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Biomedical subjects

J J Murphy

Publications and source records attributed to J J Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1995

The first reported outbreak of diarrheal illness associated with Cyclospora in the United States.

OBJECTIVE: To investigate and characterize the epidemiology of a diarrheal outbreak associated with a potentially new pathogen, Cyclospora species (previously referred to as Cyanobacteria [blue-green algae]-like bodies). DESIGN: Three retrospective cohort studies supported by laboratory studies, environmental investigation, and community surveillance. SETTING: A hospital in Chicago. PARTICIPANTS: Housestaff physicians and hospital administrative staff. MEASUREMENTS: Identification of clinical features associated with illness and potential risks for acquisition of infection. RESULTS: Illness was characterized by watery diarrhea, abdominal cramping, decreased appetite, and low-grade fever. Symptoms typically occurred in a distinctive cycle of remissions and exacerbations lasting up to several weeks. Stool cultures and examinations for known ova and parasites were negative. Microscopic examination of stool specimens from 11 ill persons showed many spherical bodies, 8 to 10 microns in diameter, that were identified as Cyclospora organisms. The organisms disappeared by 9 weeks after onset of illness in the 7 patients from whom follow-up specimens were obtained. Epidemiologic studies implicated tap water from a physicians' dormitory as the most likely source of the outbreak. Environmental investigation suggested that stagnant water in a storage tank may have contaminated the water supply after a pump failure. CONCLUSIONS: This is the first reported outbreak of diarrhea associated with Cyclospora in the United States. Cyclospora may be a human enteric pathogen able to produce bouts of acute and relapsing diarrhea, and it should be considered in assessments of patients with unexplained, prolonged diarrheal illness.

Adult↗
PubMed1995

Necrotizing fasciitis in childhood.

Necrotizing fasciitis is a rare entity in the pediatric population. Five cases of this soft tissue infection were treated at the authors' institution between January and December 1993. Three of the children were profoundly neutropenic secondary to chemotherapy. All five were treated with aggressive surgical debridement, frequent dressing changes, broad-spectrum antibiotics, and nutritional support. In addition, the patients with neutropenia received a combination of granulocyte-colony stimulating factor and granulocyte transfusions. One child died of overwhelming sepsis and bone marrow graft failure. The others eventually made a complete recovery. Necrotizing fasciitis may be becoming a more common problem in children. Aggressive chemotherapeutic regimens and more frequent use of bone marrow transplantation could be a factor in this. Early diagnosis and aggressive surgical therapy is critical. However, mortality may be significant, especially in patients with neutropenia. Leukocyte response to the infection may be a prognostic marker. Pseudomonas and enteric gram-negative organisms are seen frequently in immunocompromised children with necrotizing fasciitis. Antimicrobial selection should supply adequate coverage of these organisms.

Adolescent↗
PubMed1995

Obstructive jaundice caused by neuroblastoma managed with temporary cholecystostomy tube.

Neuroblastoma presenting as obstructive jaundice is very rare. The authors present two cases of neuroblastoma, one primary and one recurrent, manifesting as a malignant obstruction of the extrahepatic biliary system. Various methods of biliary decompression were considered in these children including transhepatic or retrograde biliary stenting and internal cholecystoenteric bypass. An attempt at percutaneous transhepatic stent placement failed in one case. In each patient, a simple insertion of a cholecystostomy tube proved effective. Immediately postoperatively, both patients had rapid resolution in symptoms and a decrease in bilirubin levels. Transient mild cholangitis in both children was successfully treated with antibiotics. Chemotherapy reduced the tumor size in each case, and the cholecystostomy tubes were removed within 3 weeks, after cholangiography showed patency of the distal common bile ducts. Temporary cholecystostomy tube drainage and systemic chemotherapy proved to be a safe, simple, and effective method for managing obstructive jaundice caused by neuroblastoma in these two cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Morbidity in neurologically impaired children after percutaneous endoscopic versus Stamm gastrostomy.

Neurologically impaired children frequently require a feeding gastrostomy. Few reports are available comparing the incidence of postoperative complications and symptomatic gastroesophageal reflux after endoscopic versus operative Stamm gastrostomy in this group of children. We undertook a retrospective study of 63 consecutive neurologically impaired children requiring a feeding gastrostomy, with an average of 23 months of follow-up. No child had symptomatic gastroesophageal reflux. Thirty children had a percutaneous endoscopic gastrostomy and 33 had a Stamm gastrostomy, depending on the preference of the surgeon. The two groups were comparable in age range, cause of neurologic impairment, and indication for gastrostomy. Minor complications occurred in 30%. All three major complications occurred after Stamm gastrostomy, including two postoperative deaths. Symptomatic gastroesophageal reflux developed in 60%. The incidence of fundoplication after gastrostomy was 10% in the percutaneous endoscopic gastrostomy group and 39% after Stamm gastrostomy (p < .025). Morbidity was lower after percutaneous endoscopic gastrostomy than after Stamm gastrostomy in this group of neurologically impaired children. Fundoplication for symptomatic gastroesophageal reflux was infrequent after percutaneous endoscopic gastrostomy and significantly more common after Stamm gastrostomy. Percutaneous endoscopic gastrostomy is recommended as the initial procedure in neurologically impaired children without symptomatic gastroesophageal reflux who require a feeding gastrostomy.

Case-Control Studies↗
PubMed1994

Metabolic fate of S,S,S-tributyl phosphorotrithioate (DEF) in the lactating goat.

1. Metabolism of [1-14C] DEF (S,S,S-1-14C-tributyl phosphorotrithioate, 1) in the lactating goat has been investigated. A goat was dosed orally by capsule on 3 consecutive days at a rate of 0.82 mg/kg body weight/day based on 25 times the maximum DEF residue anticipated in animal feed. 2. Urine and milk were collected throughout the study. The goat was killed 21 h following the last treatment, and kidney, liver and composite samples of muscle and fat were collected. The radioactive residue levels (following the three doses) were 3.45 ppm in liver, 0.35 ppm in kidney, 0.19 ppm in fat, 0.06 ppm in muscle and 0.12 ppm in milk collected at the final 16 h and prior to killing. 3. Urinary metabolic profile indicated that DEF was efficiently metabolized to many metabolites. Tissue and milk extracts also indicated that DEF was extensively metabolized. 4. DEF comprised 31 and 5% of the total radioactive residue in fat and milk, respectively. The amount of DEF in liver, kidney and muscle represented < 1% of the total radioactive residue. 5. A major metabolite, 3-hydroxybutylmethyl sulphone (HBM sulphone, UP3), was found in tissue, milk and urine. The identification of this metabolite was accomplished by a combination of MS, nmr and comparison with an authentic standard. The glucuronide (UP1) and sulphate (UP2) conjugates of HBM sulphone were found in urine, and the sulphate conjugate was a major metabolite in kidney. 6. The hydrolytic products of DEF, S,S-dibutyl phosphorodithioate (Dibufos, U16) and S-butyl phosphorothiate (Bufos, U8), were identified as minor components in urine, comprising 5 and 4% of the total radioactive residue, respectively. Butyl mercaptan was not found, but mixed disulphides of butyl mercaptan with either glutathione (U10, 3%) or N-acetyl cysteine (U13, 2%) were found. 7. Direct evidence for the incorporation of DEF residue into natural constituents was also established. Fatty acids from milk and fat were isolated and shown to be radioactive.

Animals↗
PubMed1993

A B cell specific immediate early human gene is located on chromosome band 1q31 and encodes an alpha helical basic phosphoprotein.

We have determined the cDNA sequence of a human B cell specific, immediate early gene, designated 1R20, which is inducible in response to several B cell activation signals. The cDNA sequence predicts a 196 amino acid open reading frame comprising numerous highly basic residues and the predicted structure contains several potential alpha helical domains together with eight consensus protein phosphorylation sites. The 1R20 gene has been localised by fluorescence in situ hybridisation to chromosome band 1q31, a region known to be implicated in the pathogenesis of haemopoietic malignancies.

Amino Acid Sequence↗
PubMed1993

Multiple signaling pathways mediate anti-Ig and IL-4-induced early response gene expression in human tonsillar B cells.

We have analyzed the relationship between the signaling pathways coupled to surface immunoglobulin and interleukin (IL)-4 receptors in human B cells from the patterns of expression of a panel of phorbol ester-inducible early response genes (ERG) activated by anti-IgM and IL-4 stimulation in vitro. Anti-IgM stimulation led to the induction of all eleven ERG tested. Two of these, the proto-oncogene, c-fos and an anonymous ERG 1R20 were insensitive to protein kinase C (PKC) inhibition with the drug, staurosporine and retained inducibility after down-regulation of PKC activity by purging with phorbol ester. These observations are consistent with previous data showing anti-IgM signaling through both PKC-dependent and PKC-independent pathways. c-fos and 1R20 were also the only ERG inducible in response to IL-4 stimulation and whilst ionomycin induced only c-fos, dibutyryl cyclic adenosine monophosphate stimulation led to induction of both c-fos and 1R20. These observations lend support to a role for the adenylate cyclase pathway being important for coupling of IL-4-generated signals to B cells responses. None of the anti-IgM-responsive ERG was further induced when B cells were co-stimulated with a combination of anti-IgM and IL-4, suggesting that the signaling cascades from these two agents are integrated downstream of third messenger pathways to synergistically promote B cell proliferation.

Alkaloids↗
PubMed1993

Calcium ionophore-induced apoptosis of human B cells is preceded by the induced expression of early response genes.

We have investigated the effects of calcium ionophore on apoptosis of Ramos human B cells. Our results show that the calcium ionophore A23187 at defined concentrations leads to apoptosis of Ramos cells. The majority of cells (> 90%) undergo apoptosis in response to ionophore. The response is rapid and nuclear condensation and DNA degradation can be detected within 2 h after addition of ionophore. In attempts to define the changes in gene expression preceding apoptosis, we investigated the expression of a panel of early response genes in these cells after ionophore addition. We show that calcium ionophore-induced apoptosis of Ramos cells is preceded by the induced expression of a number of early response genes. These results are consistent with calcium ionophore initiating changes in gene expression which may be important in signaling these cells to undergo apoptosis.

Apoptosis↗
PubMed1993

Phorbol ester induction of early response gene expression in lymphocytic leukemia and normal human B-cells.

The spectrum of early response genes induced following phorbol ester (phorbol 12-myristate 13-acetate-PMA) stimulation of B-chronic lymphocytic leukemia cells was compared with that in normal tonsillar B-cells by using a panel of 20 gene probes. Of these, 2 (fos-B and Fra-1) were not expressed in either cell type; 11 displayed a comparable pattern and magnitude of induction in both the cell types, and one anonymous gene (5L3) that was inducible in leukemic cells was not detectably expressed in normal B-cells. Four further anonymous cDNAs (1R21, 10A, 1R19 and 3L11) detected transcripts that were constitutively expressed in normal B-cells with a concomitant reduction in inducibility compared with leukemic B-cells, whilst jun-B and jun-D, which were both inducible in normal B-cells, were constitutively expressed and only marginally PMA-inducible in leukemic B-cells. These data demonstrate clear differences in the PMA-activated early response gene regulatory pathways between normal and lymphocytic leukemia B-cells, which may reflect perturbations in signal transduction pathways that manifest in the differentiation arrest characteristic of these malignant B-cells.

B-Lymphocytes↗
PubMed1993

An immediate early human gene encodes an Id-like helix-loop-helix protein and is regulated by protein kinase C activation in diverse cell types.

Transcription factors characterized by the presence of a helix-loop-helix (HLH) domain play a central role in the regulation of cell growth/differentiation and tumorigenesis. We report here the cDNA sequence of a human early-response gene, designated HLH 1R21, encoding a 15-kDa HLH protein that lacks a basic, DNA-binding domain and which by a number of criteria appears to be the human homologue of mouse HLH 462. Like its murine counterpart, HLH 1R21 protein functions as an Id (inhibitor of DNA binding) transcription factor by inhibiting the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer oligonucleotide in vitro. However HLH 1R21 does not inhibit the binding of HLH Max protein to a Max-binding oligonucleotide in vitro, indicating that it has limited promiscuity in its ability to antagonize the function of other HLH transcription factors. In addition, HLH 1R21 mRNA transcripts are regulated by phorbol ester treatment of a diverse range of human cell lines and, when overexpressed in mouse NIH3T3 cells, HLH 1R21 induces a morphologically transformed phenotype.

3T3 Cells↗
PubMed1992

Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients.

OBJECTIVES: To study the incidence of eosinophilia-myalgia syndrome, the risk factors associated with the syndrome, and the clinical spectrum of illness associated with L-tryptophan use in an exposed population. DESIGN: Retrospective cohort and nested case-control studies of risk factors for eosinophilia-myalgia syndrome using inpatient and outpatient chart reviews, telephone interviews, and in-person patient interviews. Descriptive study of clinical course of L-tryptophan users. SETTING: Office practice of one psychiatrist based in a small city (population 43,467) in South Carolina. PATIENTS: Eligible subjects were all patients from the practice who used L-tryptophan during the 1989 study interval. Of these, 418 (87%) were interviewed. MAIN OUTCOME MEASURES: Clinical spectrum of illness associated with L-tryptophan use, including definite and possible cases of eosinophilia-myalgia syndrome. RESULTS: Among the 418 interviewed L-tryptophan users, we identified 47 definite cases (11%) and 68 possible cases (16%) of eosinophilia-myalgia syndrome, most of which involved patients who were using one retail brand of L-tryptophan (brand A). Among the 157 brand A users, we identified 45 definite cases (29%) and 36 possible cases (23%) of eosinophilia-myalgia syndrome, and the risk for the syndrome increased as the brand A dose increased. Fifty percent (19 of 38) of those using more than 4000 mg/day developed definite eosinophilia-myalgia syndrome, and 84% (32 of 38) developed either definite or possible eosinophilia-myalgia syndrome. On multivariate analysis, risk for definite eosinophilia-myalgia syndrome was associated with brand A dose and age of the patient; however, gender, race, and use of other medications were not associated with the syndrome. CONCLUSIONS: These results suggest that many people exposed to the agent causing eosinophilia-myalgia syndrome may develop illness, and dose of presumably contaminated L-tryptophan is the single most important predictor of eosinophilia-myalgia syndrome. The broad range of signs and symptoms reported by patients using L-tryptophan illustrates that a strict case definition may identify only about half of those affected.

Adult↗