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Biomedical subjects

S L Hall

Publications and source records attributed to S L Hall.

At least 55 records · Page 3Linked to original sources
PubMed1990

Antibody responses of humans and nonhuman primates to individual antigenic sites of the hemagglutinin-neuraminidase and fusion glycoproteins after primary infection or reinfection with parainfluenza type 3 virus.

An unusual feature of human parainfluenza virus type 3 (PIV3) is ita ability to cause reinfection with high efficiency. The antibody responses of 45 humans and 9 rhesus monkeys to primary infection or subsequent reinfection with PIV3 were examined to identify deficiencies in host immunologic responses that might contribute to the ability of the virus to cause reinfection with high frequency. Antibody responses in serum were tested by using neutralization and hemagglutination inhibition (HI) assays and a monoclonal antibody blocking immunoassay able to detect antibodies to epitopes within six antigenic sites on the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein and eight antigenic sites on the fusion (F) protein. Primary infection of seronegative infants or children with PIV3 stimulated strong and rather uniform HI and neutralizing antibody responses. More than 90% of the individuals developed antibodies to four of the six HN antigenic sites (including three of the four neutralization sites), but the responses to F antigenic sites were of lesser magnitude and varied considerably from person to person. Young infants who possessed maternally derived antibodies in their sera developed lower levels and less frequent HI, neutralizing, and antigenic site-specific responses to the HN and F glycoproteins than did seronegative infants and children. In contrast, children reinfected with PIV3 developed even higher HI and neutralizing antibody responses than those observed during primary infection. Reinfection broadened the HN and F antigenic site-specific responses, but the latter remained relatively restricted. Adults possessed lower levels of HI, neutralizing, and antigenic site-specific antibodies in their sera than did children who had been reinfected, suggesting that these antibodies decay with time. Rhesus monkeys developed more vigorous primary and secondary antibody responses than did humans, but even in these highly responsive animals, response to the F glycoprotein was relatively restricted following primary infection. Bovine PIV3 induced a broader response to human PIV3 in monkeys than was anticipated on the basis of their known relatedness as defined by using monoclonal antibodies to human PIV3. These observations suggest that the restricted antibody responses to multiple antigenic sites on the F glycoprotein in young seronegative infants and children and the decreased responses to both the F and HN glycoproteins in young infants and children with maternally derived antibodies may play a role in the susceptibility of human infants and young children to reinfection with PIV3.

Adult↗
PubMed1990

Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth.

To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Calcitonin (but not calcitonin gene-related peptide) increases mouse bone cell proliferation in a dose-dependent manner, and increases mouse bone formation, alone and in combination with fluoride.

Previous in vitro studies have shown that salmon calcitonin had direct effects to increase parameters associated with embryonic chicken bone formation and to increase mouse and chicken osteoblast-line cell proliferation. The current studies demonstrate increased cell proliferation (i.e., [3H]-thymidine incorporation into DNA and tetrazolium salt reduction/deposition) in the osteoblastic murine cell line MC-3T3-E1 in response to salmon calcitonin (P less than 0.005) and to human calcitonin (P less than 0.005), but not to human calcitonin gene-related peptide. The current studies also show that salmon calcitonin increased several indices of murine bone formation. We found that 72 hours of exposure to salmon calcitonin [at 5 mU/ml-about 0.37 nM; mU/ml = milliunits of calcitonin activity/ml incubation medium (at 4,000 U/mg protein)] increased net 45Ca deposition (121% of control, P less than 0.05), net [3H]-proline incorporation 149% of control, P less than 0.001), and alkaline phosphatase activity (146% of control, P less than 0.01), in neonatal mouse half-calvaria. The calcitonin-dependent increase in alkaline phosphatase activity was not affected by co-incubation with 1 nM parathyroid hormone. Co-incubation with fluoride (which also increased net [3H]-proline incorporation and alkaline phosphatase activity in neonatal mouse half-calvaria, P less than 0.05, for each) enhanced the osteogenic response to low-dose calcitonin, (i.e., co-incubation with fluoride shifted the biphasic calcitonin dose-response curve to a range of lower calcitonin concentrations). The calcitonin-fluoride combinations had proportional effects on net [3H]-proline incorporation and alkaline phosphatase in the treated mouse calvaria (r = 0.78, P less than 0.005).

Alkaline Phosphatase↗
PubMed1989

Alkaline phosphatase activity from human osteosarcoma cell line SaOS-2: an isoenzyme standard for quantifying skeletal alkaline phosphatase activity in serum.

Earlier we described a kinetic assay for quantifying skeletal alkaline phosphatase (ALP) isoenzyme activity in serum. The precision of the assay depends on including ALP standards for the skeletal, hepatic, intestinal, and placental isoenzymes. We wondered whether human osteosarcoma cells could provide an efficient alternative to human bone or Pagetic serum as a source of the skeletal ALP standard. ALP activities prepared from five human osteosarcoma cell lines were compared with a bone-derived ALP standard with respect to heat stability and sensitivity to chemical effectors. Two of the cell lines (SaOS-2 and TE-85) contained ALP activities that resembled the bone-derived standard. We selected SaOS-2 cells for additional evaluation (as a potential source of isoenzyme standard), because they contained 40-50 times more ALP activity than did the TE-85 cells. To include the SaOS-2 cell-derived ALP activity in the quantitative isoenzyme assay, we diluted the enzyme in a solution containing heat-inactivated (i.e., ALP-negative) human serum. Surprisingly, this dilution caused a 60-125% increase in maximum enzyme activity. In the quantitative assay of ALP isoenzyme in serum, the SaOS-2 derived ALP was indistinguishable from the serum skeletal ALP standard, with respect to the above criteria and assay variations. Evidently ALP from SaOS-2 cells is suited as a standard for measuring skeletal ALP activity in this assay.

Alkaline Phosphatase↗
PubMed1988

Molecular analyses of conjugative, gentamicin-resistance plasmids from staphylococcal clinical isolates.

Gentamicin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains which were isolated from infants with staphylococcal bacteremia were analyzed for the presence of self-transmissible gentamicin-resistance (Gmr) plasmids. Conjugative GMr plasmids of approximately 43.8-63 kilobases (kb) were found in all S. aureus strains. Inter- and intra-species transfer of Gmr plasmids by conjugation was observed from S. aureus to S. aureus and to S. epidermidis recipient strains. However, neither inter- nor intra-species transfer of gentamicin resistance by conjugation was observed with nine out of nine S. epidermidis donor strains which were mated with either S. epidermidis or S. aureus recipient strains. These conjugative Gmr plasmids were unable to comobilize a smaller (15-kb) plasmid present in all but two S. aureus clinical isolates. Many of the conjugative Gmr plasmids also carried genetic determinants for kanamycin, tobramycin, neomycin, and ethidium bromide resistance, and for beta-lactamase synthesis. EcoRI restriction endonuclease digests of the S. aureus Gmr conjugative plasmids revealed three different digestion patterns. Four EcoRI restriction endonuclease digestion fragments of 15, 11.4, 6.3, and 4.6 kb in size were common to all plasmids. These plasmids and conjugative Gmr staphylococcal plasmids from other geographical regions shared restriction digestion fragments of similar molecular weights. DNA hybridization with biotinylated S. aureus plasmid pIZ7814 DNA revealed a high degree of homology among these plasmids. A 50.9-kb plasmid from one of the nonconjugative S. epidermidis clinical isolates showed homology with the probe DNA but lacked a portion of a 6.3-kb fragment which was present in all conjugative plasmids and believed to carry much genetic information for conjugation.

Conjugation, Genetic↗
PubMed1988

The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation.

The studies summarized in this report were intended to determine whether salmon calcitonin had direct effects on bone formation indices in vitro. The results of these investigations demonstrate acute effects of calcitonin on skeletal tissues derived from embryonic chickens to increase calvarial cell proliferation ([3H]thymidine incorporation into DNA) and bone matrix synthesis ([3H]proline incorporation into collagen, as [3H]hydroxyproline) in intact calvaria and tibiae. The effects of calcitonin on [3H]thymidine incorporation were significant at 1 mU/ml (0.08 nM; P less than 0.05), additive with respect to the action(s) of F (calcitonin increased the maximum effect of F, and F increased the effect of low dose calcitonin; P less than 0.01 for each), associated with an increase in total cell protein (r = 0.82; P less than 0.02), and inversely dependent on osteoblastic differentiation (r = -0.96; P less than 0.005). The effects of calcitonin to increase bone matrix synthesis ([3H]hydroxyproline incorporation, 139% and 155% of untreated control values for tibiae and calvaria, respectively; P less than 0.005 for each) were maximal at approximately 5 mU/ml (0.4 nM) and associated with a proportional increase in alkaline phosphatase activity in the bones (r = 0.71; P less than 0.05 for tibiae). These effects of calcitonin were not dependent on continuous exposure. [3H]Thymidine incorporation was increased in calvarial cells 16 h after a 4-h limited (inductive) exposure to calcitonin (at 3 mU/ml; P less than 0.01). [3H]Proline incorporation in embryonic chicken calvaria was also increased during 3 days of limited exposure (i.e. 4 h/day) to 10 mU/ml calcitonin (P less than 0.02). The proliferative action(s) of calcitonin was not unique to chicken osteoblastline cells. Salmon calcitonin also increased [3H]thymidine incorporation in the transformed murine calvarial cell lines MMB and MC-3T3-E1 and in primary cultures of cells prepared from newborn mouse calvaria (P less than 0.05 for each). Furthermore, these effects were observed at calcitonin doses (3-30 mU/ml) that also decreased murine bone resorption (i.e. 45Ca release from prelabeled neonatal mouse calvaria; P less than 0.01).

Alkaline Phosphatase↗
PubMed1988

Colonization with slime-positive coagulase-negative staphylococci as a risk factor for invasive coagulase-negative staphylococci infections in neonates.

Mucocutaneous cultures obtained at admission and subsequent weekly nasopharyngeal cultures were obtained on 182 infants in the neonatal intensive care unit (NICU) over 3 months to assess whether a relationship existed between colonization with coagulase-negative staphylococci and invasive infection, particularly with respect to slime production. Nasopharyngeal colonization by coagulase-negative staphylococci occurred in a mean of 58% of infants weekly, with an equal prevalence of slime-positive and slime-negative isolates over time. Colonization of the nasopharynx on admission increased from 8.9% of those admitted within the first day of life to 33% of those admitted thereafter (p less than 0.005). The presence of slime-positive coagulase-negative staphylococci on admission was not predictive of later patterns of colonization with respect to slime. Of infants not colonized on admission who had subsequent cultures, 72% became colonized with coagulase-negative staphylococci that were equally likely to be slime-positive or slime-negative. The incidence of invasive infections was 4.4%. Infants with slime-positive mucocutaneous colonization were more likely to develop invasive coagulase-negative staphylococci disease than infants with slime-negative or no colonization (8.4% versus 1.1%; p less than 0.025). The incidence of slime-positive coagulase-negative staphylococci isolates from blood cultures was 6/7 (86%) whereas those from mucocutaneous cultures was 131/260 (50%) (p = 0.06). Colonization with slime-positive coagulase-negative staphylococci is a significant risk factor for developing invasive coagulase-negative staphylococci disease and these organisms are responsible for the majority of coagulase-negative staphylococci invasive infections.

Coagulase↗
PubMed1987

Characteristics of coagulase-negative staphylococci from infants with bacteremia.

Twenty-nine infants were identified as having coagulase-negative staphylococcal (C-S) bacteremia. Fourteen infants had pneumonia and 10 had central line-associated bacteremia. Twenty-four of 29 (83%) had invasion of the mucocutaneous barrier at the time the positive blood culture was drawn. Clinical signs and symptoms were nonspecific. Apnea/bradycardia was the most prevalent clinical feature, occurring in 20 (69%) infants. Staphylococcus epidermidis was the most frequent blood culture isolate, occurring in 21 (72%) cases. Slime production by C-S blood culture isolates occurred in 23 (79%) cases. There was no prevalent antibiotic resistance pattern, phage type or plasmid profile among blood culture isolates from infants with bacteremia. Mucocutaneous isolates of C-S from infants with bacteremia were compared with those from infants without invasive disease. Infants with bacteremia had a significantly higher percentage of slime-producing organisms (75% vs. 58%, P = 0.027) and a significantly higher percentage of S. epidermidis species (79% vs. 53%, P = 0.001) than isolates from infants without bacteremia. Our data support the relationship of slime production and the S. epidermidis species of C-S as virulence factors in infants with foreign bodies. Testing C-S for slime production is a relatively simple laboratory procedure which may be an additional aid in the evaluation of their clinical significance.

Bacteriophage Typing↗
PubMed1987

Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid.

We have determined that the organic matrix of calcium oxalate kidney stones contains a glycoprotein inhibitor of calcium oxalate crystal growth (nephrocalcin) that resembles nephrocalcin present in the urine of patients with calcium oxalate stones and differs from nephrocalcin from the urine of normal people. Pulverized calcium oxalate renal stones were extracted with 0.05 M EDTA, pH 8.0; nephrocalcin eluted in five peaks using DEAE-cellulose column chromatography, and each peak was further resolved by Sephacryl S-200 column chromatography. Four of the five DEAE peaks corresponded to those usually found in nephrocalcin from urine; the fifth eluted at a lower ionic strength than any found in urine. Amino acid compositions and surface properties of nephrocalcins isolated from kidney stones closely resembled those of nephrocalcins isolated from urine of stone-forming patients: they differed from normal in lacking gamma-carboxyglutamic acid residues, and in forming air-water interfacial films that were less stable than those formed by nephrocalcin from normal urine.

1-Carboxyglutamic Acid↗
PubMed1987

Neonatal intussusception associated with neonatal small left colon syndrome.

A newborn infant with intestinal obstruction resulting from intussusception associated with neonatal small left colon syndrome is described. Differences between neonatal and infantile intussusception are detailed. Chronic loose intussusception in utero is proposed as one cause of the neonatal small left colon syndrome. Consideration should be given to doing a rectal biopsy and a sweat chloride test to differentiate neonatal small left colon syndrome from Hirschsprung's disease and cystic fibrosis, respectively, when the clinical diagnosis is not readily apparent.

Adult↗
PubMed1987

Ten-year survey of positive blood cultures among admissions to a neonatal intensive care unit.

A 10-year survey of positive blood cultures was conducted among 6,616 infants admitted to an intensive care unit from 1974-1983. Group B streptococci (59) and E. coli (32) were the most common pathogenic organisms isolated from the early onset group (less than 72 hours of age). The percentage of infants with bacteremia, the birth weight distribution of infected infants, and the organisms isolated did not change in the early onset group throughout the study period. Coagulase negative staphylococci (471), S. aureus (126), E. coli (33), Klebsiella sp. (30), and enterococci (30) were the most frequent organisms isolated from the late onset group. The frequency of infection in the late onset group did not change as a function of time but was associated with decreasing birth weight during the study period. Methicillin and gentamicin resistance among coagulase negative staphylococci preceded that of S. aureus by one to three years, suggesting interspecies transfer of bacterial resistance among staphylococci. The data indicate that whereas the epidemiology of early-onset septicemia has remained relatively stable during the study period, the incidence of late onset bacteremia is increasing with improved survival rates of low birth weight infants. Antibiotic administration in the late onset group should include consideration of hospital-acquired, multiply antibiotic resistant organisms as well as maternally-acquired bacterial flora.

Blood↗
PubMed1985

Wegener granulomatosis in pediatric patients.

Wegener granulomatosis is more easily recognized as a distinct clinical entity than other vasculitides because the initial clinical features frequently include granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. Although the disease has been lethal in the past, prolonged survival and avoidance of end-stage kidney disease can now be expected when cyclophosphamide therapy is introduced early in the course. We report four children with Wegener granulomatosis in whom the initial clinical findings suggested Henoch-Schönlein purpura. In two of the patients Wegener granulomatosis was not recognized until after end-stage kidney disease had developed. The course in these patients emphasizes the need for attention to even scant evidence of inflammation of the upper or lower respiratory tract in patients with glomerulonephritis. Appropriate diagnostic studies may then lead to recognition of Wegener granulomatosis and the prompt institution of appropriate treatment.

Adolescent↗
PubMed1985

Polyadenylylation of sea urchin histone RNA sequences in transfected COS cells.

The region of pSV2neo that encompasses the simian virus 40 early polyadenylylation signal was replaced with a DNA fragment that spans the 3' end of a sea urchin (Psammechinus miliaris) histone H2A gene. This clone, pMK2.H2A(3'), was used to transfect COS cells. RNA analysis revealed that transcripts from pMK2.H2A(3') were polyadenylylated at a site 85 nucleotides downstream from the expected 3' end of mature H2A mRNA. Nucleotide sequencing showed that the site of poly(A) addition was located 10 nucleotides downstream from a cluster of four A-A-U-A-A-A sequences. The lower accumulation of MK2.H2A(3') mRNA, which was 5-10% that of SV2neo mRNA, suggests that the H2A polyadenylylation signal is relatively inefficient. The relationship of the above findings to the 3' end processing of other histone mRNAs is discussed.

Animals↗
PubMed1984

Rapid recovery of mycobacteria from clinical specimens using automated radiometric technic.

Automated radiometric technic (BACTEC Johnston Laboratories, Towson, MD) was compared with conventional mycobacterial culture procedure (Lowenstein-Jensen plus Gruft modification of Lowenstein-Jensen) in this study of 1,000 clinical specimens. In addition, 8-azaguanine inhibition was tested by radiometric technic as a rapid procedure for the differentiation of Mycobacterium tuberculosis from other mycobacterial species. A total of 59 mycobacteria was recovered. Of 28 clinically significant isolates (M. tuberculosis, M. kansasii, M. avium, M. fortuitum), the BACTEC system detected 26 (93%). Conventional methods recovered 23 (82%). The BACTEC system required an average of seven days to recover M. tuberculosis from smear-positive specimens compared with 18 days required by Lowenstein-Jensen or Gruft slants. From smear-negative specimens, the BACTEC detected M. tuberculosis in an average of 20 days versus 28 days by conventional procedure. All 20 isolates of M. tuberculosis were inhibited by 8-azaguanine, whereas 39 isolates of mycobacteria other than M. tuberculosis were not inhibited. The BACTEC system accomplishes more rapid recovery of mycobacteria and provides a higher yield than conventional methods.

Bacteriuria↗
PubMed1983

A rapid diagnosis of Campylobacter enteritis by direct smear examination.

Diagnosis of Campylobacter enteritis by direct smear examination of stool specimens, using 1% aqueous basic fuchsin, was compared with a conventional cultural method (Campy-BAP). After examination of 485 stool specimens the direct smear method produced a sensitivity and specificity of 94% and 99.5%, respectively.

Campylobacter↗