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Biomedical subjects

F B Johnson

Publications and source records attributed to F B Johnson.

At least 19 recordsLinked to original sources

Topographical analysis of the G virion of Aleutian mink disease parvovirus with monoclonal antibodies.

The topography of the Aleutian mink disease parvovirus (ADV) G virion was analyzed with monoclonal antibodies and polyclonal antiserum. There was homology between the two major structural proteins as others have previously reported. Trypsin treatment of the virion with subsequent immunoblotting revealed that VP2 represents the main peptide on the exterior of virion and that VP1 is probably embedded within the capsid. Additional analyses of the trypsin-treated virions showed that VP2 is responsible for binding complement and that it also represents the structural part of the virion that binds to cellular receptors. A third protein, p34, was detected that might represent a third structural polypeptide because of its many unique epitopes relative to the other peptides detected.

Aleutian Mink Disease Virus

Differential regulation of transcription preinitiation complex assembly by activator and repressor homeo domain proteins.

Different eukaryotic transcription factors can act through the same upstream binding site to differentially regulate target gene expression, but little is known of the underlying mechanisms. Here, we show that Ultrabithorax and even-skipped homeo domain proteins (UBX and EVE) of Drosophila melanogaster exert active and opposite effects on in vitro transcription when bound to a common site upstream of a core promoter. Both the activator UBX and the repressor EVE affect the extent but not the rate constant of preinitiation complex (preIC) formation. Both regulators act early in preIC assembly and are dispensable later. Assembling complexes become resistant to regulation by the bound proteins, but activation by UBX is restored upon ATP or dATP addition, and regulation by both proteins is restored after the addition of all four nucleoside triphosphates and transcription initiation. The results establish that upstream activators and repressors can function by fundamentally similar mechanisms, by differentially regulating an early step in preIC assembly, leading to formation of functionally distinct transcription complexes. A subsequent step renders mature complexes transiently refractory to activation and repression. Implications for the mechanism of transcription complex assembly and turnover and its regulation are discussed, including a new role for ATP in turnover.

Adenosine Triphosphate

Fourier transform infrared microscopic identification of foreign materials in tissue sections.

Fourier-transform infrared microspectroscopy was used to identify polymeric microparticles, such as polyethylene, polysulfone, polytetrafluoroethylene, polyurethane, silicon-based, and nylon-based plastics, in tissue sections. Foreign particles as small as 30 microns in diameter were identified. In addition to being a nondestructive technique, infrared microscopy allows for more precise structural identification of polymeric materials than do X-ray or scanning electron microscopy.

Biopsy

Identification of titanium in human tissues: probable role in pathologic processes.

Six cases of titanium dioxide exposure involving lung, skin, and synovium are described, with a review of the literature. The patients, four men and two women, were between the ages of 22 and 65 years. The pulmonary changes were characterized by fibrosis and numerous macrophages with abundant deposition of a black pigment. Adjacent areas of bronchopneumonia were also observed. In the skin a severe necrotizing lesion involving the subcutaneous tissue with extension to the muscle was observed in one case and a nonspecific inflammatory response was observed in another; both cases showed abundant black pigment deposition. Electron microscopy and energy dispersive x-ray analysis demonstrated the presence of large quantities of titanium in the pigment granules. There may be a combination of black pigment deposition and fibrosis, necrosis, or a xanthomatous or granulomatous reaction, that, together with negative results on special staining and culture studies for organisms, should raise the suspicion of titanium-associated injury and prompt the study of the affected tissues by x-ray analysis for positive identification.

Adult

Cutaneous reaction from a broken thermometer.

A cutaneous and soft tissue reaction that resulted from a broken thermometer inside the mouth of a 10-year-old boy is described. Metallic mercury globules and glass pieces were identified in the excised tissue. On histologic examination, a zone of necrosis, polymorphonuclear leukocytes, macrophages, and multinucleated giant cells surrounded metallic mercury that appeared as dark opaque globules. Dense fibrosis and reactive lymphoid hyperplasia were also noted in the dermis and deeper tissues. The gold lysis test, scanning electron microscopy, and energy-dispersive x-ray analysis confirmed the presence of mercury in the tissue. A literature review on cutaneous mercury granuloma illustrates its unpredictable course. The cutaneous reaction may remain localized, but some cases are associated with an elevated mercury level in blood and urine, pulmonary embolism, mercury poisoning, and even with fatal outcome. Various manifestations of mercury poisoning and guidelines for the management of cutaneous mercury granuloma are discussed.

Child

Suitability of infection of cells in suspension for detection of herpes simplex virus.

Detection of herpes simplex virus in clinical specimens by the suspension-infection technique was compared with detection by conventional cell culture. The sensitivity and specificity of the suspension-infection technique compared with those of conventional culture were 95.9 to 98.2% and 97.5 to 100%, respectively, depending on the cell line used in the tests. The mean time to diagnosis by the suspension-infection technique was 1 day, compared with 4.8 days by conventional culture. Comparable detection of low-level positive specimens was observed with the methods. In a clinical setting, the isolation rates obtained by suspension-infection and conventional culture were indistinguishable. These results indicate that the suspension-infection method can be used for the detection of herpes simplex virus and can yield rapid diagnostic results without a time-consuming centrifugation step.

Animals

Teflonomas of the larynx and neck.

Intracordal fluorocarbon (Teflon, Mentor O and O Inc, Norwell, MA) injection has been used for decades to correct paralytic dysphonia, a result of unilateral laryngeal paralysis. Infrequently, the Teflon extravasates and infiltrates into the soft tissues of the neck and larynx producing a mass that clinically simulates a malignant lesion. We report eight cases of so-called "Telonomas" of the larynx and neck that have been identified in the files of the Armed Forces Institute of Pathology Otolaryngic Tumor Registry and from the Cytopathology Service at the George Washington University Medical Center. Patients ranged in age from 31 to 72 years. Vocal cord paralysis, treated by Teflon injection, was caused by primary laryngeal carcinoma or metastatic carcinoma (breast, lung) involving the recurrent laryngeal nerve, surgical trauma to the recurrent laryngeal nerve, or postviral neuritis. Subsequent symptomatology, related to extravasation of the Teflon with a resulting "Teflonoma", included a neck mass or persistent hoarseness. Infrequently, there was associated airway obstruction or voice changes. Diagnosis was made by fine needle aspiration or by excision of the suspicious mass and subsequent identification of a foreign body granulomatous reaction with associated birefringent material. Infrared absorption spectrophotometry identified the foreign material as a fluorocarbon which was further substantiated by scanning electron microscopy and energy dispersive x-ray analysis. Surgical removal of the mass alleviated all symptoms.

Adult

The nature of hyaline (eosinophilic) globules and vascular slits of Kaposi's sarcoma.

Ultrastructural studies of Kaposi's sarcoma (KS) from skin biopsies of 24 patients (eight with acquired immunodeficiency syndrome (AIDS) and 16 without) were performed to delineate the nature of hyaline globules and vascular slits. These structures have been regarded as one of the important criteria for the recognition of KS under light microscopy. Histochemical and immunochemical studies were also performed to correlate with the electron microscopic (EM) observations. The most remarkable EM findings of KS were the intracytoplasmic lumen formation and erythrophagocytic activities of the neoplastic cells, particularly in the mature nodular, or neoplastic stage. The spindle-shaped or ovoid neoplastic cells frequently contained one to several intact and fragmented red blood cells. The intracellular and extravasated erythrocytes were often arranged in single files, giving these vascular slits an elongated appearance on longitudinal sections. The phagocytic activities of the neoplastic cells were demonstrated by the presence of membrane-bound lysosomes containing phagocytized erythrocytes and their partially digested forms (erythrophagosomes) adjacent to pinocytotic vesicles, prominent rough endoplasmic reticulum, and Golgi apparatus, as well as scattered, small, membrane-bound lysosomal granules, some of which were attached to the erythrophagosomes. The erythrophagosomes underwent various stages of disintegration. The partially digested red cells varied from 0.4 to 10 microns in diameter. The results of histochemical and immunochemical findings also strongly suggested that erythrophagosomes were most likely the hyaline globules (bodies) seen in light microscopy. The exact mechanism of erythrophagocytosis is uncertain. However, its consequences, erythrophagosomes, and intracytoplasmic lumen formation, particularly in the nodular or neoplastic stage in patients with and without AIDS, are among the important histologic features of KS.

Acquired Immunodeficiency Syndrome

Stimulation of transcription by an Ultrabithorax protein in vitro.

The Ultrabithorax (Ubx) gene of Drosophila melanogaster encodes a family of UBX proteins that are thought to specify the developmental fates of segments in the posterior thorax and anterior abdomen by controlling the expression of a set of target genes. UBX proteins bind DNA in vitro, and they activate or repress different natural and synthetic target promoters in cultured cells. Here it is shown that a purified UBX protein can stimulate transcription of a synthetic target gene in extracts of cultured D. melanogaster cells. Stimulation is dependent on the presence of upstream, promoter-region binding sites but is independent of binding site orientation. A naturally occurring binding site cluster and a binding site consensus sequence consisting of TAA trinucleotide repeats can mediate this activation. A minimal promoter fused to such sites is activated by UBX, suggesting that transcriptional stimulation could result from an interaction between the promoter-bound protein and the general transcriptional machinery.

Animals

Transport of viral specimens.

The diagnosis of viral infections by culture relies on the collection of proper specimens, proper care to protect the virus in the specimens from environmental damage, and use of an adequate transport system to maintain virus activity. Collection of specimens with swabs that are toxic to either virus or cell culture should be avoided. A variety of transport media have been formulated, beginning with early bacteriological transport media. Certain swab-tube combinations have proven to be both effective and convenient. Of the liquid transport media, sucrose-based and broth-based media appear to be the most widely accepted and used. Studies on virus stability show that most viruses tested are sufficiently stable in transport media to withstand a transport time of 1 to 3 days. Some viruses may withstand longer transport times. In many cases, it is not necessary to store virus specimens in a refrigerator or send them to the laboratory on wet ice or frozen on dry ice. However, the specimen should not be exposed to environmental extremes. Modern viral transport media allow for more effective use of viral culture and culture enhancement techniques for the diagnosis of human viral infections.

Culture Media

Lycopodium granuloma.

The spores of Lycopodium (L) clavatum were used as a component of a dusting powder in many hospitals during the 1920's and 1930's. When L spores enter surgical wounds a lesion clinically resembling tuberculosis or neoplasia may develop months or even years later. We recently encountered a case of L granuloma occurring in a patient 50 years after an appendectomy. Three additional cases found in the files of the AFIP are also reported.

Aged

Liesegang rings in tissue. How to distinguish Liesegang rings from the giant kidney worm, Dioctophyma renale.

Liesegang rings (LRs) are periodic precipitation zones from supersaturated solutions in colloidal systems. They are formed by a process that involves an interplay of diffusion, nucleation, flocculation or precipitation, and supersaturation. Examples include LRs of calcium carbonate in oölitic limestone (in nature), LRs of silver chromate in gelatin (in vitro), and LRs of glycoprotein in pulmonary corpora amylacea (in vivo). Here we describe LRs in lesions from 29 patients--mostly lesions of the kidney, synovium, conjunctiva, and eyelid. The LRs formed in cysts, or in fibrotic, inflamed, or necrotic tissue. The LRs in this study varied greatly in shape and size, measuring 7-800 microns. Special stains and energy-dispersive radiographic analysis or scanning electron microscopy revealed that some LRs contained calcium, iron (hemosiderin), silicon, and sulfur. Some pathologists have mistaken LRs for eggs, larvae, or adults of the giant kidney worm, Dioctophyma renale. D. renale is a large blood-red nematode that infects a variety of fish-eating mammals, especially mink. Fourteen documented infections of humans have been recorded, usually with adult worms expelled from the urethra. The adult worms are probably the largest helminth to parasitize humans. Eggs of D. renale are constant in size (60-80 microns X 39-47 microns), contain an embryo, and have characteristic sculpturing of the shell. Liesegang rings should not be mistaken for eggs, larvae, or adults of D. renale, or for any other helminth.

Chemical Precipitation

Suitability of new chlamydia transport medium for transport of herpes simplex virus.

A new chlamydia transport medium (ChlamydiaPort; Scott Laboratories, Inc., Fiskeville, R.I.) was evaluated for its suitability as a transport medium for herpes simplex virus (HSV). Two laboratory HSV strains (McIntyre and 333) and two clinical isolates (AO218 and AO301) were suspended in ChlamydiaPort, ViraPort (Scott Laboratories), and cell culture medium and maintained at 2 and 22 degrees C. Samples were tested at various time intervals to determine surviving virus. The range of half-lives of the HSV strains held at 2 degrees C in ChlamydiaPort medium was from 3.5 to 10 days, while virus stability was greater in ViraPort and less in cell culture medium. These HSV strains held at 22 degrees C in ChlamydiaPort had half-lives from 1.5 to 6 days, which were significantly greater than the half-lives of the viruses held in either tissue culture medium or ViraPort. Clinical specimens were tested for virus by using the Selecticult-HSV (Scott Laboratories) system to determine the performance of the transport medium under field conditions. Clinical specimens maintained up to 5 days at ambient temperatures in ChlamydiaPort medium appeared suitable for diagnostic testing without detectable loss of positive specimens. In addition, there was a significant decrease in the average time required for diagnosis when compared with a standard transport system, Virocult (Microdiagnostics, Cleveland, Ohio). These results show that HSV infections can be successfully diagnosed in distant virology laboratories by shipping specimens in ChlamydiaPort transport medium at ambient temperatures.

Chlamydia

Identification and significance of magnetite in human tissues.

Magnetite or iron oxide has been identified in humans as well as certain animals and bacteria. With the current popularity of magnetic resonance imaging, the presence of these ferromagnetic particles in the tissues may impose biological significance. So far, identification of magnetite in tissue has been mainly based on magnetometry. Hence, a simple technique for direct identification of the magnetic particles in tissues is described. Lung tissues with abundant iron material and particles were digested in 1N sodium hydroxide solution. After rinsing, the sediments were suspended in 95% alcohol and placed on a glass slide located on a strong magnet. The iron-containing particles from the digestion procedure were aligned in a parallel manner along the north-south poles of the magnet and were confirmed to be magnetite by x-ray diffraction. No such effect was observed with hemosiderin-containing granules from the control liver tissues. The results of this experiment show that the "biological magnetite" is distinctly different from hemosiderin and has characteristic properties when subjected to a magnetic field.

Adult

Sodium orthophosphate hydrate (NA3PO4.12H2O): a new type of human urinary stone.

In a series of electron microscopic studies of human urinary stones, a stone composed of sodium orthophosphate hydrate was identified. The stone was recovered from a patient who succumbed to advanced renal failure. A massive failure of the sodium pump, which cotransports phosphate across the brush border membrane of the proximal tubules is thought to be responsible for such an exceptional stone. This appears to be the first description of sodium phosphate crystal in a human urinary stone. Electron microscopy is a useful tool for stone analysis.

Aged

Modified radical neck dissection and postoperative radiotherapy in squamous cell head and neck cancer.

Between 1978 and 1982, 41 patients with clinically staged N1, N2, or N3b disease underwent unilateral or bilateral modified radical neck dissection. Five patients died free from their original disease with less than 24 months follow-up. Twenty-four patients with histologically positive nodes received postoperative radiotherapy with 2 (8 percent) neck recurrences. Another four patients with histologically positive nodes refused postoperative radiotherapy and had two (50 percent) neck recurrences. Three patients did not respond to radiotherapy at the time of their surgery and had no neck recurrences. The final five patients had histologically negative nodes, did not receive radiotherapy, and had no neck recurrences. These results suggest that modified radical neck dissection can be used in lieu of the classical radical dissection in many patients with clinically positive nodes who have squamous cell head and neck cancer without compromising survival.

Carcinoma, Squamous Cell