Biomedical subjects

J J Sullivan

Publications and source records attributed to J J Sullivan.

At least 19 recordsLinked to original sources

PubMed2001

Keratoacanthoma with perineural invasion: a report of 40 cases.

Keratoacanthoma is a unique clinicopathological entity, despite a recent trend to regard it as a variant of squamous cell carcinoma. The occurrence of perineural invasion is an uncommon phenomenon in keratoacanthomas, with a predilection for lesions on the face. We studied a series of 40 cases of keratoacanthoma in which perineural invasion occurred. Of the 40 cases, 27 were from the head or neck region. We found no metastasis or direct death attributable to the presence of perineural invasion in the 35 cases in our series for whom follow-up data were available. In only one case did local recurrence occur and this was not considered by the authors to be directly attributable to the presence of perineural invasion. These findings add further support to the notion that keratoacanthoma is biologically different from squamous cell carcinoma.

Adult↗

PubMed2000

Evaluation and validation of a commercial ELISA for diazinon in surface waters.

The performance of a commercially available microtiter plate ELISA kit for the determination of diazinon was evaluated for sensitivity, selectivity, intra-assay repeatability, accuracy, and matrix effects in fortified distilled water and filtered and unfiltered environmental surface water samples. Repeatability and reproducibility studies show that the kit satisfies current EPA criteria for the assessment of analytical methods. Mean recoveries from spiked samples averaged 80.3, 95.5, and 103.5% from distilled, unfiltered surface, and filtered surface waters, respectively. The experimentally determined method detection limit (MDL) for the commercial diazinon microtiter plate format (0.0159 microg L(-)(1)) was comparable to the least detectable dose (LDD) established by the manufacturer (0.022 microg L(-)(1)). Specificity studies indicate that the diazinon polyclonal antibody can readily distinguish the target compound from other structurally similar organophosphorus analogues, with the exception of diazoxon. Cross-reactivity with the oxon was approximately 29%, while reactivity with pirimiphos-methyl, pirimiphos-ethyl, and chlorpyrifos-ethyl was negligible. A slight matrix effect was discovered to be present in both filtered and unfiltered environmental water matrixes, but its effect on the immunoassays is insignificant within experimental error. For validation of the microtiter plate ELISA format, environmental surface and storm runoff water samples were collected, split, and analyzed directly by ELISA and by liquid-liquid extraction followed by GC (California State Department of Food and Agriculture method EM 46.0). Results of the two analytical methods were then compared statistically. A close correlation was found between methods for unspiked and untreated river water samples (r = 0.969) while a much less robust correlation was obtained for runoff waters (r = 0.728). Results from runoff waters exhibit a particularly high positive bias for the ELISA method relative to the GC method. Cross-reactivity of diazoxon and probably other unidentified cross-reacting components may be responsible for the exaggerated account of the target analyte in surface and runoff waters. While excellent for screening purposes, further study is required to elucidate and quantify the factors responsible for the consistent overestimation of ELISA results before the kit can be employed routinely for regulatory compliance monitoring.

Diazinon↗

PubMed2000

Promoter interference in a bacteriophage lambda control region: effects of a range of interpromoter distances.

The p(R) and p(RM) promoters of bacteriophage lambda direct transcription in divergent directions from start sites separated by 83 phosphodiester bonds. We had previously shown that the presence of an RNA polymerase at p(R) interfered with open complex formation at p(RM) and that this effect was alleviated by the deletion of 10 bp between the two promoters. Here we present a detailed characterization of the dependence of the interference on the interpromoter distance. It was found that the reduced interference between the two promoters is unique to the 10-bp deletion. The relief of interference was demonstrated to be due to the facilitation of a step subsequent to RNA polymerase binding to the p(RM) promoter. A model to explain these observations is proposed. A search of known Escherichia coli promoters identified three pairs of divergent promoters with similar separations to those investigated here.

Bacteriophage lambda↗

PubMed1999

Two human neonatal IgM antibodies encoded by different variable-region genes bind the same linear peptide: evidence for a stereotyped repertoire of epitope recognition.

Two monoclonal IgM Abs have been produced from lymphocytes isolated from two human umbilical cord bloods. These mAbs recognize a conformational epitope present in a CNBr digestion fraction of lactoferrin. Linear epitopes recognized by each mAb were selected from several phage display peptide libraries. In each case, phages displaying a peptide with a motif defined by [WF],G,[EQS],N were recovered. Phages displaying that motif bound equally well to either mAb but did not bind to control IgM. A peptide bearing this motif competed with the phage-displayed peptides for binding to either mAb. The same peptide also competes with a component of the CNBr digestion fraction of lactoferrin for Ab binding in ELISA. The Abs use different families of VH, JH, and VK gene cassettes but use the same JK cassette. All segments are virtually identical to their germline gene counterparts. This work provides further evidence that certain innate specificities are stereotyped among individuals.

Antibodies, Monoclonal↗

PubMed1999

The human uniqueness of HIV: innate immunity and the viral Tat protein.

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period of post-infection latency, the titers of those natural antibodies decline and other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with HIV Tat protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparently induced Tat-reactive antibodies do arise. Evidence of a temporal relationship between the decline of the Tat reactive natural antibodies and progression of HIV pathogenesis, including demise of CD4+T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tat-related pathogenicity may be limited by the immune system recognition of the natural antibody-reactive sequences of Tat as "self" with consequent induction of tolerance and restriction of production of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resistance to tolerance-based diminishment of the protective natural antibodies. Although not yet defined, that characteristic may be shared by the occasionally observed HIV+ humans known as LTNP (longterm-non-progressors).

Animals↗

PubMed1998

Promoter recognition by Escherichia coli RNA polymerase: effects of the UP element on open complex formation and promoter clearance.

Escherichia coli promoters for transcription of ribosomal and tRNAs are greatly activated by an A+T-rich "UP" element upstream of the -35 region. These same promoters have also been found to otherwise deviate in several respects from the consensus promoter sequence. Here we present the results of a kinetic characterization of the interaction of Escherichia coli RNA polymerase with UP element-containing promoters which by virtue of consensus or near-consensus sequence features should be among the most optimal that can be encountered by Escherichia coli RNA polymerase. We show that for such promoters, (1) the second-order rate constant describing formation of the initial (closed) complex is close to that expected for a diffusion-limited process, (2) the extent of activation by the UP element is temperature-sensitive, (3) the UP element accelerates a process after DNA binding by RNA polymerase, and (4) the presence of the UP element delays promoter clearance upon addition of nucleoside triphosphates to preformed RNA polymerase-promoter complexes. Finally, we provide evidence in support of models which describe the DNA melting process accompanying open complex formation as initiating in the -10 promoter region and progressing in the downstream direction.

Base Sequence↗

PubMed1998

Erysipelothrix rhusiopathiae: an uncommon but ever present zoonosis.

Erysipelothrix rhusiopathiae is an important animal pathogen with a worldwide distribution, yet this zoonotic infection is rarely reported in humans. Three cases of E. rhusiopathiae infection, which illustrate the varied clinical presentations of this pathogen in humans, are presented together with the pathological findings and treatment regimens.

Adult↗

PubMed1998

Identifying the integrated electromyographic threshold using different muscles during incremental cycling exercise.

BACKGROUND: The purpose of this study was to identify the IEMG threshold in the vastus lateralis (VL) and rectus femoris (RF) muscles during progressive, incremental exercise and to relate these thresholds to the ventilatory threshold (Tvent). METHODS: Ten men (age: 23.40 +/- 3.13 yrs, mass 76.64 +/- 8.13 kg, % fat: 8.81 +/- 2.32, VO2peak: 66.37 +/- 10.61 ml.kg.min-1) with cycling experience completed a graded exercise test on a cycle ergometer by cycling at 90 rpm using 45 watt increments at two minute intervals. Oxygen uptake was measured continuously and the IEMG activity of the VL and RF was calculated during the last 5 s of each minute. The mean for the IEMG of 6 to 7 complete pedal revolutions was used as the final value. Tvent was visually identified using the VE/VO2 and V-slope methods. The IEMG threshold for VL and RF was visually identified at the inflection point where a non-linear increase in IEMG occurred. Comparisons between Tvent and IEMG thresholds were made using dependent means "t"-tests. RESULTS: Results showed that an IEMG threshold was identified in all 10 subjects for the RF, but in only 5 of 10 subjects for the VL. However, when identified, the IEMG threshold for VL was similar to RF.VO2 at IEMG threshold for RF (3.53 +/- 0.36 L.min-1) was not significantly different from Tvent (3.36 +/- 0.42 L.min-1). CONCLUSIONS: These results show that the IEMG threshold is more consistently detected in the RF compared to VL during incremental cycling exercise. In addition, the IEMG threshold for RF was closely related to Tvent and provides an alternative means to assess the ventilatory threshold.

Adult↗

PubMed1997

Spectroscopic determination of open complex formation at promoters for Escherichia coli RNA polymerase.

A considerable amount of effort has been expended studying the kinetics of association of Escherichia coli RNA polymerase with promoter DNA in forming the open complex. Strand separation occurs over about 12 base pairs and includes the transcription start site. However, these efforts have been significantly hampered by the lack of a sensitive, real time method by which formation of an open complex could be assayed. Here, we employ short (86 bp) synthetic promoters with 2-aminopurine (2-AP) substitutions in the region that becomes single-stranded to spectroscopically monitor open complex formation. We demonstrate that promoters bearing the substitutions behave in a manner similar to that of those containing only the four common bases with respect to both the region of strand separation and start site selection. Open complex formation was found to yield an increased fluorescence signal with an emission maximum characteristic of 2-aminopurine. This spectroscopic assay for open complex formation was found to be well-suited to the investigation of a strong promoter, allowing open complex formation to be followed over a time scale of seconds with a stopped flow apparatus. The introduction of two additional nonconsensus base pairs in the -35 region resulted in a promoter for which open complex formation was 100-fold slower. The same substrates were also used to monitor the promoter re-annealing that ensues upon initiation of RNA synthesis. Similar rates for this process were observed for the two promoter variants employed in this study.

2-Aminopurine↗

PubMed1997

Innate natural antibodies. Primary roles indicated by specific epitopes.

Two members of a unique class of natural antibodies have been identified in all of a large cohort of sera from clinically normal humans of broad age distribution. By means of a series of 10-12 mer peptides the epitope for each of those antibodies was characterized with regard to amino acid identity and conformation. Similar epitope specificity was revealed for the IgM isotopes of cord blood and early post natal sera and for IgM and IgG of adult sera, suggesting that the class of natural antibodies represented by the two identified in this study includes those genomically coded for at their effector level of maturation in the B cells of the neonate. Assay of series of specimens from each of four clinically normal adults revealed that those two natural antibodies are present at relatively constant titer, unique to each individual, over four to five and a half year periods. Those observations imply that the primary function of that class of natural antibodies may be related to maintenance of homeostasis and the molecular identity of each of the two epitopes suggests a role, for each, as monitor or control in intracellular traffic. The previous identification of those epitopes in a conserved protein of HIV also provides support for the proposition that a secondary function of natural antibodies, arising from fortuitous coincidence of the identity of the epitopes, may be that of early defense against infectious invaders.

Adult↗

PubMed1997

Keratoacanthoma: the Australian experience.

Comment is offered on the roughly 50 years experience of Australian clinicians with the various types of keratoacanthoma, and local contributions to knowledge in this area is indicated. The higher incidence in warmer areas, with consequent early acceptance of the entity, is documented. Effects of immunosuppression are recorded, and viral and immunological studies noted. Aspects of special sub-groups, such as multiple and subungual, and of treatment, are briefly discussed, and future areas of research mentioned.

Australia↗

PubMed1997

An innate natural antibody is reactive with a cryptic sequence of lactoferrin exposed on sperm head surface.

Lactoferrin (LF), an 80-kDa glycoprotein of ubiquitous occurrence in body fluids, is multifunctional and capable of assuming different configurations to serve those functions. The capacity of LF to undergo endocytosis and the recent demonstration of LF binding to sequence specific DNA indicate that a function or capability of LF, in addition to iron chelation, bacteriostasis, and receptor-specific lymphocyte binding, may be that of gene activation or silencing. The data of this report present a human physiological system, that of sperm entry into the oocyte in performance of fertilization in which, since LF is a component of the sperm protein coat, that capability could be expressed. However, the configuration of LF in that locus is one in which a revealed cryptic sequence provides the specific binding site for a natural antibody present in the fertilization milieu. The presence of that antibody suggests that a system of control of the potential interaction of LF with the intra-ooplasmic DNA, that of gametes or pronuclei, is operative. The configuration of LF on the sperm surface and designation of the reactive site for the natural antibody were enabled by a monoclonal antibody secreted by a hybridoma derived from a human cord blood B cell. Thus, in addition to information concerning the molecular flexibility of LF, these observations support the proposition that the repertoire of natural antibodies provides an innate homeostatic system, with each antibody serving a specific role.

Antigen-Antibody Reactions↗

PubMed1997

The effect of exercise induced glycogen depletion on the lactate, ventilatory and electromyographic thresholds.

BACKGROUND: This study compared the integrated electromyogram (IEMG), lactate, and ventilatory thresholds under normal glycogen (NG) and depleted glycogen (DG) conditions for the purpose of determining the presence of a possible relationship between neuromuscular, metabolic and respiratory thresholds. MATERIALS AND METHODS: Six trained, male cyclists (Age = 24.0 +/- 2.45 yrs, Ht = 1.76 +/- 0.84 m, Mass = 76.22 +/- 10.03 kg, % Fat = 8.57 +/- 1.50, VO2 peak = 68.97 +/- 10.46 ml . kg-1 . min-1) completed a progressive, incremental cycle ergometer test under NG and DG conditions in a randomized order. Glycogen depletion was accomplished by having the subjects: (1) engage in a 12 hour fast prior to the exercise test, (2) complete a 1.5 hour ride at their ventilatory threshold, and (3) complete 4 to 8 one-minute rides at 100% of VO2 peak. Six hours following the depletion rides, the subjects completed the exercise test (90 rpm, 45 watts/2 min). Blood was withdrawn through a forearm venous catheter each minute and later analyzed for blood lactate. Metabolic data were measured every 30s and the IEMG of the rectus femoris was recorded during the last 10s of each minute of the exercise test. Results showed that under NG, the IEMG (TIEMG), lactate (Tlac), and ventilatory (Tvent) thresholds occurred at a similar VO2 (TIEMG = 3.46 +/- 0.31, Tlac = 3.51 +/- 0.34, Tvent = 3.36 +/- 0.42 L . min-1). However, under DG there was a significant shift in the TIEMG to a higher VO2 (TIEMG = 4.41 +/- 0.54 L . min-1 = p 0.003). Tlac was not significantly greater following glycogen depletion, but had shifted to a higher VO2 in relation to the Tvent (Tlac = 3.96 +/- 0.40 L . min-1, Tvent = 3.37 +/- 0.64 L . min-1 = p 0.01). These data show that lactate accumulation and muscle activation of the vastus lateralis and rectus femoris are not the controlling mechanisms of the ventilatory threshold during progressive, incremental cycling exercise.

3-Hydroxybutyric Acid↗

PubMed1996

Schistosomiasis in Lake Malawi.

BACKGROUND: In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS: A volunteer cohort of expatriates and visitors representing a cross-section of Malawi's foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawi's southwestern shore. FINDINGS: The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION: S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.

Adult↗

PubMed1996

Sporozoite transmission of three strains of Plasmodium knowlesi to Aotus and Saimiri monkeys.

Attempts were made to infect Aotus and Saimiri monkeys with sporozoites of 3 strains of Plasmodium knowlesi to determine the potential of these animals in a monkey/malaria model. Splenectomized Saimiri and Aotus monkeys were infected with the H strain of P. knowlesi via sporozoites from Anopheles dirus mosquitoes. Prepatent periods ranged from 5 to 16 days. Saimiri monkeys infected with the Philippine strain had prepatent periods ranging from 6 to 8 days. Saimiri monkeys infected with the Hackeri strain had prepatent periods ranging from 6 to 11 days. Exoerythrocytic (EE) stages of the Philippine strain were readily demonstrated; EE stages of the H strain were less abundant. Results indicate that the Philippine strain of P. knowlesi in Saimiri monkeys has a course of parasitemia and EE stages similar to those previously seen in macaques and could serve as a reproducible model for biologic and immunologic studies.

Animals↗

PubMed1995

Rectal irrigations for the prevention of postoperative enterocolitis in Hirschsprung's disease.

The purpose of this clinical trial was to examine the role of rectal irrigations in the prevention of postoperative enterocolitis in children with Hirschsprung's disease. Over the past 22 years 177 children had surgical treatment for Hirschsprung's disease at a single pediatric hospital. Five children have died of other causes. Of the remaining 172 patients, follow-up clinical information was obtained from 135 (78%). In 1989, all of the children undergoing surgical reconstruction for Hirschsprung's disease were placed on routine postoperative rectal irrigations with normal saline. The parents were instructed in the irrigation technique before leaving the hospital. Irrigations were started 1 to 2 weeks postoperatively and were performed two times a day for 3 months, then once a day for an additional 3 months. There were no complications from the irrigations themselves. A previous report from the authors' institution has documented five sudden deaths over the past 22 years from fulminant postoperative enterocolitis. These five children all had an unremarkable postoperative recovery, then developed a rapidly progressive diarrheal illness. All of these deaths occurred before the institution of routine postoperative irrigations. Of the 135 patients in this review, 40 had the postoperative rectal irrigations. The remaining 95 children serve as historical controls. Data analysis showed that 34 of the 95 children in the nonirrigation cohort developed postoperative enterocolitis compared with 3 of 40 in the rectal irrigation cohort; P < .001 using Fisher's exact test. In the authors' experience, routine postoperative rectal irrigations have significantly decreased the incidence and severity of enterocolitis in children after surgical correction of Hirschsprung's disease.

Child↗

PubMed1995

Gastrointestinal function after surgical correction of Hirschsprung's disease: long-term follow-up in 135 patients.

This study is a retrospective review of all children treated for Hirschsprung's disease over the past 22 years at a single pediatric institution. During this time 177 patients had definitive surgical reconstruction. Five children died of causes unrelated to Hirschsprung's disease, and five children died from enterocolitis after an uneventful postoperative course. Clinical follow-up information was obtained from 135 (78%). Demographic data includes the following: sex ratio 74% male, 26% female; current mean age 9.9 years; mean length of follow-up 7.9 years (range, 3 months to 21.5 years). Mean age at surgical reconstruction was 1.6 years. Definitive surgical procedures included endorectal pull-through (Soave), 21%; modified Duhamel, 67%; extended side-to-side ileocolic anastomosis, 8%; rectal myomectomy, 4%. Transition zone was within rectum or rectosigmoid region in 86%. Overall, 32% (43/135) report difficulty with fecal soiling, and 12.6% (17/135) identify this as a severe problem. These numbers include patients with trisomy 21 and total colonic aganglionosis. Severe fecal soiling was reported in 7.1% (2/28) after an endorectal pull-through, and in 12.1% (11/91) after the modified Duhamel. The difference in incidence of soiling after these two procedures is not statistically significant. However, 40% (4/10) of the patients after the long side-to-side anastomosis for total colonic aganglionosis report severe problems with fecal soiling (P = .03). Surgical reconstruction for Hirschsprung's disease provides near-normal gastrointestinal function for the majority of children, but long-term follow-up shows significant residual problems with soiling in 12.6% of the patients. This is consistent with reported experience worldwide.

Adolescent↗

PubMed1994

Predictors of mortality in pulmonary contusion.

BACKGROUND: Associated injuries and central nervous system (CNS) trauma are historically associated with poor outcome in patients with pulmonary contusions, but the value of specific factors reflecting shock, fluid resuscitation requirement and pulmonary parenchymal injury in predicting mortality in this population is not well established. METHODS: The medical records of 100 consecutive patients with pulmonary contusion, admitted over a 5-year period, were retrospectively reviewed. Survivors and nonsurvivors were compared in terms of age, Injury Severity Score (ISS), Glasgow Coma Score (GCS), PaO2/FiO2 (oxygenation ratio), the severity and adequacy of shock resuscitation reflected in plasma lactate, resuscitation volume and transfusion requirements, using one-way ANOVA. To determine the contribution of individual, interdependent variables to mortality, the data were then analyzed using multivariable analysis. RESULTS: ISS and transfusion requirement were significantly higher, and GCS and PaO2/FiO2 at 24 and 48 hours after admission were significantly lower in nonsurvivors than in survivors. After multiple regression analysis, the factors most strongly associated with mortality included patient age, oxygenation ratio at 24 hours after admission, and resuscitation volume. CONCLUSIONS: Outcome in patients with pulmonary contusion is dependent upon a number of variables including the severity of pulmonary parenchymal injury as reflected in PaO2/FiO2 ratio.

Adult↗