Influence of magnesium ion concentration and PCR amplification conditions on cross-species PCR.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Kohler
Publications and source records attributed to S Kohler.
The differential diagnosis of pagetoid cells in the epidermis.
In addition to Paget's disease, a heterogeneous group of processes with diverse histogeneses can give rise to intraepidermal pagetoid cells. These diseases share as their common denominator the presence of discrete non-Malpighian or abnormal Malpighian cells occurring singly or in nests within the epidermis. Either Pagetoid cells can represent the only histologic change, as in pagetoid squamous cell carcinoma in situ or superficial spreading malignant melanoma in situ, or they can be an expression of an associated dermal or internal malignancy, as in sebaceous carcinoma or breast carcinoma. The histologic appearance of the pagetoid cells in these diverse disorders can be quite similar, rendering the differential diagnosis difficult. A review of the entities that enter into the differential diagnosis of intraepidermal pagetoid cells is presented, emphasizing their distinguishing histologic and immunophenotypic features and differential diagnosis.
Adenocarcinoma, Sebaceous↗
Fanconi anemia group A and D cell lines respond normally to inhibitors of cell cycle regulation.
Cells from patients with Fanconi anemia (FA) show decreased viability and decreased chromosome stability after treatment with DNA cross-linking agents, compared to normal cells. FA cells also show a relative accumulation at the G2/M transition after such treatment. This has suggested a possible checkpoint abnormality. In the studies presented here, treatment with hydroxyurea, caffeine or inhibitors of cell cycle kinases did not reveal abnormalities in survival or chromosome stability in FA-A or FA-D cells. Chromosomal breaks introduced by hydrogen peroxide or methyl methanesulfonate accumulated to the same extent in FA-A or FA-D cells as in normal cells. We conclude that FA-A and FA-D cells respond normally to agents known to alter the cell cycle or introduce DNA strand breaks. FA cells process strand breaks and a variety of DNA monoadducts normally. Our results are compatible with repair of DNA crosslinks being slower in FA than in normal cells and FA cells having normal cell cycle checkpoints.
Antibiotics, Antineoplastic↗
A young boy with a large hemifacial plaque with histopathologic features of trichoepithelioma.
Trichoepitheliomas commonly appear as sporadic solitary lesions or, more rarely, as multiple lesions that are often dominantly inherited. We describe an 8-year-old boy with multiple facial papules that coalesced into a large plaque. This presentation of multiple trichoepitheliomas may represent an unusual type of nevus.
Biopsy↗
Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease.
Skin biopsies are commonly performed after allogeneic bone marrow transplantation (BMT) to help establish the origin of a new skin rash in a transplant recipient. Histologic criteria and a grading system for acute graft-versus-host reaction of the skin are well established. Histologic diagnosis, however, can be difficult and is based on interpretation of subtle changes that show significant overlap with features seen in other entities that can be responsible for a skin rash in the posttransplantation period such as drug reactions, viral exanthems, and the effects of chemotherapy. We retrospectively reviewed 179 skin biopsies from 137 patients who had undergone allogeneic BMT. We compared 98 skin biopsies from 71 patients with acute graft-versus-host disease (GvHD) with 81 biopsies from 66 patients who underwent biopsy to exclude GvHD but did not go on to develop the disease on clinical grounds. Two observers reviewed each slide without knowledge of the clinical situation and graded 16 histologic parameters. No single parameter (e.g., dyskeratotic keratinocytes, basal vacuolization, satellitosis, necrotic cells in appendages) achieved statistical significance on univariate analysis. A search for factors to separate GvHD biopsies from non-GvHD biopsies using logistic regression failed to reveal a single best predictor or a combination of predictors. We conclude that skin biopsies after allogeneic BMT are of limited use in predicting the progression of a skin rash to clinical grade II or higher GvHD.
Acute Disease↗
Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal.
It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyperconvoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures. The histologic features of erythrodermic MF and Sezary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.
Analysis of Variance↗
Absence of human herpesvirus 8 and Epstein-Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ-transplant patients.
Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic role in cutaneous epithelial oncogenesis in immunocompromised patients.
Adolescent↗
A case of extramammary Paget's disease mimicking pemphigus vulgaris on histologic examination.
We present a case of extramammary Paget's disease (EMP) on the vulva of a 77-year-old female that on histologic examination resembled pemphigus vulgaris. The diagnosis of EMP was established with the help of a periodic acid-Schiff stain and immunophenotyping. Ultrastructural studies revealed no desmosomes between tumor cells and keratinocytes and only rare desmosomes between adjacent tumor cells. A high number of tumor cells with scant desmosomes may be the ultrastructural correlate with cellular discohesion in the lower epidermis and with the histologic resemblance to pemphigus vulgaris.
Aged↗
[The spontaneous reduction of a twin pregnancy in two mares].
Twin pregnancies are a serious problem in stud medicine as they terminate in most cases in abortion, stillbirth or the delivery of dead or weak and deformed foals. In recent years, the introduction of sonography has greatly improved the management of mares with twin conceptuses, in particular monitoring the phenomenon of spontaneous embryo reduction to a single vesicle. This allows supervision of pregnancy with relatively little expenditure and loss of time. We document the spontaneous reduction to single vesicles of unilateral twin pregnancies in a draught- and a warmblood-mare. In both mares diagnosis of twins was made 17 days after covering; they probably resulted from synchronous double-ovulations. After another 5 days, distinct signs of the loss of one conceptus were recognized and, subsequently, only single pregnancies existed. No interventions were necessary.
Abortion, Veterinary↗
Gross cystic disease fluid protein-15 reactivity in extramammary Paget's disease with and without associated internal malignancy.
Extramammary Paget's disease (EMP) is a rare eczematoid disorder occurring mainly in apocrine-gland-bearing regions. Its histogenesis is controversial. Several investigators have proposed that EMP is a heterologous entity, with some cases representing a de novo adenocarcinoma in situ arising in the epidermis and others being epidermotropic metastases or a direct extension of an associated internal malignancy. We have studied 26 cases of EMP with and without associated internal malignancy for their reactivity with a monoclonal antibody directed at gross cystic disease fluid protein-15 (GCDFP-15). The diagnosis of EMP has been previously established for all cases using histochemical and immunohistochemical stains. Six of our 26 cases had a concomitant underlying carcinoma (one transitional cell carcinoma of the bladder, four adenocarcinomas of the rectum, one adenosquamous carcinoma. Only one of these six cases showed reactivity with GCDFP-15. In contrast, 16 of 20 cases of EMP without associated internal malignancy were strongly reactive with GCDFP-15 (> 5% of tumor cells). Variable GCDFP-15 reactivity in cases of EMP with and without associated internal malignancy supports the concept that EMP is a heterologous disorder. Positive GCDFP-15 in a patient with EMP may indicate a low probability of associated internal malignancy and may provide valuable clinical information.
Adenocarcinoma↗
Polyostotic fibrous dysplasia with severe pathologic compression fracture of L2.
A case of a progressive pathologic compression fracture of L2 due to polyostotic fibrous dysplasia is presented. Such unusually severe involvement, requiring decompression and surgical fusion, in the absence of significant recent or remote trauma, has not previously been reported.
Adult↗
Cerebral metabolite patterns in dialysis patients: evaluation with H-1 MR spectroscopy.
PURPOSE: To analyze metabolic changes in the brain of patients undergoing dialysis. MATERIALS AND METHODS: Sixteen patients undergoing hemodialysis, 10 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and 42 healthy volunteers underwent magnetic resonance (MR) spectroscopy and MR imaging. Spectra were obtained from one occipital gray matter voxel and one parietal white matter voxel. Changes in N-acetylaspartate (NAA), choline (Cho), myo-inositol and glycine (Myo), and creatine (Cr) were analyzed and the results presented as ratios, with Cr as the reference. RESULTS: Three abnormalities were observed in the spectra of the hemodialysis patients: (a) significant elevation of the Cho/Cr ratio in gray matter, (b) significant elevation of the Myo/Cr ratio in gray matter, and (c) significant reduction of the NAA/Cr ratio in gray and white matter. The strongest metabolic alterations were found in cortical gray matter. In CAPD patients, only gray matter Cho/Cr ratio was significantly elevated. An increased frequency of focal white matter lesions was observed on MR images in the dialysis patients. CONCLUSION: Proton MR spectroscopy is useful for in vivo monitoring of metabolic alterations in the brain due to chronic dialysis.
Adult↗
Clearance of Histoplasma capsulatum variety capsulatum antigen is useful for monitoring treatment of experimental histoplasmosis.
We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum antigen concentration in tissues and blood provided a marker for antifungal effect of itraconazole in a nonlethal murine model of histoplasmosis. Treatment with itraconazole (Sporanox), in cyclodextrin, was evaluated in a pulmonary model of histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of infection. All mice were sacrificed on day 15 of infection. Blood, spleen, and lung tissues were removed for culture and quantification of antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267. Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The cyclodextrin formulation of itraconazole (Sporanox) demonstrated antifungal activity in experimental histoplasmosis. Antigen detection was a useful marker for antifungal effect.
Animals↗
PMC Patient Severity Scale: derivation and validation.
OBJECTIVE: This study describes the derivation and validation of the Patient Management Category (PMC) Severity Scale, which provides a method of assessing the overall severity of a hospitalized patient's illnesses, based on the patient's unique clinical conditions, their interaction, and the resultant, combined risk of morbidity and mortality. DATA SOURCES: Derivation of the PMC Severity Scale was based on clinical judgment together with empirical analysis of more than a half million patients discharged from acute care hospitals in Maryland during 1989. The scale was validated by using two distinct calendar years (1988 and 1990) of patients data from the same Maryland hospitals and a six-month patient database from California (1990). STUDY DESIGN: The PMC Severity Scale is an ordinal scale with seven levels: Level 7 represents the greatest likelihood of death and major disease burden. The scale quantifies the severity of each of the patient's disease(s) and accounts for the effect of all coexisting conditions and complications. DATA EXTRACTION METHODS: Publicly available, statewide all-payer claims databases were acquired from Maryland and California. PRINCIPAL FINDINGS: The independent relationships between the PMC Severity Scale with mortality and with length of stay are statistically different across severity levels within each population tested, but the relationships are statistically similar over time. Further, the PMC Severity Scale was determined to be a stable predictor of mortality and LOS across two diverse geographic regions. CONCLUSIONS: Since the severity of a patient's illness is one of the factors that influences the outcomes of care, the PMC Severity Scale can be used successfully as a risk adjustment tool in a variety of quality applications.
California↗
Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia.
Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU-MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT.
Child, Preschool↗
Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino-terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 translocations disrupt the HRX gene between these two motifs, and in a t(11;19)-carrying cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation.
Acute Disease↗
Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7).
Adolescent↗
Consistent involvement of the bcr gene by 9;22 breakpoints in pediatric acute leukemias.
To investigate the relationship of bcr-abl fusion mRNAs with childhood acute lymphoblastic leukemias (ALL), we examined 27 pediatric Philadelphia chromosome (Ph1)-positive acute leukemias using a reverse polymerase chain reaction (PCR) procedure. In cells from 24 leukemias, single bcr-abl PCR products were detected that corresponded to breakpoints in the minor breakpoint cluster region (mbcr in intron 1 of the bcr gene) associated with production of the P190 fusion protein. Cells from the three remaining leukemias contained breakpoints in the major breakpoint cluster region (Mbcr) as shown by PCR and Southern blot analyses. These three leukemias also contained low levels of the mbcr PCR product that may have resulted from alternative splicing of the bcr-abl precursor RNA. A screen of 35 additional leukemias from patients who failed therapy before day 180 (induction failures or early relapses) found one case with unsuccessful cytogenetics to express Mbcr-abl RNA. All four children with Mbcr breakpoints had white blood cell levels in excess of 250,000 at presentation (compared with 2 of 24 with mbcr breakpoints) and two had hematologic and clinical features suggestive of chronic myelogenous leukemias (CML) in lymphoid blast crisis. Our results indicate that in Ph1-positive pediatric leukemias, all 9;22 breakpoints occur in one of the two known breakpoint cluster regions in the bcr gene on chromosome 22. The reverse PCR reliably detected all patients with cytogenetic t(9;22) and is capable of detecting additional Ph1-positive leukemias that are missed by standard cytogenetics. Furthermore, the Mbcr-type breakpoint, associated with production of p210, can be seen in childhood leukemias presenting either as clinical ALL or as apparent lymphoid blast crisis of CML, suggesting that t(9;22) breakpoint locations do not exclusively determine the biologic and clinical features of pediatric Ph1-positive ALL.
Adolescent↗