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Biomedical subjects

D I Friedman

Publications and source records attributed to D I Friedman.

At least 19 recordsLinked to original sources
PubMed2006

Retinal migraine reappraised.

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Herein we summarize the clinical features and prognosis of 46 patients (six new cases and 40 from the literature) with retinal migraine based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most common in women in the second to third decade of life. Contrary to ICHD-2 criteria, most have a history of migraine with aura. In the typical attack monocular visual features consist of partial or complete visual loss lasting <1 h, ipsilateral to the headache. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, perhaps representing an ocular form of migrainous infarction. Based on this observation, the authors recommend migraine prophylactic treatment in an attempt to prevent permanent visual loss, even if attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic criteria for retinal migraine.

Adolescent↗
PubMed2004

Doxycycline and intracranial hypertension.

The authors report seven patients from six neuro-ophthalmology referral centers who developed pseudo-tumor cerebri during treatment with doxycycline. All four female patients and one of three male patients were obese. Vision was minimally affected in most patients, but two had substantial visual acuity or visual field loss at presentation. Discontinuation of doxycycline, with or without additional intracranial pressure-lowering agents, yielded improvement, but permanent visual acuity or visual field loss occurred in five patients.

Acne Vulgaris↗
PubMed2001

Interactions of an Arg-rich region of transcription elongation protein NusA with NUT RNA: implications for the order of assembly of the lambda N antitermination complex in vivo.

The E. coli NusA transcription elongation protein (NusA(Ec)), identified because of its requirement for transcription antitermination by the N protein, has an Arg-rich S1 RNA-binding domain. A complex of N and NusA with other host factors binding at NUT sites in the RNA renders RNA polymerase termination-resistant. An E. coli haploid for nusA944, having nine different codons replacing four normally found in the Arg-rich region, is defective in support of N action. Another variant, haploid for the nusAR199A allele, with a change in a highly conserved Arg codon in the S1 domain, effectively supports N-mediated antitermination. However, nusAR199A is recessive to nusA944, while nusA(Ec) is dominant to nusA944 for support of N-mediated antitermination, suggesting a competition between NusA944 and NusAR199A during complex formation. Complex formation with the variant NusA proteins was assessed by mobility gel shifts. NusAR199A, unlike NusA(Ec) and NusA944, fails to form a complex with N and NUT RNA. However, while NusAR199A, like wild-type NusA, forms an enlarged complex with NUT RNA, N, RNA polymerase, and other host proteins required for efficient N-mediated antitermination, NusA944 does not form this enlarged complex. Consistent with the in vivo results, NusA944 prevents NusAR199A but not NusA(Ec) from forming the enlarged complex. The simplest conclusion from these dominance studies is that in the formation of the complete active antitermination complex in vivo, NusA and N binding to the newly synthesized NUT RNA precedes addition of the other factors. Alternative less effective routes to the active complex that allows bypass of this preferred pathway may also exist.

Alleles↗
PubMed2001

Bacteriophage lambda: alive and well and still doing its thing.

The lambda (lambda) family of bacteriophages continues to provide significant insights into the understanding of basic biological processes, as well as useful technological innovations. Areas in which recent advances have occurred include transcription elongation, repressor interactions, genomics and post-transcriptional regulation. The homologous lambda recombination functions have been exploited as an efficient in vivo recombinant engineering system for functional genomic studies. The virulence of some pathogenic strains of Escherichia coli is enhanced by the expression of Shiga toxin (stx) genes encoded on a resident lambdoid prophage. Recent work suggests that the phage regulatory network may be a significant contributor to toxin production and release by these pathogenic E. coli.

Bacteriophage lambda↗
PubMed2001

The operator-early promoter regions of Shiga-toxin bearing phage H-19B.

Genes (stx) encoding Shiga toxins (Stx), major virulence factors in some pathogenic strains of Escherichia coli (STEC), are located in prophages of the lambda family. Agents that induce prophages lead to high levels of Stx, suggesting a role for the prophage in stx expression. Activation of the phage regulatory cascade has been shown to contribute to Stx production and release. Therefore, repressor-operator interactions that maintain prophage repression appear important in regulating expression of a major bacterial virulence factor. To determine if the operators of an stx-bearing phage have distinctive features, we characterized the operator regions of H-19B, a lambdoid phage carrying stx1 genes. H-19B mutants that grow in the presence of repressor (classically called virulent mutants) were selected and the mutations definitively identified the operators. The H-19B operators, as those in other lambdoid phages, comprise variations of an inverted repeat. Four repeats were identified in O(R) rather than the three found in each of the operators of other lambdoid phages. Primer extensions identified the transcription start sites of P(R) and P(RM), the two promoters in O(R) regulated by repressor.

Bacteriophage lambda↗
PubMed2001

Role for a phage promoter in Shiga toxin 2 expression from a pathogenic Escherichia coli strain.

Shiga toxins (Stxs), encoded by the stxA and stxB genes, are important contributors to the virulence of Escherichia coli O157:H7 and other Stx-producing E. coli (STEC) strains. The stxA and stxB genes in STEC strains are located on the genomes of resident prophages of the lambda family immediately downstream of the phage late promoters (p(R')). The phage-encoded Q proteins modify RNA polymerase initiating transcription at the cognate p(R') promoter which creates transcription complexes that transcend a transcription terminator immediately downstream of p(R') as well as terminator kilobases distal to p(R'). To test if this Q-directed processive transcription plays a role in stx(2)AB expression, we constructed a mutant prophage in an O157:H7 clinical isolate from which p(R') and part of Q were deleted but which has an intact pStx, the previously described stx(2)AB-associated promoter. We report that production of significant levels of Stx2 in this O157:H7 isolate depends on the p(R') promoter. Since transcription initiating at p(R') ultimately requires activation of the phage lytic cascade, expression of stx(2)AB in STEC depends primarily on prophage induction. By showing this central role for the prophage in stx(2)AB expression, our findings contradict the prevailing assumption that phages serve merely as agents for virulence gene transfer.

Animals↗
PubMed2001

Papilledema and pseudotumor cerebri.

There is perhaps no neuro-ophthalmic sign that is as ominous as papilledema. True papilledema from increased intracranial pressure may be a harbinger of serious neurological disease. There, however, are other conditions that may mimic papilledema, contributing to the diagnostic dilemma. This article concerns the detection and differential diagnosis of papilledema, focusing on increased intracranial pressure without a mass lesion (pseudotumor cerebri).

Diagnosis, Differential↗
PubMed2000

Charged tmRNA but not tmRNA-mediated proteolysis is essential for Neisseria gonorrhoeae viability.

tmRNA, through its tRNA and mRNA properties, adds short peptide tags to abnormal proteins, targeting these proteins for proteolytic degradation. Although the conservation of tmRNA throughout the bacterial kingdom suggests that it must provide a strong selective advantage, it has not been shown to be essential for any bacterium. We report that tmRNA is essential in Neisseria gonorrhoeae. Although tagging per se appears to be required for gonococcal viability, tagging for proteolysis does not. This suggests that the essential roles of tmRNA in N.gonorrhoeae may include resolving stalled translation complexes and/or preventing depletion of free ribosomes. Although derivatives of N.gonorrhoeae expressing Escherichia coli tmRNA as their sole tmRNA were isolated, they appear to form colonies only after acquiring an extragenic suppressor(s).

Base Sequence↗
PubMed2000

N-mediated transcription antitermination in lambdoid phage H-19B is characterized by alternative NUT RNA structures and a reduced requirement for host factors.

Gene expression in lambdoid phages in part is controlled by transcription antitermination. For most lambdoid phages, maximal expression of delayed early genes requires an RNA polymerase modified by the phage N and host Nus proteins at RNA NUT sites. The NUT sites (NUTL and NUTR) are made up of three elements: BOXA, BOXB and an intervening spacer sequence. We report on N antitermination in H-19B, a lambdoid phage carrying shiga toxin 1 genes. H-19B N requires NusA, but not two other host factors required by lambda N, NusB and ribosomal protein S10. The H-19B NUT site BOXA is not required, whereas the BOXB is required for N action. H-19B nut sites have dyad symmetries in the spacer regions that are not in other nut sites. Changes in one arm of the dyad symmetry inactivate the NUT RNA. Compensating changes increasing the number of mutant nucleotides but restoring dyad symmetry restore activity. Deletion of the sequences encoding the dyad symmetry has little effect. Thus, the specific nucleotides composing the dyad symmetry seem relatively unimportant. We propose that the RNA stem-loop structure, called the 'reducer', by sequestering nucleotides from the linear RNA brings into proximity sites on either side of the dyad symmetry that contribute to forming an active NUT site.

Bacteriophage lambda↗
PubMed2000

Multiple sclerosis simulating a mass lesion.

The cases of two young women with a homonymous hemianopia are described. Both women had a progressively enlarging mass lesion that was seen with neuroimaging studies. One patient had neurologic deterioration despite intravenous corticosteroid treatment. In each case, results of a stereotactic biopsy showed demyelination that was consistent with multiple sclerosis. Multiple sclerosis infrequently presents as a mass lesion. The atypical clinical and radiographic features of large demyelinating plaques may lead to an erroneous diagnosis of a brain tumor, infection, or demyelination from other causes.

Adult↗
PubMed1999

Pseudotumor cerebri.

Pseudotumor cerebri is an unusual syndrome of increased intracranial pressure without a space-occupying mass. Many associations are known, but the pathogenesis remains a mystery. The diagnosis and treatment of pseudotumor cerebri are often challenging. Because it is not rare, neurosurgeons, neurologists, and ophthalmologists frequently work in concert to manage these patients. This article reviews the diagnostic criteria and differential diagnosis of pseudotumor cerebri. The medical and surgical treatments currently employed in this disorder are discussed.

Adolescent↗
PubMed1998

Arrangement and functional identification of genes in the regulatory region of lambdoid phage H-19B, a carrier of a Shiga-like toxin.

H-19B is a lambdoid phage that carries the genes (stx-I) encoding the two toxin subunits of a Shiga-like toxin; Escherichia coli lysogens of H-19B are converted to toxin producers. Based on the determination of a 17-kb region of the H-19B genome and functional studies, we have identified the early regulatory region and associated genes of H-19B, as well as the location of the late regulatory region and the toxin and lysis genes. A comparative analysis of the sequence of the H-19B genome reveals the presence of ORFs and genes found in analogous positions on the genomes of a number of other lambdoid phages. A cloned genomic fragment that confers immunity to an infecting H-19B phage contains an ORF of an analogous size and genomic location for a repressor gene, adjacent to a putative operator region. The lambda replication genes, O and P, are conserved in H-19B except for a 39-bp insert in the O gene creating two new O protein-binding sites in the origin of replication (ori), giving H-19B six binding sites as opposed to the four sites found in lambda. We identify ORFs and sequences involved in transcriptional regulation encoding N-like antitermination systems like those found in other lambdoid phages and nearly identical to sequences found in phage HK97. Our functional studies show that these sequences support antitermination even though they contain significant differences from those of other lambdoid phages. We also identify ORFs and sequences analogous to the Q-p'R late antiterminators-promoters found in other lambdoid phages. The Shiga-like stx-I genes are located directly downstream of the promoter, p'R, for the late genes, and upstream of the lysis genes.

Bacterial Toxins↗
PubMed1998

Incidence of dog bite injuries treated in emergency departments.

CONTEXT: Dog bites that result in injuries occur frequently, but how frequently dog bite injuries necessitate medical attention at a hospital or hospital admission is unknown. OBJECTIVE: To describe the incidence and characteristics of dog bite injuries treated in US emergency departments (EDs). DESIGN: Emergency department survey from the National Center for Health Statistics National Hospital Ambulatory Medical Care Survey for 1992 to 1994. PATIENTS: National probability sample of patients visiting EDs. MAIN OUTCOME MEASURE: Incidence of dog bites treated in EDs, defined as a cause of injury recorded as the E-code E906.0. RESULTS: The 3-year annualized, adjusted, and weighted estimate of new dog bite-related injury visits to US EDs was 333687, a rate of 12.9 per 10000 persons (95% confidence interval [CI], 10.5-15.4). This represents approximately 914 new dog bite injuries requiring ED visits per day. The median age of patients bitten was 15 years, with children, especially boys aged 5 to 9 years, having the highest incidence rate (60.7 per 10000 persons for boys aged 5 to 9 years). Children seen in EDs were more likely than older persons to be bitten on the face, neck, and head (73% vs 30%). We estimated that for each US dog bite fatality there are about 670 hospitalizations and 16000 ED visits. CONCLUSIONS: Dog bite injuries are an important source of injury in the US population, especially among children. Improved surveillance and prevention of dog bite-related injuries, particularly among children, are needed.

Adolescent↗
PubMed1998

Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release.

Analysis of the DNA sequence of a 17 kb region of the coli lambdoid phage H-19B genome located the genes encoding shiga-like toxin I (Stx-I) downstream of the gene encoding the analogue of the phage lambda Q transcription activator with its site of action, qut at the associated pR' late promoter, and upstream of the analogues of lambda genes encoding lysis functions. Functional studies, including measurement of the effect of H-19B Q action on levels of Stx expressed from an H-19B prophage, show that the H-19B Q acts as a transcription activator with its associated pR'(qut) by promoting readthrough of transcription terminators. Another toxin-producing phage, 933W, has the identical Q gene and pR'(qut) upstream of the stx-II genes. The H-19B Q also activates Stx-II expression from a 933W prophage. An ORF in H-19B corresponding to the holin lysis genes of other lambdoid phages differs by having only one instead of the usual two closely spaced translation initiation signals that are thought to contribute to the time of lysis. These observations suggest that stx-I expression can be enhanced by transcription from pR' as well as a model for toxin release through cell lysis mediated by action of phage-encoded lysis functions. Functional studies show that open reading frames (ORFs) and sites in H-19B that resemble components of the N transcription antitermination systems controlling early operons of other lambdoid phages similarly promote antitermination. However, this N-like system differs significantly from those of other lambdoid phages.

Amino Acid Sequence↗
PubMed1998

Idiopathic intracranial hypertension and orthostatic edema may share a common pathogenesis.

Our aim was to determine the frequency of orthostatic edema (OE) in patients with idiopathic intracranial hypertension (IIH). We evaluated 30 women with IIH for evidence of OE by comparing sodium and water excretion in the recumbent and standing postures and morning and evening body weights. Data were compared with findings in 30 women with OE, 22 weight-matched obese normal subjects, and 20 lean normal subjects. The effect of treatment with diuretics or diuretics plus sympathomimetic agents was compared. Seventy-seven percent of IIH patients had evidence of peripheral edema and 80% had significant orthostatic retention of sodium or water. Excretion of a standard saline load and of a tap water load was significantly impaired in the upright posture in the IIH and OE patients compared with the lean and obese normal subjects. Diuretic therapy induced weight loss (up to 9 kg) and decreased mean weight gain from morning to evening in 5 of 12 patients treated. In seven patients also treated with diuretics plus sympathomimetic drugs, the diuretic-induced morning weight loss and morning to evening weight gain were both significantly improved with the addition of sympathomimetic agents. Therapy reduced the frequency or severity of headaches in seven patients and reduced papilledema in four patients who received no other concurrent treatment for IIH. The orthostatic retention of sodium and water and the consequent edema is very similar in IIH and OE patients, suggesting a common pathogenesis for both disorders. Diuretic therapy, dietary salt and water restriction, and planned periods of recumbency merit study as a treatment for these patients.

Adult↗
PubMed1998

Unusual ocular motility disturbances with increased intracranial pressure.

We evaluated nine patients with external ophthalmoparesis and increased intracranial pressure. The eye movements normalized when the intracranial pressure was controlled. Investigations for an underlying cause of elevated cerebrospinal fluid pressure are warranted when ocular motility disorders are present.

Adolescent↗
PubMed1996

Identification of functional regions of the Nun transcription termination protein of phage HK022 and the N antitermination protein of phage lambda using hybrid nun-N genes.

Phages lambda and HK022 express proteins N and Nun, respectively, each of which acts with a number of Escherichia coli host Nus factors at lambda NUT RNA sites, to influence transcription elongation. The lambda nut sites, nearly identical sequences located downstream of the early promoters, pL and pR, were first identified as cis-acting signals required for the action of N in forming termination-resistant transcription complexes. Surprisingly, the Nun protein, resembling N and expressed by another lambdoid phage, HK022, also acts with Nus proteins to terminate specifically transcription initiating at pL and pR near the lambda nut sites. Based on structural considerations of the amino acid sequences, we have constructed nine hybrid N-nun genes and used these hybrids to identify functional regions of the N and Nun proteins. Three classes of hybrid gene products were identified: (1) those that, like N, support antitermination, (2) those that, like Nun, terminate transcription, and (3) those that block N action but do not terminate transcription. We find that, similar to N, the amino-terminal portion of Nun is involved in RNA recognition. The more carboxy portions influence transcription elongation, antitermination (N) and termination (Nun). Depending on the derivations of the more carboxy regions, hybrids with either the N or Nun amino portions support either termination or antitermination. The activity of a hybrid protein may be influenced by the host strain depending on the nature of the rpoC locus, a locus encoding the beta' subunit of RNA polymerase. One of the hybrid proteins blocks antitermination when the rpoC locus is wild-type. The same hybrid in the presence of the rpoC100 mutation, which alters the beta' subunit, has antitermination activity. This result supports the argument that the beta' subunit plays an essential role in determining the progress of transcription elongation.

Amino Acid Sequence↗