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Biomedical subjects

L L Wright

Publications and source records attributed to L L Wright.

At least 19 recordsLinked to original sources

Characterization of superior cervical ganglion neurons that project to the submandibular glands, the eyes, and the pineal gland in rats.

These studies sought to determine whether the cell bodies of rat superior cervical ganglion neurons projecting to three very different target organs differ in terms of their size, number, location within the ganglion and/or neuropeptide content, and whether these features are altered in response to neonatal deafferentiation of the ganglion. A series of retrograde tracer, immunocytochemical, and double-labeling studies revealed differences in the size, number, location and neuropeptide content of superior cervical ganglion neurons that project to the submandibular salivary glands, eyes, or pineal gland. The mean areas of the cell bodies of neurons projecting to the submandibular gland are largest, those projecting to the eye are smallest, and those projecting to the pineal are intermediate in size. Submandibular gland projecting neurons are found throughout the ganglion, while the eye and pineal projecting populations are localized to the rostral quadrants. The different subpopulations of target organ specific superior cervical ganglion neurons are heterogeneous in their content of vasoactive intestinal peptide-, neuropeptide Y- and somatostatin-like immunoreactivity. A greater percentage of submandibular gland than of pineal projecting neurons display vasoactive intestinal peptide-like immunoreactivity, but there are no differences in the percentage of neurons displaying neuropeptide Y- or somatostatin-like immunoreactivity between the target organ specific groups. Neonatal deafferentiation does not result in changes in the size, number or distribution of target organ specific neurons, or in the percentage of immunoreactive neurons in these populations. In conclusion, these studies provide evidence that the size and distribution of neurons and percentage of peptide-containing neurons in the superior cervical ganglion is related to the target organ innervated, but provides no evidence of exclusive target organ-peptide relationships.

Afferent Pathways

Expression of lectin binding in the superficial dorsal horn of the rat spinal cord during pre- and postnatal development.

The plant lectin Bandeiraea simplicifolia I-B4 binds to the soma and central terminals of a subpopulation of unmyelinated primary sensory neurones in the adult rat. The binding site of this lectin is thought to be the terminal alpha-D-galactose residue of a membrane associated glycoconjugate which may be involved in the development of specific connections between small diameter primary sensory neurones and second order neurones in the superficial dorsal horn of the spinal cord. To begin to investigate this possibility we have examined the development of lectin binding in the dorsal horn of pre- and postnatal rats. Lectin binding first appeared on axon profiles in the superficial dorsal horn of the spinal cord at embryonic days 18/19. Previous studies in the rat have revealed that the central processes of small diameter primary sensory neurones enter the dorsal horn at embryonic days 18/19. Our findings suggest that the glycoconjugate to which this lectin binds, is expressed by the central processes of small diameter primary sensory neurones as they grow into the spinal cord. It is therefore possible that this glycoconjugate is involved in the development of topographically ordered neural connections within the dorsal horn of the spinal cord.

Animals

Role of desolvation energy in the nonfacilitated membrane permeability of dideoxyribose analogs of thymidine.

The ability of thymidine and four dideoxyribose analogs of thymidine to cross phase barriers, such as those encountered at the exo and endo faces of a membrane, has been studied in a two-phase water/chloroform system. The rate constants for entering, ka, and leaving, kb, the organic phase and the partition coefficient, Kp (ka/kb), were determined for each compound. The values of Kp were found to be proportional to the values of the rate constants for nonfacilitated diffusion, c, into human erythrocytes reported in the preceding paper [Mol. Pharmacol. 41:950-956 (1992)]. This linear relationship suggests that, in accord with the solubility-diffusion model of nonmediated membrane permeation, movement of the thymidine analogs across the potential energy barriers at the membrane interfaces is fast, relative to the rate of transbilayer diffusion. Because the compounds have similar molecular volumes and would, therefore, have similar rates of transbilayer diffusion, the differences in c reflect the differences in the distribution of the compounds across the interfaces, i.e., the Kp values. The magnitudes of the Kp values are dependent not only on the pi value of each substituent on the dideoxyribose ring but also on the position of the substituent. Analogs having a hydroxyl group in the 5'-position have a higher Kp and a higher c than the corresponding analogs with the hydroxyl group in the 3'-position. This increased lipophilicity is attributed to a decrease in desolvation energy, resulting from the ability of the 5'-hydroxyl analogs to assume a syn configuration in which a bifurcated, intramolecular, hydrogen bond can be formed to the O-4' and the C-2 carbonyl groups.

Antiviral Agents

Initial binding of 2'-deoxynucleoside 5'-triphosphates to human immunodeficiency virus type 1 reverse transcriptase.

Human immunodeficiency virus type 1 reverse transcriptase (EC 2.7.7.49), a heterodimer consisting of two polypeptide chains of molecular weights 66,000 and 51,000, fluoresces due to the presence of 36 tryptophan residues with an emission peak centered at 338 nm. The association of 2'-deoxynucleoside 5'-triphosphates with the enzyme results in a decrease in the intensity of the tryptophan emission spectrum, which can be used to calculate apparent dissociation constants. The Kd values determined for binding of the four natural 2'-deoxynucleoside 5'-triphosphates to the free enzyme range from 36.7 +/- 1.8 microM for dTTP to 47.3 +/- 3.9 microM for dATP. The 5'-triphosphate of zidovudine has a Kd of 54.1 +/- 1.3 microM. The enzyme shows no preference for purine or pyrimidine nucleotides. Hill coefficients and the results of dual ligand titration experiments demonstrate that the free enzyme possesses a single dNTP binding site for which the four natural substrates and the 5'-triphosphate of zidovudine compete. The presence of homopolymeric template-primers does not result in selective binding of the complementary 2'-deoxynucleoside 5'-triphosphate, indicating that Watson-Crick base pairing is not involved in the initial binding reaction. The major force driving the association of the ligands with the binding site is hydrophobic. Approximately 14% of the binding energy is derived from electrostatic interactions. Although Mg2+ is required for catalytic activity, it is not absolutely required for initial binding.

Binding, Competitive

Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network.

We studied the occurrence of necrotizing enterocolitis in 2681 very low birth weight infants during an 18-month period to characterize the biodemographic and clinical correlates. Proven necrotizing enterocolitis (Bell stage II and beyond) occurred in 10.1% of study infants; necrotizing enterocolitis was suspected in 17.2% of study infants. Positivity of blood cultures was related to necrotizing enterocolitis staging. The mortality rate increased only for stage III necrotizing enterocolitis (54% died). Logistic regression identified medical center of birth, race, gender, birth weight, maternal hemorrhage, duration of ruptured membranes, and cesarean section as significant risk factors. For one center the odds ratio was 3.7, whereas for another center it was only 0.3. For black boys, the odds ratio was 2.3 relative to nonblack boys; for girls, race did not affect prevalence of necrotizing enterocolitis. Age at onset was related to birth weight and gestational age. Intercenter differences in necrotizing enterocolitis prevalence were related to time required to regain birth weight and other indicators of fluid management. Gram-positive organisms predominated in positive blood cultures for stage I and II necrotizing enterocolitis; enteric bacteria were isolated more frequently in infants with stage III disease. We conclude that necrotizing enterocolitis prevalence varies greatly among centers; this may be related to early clinical practices of neonatal care.

Birth Weight

Somatostatin-, vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactivity in eye- and submandibular gland-projecting sympathetic neurons.

Studies combine the use of the retrograde tracer, fluorogold, and immunocytochemical staining to determine whether superior cervical ganglion (SCG) neurons projecting to the iris or submandibular gland (SMG) in adult male and female rats show distinctive immunoreactivity to somatostatin (SS), vasoactive intestinal polypeptide (VIP), or neuropeptide Y. Overall, more SMG-projecting neurons than eye-projecting neurons contain VIP-like immunoreactivity (VIP-LI), and more eye-projecting neurons than SMG-projecting neurons contain SS-LI and VIP-LI. Thus, postganglionic neurons of the SCG that project to specific target tissues are heterogeneous in their peptide content, and there are differences in the pattern of peptide-immunoreactivity between neurons projecting to these two target tissues. In addition, the results indicate that there may be gender differences in the expression of these neuropeptides.

Adrenergic Fibers

Gender difference in a subpopulation of rat superior cervical ganglion neurons.

The number of superior cervical ganglion (SCG) neurons is equivalent in males and females on the day of birth. By 15 days, after most of the normal neuron death has occurred, males have 20-30% more neurons than females; and this difference persists in the adult. The present study was undertaken to determine whether this difference exists uniformly throughout the ganglion, or only in a subpopulation of these neurons. To study subpopulations of SCG neurons, bilateral transection of the internal carotid nerve, the external carotid nerve, or both postganglionic nerves was performed on neonatal male and female Sprague-Dawley rats on the day of birth. Littermate sham operates served as controls. Numbers of neurons were counted in SCGs of animals on either postnatal day 4 or 15, before or after normal development of the SCG sex difference. At 4 days, the number of SCG neurons in sham-operated males had females were not different, while at 15 days, sham-operated males had more SCG neurons than did sham-operated females. The number of neurons remaining in the SCG following neonatal transection of the internal carotid nerve were not different in males and females at either 4 or 15 days postnatal. The number of SCG neurons remaining following neonatal transection of the external carotid nerve was greater in males than in females at both 4 and 15 days postnatal. It was concluded that the gender difference in survival of SCG neurons lies in neurons projecting through the internal carotid nerve. The number of neurons projecting out the external carotid nerve is equivalent in males and females.

Animals

Effects of gonadal steroids on nerve growth factor receptors in sympathetic and sensory ganglia of neonatal rats.

The numbers of neurons in the rat superior cervical sympathetic ganglion (SCG) differ in males and females, with the males having 30% more SCG neurons than females at 60 days of age. This sex difference arises during the early postnatal period, when testosterone administration increases the numbers of neurons and alters the nerve growth factor (NGF) content of the rat SCG. In contrast, there is no gender difference in number of neurons in the L1 dorsal root ganglion. In both males and females, the amount of NGF bound per ganglion increased between postnatal days 5 and 15 (P5 and P15) in both dorsal root ganglia (DRGs) and the SCG. There is also a gender difference in NGF binding: SCGs and DRGs of female rats at both P5 and P15 bind more NGF per ganglion than do those of males. This effect was more marked in DRGs than in the SCG. Treatment of neonatal females with testosterone reduced NGF binding in both SCGs and DRGs to levels comparable to males at P5, and in DRGs at P15. In contrast, treatment of males with testosterone from birth resulted in a 2-3 fold increase of NGF binding in both SCGs and DRGs as compared to controls at P15. At P15, testosterone treatment of females increased NGF binding in the SCG. Males and females had opposing responses to neonatal exposure to estradiol. Treatment with estradiol from birth increased NGF binding in SCGs and DRGs of females, but had no effect on NGF binding of SCGs, and reduced NGF binding in DRGs of males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Inhomogeneous translational diffusion of monoclonal antibodies on phospholipid Langmuir-Blodgett films.

The translational mobility of fluorescent-labeled monoclonal antibodies specifically bound to supported phospholipid bilayers containing hapten-conjugated phospholipids has been measured as a function of the surface concentration of bound antibodies using fluorescence recovery after photobleaching. Fluorescence recovery curves are fit well by a model that assumes the presence of two populations of antibodies with different lateral diffusion coefficients. The larger diffusion coefficient equals 3.5 x 10(-9) cm2/s, the smaller diffusion coefficient ranges from 1.5 x 10(-9) cm2/s to 2.5 x 10(-10) cm2/s, and the fractional fluorescence recovery associated with the smaller coefficient increases from approximately 0 to approximately 0.7 with increasing concentration of bound antibody. These results suggest that complexes of haptenated phospholipids and antibodies in phospholipid Langmuir-Blodgett films form clusters or domains in a concentration-dependent fashion.

Antibodies, Monoclonal

Cerebral blood flow velocity in term newborn infants: changes associated with ductal flow.

The effects of ductal closure on range-gated pulsed Doppler cerebral blood flow velocity (CBFV) patterns in the internal carotid, anterior cerebral, and middle cerebral arteries were studied in 10 normal term infants (mean birth weight 3302 +/- 294 g (SD) and mean gestational age 39.6 +/- 1.3 weeks). Pulsatility was calculated from flow velocities and used as an estimate of cerebral blood flow (CBF). Ductal closure was associated with a rise in mean blood pressure from 45.0 +/- 4.2 to 51.3 +/- 6.5 mm Hg (P less than 0.05) and a significant decrease in pulsatility in all three vessels (mean = 0.77 +/- 0.07 vs 0.70 +/- 0.05 (P less than 0.02]. Changes in pulsatility were correlated with changes in mean blood pressure (P less than 0.02), providing evidence that systemic blood pressure may influence postnatal cerebral arterial pulsatility indices. We also noted significant differences in the velocity and pulsatility of individual vessels that were independent of blood pressure, suggesting that Doppler flow studies may be useful in describing regional CBF patterns. The temporal association between ductal closure and decreased pulsatility suggests that CBFV patterns reflect ductal shunting in normal term newborn infants. Diastolic runoff and reduced systemic blood pressure in the presence of ductal shunting appear to reduce diastolic flow velocity and increase CBFV pulsatility in normal term infants during the first days of life. Normal mechanisms of cerebral autoregulation compensate for decreased flow with vasodilation; therefore the increased pulsatility associated with ductal shunting may be due to diastolic runoff rather than increased cerebrovascular resistance.

Blood Pressure

Development of the sex difference in neuron numbers of the superior cervical ganglion: effects of transection of the cervical sympathetic trunk.

The number of superior cervical ganglion (SCG) neurons does not differ for males and females on the day of birth, but by 15 days, after most of the normal neuron death has occurred, males have significantly more neurons than females. This difference persists in the adult. The present study was undertaken to determine whether the presence of afferent input to the SCG is required for the development of this sex difference. Bilateral transection of the cervical sympathetic trunk, which deafferents the SCG neurons, or a sham operation was performed on male and female Sprague Dawley rats on the day of birth. Numbers of neurons were counted in SCGs of animals sacrificed on either postnatal day 4 or 15, before or after normal development of the SCG sex difference. At 4 days, the number of SCG neurons in sham-operated males and females were not different, but by 15 days, females had lost a significant number of neurons, whereas the males had not. Transection of the cervical sympathetic trunk led to a significant loss of over 6,000 SCG neurons by postnatal day 4 in both males and females. Whereas some of this loss is due to axotomy of caudally projecting SCG neurons, at least half of the neuron loss is due to removal of the afferent input. At 15 days, sham-operated males had significantly more SCG neurons than did sham-operated females, but the gender difference was not significant in animals with neonatally deafferented ganglia. Thus, the normal development of the gender difference in SCG neuron numbers requires an intact afferent input.

Animals

Five vs ten days of penicillin V therapy for streptococcal pharyngitis.

To determine the effectiveness of a short (five-day) course of penicillin V potassium therapy, 172 patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis were randomly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days. The patients in the two treatment groups were comparable with respect to clinical findings, compliance, and serologic response to GABHS. A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 (18%) of the 73 patients in the five-day treatment group and in six (6%) of the 99 patients in the ten-day treatment group. These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis.

Child

The role of neuron death in the development of the gender difference in the number of neurons in the rat superior cervical ganglion.

Adult male rats have more neurons in their superior cervical ganglia than do adult females. This difference arises over the first two postnatal weeks, and is apparently related to perinatal levels of circulating testosterone. Exposure of neonatal rats to testosterone or estradiol during the first postnatal weeks results in an increase in the number of neurons in the superior cervical ganglion seen at 15, 30 or 60 days postnatally. The present studies were undertaken to determine whether this observed increase in neurons is due to an increase in neuronal proliferation or to a decrease in neuronal death. Results of autoradiographic studies show no evidence of enhanced neuronal proliferation following postnatal exposure to estradiol, but do show an increased survival of a prenatally labeled population of cells. Counts of degenerating cells in the superior cervical ganglion show that during the peak period of normal neuronal degeneration, on postnatal day 5, 17-beta-estradiol or testosterone propionate treated animals have significantly fewer degenerating superior cervical ganglion cells than do vehicle-injected littermate controls. In addition, vehicle-injected females have more degenerating cells on day 5 than do vehicle-injected males. Taken together these results provide strong evidence that the increase in superior cervical ganglion neurons seen after neonatal exposure to estradiol results from a reduction in developmental neuron death.

Animals

Sex differences in nerve growth factor levels in superior cervical ganglia and pineals.

The current studies were undertaken to determine whether males or neonatally testosterone-treated rats of either gender have elevated endogenous levels of NGF in the SCG and one of its targets, the pineal gland. The ages studied were 5 days postnatal, which is at the peak of normal neuron death in the SCG but before a significant gender difference is present; 15 days, when normal neuron death is largely complete and males have more SCG neurons than females; and 30 days, when target innervation has matured. At 5 days, while neuron death is occurring, but before there is a significant gender difference in neuron number in the SCG, pineal glands and SCGs of males had higher NGF content than those of females. The increased NGF in the ganglia of males at the time that these neurons are undergoing neuron death may play a role in the development of the sex difference in SCG neuron numbers. At 15 days, females had more NGF in their pineal glands and SCGs than did males, even though males have significantly more SCG neurons at this age than do females. This gender difference in the developmental course of NGF content could promote the survival of different populations of neurons in males and females. By 30 days, SCG and pineal NGF content of males was almost twice that of females. This is consistent with the presence of more neurons in the SCGs of males at this age. Both the pineal gland and the SCG showed a loss of approximately 80% content of NGF during the first postnatal month(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Streptozyme test for antibodies to group A streptococcal antigens.

The ability of the Streptozyme test to identify significant antibody rises in 46 patients with streptococcal pharyngitis was comparable to, but no greater than, that of the antistreptolysin O or antideoxyribonuclease B test and inferior to that of the combined use of both the antistreptolysin O and antideoxyribonuclease B tests. Serum specimens were also simultaneously analyzed with three different lots of Streptozyme reagent. Lot-to-lot variation in the reagent resulted in a significant difference in antibody titer for 18 (19%) of the 92 sera tested. Differences among the three lots also produced variation in determining whether a significant rise in titer had occurred from the acute phase to the convalescent phase serum for a given patient. These observations raise concerns about the standardization of the Streptozyme reagent and document the need for precise identification and quantitation of the streptococcal antigens used in this product.

Antibodies, Bacterial

The use of transmission ultrasonics to assess bone status in the human newborn.

The applicability of transmission ultrasonics as a method for assessment of bone status in human newborns was investigated in two studies. Sound transmission velocity (SCV) through the intact distal radius and ulna was compared to midshaft bone mineral content (BMC) and to midshaft mechanical breaking strength (MBS) in 13 postmortem newborns [gestational age (GA) = 20 to 41 wk]. Midshaft MBS, ranged from 1 to 16 kg; BMC, which ranged from 84 to 88 mg/cm in the term infant, was consistent with previous reported photon absorptiometric data. SCV in the distal radius and ulna was correlated with midshaft MBS (r = 0.69 to 0.82) and BMC (r = 0.85 to 0.93) and increased exponentially with midshaft MBS and BMC. GA was correlated with SCV (r = 0.90 to 0.95). Log GA was correlated with midshaft MBS (r = 0.87 to 0.96) and BMC (0.97 to 0.99) in each of the four measured bones. In the second study, SCV through the distal radius and ulna was measured in 85 live newborns ranging in GA from 28 to 43 wk. SCV increased linearly with GA (r = 0.71 to 0.77). These data demonstrate that SCV through the distal radius and ulna increases linearly with GA and that SCV through the distal bones of the forearm is reliably related to midshaft BMC and MBS during the third trimester of gestation. Transmission ultrasonic measurement of SCV provides a rapid, reproducible, nonionizing, and noninvasive method for assessing bone strength and mineralization in human neonates.

Bone Development

Once daily therapy for streptococcal pharyngitis with cefadroxil.

To determine if a single daily dose of cefadroxil would be effective in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis, 196 patients with GABHS pharyngitis were randomly assigned to receive either penicillin V 250 mg three times daily or cefadroxil 30 mg/kg once daily, for 10 days. Outcome was measured by the ability to isolate GABHS from the upper respiratory tract 18 to 24 hours after the onset of therapy, the impact on the clinical course, and the bacteriologic treatment failure rate. There was no significant difference in the number of patients in the cefadroxil and penicillin V treatment groups with throat cultures positive for GABHS at the 18 to 24-hour follow-up visit (0% and 2%, respectively), and the clinical responses of the patients in the two treatment groups were similar. Of the 99 patients in the three times daily penicillin V group, six (6%) had strains of GABHS isolated on one of the follow-up cultures that were identical to the strains isolated from their initial throat cultures and were considered to have bacteriologic treatment failures. Of the 96 patients in the once daily cefadroxil group, two (2%) were considered to have bacteriologic treatment failures. A single daily dose of cefadroxil appears to be as effective in the treatment of GABHS pharyngitis in this population as penicillin V given three times daily.

Adolescent