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Jonathan Cohen

Publications and source records attributed to Jonathan Cohen.

87 records · Page 5Linked to original sources
PubMed2003

Human rights in Vancouver: do injection drug users have a friend in city hall?

In april 2003, the Vancouver Police Department (VPD) initiated a crackdown in the city's Downtown Eastside, an area frequented by drug users and the site of one of the developed world's worst AIDS epidemics. Human Rights Watch (HRW) visited the city and issued a report documenting first-hand accounts of unnecessary use of force by police officers and other human rights abuses. In this article, HRW staffers Joanne Csete and Jonathan Cohen describe how the initial euphoria that greeted the election of Vancouver Mayor Larry Campbell has worn off; how a crackdown that was supposed to be aimed at drug traffickers had the effect of driving drug users away from health and harm-reduction services; and how both the VPD and city tried to discredit the HRW report. Finally, the authors discuss how concerns about the VPD have led to official complaints being filed, and they question whether police forces should be allowed to investigate themselves.

Canada↗
PubMed2003

New report profiles syringe access in California.

A case study conducted by Human Rights Watch in California reveals that counties have to declare a local health emergency if they want to set up a needle exchange program. Even where such programs have been established, police harrassment of the needle exchange clients is widespread.

California↗
PubMed2002

The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes.

The gene encoding streptococcal mitogenic exotoxin Z (SMEZ) was disrupted in Streptococcus pyogenes. Despite the presence of other superantigen genes, mitogenic responses in human and murine HLA-DQ transgenic cells were abrogated when cells were stimulated with supernatant from the smez(-) mutant compared with the parent strain. Remarkably, disruption of smez led to a complete inability to elicit cytokine production (TNF-alpha, lymphotoxin-alpha, IFN-gamma, IL-1 and -8) from human cells, when cocultured with streptococcal supernatants. The potent effects of SMEZ were apparent even though transcription and expression of SMEZ were barely detectable. Human Vbeta8(+) T cell proliferation in response to S. pyogenes was SMEZ-dependent. Cells from HLA-DQ8 transgenic mice were 3 logs more sensitive to SMEZ-13 than cells from HLA-DR1 transgenic or wild-type mice. In the mouse, SMEZ targeted the human Vbeta8(+) TCR homologue, murine Vbeta11, at the expense of other TCR T cell subsets. Expression of SMEZ did not affect bacterial clearance or survival from peritoneal streptococcal infection in HLA-DQ8 mice, though effects of SMEZ on pharyngeal infection are unknown. Infection did lead to a rise in Vbeta11(+) T cells in the spleen which was partly reversed by disruption of the smez gene. Most strikingly, a clear rise in murine Vbeta4(+) cells was seen in mice infected with the smez(-) mutant S. pyogenes strain, indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal responses.

Acute Disease↗
PubMed2002

Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection.

Mice mounting an acute phase response, induced by sterile inflammation after a single s.c. injection of casein 24 h beforehand, were remarkably protected against lethal infection with Gram-positive or Gram-negative bacteria. This was associated with enhanced early clearance of bacteremia, greater phagocytosis and oxidative burst responses by neutrophils, and enhanced recruitment of neutrophils into tissues compared with control, nonacute phase mice. Casein-induced inflammation was also associated with increased concentrations of G-CSF in serum, and administration of neutralizing Ab to this cytokine completely abrogated protection against Escherichia coli infection after casein pretreatment. Injection of recombinant murine G-CSF between 3 and 24 h before infection conferred the same protection as casein injection. In contrast, the casein-induced acute phase response affected neither serum values of TNF-alpha, IL-1 beta, or IL-6 after E. coli infection nor susceptibility to LPS toxicity. Furthermore, protection against infection was unaffected in IL-1R knockout mice, which have deficient acute phase plasma protein responses, or after nonspecific inhibition of acute phase protein synthesis by D-galactosamine or specific depletion of complement C3 by cobra venom factor. Increased production of G-CSF in the acute phase response is thus a key physiological component of host defense, and pretreatment with G-CSF to prevent bacterial infection in at-risk patients now merits further study, especially in view of increasing bacterial resistance to antibiotics.

Acute-Phase Proteins↗
PubMed2002

Toll-like receptors: the key to the stable door?

Severe sepsis continues to lead to critical illness. Few therapeutic options exist other than antibiotic therapy and general supportive care. Large numbers of patients continue to die as a consequence of overactivation of the host inflammatory response and the resultant coagulopathy and disregulation of the normal controls of vasoactive tone. It is now known that a critical part of this host response occurs at the level of innate defence, without the need for antigen processing or the clonal expansion of cells targeted against the invading pathogen. This commentary will discuss the therapeutic targets revealed by our new understanding of the Toll-like receptor. The potential clinical difficulties that may result from intervention at this pattern-recognition receptor will also be explored.

Critical Care↗
PubMed2002

Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis.

BACKGROUND: Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in a putative adaptor protein called ARH. This recessive disorder, characterised by severe hypercholesterolaemia, xanthomatosis, and premature coronary artery disease, is rare except on the island of Sardinia, Italy. Our aim was to ascertain why ARH is more common on Sardinia than elsewhere. METHODS: We obtained detailed medical histories, did physical examinations, measured concentrations of lipoproteins, and harvested genomic DNA from 28 Sardinians with ARH from 17 unrelated families. We sequenced the coding regions and consensus splice sites of ARH in probands from these families, and from 40 individuals of non-Sardinian origin who had an autosomal recessive form of hypercholesterolaemia of unknown cause. FINDINGS: Two ARH mutations, a frameshift mutation (c432insA) in exon 4 (ARH1) and a nonsense mutation (c65G-->A) in exon 1 (ARH2), were present in all of the 17 unrelated families with ARH. Three of the ARH alleles contained both mutations, as a result of an ancient recombination between ARH1 and ARH2. No regional clustering of the three mutant alleles within Sardinia was apparent. Furthermore, four Italians from the mainland with autosomal recessive hypercholesterolaemia were homozygous for ARH1. INTERPRETATION: The small number, high frequency, and dispersed distribution of ARH mutations on Sardinia are consistent with these mutations being ancient and maintained in the Sardinian population because of geographic isolation.

Adolescent↗
PubMed2002

Laryngeal mask airway--a novel method of airway protection during ERCP: comparison with endotracheal intubation.

BACKGROUND: ERCP sometimes requires deep sedation and rarely general anesthesia with airway protection. The laryngeal mask airway device is placed perorally to create a seal over the larynx. Unlike endotracheal intubation, no tube traverses the vocal cords, thus reducing airway stimulation and obviating the need to administer muscle relaxants. The feasibility of using the laryngeal mask airway during ERCP was evaluated and recovery times compared for patients undergoing ERCP with the laryngeal mask airway versus endotracheal intubation. METHODS: In this retrospective cohort study, anesthesia records were reviewed for anesthesiologist-assisted ERCP procedures performed during a 30-month period. Demographics, procedure duration, and time from endoscope removal to extubation were abstracted. Either propofol or inhalation agents were used for anesthesia in all patients. OBSERVATIONS: Anesthesiologists administered sedation for 41 ERCPs. The airway was managed in 12 patients with endotracheal intubation and the laryngeal mask airway in 20 patients. Six patients underwent laryngeal mask airway insertion and removal while prone. A therapeutic duodenoscope was passed beyond the laryngeal mask airway with little or no resistance in all cases. Repositioning the laryngeal mask airway during the procedure was required in 1 case. Laryngeal mask airway use was associated with shorter extubation time compared with endotracheal intubation (7.2 vs. 12 min.; p = 0.004). There were no airway complications. CONCLUSION: ERCP can be performed while using the laryngeal mask airway for airway protection. The laryngeal mask airway can be placed with the patient prone, obviating the need to change position. Laryngeal mask airway shortens extubation time compared with endotracheal intubation.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2002

Increased susceptibility of C1q-deficient mice to Salmonella enterica serovar Typhimurium infection.

The role of the complement system in host defense against Salmonella infection is poorly defined. Bacterial cell wall O-antigen polysaccharide can activate the alternative pathway in vitro. No studies, however, have elucidated the role of the classical pathway in immunity to Salmonella spp. in vivo. C1q-deficient mice (C1qa(-/-)) on a 129/Sv genetic background and strain-matched controls were infected intraperitoneally and intravenously with Salmonella enterica serovar Typhimurium and monitored over a 14-day period. After inoculation by either route, the C1qa(-/-) mice were found to be significantly more susceptible to Salmonella infection. Hepatic and splenic bacterial counts, performed at various time points, showed increased numbers of colonies in complement-deficient mice compared to controls. Analysis of blood clearance showed no difference between the two experimental groups during the first 15 min. However, after 20 min and until 6 h postinfection, numbers of circulating bacteria were significantly higher in complement-deficient mice. In vitro experiments using either resident or thioglycolate-elicited peritoneal macrophages showed a significant increase in the number of bacteria inside C1q-deficient macrophages compared to controls irrespective of the serum used for opsonizing the bacteria. These findings could not be explained either by an increased bacterial uptake, analyzed in vitro and in vivo using green fluorescent protein-tagged salmonellae, or by a defect in the respiratory burst or in NO production. The data presented here suggest the possibility of novel pathways by which C1q may modulate the pathogenesis of infectious diseases caused by intracellular pathogens.

Animals↗
PubMed2000

Mitogenic factor (MF) is the major DNase of serotype M89 Streptococcus pyogenes.

To investigate the role of mitogenic factor (MF) in streptococcal pathogenesis, the structural gene (mf) encoding this protein was disrupted in a clinical isolate of Streptococcus pyogenes H293, to yield the isogenic mutant H363. Growth in enriched broth and on blood agar was unaffected by disruption of mf. Cell-free broth supernatants from H293 and H363 demonstrated identical promitogenic activities when co-incubated with human peripheral blood mononuclear cells, even when diluted 100000-fold, showing that MF is not a major streptococcal mitogen compared with other secreted superantigens. Disruption of mf resulted in complete loss of DNase B production and detectable DNase activity in H363 compared with the parent strain, confirming that the single gene mf, which is present in all group A streptococcal M serotypes studied, encodes DNase B. Despite loss of DNase activity, the virulence of S. pyogenes in a mouse model of necrotizing fasciitis and myositis was unaffected.

Animals↗
PubMedDate not supplied

The immunopathogenesis of sepsis.

Sepsis is a condition that results from a harmful or damaging host response to infection. Many of the components of the innate immune response that are normally concerned with host defences against infection can, under some circumstances, cause cell and tissue damage and hence multiple organ failure, the clinical hallmark of sepsis. Because of the high mortality of sepsis in the face of standard treatment, many efforts have been made to improve understanding of the dysregulation of the host response in sepsis. As a result, much has been learnt of the basic principles governing bacterial-host interactions, and new opportunities for therapeutic intervention have been revealed.

Animals↗
PubMedDate not supplied

VLOD: high-fidelity walkthrough of large virtual environments.

We present visibility computation and data organization algorithms that enable high-fidelity walkthroughs of large 3D geometric data sets. A novel feature of our walkthrough system is that it performs work proportional only to the required detail in visible geometry at the rendering time. To accomplish this, we use a precomputation phase that efficiently generates per cell vLOD: the geometry visible from a view-region at the right level of detail. We encode changes between neighboring cells' vLODs, which are not required to be memory resident. At the rendering time, we incrementally construct the vLOD for the current view-cell and render it. We have a small CPU and memory requirement for rendering and are able to display models with tens of millions of polygons at interactive frame rates with less than one pixel screen-space deviation and accurate visibility.

Algorithms↗