Biomedical subjects

C L Jones

Publications and source records attributed to C L Jones.

At least 37 records · Page 2Linked to original sources

PubMed1999

Macrophage and myofibroblast involvement in ischemic acute renal failure is attenuated by endothelin receptor antagonists.

BACKGROUND: Endothelin (ET) may be a mediator of injury following ischemia-induced acute renal failure (ARF). ET receptor (ETR) antagonists have been reported to increase survival rates and lower serum creatinines when administered postrenal ischemia-reperfusion injury in the rat. Renal cellular and extracellular matrix responses to this therapy have not been addressed. METHODS: We investigated the use of ETR antagonists, PD 156707 (ETA) and SB 209670 (ETA and ETB) in the treatment of sublethal postischemic ARF. The right kidney of female Sprague-Dawley rats weighing approximately 200 g was removed. After five days, the left renal pedicle was occluded for 45 minutes. Twenty-four hours after renal ischemia, one of two ETR antagonists, PD 156707 (N = 7) or SB 209670 (N = 8), was administered. Experimental animals were compared with an ischemic group receiving only saline (N = 9). Three nephrectomized groups that did not undergo ischemia but that received infusions of saline (N = 6), PD 156707 (N = 6), and SB 209670 (N = 6), respectively, were also studied. Animals were sacrificed one week postischemia. Quantitation of monocytes and macrophages (Mo/Mphi), alpha-smooth muscle actin-positive myofibroblasts, and collagens type III and IV was performed by immunohistochemical staining. Cell kinetics were examined by staining for apoptosis with terminal deoxyuridine triphosphate (dUTP) nick end labeling and for proliferation with proliferating cell nuclear antigen. RESULTS: All ischemic groups of rats initially developed raised serum creatinine levels; however, no significant difference was observed between the groups (Kruskal-Wallis). Creatinines returned to preischemic values in all groups by the time of sacrifice. No significant difference in kidney weights or body weights was found between groups. Histologically, infiltration of Mo/Mphi was significantly reduced in groups treated with ETR antagonists (P < 0.001). The presence of myofibroblasts was also significantly reduced in the antagonist-treated groups (P < 0. 001). This was also paralleled by reduced quantities of collagen IV in the treated rat groups (P < 0.001). The interstitial area was also significantly greater in the saline group (P < 0.001). The amount of collagen III did not significantly differ between rat groups. Apoptosis was reduced (P < 0.001) by treatment with ETR antagonists, whereas proliferation was enhanced (P < 0.005). All non-ischemic groups showed no variation in any parameter studied at this time point. CONCLUSIONS: Treatment of ischemic ARF in the rat with ETR antagonists PD 156707 and SB 209670 attenuated cellular infiltration and matrix accumulation. An advantage of one antagonist over the other could not be determined in this study. The marked discrepancy between function and pathology (former unchanged, latter markedly improved) may be due to the time frame of this experiment, and longer outcome measures need to be assessed.

Actins↗

PubMed1999

Postural set for balance control is normal in Alzheimer's but not in Parkinson's disease.

BACKGROUND: It has been suggested that patients with dementia of the Alzheimer type have abnormalities in the basal ganglia, and thus, may have similar sensorimotor problems as patients with basal ganglia degeneration from Parkinson's disease. Whether the similarity extends to balance control is unknown. One distinguishing feature of balance disorder in Parkinson's disease is difficulty with changing postural set in terms of adapting the amplitude of leg muscle activity as a function of support condition. We, therefore, tested whether patients with Alzheimer's disease without extrapyramidal signs would show a similar problem in changing postural set as patients with Parkinson's disease. METHODS: The ability to quickly change postural set was measured by comparing leg muscle activity under two conditions of support (free stance, versus grasping a frame, or sitting) during backward surface translations, during toes up surface rotations, and during voluntary rise to toes. Results were compared among 12 healthy adults, 8 nondemented Parkinson's patients on their usual dose of medication, and 11 Alzheimer patients without extrapyramidal signs. RESULTS: Subjects with Alzheimer's, but not Parkinson's, disease performed similarly to the healthy control subjects. They changed postural set immediately, by suppressing leg muscle activity to low levels when supported. Parkinson subjects did not change postural set immediately. They did not suppress the tibialis anterior in voluntary rise to toes when holding, nor the soleus in perturbed sitting as much as the healthy control and Alzheimer subjects in the first trial. Instead, the Parkinson subjects changed set more slowly, over repeated and consecutive trials in both protocols. The onset latencies of soleus responses to backward surface translations and perturbed sitting, as well as tibialis anterior responses to toes up rotations, were the same for all three groups. CONCLUSION: Alzheimer patients without extrapyramidal signs, unlike nondemented Parkinson's disease patients, have no difficulty in quickly changing postural set in response to altered support conditions. Our results, therefore, do not support the hypothesis that Parkinson's and uncomplicated Alzheimer's diseases share common postural set problems that may contribute to disordered balance control.

Adaptation, Physiological↗

PubMed1999

Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS.

The vascular effects of carbon monoxide (CO) resemble those of nitric oxide (NO), but it is unknown whether the two messengers converge or exhibit reciprocal feedback regulation. These questions were examined in microdissected perfused renal resistance arteries (RRA) studied using NO-sensitive microelectrodes. Perfusion of RRA with buffers containing increasing concentrations of CO resulted in a biphasic release of NO. The NO response peaked at 100 nM CO and then declined to virtually zero at 10 microM. When a series of 50-s pulses of 100 nM CO were applied repeatedly (150-s interval), the amplitude of consecutive NO responses was diminished. NO release from RRA showed dependence on L-arginine but not D-arginine, and the responses to CO were inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthases (NOS). CO (100 nM) also suppressed NO release induced by 100 microM carbachol, a potent agonist for endothelial NOS (eNOS). RRA from rats in which endogenous CO production from inducible HO was elevated (cobalt chloride 12 h prior to study) also showed suppressed responses to carbachol. Furthermore, responses consistent with these findings were obtained in juxtamedullary afferent arterioles perfused in vitro, where the vasodilatory response to CO was biphasic and the response to acetylcholine was blunted. Collectively, these data suggest that the CO-induced NO release could be attributed to either stimulation of eNOS or to NO displacement from a cellular storage pool. To address this, direct in vitro measurements with an NO-selective electrode of NO production by recombinant eNOS revealed that CO dose-dependently inhibits NO synthesis. Together, the above data demonstrate that, whereas high levels of CO inhibit NOS activity and NO generation, lower concentrations of CO induce release of NO from a large intracellular pool and, therefore, may mimic the vascular effects of NO.

Acetylcholine↗

PubMed1998

Differential induction of Cyp1a1, Cyp1b1, Ahd4, and Nmo1 in murine skin tumors and adjacent normal epidermis by ligands of the aryl hydrocarbon receptor.

Products of several phase I and II genes transcriptionally activated by ligands of the aryl hydrocarbon receptor (AHR) were quantitated in cutaneous samples isolated from non-tumor-bearing SENCAR or SSIN mice, and animals bearing skin tumors generated in initiation-promotion protocols. The constitutive 7-ethoxyresorufin O-deethylase (EROD) activities in papillomas and squamous cell carcinomas were less than or equal to 37% of the values measured in the adjacent normal cutaneoustissue. Dermal and epidermal EROD specific activities in microsomal samples prepared from both tumor-bearing and non-tumor-bearing mice were elevated 9- to 14- and 43- to 77-fold, respectively, above constitutive levels 16-20 h after a single topical application of 100 nmol of dibenz[a,c]anthracene (DB[a,c]A). EROD specific activities in tumors were maximally elevated two-fold after topical application of DB[a,c]A. Western blot, northern blot, and reverse transcription (RT)-polymerase chain reaction (PCR) analyses confirmed that the EROD measurements reflected cutaneous cytochrome P450 (CYP) 1A1 protein, mature mRNA, and heterogeneous nuclear RNA contents, respectively. Analyses of CYP1A1, CYP1B1, cytosolic aldehyde dehydrogenase class 3, and NAD(P)H:menadione oxidoreductase (NMO1) mRNA content by RT-PCR revealed significant increases in all four mRNAs in the normal tissue adjacent to papillomas after exposure to 4 nmol of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but no increases in the tumors. NMO1 mRNA content in acetone-treated papillomas approached the levels detected in TCDD-treated normal skin. RT-PCR analyses also demonstrated elevated constitutive aryl hydrocarbon receptor nuclear translocator mRNA content (an approximately two-fold increase) in skin tumors. In contrast, AHR mRNA content in the tumors was about 20% of that measured in adjacent normal tissue. Collectively, these studies demonstrated that ligand-induced, AHR-mediated processes are absent in murine skin tumors that develop in initiation-promotion protocols.

Aldehyde Dehydrogenase↗

PubMed1998

Renal tuberculosis in an Australian-born child.

This report describes a case of renal tuberculosis, complicated by hypertension and ureteric obstruction, in a previously well Australian born child. Despite antituberculous chemotherapy and ureteric stenting, there was a progressive loss of renal function in the right kidney until surgical nephrectomy allowed full recovery. A high level of clinical suspicion is necessary for a diagnosis of genitourinary tuberculosis. Ureteric cicatrisation and obstruction occasionally may occur with healing, and therefore serial renal tract imaging during treatment is necessary to detect this complication.

Child↗

PubMed1998

Hemolytic-uremic syndrome following urinary tract infection with enterohemorrhagic Escherichia coli: case report and review.

A 6-week-old child with acute urinary tract infection caused by Shiga toxin-producing Escherichia coli (STEC) O5:H-developed hemolytic-uremic syndrome (HUS). Molecular and phenotypic analysis of the urinary isolate indicated that it lacked uropathic properties and that it was probably of intestinal origin. Nevertheless, the patient did not experience a diarrheal prodrome, nor was STEC or Shiga toxin detected in his feces at any time. Examination of the patient's serum pointed to recent infection with E. coli O5, with no evidence of exposure to E. coli O157, O111, or O26. A review of 13 previously reported cases of HUS associated with acute urinary tract infection indicated that this was the first case of nondiarrheal HUS in which infection with the most common STEC serogroups was specifically excluded. This case illustrates the need to investigate patients with nondiarrheal HUS for infection with STEC.

DNA, Bacterial↗

PubMed1998

Development of an instrument to measure terminal restlessness.

Terminal restlessness is a clinical phenomenon that is frequently observed but poorly defined. Its management is important in providing good quality palliative care. We present the development of an objective observer-rated instrument to measure terminal restlessness.

Humans↗

PubMed1998

Evolution of tubulointerstitial fibrosis in experimental renal infection and scarring.

Renal tubulointerstitial fibrosis may result from a loss of tubulointerstitial volume, which produces a disproportionate increase in the density of matrix. This study examines the relationship between fibrogenesis and collapse in scar formation after experimental renal infection. Escherichia coli were inoculated into the renal cortex of Sprague Dawley rats, with saline substituted in a control group. Glomerular, tubular, and interstitial profile areas were determined. Density of glomerular profiles was used as a measure of tubulointerstitial collapse. Collagen type I, III, and IV expression was examined by in situ hybridization and immunohistochemistry. Myofibroblasts were identified by alpha smooth muscle actin immunohistochemistry, and matrix metalloproteinase-1 (MMP-1) and MMP-2 were localized with appropriate antisera. Acute interstitial edema was followed by increasing density of glomerular profiles, paralleled by loss of interstitial volume and progressive tubular atrophy. Glomerular profile area remained unchanged. Density of glomerular profiles was not temporally related to myofibroblast accumulation. Procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) transcription was focal, spatially related but temporally ordered. Collagen I, III, and IV immunostaining was increased from days 3, 24, and 100, respectively (P < 0.05 versus day 0 and day 100 saline). However, when corrected for glomerular density, collagen I immunostaining decreased between days 24 and 100, whereas collagen III and IV no longer differed from day 0. MMP staining within the lesion was confined to occasional interstitial and epithelial cells throughout. It is concluded that in this model, contraction and collapse of the tubulointerstitial parenchyma has a greater influence than new collagen production on final fibrotic density.

Analysis of Variance↗

PubMed1997

An autoinhibitory control element defines calcium-regulated isoforms of nitric oxide synthase.

Nitric oxide synthases (NOSs) are classified functionally, based on whether calmodulin binding is Ca2+-dependent (cNOS) or Ca2+-independent (iNOS). This key dichotomy has not been defined at the molecular level. Here we show that cNOS isoforms contain a unique polypeptide insert in their FMN binding domains which is not shared with iNOS or other related flavoproteins. Previously identified autoinhibitory domains in calmodulin-regulated enzymes raise the possibility that the polypeptide insert is the autoinhibitory domain of cNOSs. Consistent with this possibility, three-dimensional molecular modeling suggested that the insert originates from a site immediately adjacent to the calmodulin binding sequence. Synthetic peptides derived from the 45-amino acid insert of endothelial NOS were found to potently inhibit binding of calmodulin and activation of cNOS isoforms. This inhibition was associated with peptide binding to NOS, rather than free calmodulin, and inhibition could be reversed by increasing calmodulin concentration. In contrast, insert-derived peptides did not interfere with the arginine site of cNOS, as assessed from [3H]NG-nitro-L-arginine binding, nor did they potently effect iNOS activity. Limited proteolysis studies showed that calmodulin's ability to gate electron flow through cNOSs is associated with displacement of the insert polypeptide; this is the first specific calmodulin-induced change in NOS conformation to be identified. Together, our findings strongly suggest that the insert is an autoinhibitory control element, docking with a site on cNOSs which impedes calmodulin binding and enzymatic activation. The autoinhibitory control element molecularly defines cNOSs and offers a unique target for developing novel NOS activators and inhibitors.

Amino Acid Sequence↗

PubMed1997

Differentiation status of cultured murine keratinocytes modulates induction of genes responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Primary murine keratinocytes were cultured in a chemically defined, serum-free medium which facilitated manipulation of their differentiation status. Exposure of basal cell and differentiating cultures to >/= 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) preferentially elevated 7-ethoxyresorufin O-deethylase specific activities in differentiating cultures (28-fold versus 4-fold increases after 36 h of exposure). Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) analyses demonstrated the presence of constitutive mRNA transcripts corresponding to four known TCDD-inducible genes (e.g., Cyp1a1, Cyp1b1, Ahd4, and Nmo1) in both differentiating and proliferating cultures of murine keratinocytes. All four genes were induced in differentiating cultures following exposure to TCDD. No induction occurred in comparably treated basal cell cultures. Indirect immunofluorescence analyses demonstrated the presence of aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins in both basal and differentiating keratinocytes. Both proteins appeared to be associated with the nucleus and their nuclear association was independent of prior exposure to TCDD. These studies suggest that AHR activation in murine skin is regulated as a function of the keratinocyte differentiation program.

Aldehyde Dehydrogenase↗

PubMed1997

Downregulation of aryl hydrocarbon receptor function and cytochrome P450 1A1 induction by expression of Ha-ras oncogenes.

The immortalized human epithelial cell line MCF10A has the phenotypic characteristics of normal breast cells. Exposure of MCF10A cultures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) stimulated the transcriptional activation of cytochrome P450 1A1 (CYP1A1), and CYP1B1, and NAD(P)H:quinone oxidoreductase. Northern blot hybridization and nuclear run-on assays demonstrated that transcriptional activation of these genes was suppressed in stably transfected cultures expressing an Ha-ras oncogene (the MCF10A-NeoT line). Similar suppression did not occur in stably transfected lines carrying the expression vector or a normal c-Ha-ras protooncogene. Western blot analyses and immunofluorescence microscopy demonstrated that the lack of inducibility in MDF10A-NeoT cells reflected neither reductions in aryl hydrocarbon receptor (AHR) and aryl hydrocarbon nuclear translocator protein nor prevention of TCDD-induced AHR translocation to the nucleus. Suppression did correlate with reductions in DNA-AHR complex formation, as analyzed by gel retardation assays of soluble cell extracts treated in vitro with TCDD. The induction of Cyp1a-1 by TCDD was also analyzed in transgenic mice that expressed a v-Ha-ras oncogene exclusively in their keratinocytes. Relative to littermates lacking the transgene, the induction of Cyp1a-1 by TCDD was partially suppressed (about 50%) in the epidermises of v-Ha-ras-positive transgenic mice. However, normal levels of Cyp1a-1 induction occurred in the livers of the same mice. induction of Cyp1a-1 by TCDD was also suppressed (more than 98%) in chemically induced skin papillomas having Ha-ras mutations, relative to uninvolved surrounding skin. These studies suggest that the p21-ras protein controls signal transduction pathways capable of modulating AHR function.

Animals↗

PubMed1997

Effect of antibodies on the chain length and growth of Streptococcus sobrinus.

Passive immunization has been suggested as a method to prevent colonization of teeth by mutans streptococci. However, the mechanism of action of antibodies, both polyclonal and monoclonal, is not clear. In this study we investigated the effect of polyclonal antibodies (pAbs) and a monoclonal antibody (OMVU10) on the chain length and growth of Streptococcus sobrinus. During growth in broth S. sobrinus formed significantly longer chains in the presence of pAbs in comparison to pre-immune serum (p < 0.01), but pAbs did not influence the growth rate of S. sobrinus in broth. OMVU10 did not influence the growth rate nor the chain length. In order to study the effect of the antibodies on adhesion and growth on a surface, S. sobrinus was grown on hydroxyapatite discs in the presence of two other bacteria, Streptococcus oralis and Actinomyces viscosus. No effect of the antibodies was found on the total cultivable count of the three bacteria after growth on hydroxyapatite discs. However, the morphology of the S. sobrinus microcolonies was different after growth in the presence of both pAbs and OMVU10. The colonies were less dense and chains of S. sobrinus could be seen using a confocal laser microscope. After growth in the presence of the control antibodies, the colonies were dense and no long chains could be observed. It was concluded that pAbs influenced the chain length, in broth and on hydroxyapatite discs, and the colony morphology of S. sobrinus on hydroxyapatite discs, whereas OMVU10 influenced the colony morphology of S. sobrinus on hydroxyapatite discs.

Aggregatibacter actinomycetemcomitans↗

PubMed1996

An extreme example of the neonatal form of Bartter's syndrome.

A male infant is described who had polyuria over the 4 months of his life with urine volumes exceeding 1,000 ml/kg per day, severe serum electrolyte losses, metabolic alkalosis and increased plasma renin activity (56 ng/ml per hour). He had a normal blood pressure and glomerular filtration rate when fluid replete. The urine flow rate was about 25% of the glomerular filtration rate. Renal histology showed hyperplasia of the juxtaglomerular apparatus and abnormalities of the proximal tubules. The features of this case suggest an extreme form of Bartter's syndrome presenting from the first days of life.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Clinical correlates of bombesin-like peptide receptor subtype expression in human lung cancer cells.

The importance of the expression of the autocrine growth system for bombesin-like peptides (BLPS) to the biological behavior of human lung cancer has not been determined. Three BLP receptor subtypes have been identified in human lung and lung cancer cells: gastrin-releasing peptide (GRP) receptor, neuromedin B (NMB) receptor, and bombesin receptor subtype 3 (BRS-3). The goals of this study were: (1) to determine BLP receptor subtype expression by human lung cancer cell lines by RT/PCR; (2) to evaluate possible clinical correlates of characteristics of the patients from whom the cell lines were derived with patterns of BLP receptor expression. Degenerate PCR primers were designed to amplify all known BLP receptors and yielded products from 19/20 small cell lung carcinoma (SCLC) and 12/13 non-small cell lung carcinoma (NSCLC) cell lines. GRP receptor was the most commonly expressed BLP receptor subtype, being detected in 17/20 SCLC and 11/13 NSCLC. Eleven of 20 SCLC expressed NMB receptors, and 5/20 expressed BRS-3, compared with 4/13 and 1/13, respectively, in NSCLC cell lines. Evaluation of the clinical data of the patients from whom the cell lines were derived revealed expected age, sex, smoking history and survival based on histology and stage. Patients from whom cell lines expressed GRP receptor experienced a better survival than those whose cell lines did not (367 +/- 274 days vs. 211 +/- 114 days), but the results were not statistically significant. RT/PCR analysis is a feasible, sensitive and specific means of determining BLP receptor expression in lung cancer cells and may yield prognostic information in patient tissue.

Biomarkers, Tumor↗

PubMed1996

Left ventricular abnormalities in children, adolescents and young adults with renal disease.

The cardiac abnormalities that complicate chronic renal failure and renal replacement therapy are not well characterized in young people. These abnormalities are becoming more important because successful renal transplantation has resulted in children with end-stage renal failure living longer. Echocardiographic abnormalities of cardiac function and structure were studied in children and young adults (< 27 years old) with chronic renal failure (CRF, N = 32), end-stage renal failure treated with chronic peritoneal dialysis (CPD, N = 10) or renal transplantation (N = 30) or controls (N = 60). Left ventricular mass indexed for height (LVM/Ht and LVM/Ht2.7) and body surface area (LVM/SA), fractional shortening, measurement of left ventricular diastolic function (peak E and A wave velocities and the EA ratio) and structural (such as valvular) abnormalities were determined by echocardiography. The median (and range) of LVM/Ht in the groups were control 51.8 (23.1 to 119.8), CRF 60.2 (22.2 to 135.8), CPD 80.2 (14.5 to 100.9) and transplant group 97.8 (51.2 to 182.1) g/m. The increases in LVM/Ht, LVM/Ht2.7 and LVM/SA in the transplant group were significant (P < 0.01). The CRF group had significantly increased LVM/Ht2.7 and LVM/SA (P < 0.01). Systolic function was not significantly different between the groups. A significant correlation between creatinine and LVM indexed for height was found in the CRF group. Systolic or diastolic blood pressure could not be correlated with LVM indices in the transplant group. Changes in diastolic function were found (increased peak A wave velocity and decreased E/A ratios in the CRF and CPD groups, and increased peak E wave velocity in the transplant group). The study demonstrated that left ventricular hypertrophy is a frequent and often severe finding in children with chronic renal failure and those treated with renal replacement therapy. Factors other than hypertension and anaemia are important, and evidence was found for a link between serum creatinine and increased left ventricular mass prior to end-stage renal failure.

Adolescent↗

PubMed1996

Parents of children with cancer: a longitudinal study of emotional distress, coping style, and marital adjustment two and twenty months after diagnosis.

Evaluated emotional distress, coping style, and marital adjustment in 84 parents (42 couples) of children with cancer 2 months after diagnosis and again about 20 months after diagnosis. As expected, mothers' mean state anxiety and trait anxiety scores decreased to near normal levels over time. Fathers' scores were lower initially and did not change. Neither mothers' nor fathers' mean marital adjustment scores changed over time. Marital adjustment at treatment follow-up was predicted by depression and the spouse's marital satisfaction in mothers, and depression, child health status, and spouse's marital satisfaction in fathers. In contrast to findings obtained 2 months after diagnosis, coping style was not related to marital adjustment at follow-up. Results are discussed in terms of possible gender differences in the role of social support in marital adjustment and the stability versus situational specificity of coping styles.

Adaptation, Psychological↗

PubMed1996

Oncogenic signaling.

Cancer develops when one or more cells begin to grow uncontrollably, presumably as a result of alterations in the highly regulated processes of normal cell division. These changes may result from germline or somatic mutations in genes that control normal cell proliferation, resulting in oncogenes. Oncogenes--originally defined as viral genes that transformed mammalian host cells--code for proteins with diverse functions. Antioncogenes, or tumor-suppressor genes, code for proteins acting as brakes in the cell cycle. Mutations in or deletions of these genes release the brakes. An overview of cellular signaling pathways, how they may be altered in cancers, and recently reported clinical implications of abnormal expression of some oncogenes and tumor-suppressor genes will be presented here.

Genes, Tumor Suppressor↗

PubMed1996

Herpes simplex virus infection in the neonate: clinical presentation and management.

Herpes simplex virus (HSV) infections in the neonate can be acquired during pregnancy and during and following the birth process. The most common mode of transmission is from exposure to the virus in the birth canal at the time of delivery. HSV is among the less common infections in neonates. This often leads to delay in diagnosis and treatment, increasing the risk of a poor or fatal outcome. Clinically, HSV infection often presents in preterm or term infants with signs and symptoms similar to those of bacterial sepsis. Their immature immune systems puts preterm infants at higher risk for serious disease. A positive maternal history of HSV is not needed to support diagnosis; typically the mother is asymptomatic. Primary maternal infection usually leads to more serious disease in the neonate. It is important that caregivers recognize the subtle signs and symptoms of HSV infection so early diagnosis and prompt treatment can be instituted.

Acyclovir↗