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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
  • Peer Reviewed
Dermatology Online Journal, Volume 20, Issue 2 (2014)

Cutaneous metastasis is an uncommon but well recognized phenomenon occurring as a result of internal malignancy. Cancers most often associated with cutaneous metastasis are melanoma and primary malignancies of the breast and head and neck. Cutaneous metastatic prostate cancer is rare, representing only 1% of cases. Herein we report a case of advanced prostate cancer with multiple cutaneous metastases and briefly review the literature highlighting the clinical and histopathological features as well as a management approach to the patient with metastatic prostate cancer involving the skin.

    Cover page: Eruptive nodules of the head and neck: a case report of metastatic prostate cancerCreative Commons 'BY-NC-ND' version 4.0 license
    • Article
    • Peer Reviewed
    Dermatology Online Journal, Volume 21, Issue 3 (2015)

    Effective treatments for moderate to severe psoriasis are phototherapy and biologics. These treatments are similar in that they both decrease cutaneous immune system hyperactivity yet do so via different mechanisms. Our patient, a 63 year old Asian male had a rapid response to treatment with the high dose excimer laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A pre-treatment biopsy of a psoriatic plaque was found to contain relatively low levels of IFN-γ (Th1) and IL-17 (Th17) secreting T cells. Following treatment with the excimer laser, the patient had a quick improvement in PASI that was reflected by a 3-fold reduction in the number of live T cells found in the post-treatment biopsy. Although ustekinumab and the excimer laser both result in decreased levels of these cytokines, the excimer laser directly causes apoptosis of T cells and induces DNA damage in antigen presenting cells. Thus, the broader effects of phototherapy on immune cells compared to the targeted inhibition of IL-12 and IL-23 by ustekinumab likely account for the superior response observed.

     

      Cover page: Successful use of the excimer laser for generalized psoriasis in an ustekinumab non-responderCreative Commons 'BY-NC-ND' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2017)

      Background

      Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis.

      Objective

      To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis.

      Methods

      Systematic review of published cases of TNF-α inhibitor-induced psoriasis.

      Results

      We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%).

      Limitations

      Retrospective review that relies on case reports and series.

      Conclusion

      While TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.
        Cover page: Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2022)
        The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions.
          Cover page: Clinical application of a scale to assess genomic healthcare empowerment (GEmS): Process and illustrative case examples
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2022)
          The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues.
            Cover page: Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome (NODRS)
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2022)

            Purpose

            Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).

            Methods

            Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.

            Results

            DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.

            Conclusion

            We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.
              Cover page: A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder
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