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Malignant transformation of angiomyolipoma.

Angiomyolipomas are well recognized but uncommon tumors that can involve the kidney. To our knowledge a well documented case of malignant change of angiomyolipoma has never been reported. We report a case of renal angiomyolipoma and leiomyosarcoma with a clearly identified transition of benign to malignant elements seen in the resected tissue.

Adult

A population-based assessment of the continuity of ambulatory care.

A strategy is described in which explicit patient care criteria are used to measure the continuity of the health problem solving process. Prevalent diseases are selected to represent the work load of the health system. Continuity is defined in terms of rates of transition between the major clinical elements: screening, the definitive diagnostic evaluation, treatment, and follow-up evaluation. Results define critical dropout patterns and promote constructive assessment of the health care system. Sample data from the Indian Health Service are presented and discussed.

Ambulatory Care

The effect of evolution on homologous proteins: a comparison between the chromophore microenvironments of Italian water buffalo (Bos bubalus, L.) and sperm whale apomyoglobin.

The perturbing effect of guanidium hydrochloride and pH on the molecular structure of water buffalo apomyoglobin has been investigated by circular dichroism in the far and near ultraviolet and by fluorescence. In the wavelength region between 320 and 260 nm the circular dichroic spectrum of the globin is highly structured and the contributions of the aromatic chromophores have been resolved. Buffalo apomyoglobin undergoes a structural transition at neutral pH which involves elements of the secondary and tertiary structure, as indicated by changes of dichroic activity of the peptide and aromatic chromophores and the fluorescence of the two tryptophanyl residues. The possibility of charge-transfer complex between indole and imidazole is discussed. A major structural transition with abrupt unfolding takes place in the pH region between 5.6 and 4.3. Below pH 4.3 the peptide helical residues, which survive the acid transition, appear to be resistent to further acidification to pH 2.0 while tryptophanyl emission is quenched and shifted to longer wavelengths. A structural transition occurs also in alkali above pH 10, which has been detected by the same techniques. The relationships between buffalo and sperm whale apomyoglobin are discussed.

Animals

[Histology of the pigmented granular rankenneuroma (author's transl)].

We report on a case of a 40 years old female patient with a lentil-sized tumor of the left pinna present since early childhood. Histologic examination revealed pigmented granular "rankenneuroma". The lesion is unencapsulated but fairly well marginated in the dermis. It is composed of varying numbers of spindle-shaped or polyhedral cells arranged in intertwining and parallel bands separated by strands of collagen. The fascicles follow the preexisting nerve truncs. All layers of the dermis may be involved, but only rarely is the superficial subcutaneous tissue invaded. The fascicles of the tumor are generally constructed in a similar fashion. In the center one see argyrophile granular alterated unpigmented cells- Those elements are surrounded by mostly bipolar cells containing varying amounts of melanin. Silverstaining shows transition from spindle-shaped cells to granular degenerated elements. It is thought that the tumor most likely originates from the proliferation of the granular degenerated Schwann cells. The characteristic feature of tumor parenchyme is the association of the granular Schwann cells with cutaneous melanoblasts.

Adult

[Electron microscopic study of the formation of pancreatic endocrine A-cells from acinar epithelium in normal and experimental conditions].

Electron microscope studies in the pancreas of intact white rats and cats and after folliculin administration showed presence of acinar-islet cells with zymogen and endocrine A-granules. Different structure organellas, different amount of zymogen and incretory granules in these cells gave an idea of the process of acino-insular transformation. At later stages of the transformation, participation of the elements of laminar complex of the transitional cells in formation of secretory A-granules, was noted. Presence of the acinar-islet cells in normal and a high amount of them in the pancreas of experimental animals corroborated the essential role of the acinar-islet transformation in the genesis of A-cells of the Langerhans islets.

Animals

Spindle cell carcinoma of the larynx.

A clinicopathologic correlation of 39 cases of a histologically biphasic malignant neoplasm of the larynx is presented. The histologic pattern of this entity was mainly that of a malignant spindle cell process, but a definite squamous cell carcinoma component was evident. Grossly the tumors were usually prominently polypoid. A morphologic transition of the squamous cell carcinomatous element into the spindle cell component was strongly suggested, supporting the contention that this entity is pathogenetically a pleomorphic or spindle cell squamous cell carcinoma. Follow-up information on 20 cases indicated a two-year mortality of 40 per cent, refuting the contention that this entity is of low-grade malignancy. Complete surgical removal of the neoplasm, with or without irradiation, offered the best therapeutic approach. Irradiation alone was unsuccessful.

Aged

[Malignant mesodermal mixed tumor of the bladder: report of a case].

A 59-year-old male took total cystourethrectomy on July, 1991, since the bladder tumor recurred 2 years and 4 months after transurethral resection. Six months after total cystourethrectomy, an abnormal mass shadow appeared on the right lower lung field. Metastatic lung tumor was strongly suspected from CT scan. Despite chemotherapy, the pulmonary lesion grew rapidly and the patient died. From the autopsy, metastatic lesions were found in the bilateral lung fields, skin (face, head and abdominal wall), pleura, bilateral kidneys, small intestine and lymph nodes (para-aortic and mesenteric). The primary bladder tumor contained histologically transitional cell carcinoma as the epithelial element and sarcomatous changes with osteoid formation as the non-epithelial elements. Thus, the primary lesion was diagnosed as a malignant mesodermal mixed tumor. However, all of the metastatic lesions showed only sarcomatous changes. Only 10 cases of malignant mesodermal mixed tumor of the bladder have been reported in Japan since Fujita's report. In general, total cystectomy is necessary for the treatment of this disease. It has a poor prognosis; 5 of the 10 patients died within one year after operation.

Humans

Exploring Regulatory Roles of Transposable Elements in EMT and MET through Data-Driven Analysis: Insights from regulaTER.

Gene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in a given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded from https://github.com/karakulahg/regulaTER.

DNA Transposable Elements

Transition of Staphylococcus aureus tetracycline resistance plasmid pT181 from independent multicopy replicon to predominantly integrated chromosomal element over 65 years.

Mobile genetic elements (MGEs), including plasmids, phages and genome islands, are major sources of bacterial genetic diversity. The small plasmid pT181 confers tetracycline resistance in bacterial pathogen Staphylococcus aureus via an efflux pump, TetK. pT181 was one of the earliest sequenced S. aureus plasmids, and has been isolated in both clinical and livestock-associated strains for decades, both as an independent replicon and integrated in the chromosome as part of staphylococcal cassette chromosome mec (SCCmec). Bacterial genome analysis tools and high-quality sequences with metadata are publicly available, but these resources remain underleveraged for examining historical data, especially when studying the spread of MGEs across a species and over time. Using publicly available reads and metadata, we explored the evolution of pT181 over almost seven decades of samples to identify temporal trends in sequence evolution, copy number changes, and spread across S. aureus and beyond. pT181 was prevalent across S. aureus (found in 9.5% of 83,366 genomes tested), with a conserved sequence outside of three hypervariable regions. The history of pT181 since 1954 is characterized by spread across strains, significant variation in plasmid copy number of the independent replicon, and increasing frequency of integration of the plasmid into the S. aureus chromosome. We have identified multiple chromosomal integration locations of the plasmid, including outside of the previously characterized SCCmec. We find that pT181 has been transferred across staphylococcaceae and into a Gram-negative species. The repeated integration of pT181 into the chromosome may indicate co-evolution of the plasmid and the host, potentially to facilitate increased antibiotic resistance.

Journal Article

Ultrastructure of cerebellar hemangioblastoma.

Light and ultrastructural features of a cerebellar hemangioblastoma in a 56-year-old man are described in detail. The neoplasm was composed of three major cell types: endothelial cells, pericytes, and stromal cells. The endothelial cells lined the fenestrated vascular channels. The pericytes were ensheathed by their own basal lamina which separated them from the basal lamina covering the endothelium. The stromal cells contained, in addition to the conventional organelles, numerous membrane-bound lipid inclusions, annulate lamellae, and nuclear bodies. There were also present transitional cells which shared the fine structure of all the three major cell types. Histogenetically, the tumor was considered to be of vascular origin. The stromal cells represented the stem cells which, under the neoplastic influence, continued to proliferate and differentiate into "vasoformative" elements (pericytes and endothelium) which formed new blood vessels. The transitional forms between the stromal cells and the "vasoformative" elements suggested that the cellular components of a hemangioblastoma shared a common ancestry, most likely of an angioblastic lineage.

Cell Nucleus

What is the meaning of colorectal transit time measurement?

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P less than 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P less than 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P less than 0.001). This may explain why a large percentage of constipated patients have been found by most authors to have "normal" colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.

Adult

Hydration and preferential molecular adsorption on titanium in vitro.

Surface sensitive spectroscopies, Auger electron and X-ray photoelectron (XPS), were used to determine changes in titanium oxide composition, oxide stoichiometry, and adsorbed surface species as a function of exposure to human serum in a balanced electrolyte (serum/SIE) and 8.0 mM ethylenediaminetetraacetic acid in a balanced electrolyte (EDTA/SIE) at 37 degrees C. Before immersion, the oxide was near ideal TiO2, covered by two types of hydroxyl groups: acidic OH(s) with oxygens doubly coordinated to titanium, and basic Ti-OH groups singly coordinated. After extended exposure to both solutions, up to 5000 h (ca. 208 d), the surface concentration of OH groups increased and non-elemental P appeared. The P LVV Auger transition and P 2p spectra indicated the peak positions were similar to reference phosphate compounds. The adsorbed phosphate species were presumed to be either Ti-H2PO4 or Ti-HPO4-. The XPS data suggested that a lipoprotein and/or glycolipid film was adsorbed to the specimens exposed to serum/SIE. Analysis of the preferential lipoprotein/glycolipid adsorption using electrostatic bonding concepts contributed to the refinement of the hierarchical model for the Ti-tissue interface. The salient features are that Ti metal is not in direct contact with the biological milieu, rather there is a gradual transition from the bulk metal, near-stoichiometric oxide, Ca and P substituted hydrated oxide, adsorbed lipoproteins and glycolipids, proteoglycans, collagen filaments and bundles to cells.

Adsorption

Primary non-urachal adenocarcinoma of the bladder.

The clinical course of 34 patients with non-urachal adenocarcinoma of the bladder was reviewed and compared to the world experience. The 5-year survivorship was 19 per cent, with only 1 patient being free of disease. Metaplasia with formation of glandular elements reflects the unstable potential of the transitional cell and may be associated with the biologic aggressiveness of the tumor.

Adenocarcinoma

Adenosquamous carcinoma of the lung. Clinicopathologic and immunohistochemical features.

Adenosquamous carcinomas (ASC) of the lung comprise only 1.8% of all pulmonary cancers. Eleven patients with this disease (6 men and 5 women; mean age, 62 years [range, 51 to 78 years]) were treated. On the basis of pathologic and immunohistochemical evidence, the tumors were separated into three groups: five ASCs of predominantly glandular type, which may originate from squamous metaplasia in a preexisting adenocarcinoma; three mixed type ASCs, possibly derived from the transition of undifferentiated carcinoma to two different elements; and three predominantly squamous type ASCs resembling high-grade muco-epidermoid carcinoma. The 5-year survival rate of 35% for patients with ASCs was the same as that for patients with other nonsmall cell carcinomas. For two patients with ASCs of the predominantly glandular type and for one with the mixed type, resection was incomplete because of extensive local disease. All tumors of the predominantly squamous type could be excised completely. However, differences in the malignant potential of these three types of ASCs are still controversial.

Adenocarcinoma

A study of interface effects in 60Co beams using a thin-walled parallel plate ionization chamber.

A large plane-parallel ionization chamber has been constructed to investigate interface effects in 60Co beam. The designed geometry yields negligible perturbation from the side walls, as opposed to the large effects existing in commercially available plane-parallel chambers. The chamber has been used to investigate interface phenomena in transition zones using a wide range of elements (Z = 4-82) as front- and back-scattering media and a clinically relevant 60Co gamma-ray field size. The effects of varying the chamber height discretely (0.5-11 mm) and increasing the wall thickness (1-9 mg/cm2) have been investigated. The variation of the measured ionization with the experimental setup (air gap between backscatter material and chamber wall, measurements at dmax and at 5-cm depth, varying the material both in front of and behind the chamber, etc.) has also been investigated. The simple geometry of the ion chamber has been found optimum for benchmark studies of Monte Carlo calculations. The ion chamber is suited for investigating experimentally the effects of varying transport parameters used in Monte Carlo simulations. The results presented show that the complex physical mechanisms governing 60Co interface dosimetry still make Monte Carlo condensed-history (macroscopic) techniques uncertain. It has been found that the EGS4 Monte Carlo system, together with the user code DOSRZ V4.0 and the PRESTA algorithm, yields good agreement with experiments for low and medium Z (main interest in dosimetry and radiotherapy), but may underestimate up to 10% the backscatter from high-Z materials even when transport parameters are optimized.

Algorithms

Characterization of the apolipoprotein B polypeptide of human plasma low density lipoprotein in detergent and denaturation solutions.

Apolipoprotein B, the polypeptide moiety of human serum low density lipoprotein, is subject to degradation (as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) both in the intact particle and after delipidation. Protease inhibitors, sodium azide, and nitrogen saturation did not influence the rate or degree of degradation. Lipid-free apolipoprotein B prepared by gel exclusion chromatography in sodium dodecyl sulfate bound a limited number of detergent molecules (up to 300) in monomeric sodium dodecyl sulfate solutions; circular dichroic spectra of this complex were similar to spectra of the intact lipoprotein. Near the critical micelle concentrations, a large, cooperative increase in detergent binding occurred, accompanied by circular dichroic changes indicating increased alpha helicity. By sucrose density centrifugation, lysopalmitoyl phosphatidylcholine could be substituted for the anionic detergent; about 300 mol of lysolipid were bound to the polypeptide. Replacement of detergent with guanidine hydrochloride by dialysis produced a soluble polypeptide with no ordered structure at denaturant concentrations above 7 M. At lower guanidine hydrochloride concentrations, structural elements were regained in a broad, reversible transition. It appears that apolipoprotein B is an easily degraded polypeptide with regions resembling water-soluble proteins but other regions which interact with lipid (or synthetic amphiphiles) and produce an overall insolubility in aqueous solution in the absence of amphiphilic ligands.

Apolipoproteins

Molecular properties of a major cell surface protein from chick embryo fibroblasts.

The molecular structure of chick embryo fibroblast cell surface protein has been investigated by ultracentrifugation, circular dichroism, and fluorescence. Most measurements were restricted to alkaline solutions because of the limited solubility of this protein at more neutral pH values. A very high frictional ratio for the protein suggests an asymmetric structure. However, there are elements of organized structure since typical thermal transition curves were found by several methods. Consequently, a model in which ordered domains are connected by flexible polypeptide chains seems to account for all the hydrodynamic and optical data.

Animals

Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer.

A retinoid X receptor (RXR) response element was located within the functionally defined hepatitis B virus (HBV) enhancer element. A short segment of the enhancer that contains this region has been shown with genetic analysis to play a key role in the regulation of enhancer function and to represent a major determinant of liver-specific activity. Both the full-length protein and the DNA-binding domain of the liver-specific receptor RXR alpha bound to the putative retinoic acid response element in the HBV enhancer. In vivo, an HBV enhancer-reporter gene construct responds to induction with retinoic acid when cotransfected with an RXR alpha expression vector. A single-base transition (G----A) in the HBV retinoic acid response element leads to a dramatic reduction both in the in vitro binding activity of RXR alpha and the in vivo activity of the HBV enhancer. Thus, retinoic acid and the RXR alpha are implicated as being significant determinants in the liver-specific regulation of HBV gene expression and the resultant disease pathogenesis.

Base Sequence