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Biomedical subjects

V Harris

Publications and source records attributed to V Harris.

At least 19 recordsLinked to original sources

A transactivator of c-myc is coordinately regulated with the proto-oncogene during cellular growth.

A recently cloned nuclear protein, which binds a far upstream element (FUSE) of the human c-myc proto-oncogene, stimulates promoter driven expression in undifferentiated cells. In concert with a loss of c-myc expression, both FUSE binding protein (FBP) mRNA and protein levels disappeared in HL60 cells after PMA-induced differentiation, due to a drop in the rate of transcription that was measured by nuclear runoff. During the differentiation of these cells, the brief half-lives of FBP mRNA (3 h) and protein (1.5 h) did not change, allowing for the rapid down-regulation of nuclear protein levels, as detected by immunohistochemical staining. Like c-myc, FBP is expressed in proliferating cells from a variety of lineages, but not in quiescent cells. When T cells and fibroblasts were stimulated to transit from G0 into the cell cycle, there was a dramatic rise of both FBP mRNA and DNA sequence specific nuclear FBP binding activity, which correlated with the appearance of c-myc mRNA. In contrast to the transient expression of many other immediate early growth response genes, both FBP and c-myc expression were sustained for more than 24 h. In fibroblasts, the coordinate expression of FBP and c-myc throughout all phases of the cell cycle is consistent with FBP's role as a growth-dependent regulator of c-myc expression.

Base Sequence

Targeted melting and binding of a DNA regulatory element by a transactivator of c-myc.

A far upstream element (FUSE) of c-myc stimulates promoter activity when bound by a newly identified trans-acting protein, which is expressed in cycling cells. Since FUSE binding protein (FBP) binds only the noncoding strand (NCS) of its regulatory element in a sequence-specific manner, and not double-stranded (ds) DNA, formation of the protein DNA complex in vivo first requires unwinding of the DNA helix. In this report, we show evidence that FBP forces strand separation of short stretches of linear dsDNA. Because FUSE is contained within a region of helical instability that is partially unwound in negatively supercoiled DNA, it is a target for more extensive duplex strand separation by FBP, which first exposes and then selectively binds its NCS cognate sequence. In contrast, other single-stranded DNA binding proteins (SSBs) do not demonstrate this FUSE targeting activity. The novel linkage of regional dsDNA melting with cis-element binding by a transcriptional activator has broad implications in the regulation of eukaryotic gene expression.

Base Sequence

Effect of ischemia and reperfusion on lambda of the lumped constant of the [14C]deoxyglucose technique.

We measured the parameter lambda, which is the ratio of the distribution spaces of 2-deoxy-D-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. lambda is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a programmed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sampled regionally (4 to 7-mg samples) for local concentrations of glucose, ATP, phosphocreatine (PCr), and lactate. In a separate series of cats, the infusion of [14C]DG was started after 2 h of occlusion and 3 h of recirculation. In both series, lambda declined slightly for increased levels of tissue glucose and increased appreciably as tissue glucose decreased. A similar relationship was observed between lambda and ATP and PCr, although the correlation was not as clear. Since lambda, and hence the lumped constant, increases in ischemia as well as in postischemic tissue, it is important to measure tissue glucose concentration if quantitative values of local cerebral glucose metabolism are desired in this condition.

Adenosine Triphosphate

Investigation of an outbreak of methicillin-resistant Staphylococcus aureus in patients with skin disease using DNA restriction patterns.

OBJECTIVE: To investigate an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) among patients using chromosomal typing of the isolates. DESIGN: Comparison of epidemiological and clinical data to endonuclease restriction fragmentation analysis (RFA) of the MRSA isolates associated with an outbreak. Total DNA from the MRSA isolates was restricted with HINDIII and HAEIII for typing. SETTING: Tertiary care academic medical center. METHODS: An epidemiological investigation of an outbreak of MRSA among patients in private rooms was evaluated by routine infection control methods. The MRSA isolates from blood cultures of 7 patients and the nares of a nurse were collected during the outbreak. MRSA isolates from 23 patients not associated with the outbreak also were collected. The total DNA of the MRSA isolates were restricted with HINDIII and HAEIII and electrophoresed on 0.6% agarose gels. RESULTS: MRSA from 4 of the 7 bacteremic patients and the nurse on the outbreak unit had the same endonuclease restriction pattern. The patients were linked in that they were compromised by severe psoriasis or skin ulcers, were on the unit during the same period, and had oatmeal baths in a common bathtub. Of 50 staff members screened, the nurse was the only person detected as colonized by the strain. The other 3 patients on the unit as well as the 23 patients in other locations not associated with the outbreak had MRSA isolates with different RFA patterns. The use of the bathtub was discontinued and further transmission of MRSA was stopped. CONCLUSIONS: A comparison of the relatedness of MRSA by RFA demonstrated the uniqueness of the epidemiologically linked isolates and the utility of the RFA technique in the performance of routine infection control investigations.

Bacterial Typing Techniques

gamma-Aminobutyric acid inhibits the potassium-stimulated release of somatostatin from rat spinal cord slices.

Evidence supports the idea that somatostatin (SO) is a neurotransmitter or neuromodulator of primary afferent neurons involved in nociception. Since gamma-aminobutyric acid (GABA), norepinephrine, and morphine alter nociception at the level of the spinal cord, we examined whether these agents could alter the potassium-stimulated release of somatostatin from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2 cm segment of the lumbar spinal cord removed and chopped into 0.5 x 0.5 mm pieces and perfused at 37 degrees C in individual perfusion chambers with a modified Krebs-bicarbonate buffer at a flow rate of 0.5 ml/min. Perfusates were collected at 2 min intervals and assayed for SO using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl resulted in a 3-fold increase in release of SO from a basal level of approximately 0.2 to 0.6 pg/mg tissue/min. This evoked release was calcium dependent. Pre-exposure of tissue to GABA at 10(-4) and 10(-5) M significantly inhibited the potassium-stimulated release of SO, but did not alter basal release. The GABA receptor antagonist, bicuculline methiodide, at 10(-5) but not 10(-6) M attenuated the GABA-induced inhibition of somatostatin release. Bicuculline methiodide alone did not significantly alter either basal or stimulated release. Neither baclofen (10(-5) M, 5 x 10(-5) M), norepinephrine (10(-5) M), nor morphine (10(-5) M) had any significant effect on basal or stimulated release of SO from spinal cord tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Duodenal ulcer in sickle cell anemia.

A 14-year-old black male with sickle cell anemia developed a duodenal ulcer that masqueraded as sickle cell-related abdominal pain crisis on multiple occasions. Malingering and poor therapeutic compliance aggravated the ulcer in this patient, who ultimately succumbed to a catastrophic bleed. Duodenal ulcer appears to be an infrequent but difficult to treat lesion in sickle cell disease. An in-depth review on the occurrence of duodenal ulcer in sickle cell anemia is presented. The etiological mechanisms of peptic ulcer disease in this population and the potential benefits of transfusion therapy are discussed.

Abdominal Pain

Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment.

Amylin, a peptide copackaged with insulin in beta-cell granules, was measured in the effluent of the perfused rat pancreases by means of a newly developed specific radioimmunoassay. Its secretion parallels that of insulin in response to 20 mM glucose, 10 mM arginine, or the combination thereof. The relative molar amount of secreted amylin was estimated to be 25-37% that of insulin. Treatment with a borderline diabetogenic dose of streptozotocin reduced amylin response without significantly changing the insulin response. A severely diabetogenic dose of streptozotocin totally abolished amylin release and markedly reduced insulin release. The selective impairment of amylin secretion in streptozotocin-treated rats could represent an early manifestation of beta-cell depletion or injury.

Amyloid

The aesthetic alliance: nurses and medical facials.

This article introduces and explains methods for integrating services of dermatology nurses and cosmetic dermatologists. Basic aesthetic techniques can be incorporated into the dermatology practice; or a specialist, namely a licensed aesthetician, can perform the medical facial.

Acne Vulgaris

Neural defects in Jarcho-Levin syndrome.

Neuropathologic examination of two autopsied patients with Jarcho-Levin syndrome showed no pathologic changes in the brain, spinal cord, or nerve roots of one and diastematomyelia of the thoracolumbar spinal cord in the other. The abnormalities of the spinal cord in one of our patients and in another patient described in the literature establish neural defects as a component of the Jarcho-Levin syndrome.

Female

Sonographic renal parameters as related to age.

Four hundred and fifty-four kidneys were evaluated by real time ultrasound for appearance of renal cortical echogenecity, medullary pyramids and central sinus echoes. These renal parameters were correlated with age in 227 patients ranging in age from 0-15 years. The renal parenchymal echogenicity was observed to change not abruptly at a certain age but gradually over a period of years.

Adolescent

Secretory patterns of glucoregulatory hormones in prehepatic circulation of dogs.

The temporal organization of patterns of secretion of insulin, glucagon, and somatostatin was studied in basal conditions in normal or pancreatectomized dogs fitted with an indwelling hepatic portal catheter. Portal and peripheral blood samples were collected at a 7.5- or 15-min frequency, which covered the medium range of the ultradian period. The raw data were studied using spectral analyses employing fast Fourier transformation (FFT) techniques. The results indicate that in normal dogs: 1) endogenous physiological periodicities, statistically significant at a level of alpha = 0.05 (i.e., 95% confidence interval), were found to exist for the three pancreatic hormones in portal blood between 0.54 and 1.78 h/cycle and in peripheral blood between 0.59 and 1.84 h/cycle; 2) the portal levels of the hormones are significantly higher than peripheral ones; and, 3) whereas pancreatic hormones oscillated, glucose was found to maintain a steady level. In pancreatectomized dogs, no regular rhythm was detected. Thus, whereas endogenous periodicities exist for the secretion of pancreatic hormones in the normal dog, in the pancreatectomized dog the extrapancreatic glucagon and somatostatin are secreted in nonperiodic, randomly occurring pulses.

Animals

Craniofacial and mucopolysaccharide abnormalities in Kniest dysplasia.

Serial roentgencephalograms of a male patient with Kniest dysplasia were obtained between 1 7/12 and 11 3/12 years of age and were analyzed and compared to cephalometric normative data. The patient displayed macrocephaly with increased size of the neurocranium in all three dimensions. The cranial base angle was significantly flattened, partly as a result of anterior displacement of the sella turcica. The odontoid process was short and wide. At 11 years of age there was bony fusion between the anterior arch of the atlas and the odontoid process as well as between the posterior arch of the atlas and the cranial base. The facial skeleton, including the nasal bones, infra-orbital rims, maxilla and mandible, was retropositioned relative to the anterior cranial base. The mandibular retrognathia was pronounced at an early age but improved with growth. At age 11 years the patient had a straight facial skeletal profile. Examination of the patient's 24-hour urinary excretion of keratan sulfate revealed values markedly elevated for his age. Three additional patients with Kniest dysplasia demonstrated similarly increased excretion of this glycosaminoglycan. The diagnosis of Kniest dysplasia can usually be made from roentgenograms of the extremities, the spine, and the pelvis. However, the morphologic characteristics of the head, as shown by cephalometric analysis, and the increased urinary excretion of keratan sulfate add confirmatory evidence useful in differential diagnosis.

Cephalometry

Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs.

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

Animals

Hylambatin, a structurally unique tachykinin: effects on insulin and glucagon secretion.

Hylambatin is the first example of a tachykinin which possesses a methionyl methionine residue at the C-terminus, rather than the C-terminal tripeptide -Gly-Leu-Met-NH2 which hitherto has been a characteristic feature of all members of the tachykinin family. The effect of hylambatin on the secretion of glucoregulatory hormones was examined in the rat. Hylambatin, injected intravenously in graded doses 10 and 30 min before blood collection, significantly increased both plasma glucose and plasma insulin, whereas the secretion of glucagon was not affected. This profile of action is different from that of kassinin or substance P. Should hylambatin, like other neuropeptides, be present in mammalian tissue, it may have a role in the regulation of carbohydrate metabolism.

Animals