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Biomedical subjects

M Duvic

Publications and source records attributed to M Duvic.

At least 127 records · Page 7Linked to original sources
PubMed1993

Imaging of the skin with 20-MHz US.

PURPOSE: The authors clinically evaluated a new high-frequency ultrasound (US) scanner to determine the value of US for dermatologic applications. MATERIALS AND METHODS: A 20-MHz US scanner was used to visualize normal skin at eight sites in 10 healthy volunteers and to evaluate 200 skin lesions (45 malignant, 155 benign). RESULTS: In normal skin, the dermis was markedly echogenic and sharply demarcated from hypoechoic subcutaneous fat. The epidermis was not resolved except on the palm and sole. Only three superficial lesions were not identified with US; evaluation of another three was limited by shadowing. Thickness of the lesions visualized was 0.2-26.0 mm (mean, 1.9 mm +/- 2.6). Most lesions (77%) were hypoechoic, 9% were anechoic, 12% had mixed echogenicity, and 2% were isoechoic or hyperechoic. CONCLUSION: The diagnostic role of high-frequency US appears limited. It did not help differentiate benign from malignant lesions, but it did enable accurate delineation of deep margins of lesions and allowed noninvasive measurement of thickness. These features may help in the preoperative evaluation of skin tumors and in monitoring the response to therapy for certain inflammatory conditions.

Adolescent↗
PubMed1993

A phase-I clinical study of low-dose oral interferon-alpha.

Twenty-five patients with systemic malignancies or cutaneous disorders were treated with low dosages (1-16 IU/kg/day) of oral interferon-alpha in a phase-I study. There were no grade-3 or -4 toxicities. No patients achieved a partial or complete response. One patient with renal cell carcinoma had prolonged disease stabilization lasting for 22 months. No significant changes in lymphocyte subsets including T4/T8 ratio, or serum immunoglobulins were observed. Subjective improvement in general well-being was reported by three patients. Low dosages of interferon-alpha administered orally do not appear to have any significant immunomodulatory or antitumor activity.

Administration, Oral↗
PubMed1992

Cowden syndrome and Lhermitte-Duclos disease.

BACKGROUND: Cowden syndrome (CS) is a rare but underdiagnosed autosomal dominant condition also known as "multiple hamartoma-neoplasia syndrome." Patients have multiple tricholemmomas (a type of benign skin appendage tumor) and oral papillomatosis and cutaneous keratoses. They often have goiter, gastrointestinal polyps, and hamartomatous soft tissue lesions. Breast cancer affects approximately one third of women with CS. Lhermitte-Duclos disease (LDD) is a peculiar proliferation of abnormal neuronal elements of the cerebellum that has features of a hamartoma and of a neoplasm. METHODS: The authors described two patients who have both CS and LDD. Also reviewed were 50 of approximately 62 previously described cases of LDD (identified through literature searches) in an effort to find patients with LDD who had other associated lesions. RESULTS: Only one other patient in whom both LDD and CS were recognized has been reported. In addition, a number of patients with LDD who had other neoplasms and/or thyroid lesions have been described. CONCLUSIONS: Given the rarity of these two entities, we believe that their association is not fortuitous. LDD fits into the concept of CS as a hamartoma-neoplasia syndrome. In addition, a number of patients with LDD who had other neoplasms or thyroid lesions have been reported, raising the possibility that CS and LDD are more closely linked than is generally appreciated. We suspect that there are more patients with LDD who have unrecognized CS. Patients with either of the two diseases should be examined and followed up for evidence of the other.

Adult↗
PubMed1992

The gene for a novel epidermal antigen maps near the neurofibromatosis 1 gene.

Recently the M17S1 gene, encoding an epidermal antigen thought to play a role in cell adhesion, was mapped to chromosome bands 17q11-q12, placing it in the vicinity of the gene for the genetic disorder neurofibromatosis 1 (NF1). The pleomorphic cutaneous lesions of NF1 and the precedent for other genes being embedded within the NF1 gene prompted us to investigate whether the M17S1 gene mapped near, or within, the NF1 gene. Genetic linkage analyses revealed that M17S1 was tightly linked to NF1 and mapped within the interval bounded by D17S58 and D17S54. Physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast artificial chromosomes, and an NF1 patient with a deletion involving an entire NF1 allele demonstrated that M17S1 is located at least 180 kb centromeric to the NF1 gene. The distance between the genes suggests that M17S1 is unlikely to contribute to the NF1 phenotype since a gross chromosomal rearrangement would be required to disrupt expression of both genes.

Animals↗
PubMed1992

HIV and skin disease: the molecular biology of the human immunodeficiency virus.

The human immunodeficiency virus (HIV) is a member of a family of retroviruses that cause chronic persistent infections in animals and in humans. The structure of this virus resembles that of other retroviruses but also contains important and complex regulatory elements. The expression of HIV can be influenced by the action of exogenous agents and cytokines. HIV has been isolated from a number of cell types, including cells in the skin, using sensitive detection methods such as the polymerase chain reaction and in situ hybridization. This article is a basic overview of the molecular biology of HIV and its presence in skin.

Animals↗
PubMed1992

Type I keratinocyte transglutaminase: expression in human skin and psoriasis.

A 92-kD transglutaminase (TGase K), expressed in human cultured keratinocytes and stratum corneum, catalyzes a critical step in the formation of the cornified envelope of terminal differentiation. A rabbit polyclonal antibody to TGase K was used to isolate overlapping cDNA clones from a human keratinocyte cDNA expression library. The cDNA clones were sequenced and unequivocally identified as TGase K by comparison to the N-terminal amino acid sequences of two cyanogen bromide fragments from the purified enzyme. The mRNA for Tgase K is expressed in cultured keratinocytes but not in A431 squamous carcinoma cells, in fibroblasts, or in other non-epithelial tissues and cells. Although TGase K protein expression is limited to the upper layers of normal epidermis, the mRNA is generally present throughout the epidermis, suggesting the possibility of post-transcriptional regulation. Precocious expression of TGase K protein occurs in psoriasis, and quantitative Northern blot analysis of TGase K mRNA from normal and involved epidermal biopsies from psoriasis patients suggests that TGase K mRNA levels are increased in psoriatic lesions. By using quantitative laser scanning confocal microscopy (LSCM) and in situ hybridization, the increase of the TGase K mRNA was in the range of 3-7 times in the psoriatic epidermis and was significantly higher compared with normal skin and with paired adjacent skin. Quantitative LSCM provides a powerful and direct method for analysis of gene expression in skin.

Amino Acid Sequence↗
PubMed1992

Buschke-Ollendorff syndrome associated with elevated elastin production by affected skin fibroblasts in culture.

Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2-8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin fibroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-beta 1 (TGF beta 1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGF beta 1-stimulated elastin production, was able to reduce elastin production in basal and TGF beta 1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis.

Blotting, Southern↗
PubMed1992

Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia.

This is a case report and review of the literature on the blue rubber bleb nevus syndrome. The clinical features of the syndrome are discussed, with emphasis on chronic gastrointestinal bleeding and resulting anemia. A new therapeutic modality, colonoscopy with laser photocoagulation, is recommended as a safe, effective, and less invasive method of controlling bleeding from colonic hemangiomas than surgical resection and repeated transfusions. This technique is less helpful for patients with prominent involvement of the small intestine.

Anemia↗
PubMed1991

Binding of triple helix forming oligonucleotides to sites in gene promoters.

A class of triplex-forming oligodeoxyribonucleotides (TFOs) is described that can bind to naturally occurring sites in duplex DNA at physiological pH in the presence of magnesium. The data are consistent with a structure in which the TFO binds in the major groove of double-stranded DNA to form a three-stranded complex that is superficially similar to previously described triplexes. The distinguishing features of this class of triplex are that TFO binding apparently involves the formation of hydrogen-bonded G.GC and T.AT triplets and the TFO is bound antiparallel with respect to the more purine-rich strand of the underlying duplex. Triplex formation is described for targets in the promoter regions of three different genes: the human c-myc and epidermal growth factor receptor genes and the mouse insulin receptor gene. All three sites are relatively GC rich and have a high percentage of purine residues on one strand. DNase I footprinting shows that individual TFOs bind selectively to their target sites at pH 7.4-7.8 in the presence of millimolar concentrations of magnesium. Electrophoretic analysis of triplex formation indicates that specific TFOs bind to their target sites with apparent dissociation constants in the 10(-7)-10(-9) M range. Strand orientation of the bound TFOs was confirmed by attaching eosin or an iron-chelating group to one end of the TFO and monitoring the pattern of damage to the bound duplex DNA. Possible hydrogen-bonding patterns and triplex structures are discussed.

Animals↗
PubMed1991

Human immunodeficiency virus (HIV) transcripts identified in HIV-related psoriasis and Kaposi's sarcoma lesions.

Persons with HIV infection sometimes develop aggressive psoriasis or Kaposi's sarcoma (KS) not usually seen in other immunosuppressed patients. However, a specific and direct pathophysiological role for HIV-1 in these AIDS-associated disorders remains unclear since HIV has not been easily detected in these skin lesions. By combining in situ hybridization with the sensitive detection technique of confocal laser scanning microscopy, we have demonstrated HIV RNA transcripts in 5 of 15 lesional skin biopsies from HIV-infected psoriasis patients, and in 3 of 8 Kaposi's sarcoma biopsies from HIV-infected patients. HIV transcripts were not detected in normal appearing skin from HIV-infected patients or in psoriatic and normal skin biopsies from uninfected individuals (P = 0.006). Although previous attempts to demonstrate viral sequences in psoriasis and KS lesions have been unsuccessful, in situ hybridization with confocal microscopy has shown the presence of HIV RNA transcripts predominantly within CD4+, Factor XIIIa positive dermal dendrocytes. HIV or cytokines produced by infected cells in skin lesions may therefore play a direct role in the pathogenesis of HIV-associated psoriasis and KS.

Adult↗
PubMed1991

HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance.

Because predisposition to autoimmunity has been associated with HLA-D alleles and alopecia areata is hypothesized to be a T-cell mediated autoimmune hair loss, we determined DR and DQ alleles in 88 white and 10 American black patients with alopecia areata as well as controls with the use of restriction fragment length polymorphism typing with cDNA probes. White patients with alopecia areata have an increase in the phenotype frequencies of DR4 and DQw8 and an increase in genotype frequencies of DR4 and DR5 (now DRw11[5]). These associations are in agreement with those reported in two other studies but are not significant when corrected by the number of HLA antigens tested. Sixty-one percent of all patients with AA have DR4 and/or DRw11(5) specificities vs 40% of controls, with more DR4,DRw11(5) and DQw7(w3), DQw8(w3) heterozygotes among patients. DQw6(w1) phenotype frequencies and DRw52a phenotype and genotype frequencies are significantly decreased in patients with alopecia areata relative to controls. This highly significant negative association with the HLA DRB3 allele DRw52a in whites persisted even when DR4- or DRw11(5)-positive individuals were excluded from the patient and control groups. These data suggest that HLA-DR4 and DRw11(5) with their associated DQw7(w3) and DQw8(w3) specificities may confer susceptibility to alopecia areata, while DRw52a may confer resistance.

Adolescent↗
PubMed1991

Improved detection of in situ hybridization by laser scanning confocal microscopy.

Laser scanning confocal microscopy (LSCM) offers a significant improvement over conventional bright-field and dark-field light microscopy for producing images of silver grains in autoradiograms of specimens prepared by in situ hybridization. The out-of-focus image of the background silver grains present in the emulsion is eliminated from the in-focus image of the radioactive probe associated with the cells by optical sectioning with the LSCM operated in a reflected light mode. The improved images produced by the LSCM provide a significant increase in the sensitivity of detecting positively labeled cells and tissues prepared by in situ hybridization. The power of this detection method is demonstrated using samples of HIV-infected human peripheral blood cells, tissue sections of human placenta and human skin. It is anticipated that the method can be universally applied to samples prepared by in situ hybridization techniques.

Cell Line↗
PubMed1991

Syphilis superinfection activates expression of human immunodeficiency virus I in latently infected rabbits.

Superinfection of latently human immunodeficiency virus (HIV)-infected rabbits with either Treponema pallidum or Shope fibroma virus (SFV) activates HIV expression. In addition, HIV-infected rabbits demonstrate prolonged cutaneous lesions (chancres) after intracutaneous challenge with T. pallidum, the causative agent of syphilis. Rabbits were infected by intravenous inoculation of 3 x 10(7) human T-cell lymphotrophic virus type III (HTLV-III)/B10 (HIV-1)-infected H9 (human) cells. Five weeks after initial infection, integrated HIV-1-specific DNA sequences were detected in the DNA of the peripheral blood lymphocytes of only one of eight rabbits using polymerase chain reactions (PCR); human DNA could not be detected at this time. Furthermore HIV infection could not be demonstrated by either seroconversion or PCR during the next 6 months. All HIV-infected rabbits remained clinically healthy and had normal white blood cell counts. Six months after HIV infection, four HIV-infected and two noninfected controls were superinfected with 10(6) T. pallidum in eight skin sites in the shaved skin of the back, and four infected and two control animals were challenged with an intradermal injection with SFV. After infection with either syphilis or SFV, the DNA from the white blood cells of all eight HIV-infected rabbits contained HIV sequences, and HIV sequences were demonstrated in dermal mononuclear cells of the syphilitic lesions by in situ hybridization. The SFV-induced tumors were rejected normally in the HIV-infected rabbits, but four of the four rabbits challenged with T. pallidum had delayed development of cutaneous lesions and three of four demonstrated larger and more prolonged lesions. White blood counts, mitogen responses, and interleukin-2 production remained within normal limits, and seroconversion for HIV was not detected. Three of four rabbits in a second group, challenged with T. pallidum 4 months after HIV-inoculation, also had delayed healing of syphilitic lesions. These results indicate that latent HIV-infection of rabbits may be activated by immunostimulation and that latently HIV-infected rabbits have impaired delayed hypersensitivity reactions. It is hypothesized that true latent HIV-infection in the rabbits is in monocytes and postulated that further immunostimulation may produce infection of lymphocytes and activation of disease.

Animals↗