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R Wieczorek

Publications and source records attributed to R Wieczorek.

At least 19 recordsLinked to original sources

Experimental and theoretical UV characterizations of acetylacetone and its isomers.

Cryogenic matrix isolation experiments have allowed the measurement of the UV absorption spectra of the high-energy non-chelated isomers of acetylacetone, these isomers being produced by UV irradiation of the stable chelated form. Their identification has been done by coupling selective UV-induced isomerization, infrared spectroscopy, and harmonic vibrational frequency calculations using density functional theory. The relative energies of the chelated and non-chelated forms of acetylacetone in the S0 state have been obtained using density functional theory and coupled-cluster methods. For each isomer of acetylacetone, we have calculated the UV transition energies and dipole oscillator strengths using the excited-state coupled-cluster methods, including EOMCCSD (equation-of-motion coupled-cluster method with singles and doubles) and CR-EOMCCSD(T) (the completely renormalized EOMCC approach with singles, doubles, and non-iterative triples). For dipole-allowed transition energies, there is a very good agreement between experiment and theory. In particular, the CR-EOMCCSD(T) approach explains the blue shift in the electronic spectrum due to the formation of the non-chelated species after the UV irradiation of the chelated form of acetylacetone. Both experiment and CR-EOMCCSD(T) theory identify two among the seven non-chelated forms to be characterized by red-shifted UV transitions relative to the remaining five non-chelated isomers.

Models, Chemical↗

Atypical cutaneous lymphoproliferative disorder in patients with HIV infection.

BACKGROUND: An inflammatory pruritic eruption which is characterized histologically by CD8+, atypical lymphocytes has been described in human immunodeficiency virus (HIV)-infected patients. This disorder has been described as "pseudo-Sezary" or a "cutaneous T cell lymphoma (CTCL)-simulant", however, as these patients do not resemble CTCL clinically, and the relationship between this entity and CTCL is unclear, a more descriptive term is "atypical cutaneous lymphoproliferative disorder" (ACLD). The purpose of this study is to categorize the clinical, histologic, and immunophenotypic features of 16 HIV-infected patients with this skin disorder seen at the New York Department of Veterans Affairs Medical Center. METHODS: A retrospective chart review was conducted on 16 HIV-infected patients with a histologic diagnosis of an atypical cutaneous lymphoproliferative infiltrate on skin biopsy. Skin biopsies were reviewed, and histologic features noted. Immunophenotyping was performed on 14 out of 16 samples; electron microscopy was performed on samples from five patients. Clinical manifestations, disease course, medication history, and response to treatment were noted. RESULTS: The patients presented with a pruritic, persistent, generalized, papular eruption. Pigment changes, including hyperpigmentation and hypopigmentation were common. Histologically, lesional biopsies were characterized by a superficial and deep polymorphous infiltrate with atypical lymphocytes which were CD8+ predominant, Ki-1 negative, and occasionally CD7 antigen depleted. Sezary-like cells were present in the infiltrate in four out of five patients by electron microscopy. None of the patients has systemic manifestations of lymphoma; however, one of the 16 patients eventually developed frank CTCL. CONCLUSIONS: HIV-infected patients can present with a pruritic, widespread disorder, often with pigment changes characterized by an atypical cutaneous lymphocytic infiltrate. This clinicopathologic disorder is a rare, reactive inflammatory condition which generally occurs in late stage HIV infection and rarely progresses to frank lymphoma.

Acquired Immunodeficiency Syndrome↗

The effect of GH on estrogen receptor expression in the rat mammary gland.

Both GH and insulin-like growth factor I (IGF-I) synergize with estrogen to induce normal mammary gland development. However, the nature of this synergy has not been explored. To gain insight into the mechanism of these interactions we have examined the effects of these substances on the estrogen receptor (ER). ER levels in the mammary gland cytosols from hypophysectomized and oophorectomized rats, were measured using two assay systems: a dextran-coated charcoal procedure to measure binding to radiolabeled steroid, and an immunologic assay employing a specific antibody to the receptor. In both assays, levels of ER were at or near baseline detection (approximately 1-2 ng/mg protein). Treating animals with either bovine or human GH significantly increased ER activity (P<0.001), whereas prolactin (PRL) and/or estradiol treatment had no effect. That this increase was at the level of transcription was demonstrated by reverse transcriptase/polymerase chain reaction. Following a single injection of GH (50 microgram), a substantial increase in ER mRNA was observed by 10 h, with levels returning to baseline within 24 h; a concomitant increase in ER itself was also observed at the 10 h time point. The effect of GH appeared to occur mainly in the mammary stroma, because there were no differences in GH stimulation of ER between gland-free and gland containing mammary fat pads. Furthermore, analysis of mammary gland ER by immunocytochemistry demonstrated that while ER was present in the epithelial cells of non-treated animals, only GH treated animals had ER clearly visible in both glandular and fat cells of the tissue. In contrast, treating animals with des(1-3)-IGF-I did not result in reproducible increases in ER, nor in the staining of fat cell nuclei for ER. These data demonstrate a specific GH effect on the ER in the mammary fat cell.

Animals↗

Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets.

Villin (V) is a glycoprotein of microvilli associated with rootlet formation. Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7-negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+) immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma range from 6% to 68% in studies using various fixations and varied anti-villin antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to possible diagnostic confusion with metastatic colonic adenocarcinoma to lung. Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected lung adenocarcinomas without rootlets (including five BAC), were immunostained with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8) using a streptavidin peroxidase technique with heat-induced epitope retrieval. All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%) lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with rootlets.

Adenocarcinoma↗

CD44 and its v6 spliced variant in lung tumors: a role in histogenesis?

BACKGROUND: CD44 is a polymorphic family of cell surface glycoproteins with a variety of functions including participation in cell adhesion and migration as well as modulation of cell-matrix interactions. Expression of the standard form of CD44 (CD44s) and its variant isoforms has been shown in both normal and neoplastic tissue and holds promise as a prognostic indicator. METHODS: The authors investigated the expression of CD44s and its v6 isoform (CD44v6) immunohistochemically in 7 fetal lungs (gestational age between 11-36 weeks) and in 80 lung tumors of various histologic types, degrees of differentiation, and clinical stages. RESULTS: In the fetal lung, CD44v6 was expressed as membranous and luminal staining of epithelial cells throughout gestation and basal staining of bronchial epithelium late in gestation. Nonneoplastic adult lung showed CD44v6 expression that was restricted to epithelial cells with membranous staining of basal bronchial cells and squamous metaplasia as well as basolateral membranous staining of type 2 pneumocytes. CD44s showed similar but less intense staining and was in addition present on lymphocytes and macrophages. Tumorlets and neuroepithelial bodies were CD44v6 negative. Nearly all squamous cell carcinomas (97%) were positive for CD44v6 with patterns similar to squamous metaplasia and with more intense staining at the periphery of tumor nests. Most adenocarcinomas (90%) were CD44v6 negative whereas most bronchioloalveolar cell carcinomas (71%) were CD44v6 positive with patterns similar to that in type 2 pneumocytes. Most large cell carcinomas (71%), carcinoid tumors (67%), and all small cell carcinomas were CD44v6 negative. CD44v6 expression did not correlate with clinical stage. CD44v6 expression in lymph node metastases was identical to that of the primary tumor. CONCLUSIONS: The results of the current study show that CD44v6 is localized differently in fetal and adult lung, suggesting a difference in function. In the fetal lung, it may modulate growth factors important in morphogenesis and maturation. In the adult nonneoplastic lung, CD44v6 is associated with stem cells, namely basal cells and type 2 pneumocytes, and may act to anchor these cells to the matrix and be important in migration during repair or neoplasia. In addition, CD44v6 expression is maintained throughout tumorigenesis in squamous cell carcinoma and bronchioloalveolar cell carcinoma, suggesting a histogenetic relationship between the stem cells and the respective tumors. Conversely, most neuroendocrine tumors and the cells of the dispersive neuroendocrine system do not express CD44v6, implying a separate histogenetic lineage in these tumors.

Adult↗

Human parvovirus B19 in bone marrows from adults with acquired immunodeficiency syndrome: a comparative study using in situ hybridization and immunohistochemistry.

Human parvovirus B19, which infects and lyses erythroid precursors, can cause severe anemia in patients with immunodeficiency. The incidence of parvovirus infection in adult acquired immunodeficiency syndrome (AIDS) patients is unknown. Eighty-one archival formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies from 73 AIDS adults were immunostained with monoclonal R92F6 against B19 VP1 and VP2 capsid proteins using streptavidin peroxidase and streptavidin alkaline phosphatase techniques. In addition, the same tissues were hybridized in situ with a digoxigenin-labeled parvovirus B19 DNA probe. Five FFPE bone marrows, from 3 HIV-negative patients with positive immunoglobulin M (IgM) serology for parvovirus B19, and 1 parvovirus B19-infected fetal liver were positive controls. By immunoperoxidase, all tissues were negative with R92F6 except the fetal liver, which exhibited strong positivity predominantly in viral inclusions. With immunoalkaline phosphatase, all positive controls were immunoreactive with R92F6; however, the AIDS marrows were negative. With in situ hybridization (ISH), all positive controls and 7 of 81 (8.6%) of AIDS marrows were positive for B19 parvovirus DNA. We conclude that ISH is more sensitive than R92F6 immunohistochemistry in parvovirus B19 detection. A small but significant number of bone marrows from AIDS adults shows evidence of human parvovirus B19 infection.

Acquired Immunodeficiency Syndrome↗

Transthyretin Ile 122 and cardiac amyloidosis in African-Americans. 2 case reports.

Two cases of cardiac amyloidosis resulting from deposition of the Ile 122 variant of transthyretin in African-Americans are presented. These cases illustrate several typical features of this disorder, including electrocardiographic abnormalities and digoxin toxicity. Transthyretin Ile 122 is a common amyloidogenic variant in African-Americans (present as a heterozygous variant in 4% of this population); therefore, the diagnosis of transthyretin Ile 122 cardiac amyloidosis should be considered in African-Americans with unexplained restrictive cardiomyopathy or arrhythmias.

Aged↗

Occurrence of polyhydroxyalkanoic acid granule-associated proteins related to the Alcaligenes eutrophus H16 GA24 protein in other bacteria.

Fifty different polyhydroxyalkanoic acid (PHA)-accumulating bacterial strains were investigated for the occurrence of phasin proteins bound to PHA granules and related to the GA24 protein of Alcaligenes eutrophus H16, by isolating PHA granules and Western blot analysis of granule-associated proteins employing antibodies raised against the GA24 protein. It could be demonstrated that th PHA granules of many poly(3-hydroxybutyrate)-accumulating bacteria exhibited a similar protein pattern, and a predominant protein of 24 +/- 2 kDa occurred in the granules of A. eutrophus strains A7, CH34, JMP222, N9A and TF93 exhibiting N-terminal amino acid sequences identical to that of the GA24 protein. Proteins bound to the granules of A. latus, Burkholderia caryophyli, B. cepacia, B. solanacearum, Pseudomonas glathei, Rhodobacter sphaeroides and Telluria mixta also gave positive immunoreactions. Granule-associated proteins of small size also occurred in various strains of the Gram positive bacteria Bacillus megaterium and R. ruber as well as in the Gram-negative bacteria Azotobacter sp., Chromatium vinosum, Comamonas acidovorans, Methylobacterium sp., Mycoplana rubra, Paracoccus denitrificans, Pseudomonas sp., Rhodospirillum rubrum, Rubrivivax gelatinosus and Thiocystis violacea; however, they gave no immunoreaction. This study clearly demonstrated that phasins are wide-spread if not essential in PHA-accumulating bacteria.

Alcaligenes↗

Alterations of the retinoblastoma gene in clinically localized, stage B prostate adenocarcinomas.

Alterations of the retinoblastoma (Rb) tumor suppressor gene and its encoded protein have been detected in a variety of malignant neoplasms. The authors have evaluated a series of 26 clinically localized stage B prostate adenocarcinomas for loss of heterozygosity (LOH) at 13q14 (including the Rb locus), rearrangements or partial deletions of the Rb gene, and alterations of Rb protein level by quantitative immunohistochemistry. LOH at the Rb locus occurred in 35% of the informative specimens. Of the specimens that showed LOH, 33% also had decreased or absent Rb protein in tumor cells by quantitative immunohistochemistry. In contrast, none of the specimens without LOH showed loss of Rb protein. Thus, LOH is correlated with loss of Rb protein. The authors conclude that alterations of the Rb tumor suppressor gene occur in a significant fraction of stage B prostate adenocarcinomas.

Adenocarcinoma↗

Analysis of a 24-kilodalton protein associated with the polyhydroxyalkanoic acid granules in Alcaligenes eutrophus.

A 5.0-kbp genomic EcoRI restriction fragment which complemented a third subclass of polyhydroxyalkanoic acid (PHA)-leaky mutants of A. eutrophus that accumulated PHA at a lower rate than the wild type was cloned from Alcaligenes eutrophus H16. A 687-bp phaPAe gene on this fragment encoded a 24-kDa protein (M(r) = 23,963), which was referred to as the GA24 protein. The GA24 protein was solubilized from the granules and purified to electrophoretic homogeneity, and antibodies against the GA24 protein were obtained. The GA24 protein bound to the surface of PHA granules, as revealed by immunoelectron microscopy of whole cells and of artificial PHA granules. The GA24 protein contributed approximately 5% (wt/wt) of the total cellular protein, and it was the predominant protein present in the granules. It was synthesized only in cells accumulating PHA and only in amounts that could be bound to the granules; no soluble GA24 protein was detected. Tn5::mob-induced phaPAe mutants which were unable to synthesize intact GA24 protein formed only one large PHA granule per cell. The amino acid sequence of the GA24 protein revealed two closely related stretches consisting exclusively of nonhydrophilic amino acids at the C-terminal region, which are presumably involved in the binding of GA24 to the granules, as was recently proposed for a similar protein in Rhodococcus ruber. The GA24 protein seems to be a representative of phasins, which are a new class of protein that form a layer at the surface of PHA granules, like oleosins, which form a layer at the surface of triacylglycerol inclusions in oilseed plants.

Alcaligenes↗

Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid.

Pubertal mammary development in the rat is largely dependent upon GH and estrogen. We recently showed that insulin-like growth factor-I (IGF-I) can substitute for GH in inducing mammary development in male rats, suggesting that IGF-I mediates GH action. The present study investigated whether IGF-I, like GH, required estradiol (E2) to act or whether IGF-I could substitute for both GH and E2. The effects of IGF-I were tested in the presence and absence of E2. Elvax pellets containing IGF-I or des(1-3) IGF-I were implanted into right lumbar mammary glands of sexually immature, hypophysectomized, oophorectomized female rats, with control BSA-containing pellets in the contralateral glands. After 5 days, both lumbar mammary glands were removed and examined in whole mounts for mammary development by counting terminal end buds and alveolar structures. E2, administered in SILASTIC brand capsules, had no independent effect on mammary development. In the absence of E2, des(1-3) IGF-I had a small, but significant, independent effect on mammary development; native IGF-I was ineffective. The addition of E2 significantly enhanced the effects of IGF-I and des(1-3) IGF-I on mammary development, similar to that noted when E2 was given along with GH. We also studied the effects of E2 and/or hGH on mammary gland IGF-I messenger RNA (mRNA) in hypophysectomized castrated male animals. E2 alone did not increase mammary gland IGF-I mRNA concentrations, but E2 enhanced the effect of hGH on IGF-I mRNA by 4- to 6-fold. These studies indicate that IGF-I can have a small independent effect on mammary development, but like GH, E2 is required for a full effect. They also indicate that E2 is capable of synergizing with GH in the production or expression of IGF-I mRNA, and that the action of E2 on mammary development may take place at multiple sites. If locally produced IGF-I does indeed mediate the action of GH in mammary development, then although E2 is capable of enhancing the effect of GH on IGF-I mRNA, its major effect in mammary development occurs after IGF-I is produced.

Animals↗

Primary lymphomatous effusions in AIDS: a morphological, immunophenotypic, and molecular study.

Lymphomas were documented in pleural effusions or ascites in 18 human immunodeficiency virus-positive (HIV+) patients. Eleven of 12 with clinical data had acquired immunodeficiency syndrome before the diagnosis of lymphoma. In 13 of 15 with data available, a body cavity was the site of initial presentation of lymphoma. Cytological subtypes were large cell immunoblastic, n = 7; large cell anaplastic, n = 6; and large cell NOS, n = 5. The high incidence of anaplastic large cell lymphoma and the conspicuous absence of Burkitt's lymphoma differ strikingly from HIV-associated lymphomas generally. Immunophenotypically, two cases were B-cell (CD19/20+, sIg+, CD/5-), one was T-cell (CD3+, CD5+, CD4+, CD8-, CD19/20-, sIg-), and 15 were null (CD45+, HLA-DR+ CD19/20-, sIg-, CD3/5-). This 83% incidence of null immunophenotype contrasts sharply with a 9% incidence among 35 tissue-based lymphomas in HIV+ patients that were similarly studied and a 0% null immunophenotype among 11 lymphomatous effusions in patients without HIV risk factors. Seven of the 18 HIV-associated lymphomas expressed CD30. Four of five cases with null immunophenotype showed Ig heavy-chain gene rearrangement, two had clonal Epstein-Barr virus integration, and none had MYC protooncogene rearrangement. These cases belong to a subgroup of high-grade HIV-associated lymphomas that occur in the setting of profound immunosuppression in which immunoblastic morphology predominates and MYC rearrangement is encountered only infrequently.

Acquired Immunodeficiency Syndrome↗

Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic profile, with comparison to cutaneous T-cell lymphoma.

Chronic actinic dermatitis (CAD) describes a persistent photosensitivity disorder in the absence of continued exposure to photosensitizers; it is characterized by a T-cell infiltrate within the epidermis and dermis. The purpose of this study was to characterize the T-cell infiltrate better immunohistochemically. Serial cryostat sections of fresh-frozen punch biopsy specimens of skin were analyzed in 11 patients with CAD and 3 patients with erythrodermic cutaneous T-cell lymphoma (CTCL). Monoclonal antibodies against the pan T-cell, pan B-cell, and T-cell subsets and the T cell-receptor (TCR) antigens were used. CD8-positive (T-suppressor-cytotoxic) cells were predominant in the epidermis of CAD, while CD4-positive (T-helper) cells were predominant in the epidermis and dermis of CTCL. CDw29-positive (T-memory) cells were predominant in all cases. The number of BF1 (beta-chain constant region of the TCR)-positive cells approximated the number of CD3-positive cells in all CAD cases but was significantly lower than the number of CD3-positive cells in two of three cases of CTCL. There was no clustering or preferential staining with any of the beta-chain variable-region antibodies in any of the specimens. These results indicate that CAD has a characteristic immunophenotype distinct from that of most cases of CTCL and that discordance between BF1 and CD3 expressions did not occur in the CAD cases.

Antigens, Differentiation, T-Lymphocyte↗

Alterations in the p53 and MDM-2 genes are infrequent in clinically localized, stage B prostate adenocarcinomas.

Alterations in the p53 gene have been described in a variety of human malignant neoplasms. We have examined 29 stage B prostate carcinomas for alterations in the p53 gene and for amplification of the MDM-2 gene. No evidence of mutations in the conserved exons 5 to 8 was found by polymerase chain reaction single-stranded conformation polymorphism analysis and no accumulation of p53 protein was found by immunohistochemistry. However, loss of heterozygosity at the p53 locus was observed in 11% of information cases. Amplification of the MDM-2 gene was not observed by Southern blot hybridization. In contrast, stage C and D prostate carcinomas showed accumulation of p53 protein in 33 to 66% of cases. We conclude that alterations in p53 function are infrequent in clinically localized prostate cancers but are more common in advanced cancers.

Adenocarcinoma↗

Phenotype of villous stromal cells in placentas with cytomegalovirus, syphilis, and nonspecific villitis.

Villous stromal cells (VSC) play an important role in fetomaternal placental immune function. We studied the phenotype of VSC in infection by cytomegalovirus (CMV) and syphilis as well as nonspecific villitis and compared the findings with gestational age-matched controls. Monoclonal antibodies directed against total leukocytes, T cells, B cells, macrophages, dendritic cells, granulocytes and HLA-DR as well as polyclonal antibodies against S-100, alpha-1 antichymotrypsin, and lysozyme were used. In controls, the immunocytochemical response for each marker was either negative or weakly positive. In contrast, the VSC in CMV-infected and nonspecific villitis showed intense reactivity to various macrophage markers. In syphilis, reactivity with macrophage markers such as lysozyme and MAC387 were weaker, and reactivity to HLA-DR and S-100 was much stronger. Endothelial cells strongly expressed the monocyte/granulocyte marker CD15 in the diseased states, especially in syphilis, relative to controls. We conclude that the phenotype of VSC is altered in disease states and that the changes are dependent to some degree on the specific subset of chronic villitis.

Antibodies, Monoclonal↗

Detection and characterization of human T-cell lymphotropic virus type I (HTLV-I) associated T-cell neoplasms in an HTLV-I nonendemic region by polymerase chain reaction.

Human T-cell lymphotropic virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATLL) occurs endemically in southwestern Japan, the Caribbean, and West Africa, but occurs sporadically in most of the rest of the world. However, because ATLL and non-HTLV-I associated T-cell neoplasms share overlapping clinicopathologic features, the prevalence of ATLL in nonendemic regions is unknown. In this study, 75 T-cell neoplasms randomly procured from the metropolitan New York City area were examined by polymerase chain reaction (PCR) for the presence of integrated HTLV-I proviral sequences. HTLV-I genomic sequences were detected by PCR in 6 of the 75 cases (8%); this result was confirmed by Southern blot hybridization. The clinicopathologic features of the HTLV-I positive and HTLV-I negative T-cell neoplasms were then compared. Although the clinicopathologic features of patients from these two groups overlapped, some findings were more commonly associated with HTLV-I positive neoplasms. Five of the six patients with HTLV-I positive neoplasms were from HTLV-I endemic areas, five were black, five were women, and five were less than 45 years of age, while the majority of the patients with HTLV-I negative T-cell malignancies were elderly white men. The incidence of hypercalcemia and lytic bone lesions was significantly more common among patients with HTLV-I positive T-cell neoplasms (P less than .001 and P = .004, respectively). The immunophenotypes of the HTLV-I positive and negative tumors were similar; however, all HTLV-I positive neoplasms were CD7 negative (P less than .001). In summary, our findings: (1) demonstrate the special clinicopathologic and immunophenotypic features of HTLV-I positive T-cell neoplasms, (2) suggest that most of the rare cases of HTLV-I-associated T-cell neoplasms occurring in HTLV-I nonendemic areas are actually endemic cases; and (3) that PCR is a sensitive, clinically useful technique for identifying HTLV-I associated T-cell neoplasms.

Adult↗