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Biomedical subjects

A Yen

Publications and source records attributed to A Yen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mid-dermal elastolysis in an adolescent subsequent to lesions resembling granuloma annulare.

First described by Shelley and Wood in 1977, mid-dermal elastolysis (MDE) is a rare acquired disorder in which there is a bandlike absence of elastic tissue limited to the mid-dermis. In their patient, MDE developed in an area previously involved with recurrent episodes of urticaria. We describe a 15-year-old white girl with well-circumscribed, minimally palpable yellow-white plaques and wrinkling diagnosed histologically as MDE in areas clinically diagnosed 5 years previously as granuloma annulare. As in the first described patient, five years elapsed between clearance of the original skin lesions and the clinical appearance of MDE. To our knowledge, we report the first adolescent case of MDE localized to previous sites of lesions clinically consistent with granuloma annulare and propose that MDE represents an abnormal end-stage reaction to multiple processes.

Adolescent↗
PubMed1997

EBV-associated Kikuchi's histiocytic necrotizing lymphadenitis with cutaneous manifestations.

The clinical and pathologic findings of Kikuchi's histiocytic necrotizing lymphadenitis may mimic those of malignant lymphoma. We describe a 6-year-old boy with generalized lymphadenopathy, spiking fever, chills, myalgias, malaise, and erythematous, crusted papules. Although cutaneous manifestations have been noted in 16% to 40% of patients with histiocytic necrotizing lymphadenitis, only three publications described skin lesions. The skin lesions and affected lymph nodes revealed histiocytic aggregates, atypical lymphoid cells, karyorrhectic debris, and patchy necrosis. Spontaneous resolution occurred in 2 months. Results of serologic studies, Epstein-Barr virus (EBV) latent membrane protein immunoperoxidase staining, EBER-1 RNA in-situ hybridization, and EBV EBNA-1 DNA polymerase chain reaction implicate EBV as the causative agent.

Biopsy↗
PubMed1997

Mycosis fungoides: an Australian experience.

Analysis was undertaken of 107 patients with mycosis fungoides who presented to St. Vincent's Hospital, Melbourne, during 1977-95. The mean age at diagnosis (55 years) was significantly older than the mean age of onset of symptoms (48 years). The mean duration of follow-up was 7.7 years. Urban residence was over-represented in this group of patients and in those with mycosis fungoides recorded at the State Cancer Registry. Eighty-four per cent were diagnosed at Stage I or II of the disease. Presentation with disease more advanced than Stage I was more likely to be found in males. Disease localized only to the trunk accounted for 45% of all patients. The mean number of biopsies prior to diagnosis was 1.4 but two-thirds were diagnosed at first biopsy. Almost 85% of patients had as their initial treatment either PUVA (44.9%), topical steroids (20.6%) or topical nitrogen mustard (18.7%) and 57% received only one or two treatment modalities during the period of the study. Stage at presentation was not related to the likelihood of clearance following treatment, recurrence, progression to a more advanced stage of disease or survival.

Adolescent↗
PubMed1997

Concentration of RB protein in nucleus vs. cytoplasm is stable as phosphorylation of RB changes during the cell cycle and differentiation.

Unphosphorylated RB (retinoblastoma tumor suppressor) protein is known to bind isolated nuclear matrix in vitro, whereas phosphorylated RB has a lower affinity, suggesting a mechanism which might contribute to differential nuclear/cytoplasmic localization as part of its regulatory activity. This motivates interest in the in vivo localization of the endogenous RB protein as its phosphorylation state changes during the cell cycle and cell differentiation. It is known that in proliferating HL-60 cells all the RB protein is phosphorylated, but the extent of phosphorylation increases with progression from G1 to S to G2 + M. It has also been previously shown that retinoic acid and 1,25-dihydroxy vitamin D3 shift the RB protein to the unphosphorylated state with cell differentiation (Yen, A., S. Varvayanis, Exp. Cell Res. 214, 250-257 (1994)). The dependence of cell cycle progression and differentiation on RB nuclear versus cytoplasmic localization, as well as the dependence of RB localization on phosphorylation state can thus be tested. Confocal image analysis of the RB protein in vivo shows that the ratio of the concentration of the RB tumor suppressor gene protein in the nucleus versus the cytoplasm remains stable as the RB protein undergoes either phosphorylation during cell cycle progression or dephosphorylation during cell differentiation induced by retinoic acid or 1,25-dihydroxy vitamin D3. For the cell cycle analysis, HL-60 human promyelocytic leukemia cells were fluorescently stained for DNA and for the RB protein. G1, S, and G2 + M subpopulations were isolated by fluorescence-activated cell sorting. For each subpopulation, the relative concentration of RB protein in the nucleus and the cytoplasm was measured by laser confocal image analysis. To determine the effect of retinoic acid-induced myeloid differentiation or 1,25-dihydroxy vitamin D3-induced monocytic differentiation, the same cell sorting and image analysis was performed on cells treated with these inducers. In all cases the concentration of the RB protein in the nucleus was approximately 2 times that in the cytoplasm. Thus, the ratio of nuclear versus cytoplasmic RB protein concentration is stable and independent of phosphorylation or dephosphorylation of RB during both the cell cycle and cell differentiation.

Cell Cycle↗
PubMed1997

Mucoepidermoid carcinoma with cutaneous presentation.

Mucoepidermoid carcinomas are malignant neoplasms that rarely involve the skin. Composed of both mucus-secreting cells and epidermoid-type cells in various proportions, mucoepidermoid carcinomas occur most commonly in salivary glands. In this case report, we describe a high-grade mucoepidermoid carcinoma with cutaneous involvement. Although this patient was referred for Mohs' micrographic surgery, further evaluation showed either direct or metastatic extension from the parotid gland to skin and distant metastases to the lung and bone. Despite extensive bone involvement, serum levels of ionized calcium, phosphorus, and lactate dehydrogenase remained normal. In view of the widespread metastases, the treatment plan was altered to radiotherapy and chemotherapy instead of surgery. Instructive lessons from this case include the recognition by dermatologists of this rare entity, the importance of a detailed history and complete evaluation of the patient before determining appropriate therapy, and the necessity of individualizing diagnostic tests to a particular patient.

Biopsy, Needle↗
PubMed1997

Human herpesvirus 8 DNA sequences in blistering skin from patients with pemphigus.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in Kaposi sarcoma (KS) and other lesions in patients both seropositive and seronegative for the human immunodeficiency virus (HIV). Kaposi sarcoma has been reported to develop in a disproportionate number of patients with pemphigus. Since HHV-8 is so strongly associated with KS, we wondered whether HHV-8 is present in pemphigus lesions from patients without KS or HIV infection. Pemphigus lesions and skin from healthy individuals were coded in a blinded fashion. Tissue-extracted DNA was tested using polymerase chain reaction, Southern blot hybridization, and automated sequencing of the polymerase chain reaction products for the presence of HHV-8 DNA. Six patients had pemphigus foliaceus, 6 had pemphigus vulgaris, and 2 had KS; 10 healthy individuals were used as controls. All 24 patients were HIV seronegative. OBSERVATION: Lesional skin from 4 of the 6 patients with pemphigus vulgaris, all 6 of the patients with pemphigus foliaceus, and both positive controls (KS) tested positive for HHV-8 DNA. Furthermore, the HHV-8 DNA sequences for KS330(233) differed between all 6 DNA specimens from pemphigus foliaceus, while 3 of the 4 DNA specimens from pemphigus vulgaris were identical. However, HHV-8 DNA was absent in all normal human skin analyzed. CONCLUSIONS: This report expands the spectrum of lesions found to contain HHV-8 DNA sequences and suggests that HHV-8 might have trophism for pemphigus lesions.

Adult↗
PubMed1996

FMS (CSF-1 receptor) prolongs cell cycle and promotes retinoic acid-induced hypophosphorylation of retinoblastoma protein, G1 arrest, and cell differentiation.

The effect of the CSF-1 receptor, cFMS, on the phosphorylation of the retinoblastoma (RB) tumor suppressor protein and on the cell cycle and cell differentiation was analyzed in a cultured promyelocytic leukemia cell capable of induced myelomonocytic differentiation. A series of cFMS-transfected HL-60 sublines with progressively higher cell surface FMS expression was derived by flow cytometric cell sorting. Overexpression of FMS increased the duration of the cell cycle, prolonging all cell cycle phases especially S phase, which doubled. The increased cell cycle generation times occurred without any detectable changes in RB expression level or phosphorylation. For retinoic acid (RA)-induced myeloid differentiation, progressive overexpression of FMS caused a greater fraction of cells to differentiate and G1/0 arrest compared to wild-type cells after the same number of cell cycle generation times. FMS overexpression also progressively increased the relative amount of dephosphorylated RB protein induced, while reducing the total amount of RB protein. The inducer-originated and FMS-driven changes in RB hypophosphorylation were not effected through changes in p21/WAF1/CIP1 in this p53-negative cell. Similar effects on differentiation and G0 arrest occurred with 1,25-dihydroxy vitamin D3 (D3)-induced monocytic differentiation. FMS did not significantly affect myeloid differentiation induced by DMSO, which does not target steroid-thyroid hormone receptors like RA and D3. While differentiation is typically associated with hypophosphorylated RB in all these cases, the kinetics indicate that the FMS-induced changes in cell cycle and cell differentiation do not depend in a direct causal fashion on the interconversion between hyperphosphorylated and hypophosphorylated RB.

Calcitriol↗
PubMed1996

Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.

The ability of subtypes of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) singly and in combination to elicit myeloid differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein dephosphorylation was determined in the human myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid (RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the above-mentioned three cellular responses. In contrast, simultaneous treatment with both an RAR-selective ligand (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three cellular processes. An RAR alpha-selective ligand used with an RXR-selective ligand generated the same responses as did all-trans RA or 9-cis RA, which affect both families of receptors, suggesting an important role for RAR alpha among RAR subtypes in eliciting cellular response. Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand. The coupling of the shift of RB to its hypophosphorylated form with G1/0 arrest and differentiation in response to ligands is consistent with a possible role of RB as a downstream target or effector of RAR alpha and RXR in combination.

Benzoates↗
PubMed1996

Leukemia cutis: Darier's sign in a neonate with acute lymphoblastic leukemia.

Infantile leukemia accounts for only 3% of childhood leukemia. Leukemia cutis occurs in 25% to 30% of infants with congenital leukemia and is more frequently associated with acute myeloid leukemia than with acute lymphoblastic leukemia. We describe an infant in whom hyperpigmented macules that developed when the patient was 2 weeks old demonstrated Darier's sign when he was 4 weeks old. Acute lymphoblastic leukemia, early pre-B-cell type, was diagnosed when the patient was 10 weeks old. Examination at that age revealed 1 to 2 cm, firm, mildly tender nodules clustered on the scalp, face, and extremities, less severe involvement of the trunk, and marked induration of the face and eyelids. Darier's sign was elicited from the less infiltrated truncal lesions. Histologic examination revealed a dense monomorphous infiltrate consisting of pleomorphic, undifferentiated cells. No mast cells were revealed by Giemsa staining. This case is to our knowledge the first reported example of leukemia cutis demonstrating Darier's sign.

Humans↗
PubMed1996

Retinoic acid-induced RB (retinoblastoma) hypophosphorylation enhanced by CGP 52411 (4,5-dianilinophthalimide), an EGF family tyrosine kinase receptor inhibitor.

Retinoic acid is a known morphogen which can regulate cell proliferation and differentiation and also induces the hypophosphorylation of the RB (retinoblastoma tumor suppressor gene) protein, a known cell cycle regulatory protein. The mechanism by which these processes occur is unclear. We find that these processes can be regulated by CGP 52411, 4,5-dianilinophthalimide, an inhibitor of tyrosine protein kinases of the EGF receptor subfamily. Retinoic acid causes the largely phosphorylated RB protein expressed in proliferating HL-60 human promyelocytic leukemia cells to shift to the unphosphorylated form, as well as causing the cells to G0 arrest and differentiate. Addition of CGP 52411 accelerated the redistribution of the RB protein expressed in HL-60 cells to the unphosphorylated form, enhancing the effects of the retinoic acid. By itself CGP 52411 had no apparent effect on the RB protein expressed in HL-60 cells. CGP 52411 also accelerated the retinoic acid-induced accumulation of cells in G1/0 and the phenotypic conversion of cells to the mature myeloid phenotype, suggesting that its target is common to the regulation of both RB phosphorylation and cell proliferation and differentiation. CGP 52411 had a similar effect on the RB phosphorylation shift induced by 1,25-dihydroxy vitamin D3, a ligand for a receptor in the same steroid thyroid hormone superfamily as retinoic acid. Increasing the concentration of CGP 52411 enhanced the acceleration of RB hypophosphorylation in the case of both retinoic acid and 1,25-dihydroxy vitamin D3. The data are consistent with the negative regulation of retinoic acid induced RB protein dephosphorylation coupled to cell cycle arrest and differentiation by a receptor tyrosine kinase sensitive to CGP 52411.

Calcitriol↗
PubMed1995

Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients.

Herpesvirus-like DNA sequences (KSHV) have been reported to be associated with various forms of Kaposi's sarcoma (KS). To determine if KSHV was associated with other proliferative skin lesions from non-AIDS immunocompromised patients, 33 skin lesions (basal cell carcinomas, squamous cell carcinomas, actinic keratoses, verruca vulgaris, atypical squamous proliferations, and seborrhoeic keratosis) from 4 organ-transplant patients receiving immunosuppressive therapy were tested for KSHV by PCR. KSHV sequences were detected in 82% of these skin lesions. Our results suggest that KSHV is associated with lesions other than KS in non-AIDS immunocompromised patients, and may also be involved in the pathogenesis of the various forms of proliferative skin lesions from organ-transplant patients.

Base Sequence↗