An intrahospital image-communication and display system was installed and is in continuous use. All images obtained in the medical intensive care unit (MICU) are digitized in the radiology department, then transmitted, stored and retrieved at the nurses' station in the MICU. This unit was easy to install, required minimal user training, and has been in continuous use for 1 year with negligible down time. The details of this system are provided in this report.

Computer Communication Networks

The influence of cephalostatic ear rods on the positions of the head and neck during postural recordings.

This study examined the effect of cephalostatic ear rods on the positions of the head and neck. The method error was assessed for postural recordings of the head and neck position made with and without ear rods. A photographic angle was correlated with the postural angles on x-ray film. The material compared 33 dental students who were recorded with ear rods in and with ear rods out. Subjects were chosen randomly to repeat the postural recordings. The differences between the mean for each postural variable were subjected to comparative analysis, using Student's t test for paired samples. A significant difference (p less than or equal to 0.05) was found between the means of the inclination of the cervical spine to the true horizontal and the means of the photographic angle. The mean values for the remaining postural variables showed an insignificant but consistent pattern of axial extension of the cervical spine. Cephalostatic ear rods may alter head and neck position during postural recordings. The method error made for recording total head and neck position with ear rods was higher than without ear rods. The difference in the photographic angle was found to have a moderate positive correlation with the difference in the cervical inclination and the total head and neck position. These data suggest that lateral cephalostatics without ear rods may be used to record total head and neck position and the photographic technique may be used as a quick, inexpensive method for the clinician to determine head and neck positional changes before and after treatment.

Adult

A comparison of acetaminophen and rimantadine in the treatment of influenza A infection in children.

Rimantadine was compared with acetaminophen in a double-blind randomly assigned therapeutic trial in 63 children presenting with influenzal symptoms. Forty-nine of the children were proven to have influenza A by culture on presentation. Forty-three of the cultures, 88%, were influenza A/H1N1 strains. Both drugs were well tolerated. Rimantadine lowered the amount of virus shed in the first 2 days after initiation of therapy. Clinical resolution of illness was not different between the two therapeutic modalities. In individuals who shed virus for 4 days, strains recovered on the last day were relatively resistant to rimantadine.

Acetaminophen

Diphtheria, tetanus, and pertussis vaccine. A comparison of the immune response and adverse reactions to conventional and acellular pertussis components.

Although the conventional Bordetella pertussis vaccine, which consists of killed whole organisms, has been shown to be effective in preventing disease, it has been associated with transient local and systemic reactions and may produce encephalopathy, though rarely. A new acellular pertussis vaccine containing partially purified protein antigens, filamentous hemagglutinin, and lymphocytosis-promoting factor hemagglutinin has been developed for use in Japan. We compared the immunogenicity and reactogenicity of conventional and acellular pertussis vaccine. Forty children aged 4 to 6 years and 40 children aged 18 to 24 months, all previously immunized at appropriate times with conventional diphtheria and tetanus toxoids and pertussis vaccine, were enrolled. We randomly assigned children to receive either conventional pertussis vaccine or acellular pertussis vaccine in a double-blind fashion. The diphtheria and tetanus components in both preparations were identical. Equivalent rises in pertussis agglutinin titers and antibodies to filamentous hemagglutinin and lymphocytosis-promoting factor hemagglutinin were measured in both vaccine groups at both ages that we studied. However, reaction rates to the two vaccines in both age groups were strikingly different. Acellular pertussis vaccine was significantly less reactogenic for fever, pain, fretfulness, abnormal gait, and local reactions at the vaccine administration site. If studies in progressively younger children confirm its reduced reactogenicity and equal immunogenicity, and if large-scale trials indicate its efficacy, the acellular pertussis vaccine may be a more appropriate candidate than the current vaccine.

Child