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Biomedical subjects

H G Brown

Publications and source records attributed to H G Brown.

At least 19 recordsLinked to original sources
PubMed2001

Management of neurocytomas: case report and review of the literature.

The purpose of this report is to review the available literature on the presentation, pathology, and treatment of central nervous system (CNS) neurocytomas. A case report of an extraventricular neurocytoma is presented along with a comprehensive literature search of patients with a diagnosis of CNS neurocytoma. CNS neurocytomas are rare neoplasms, with fewer than 240 cases reported in the literature. The majority of neurocytomas are found in the ventricular system of the brain. Immunohistochemistry is frequently used to help distinguish this tumor from other CNS neoplasms. MIB-1 proliferation index is commonly used in an attempt to predict biologic behavior. Little is known about the management of patients with this tumor, because most reports are from the pathologic literature and contain sparse information regarding clinical management. Neurocytomas are rare CNS tumors with varied biologic behavior. MIB-1 index may help direct adjuvant therapy. An excellent prognosis can be expected if a gross total resection is achieved. Postoperative radiation therapy (RT) may be considered after subtotal resection. Otherwise, RT is an option for medically inoperable or recurrent disease.

Aged↗
PubMed2001

January 2001: A 37 year old man with a history of Hodgkin's disease.

The January Cases of the Month (COM): A case of intracranial metastatic nodular sclerosing Hodgkin's disease without dural attachment in a 37-year-old previously stage III male is presented with a brief review of the literature. Both the primary tumor in the lymph node biopsy and the metastatic brain tumor showed similar histopathology and a immunohistochemical profile typical for Hodgkin's Disease. After chemotherapy, there are no signs of recurrence or systemic disease on follow-up for five months.

Adult↗
PubMed2000

"Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study.

495 medulloblastomas (MBs) from 6 Pediatric Oncology Group (POG) protocols were reviewed to assess the incidence and prognostic significance of "large cell" and "anaplastic" variants. "Large cell" medulloblastomas (LC MBs) were those with focal or diffuse, large, round neoplastic cells with prominent nucleoli. "Anaplastic" MBs (A MBs) were those with nuclei that were also large but markedly atypical with coarse chromatin and irregular shapes. Twenty-one cases were identified in the combined LC/A MB group, comprising about 4% of all MBs. Survival curves and Kaplan-Meier estimates of survival probabilities were examined separately for the LC/A MB and control groups. The logrank test for detecting poorer survival in the 21 cases was significant (p < 0.0001). Fluorescence in situ hybridization for c-myc showed amplification in 4 of 11 cases of the LC/A phenotype and 1 additional case of high level gain at 8q24 was disclosed by comparative genomic hybridization. Comparative genomic hybridization confirmed c-myc amplification and found evidence for isochromosome 17q in 3 of 4 LC/A cases studied successfully. One additional tumor showed high level gain restricted to 2p13 consistent with n-myc amplification. Monosomy 22, common in atypical teratoid/rhabdoid tumors, was not found. These results suggest that LC/A MB phenotype could be, at least in part, a correlate of c-myc, and possibly n-myc, amplification. The study thus confirms original observations about the LC MB in regard to histological features, immunohistochemical findings, c-myc amplification, cytogenetic findings, and poor prognosis.

Anaplasia↗
PubMed1999

Intracranial leiomyosarcoma in a patient with AIDS.

We report an intracranial leiomyosarcoma in the pontine cistern of a 34-year-old woman infected with the human immunodeficiency virus (HIV). The clinical, radiological and pathological data are reviewed. The tumor was Epstein-Barr virus (EBV) positive by in situ hybridization. This case emphasizes that smooth muscle neoplasms arising in the setting of immunocompromise can occur intracranially, and corroborates a hypothesis that EBV coinfection may have a role in development of these tumors.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Renal disease in Down syndrome: autopsy study with emphasis on glomerular lesions.

A range of renal diseases have been previously described in patients with Down syndrome. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Definition of underlying causes of renal failure could potentially lead to prevention of progressive renal dysfunction in this population. We report two index cases of teenaged Down patients who presented with proteinuria and focal segmental glomerulosclerosis with hyalinosis, not previously described in this population. In addition, autopsy files were reviewed at the Johns Hopkins Hospital to assess renal and especially glomerular pathology in Down patients. Additional cases, including acute glomerulonephritis with early crescents and vasculitis, minimal change disease, and membranous nephropathy, were identified; the latter two diseases had not been previously reported in patients with Down syndrome. Semiquantitative studies on glomerular changes in all cases examined through autopsy also were performed. The only pathological finding that was significantly more common in the Down syndrome group, compared with age-matched cases from the autopsy files, was cystic dilation of Bowman's space. Histological findings described as increased in the Down population in previously published autopsy studies were also present in the control population, highlighting the need to adequately control such studies. The cases of acquired glomerular disease reported here were seen largely after the first decade of life. Monitoring of Down patients for renal and especially glomerular disease should be done regularly as patients age into the second and third decades.

Adolescent↗
PubMed1998

Neurofilament-L homopolymers are less mechanically stable than native neurofilaments.

Neurofilaments are cytoskeletal components of neurones that are thought to play an important structural role in the axon. Specific functions of neurofilaments are not yet well defined; however, other intermediate filaments are known to have structural and mechanical functions in different cell types. The atomic force microscope (AFM) can be used to visualize and manipulate biological structures through direct physical contact. This allows the AFM to be used to probe the mechanical properties of these structures. In this paper we present AFM images of native neurofilaments isolated from bovine spinal cord, composed of NF-L, NF-M and NF-H, and filaments polymerized in vitro from purified NF-L. Morphologically these structures, in solution and under ambient conditions, are in agreement with previous data from electron microscopy. However, repeated scanning of NF-L homopolymers (in solution) produced significant disruptions of segments of filaments, both within and at the ends of the filaments. This disruption resulted in complete loss of portions of the filaments and in breaks in the continuity of the filaments. Repeated scanning of isolated native neurofilaments under similar conditions produced no detectable structural changes. Under extremely high applied forces the native neurofilaments were bent and distorted by the action of the AFM tip, but were never broken. These data suggest that purified NF-L is not sufficient to confer complete mechanical stability to neurofilaments.

Animals↗
PubMed1997

Entropic exclusion by neurofilament sidearms: a mechanism for maintaining interfilament spacing.

A long-range repulsive force near isolated neurofilaments was detected by exclusion of large molecules and by direct force measurements with atomic force microscopy. Adsorption of isolated native neurofilaments to a solid substrate in a high-salt solution (170 mM NaCl), in the presence of coisolating contaminants, shows that the contaminants are excluded from a zone that extends from 50-100 nm from the core of the filament. Force-distance measurements by AFM show the presence of a weak repulsive force that extends >50 nm from the core of the filament; this repulsive force is absent in homopolymers of neurofilament L or trypsinized native filaments that lack the long sidearms present in native filaments. These results suggest that neurofilament sidearms form an entropic brush, thereby providing a mechanism for maintaining interfilament spacing.

Animals↗
PubMed1995

An ultrastructural analysis of the epithelial-fiber interface (EFI) in primate lenses.

The purpose of this study was to conduct a comprehensive ultrastructural analysis of the epithelial-fiber interface (EFI) in normal adult primate (Macaque nemestrina and fascicularis; 6-9 years old, n = 10) lenses. Scanning electron microscopy (SEM) was used to initially characterize the gross size, shape and three-dimensional organization of central zone (cz) epithelial cells and the anterior ends of elongating fibers beneath these cells. This fiducial information was essential to properly orient lens pieces in freeze fracture specimen carriers for the production of replicas with unambiguously identifiable EFI. Transmission electron microscopy (TEM) of replicas and thin-sectioned material were used to ultrastructurally analyse the cz EFI. TEM thin-sectioned material was also used to ultrastructurally analyse the pregerminative (pgz), germinative (gz) and transitional zone (tz) EFI. Correlative SEM and TEM of cz EFI components revealed that the apical membrane of both epithelial and elongating fiber cells were irregularly polygonal in shape, and aligned in parallel as smooth, concave-convex surfaces. However, whereas epithelial cell apical surfaces had minimal size variation, elongating fibers were larger and considerably variable in size. Quantitative analysis of > 10000 micron2 cz elongating fiber apical surfaces failed to detect any gap junctions defined in freeze fracture replicas as complementary aggregates of transmembrane proteins (connexons) conjoined across a narrowed extracellular space. However, a comparable frequency of vesicular events was noted in this region as quantified previously in adult and embryonic chick lens. Correlative TEM analysis > 1500 linear micrometers of thin-sectioned EFI from this region confirmed the presence of epithelial-epithelial gap junctions, elongating fiber-elongating fiber gap junctions, and an extreme paucity of epithelial-elongating fiber gap junctions. In contrast, TEM analysis of > 1000 linear micrometers of thin-sectioned pgz, gz and tz EFI, confirmed the presence of epithelial-epithelial gap junctions, elongating fiber-elongating fiber gap junctions, numerous epithelial-elongating fiber adherens junctions and a few epithelial-elongating fiber gap junctions. Thus, the results of this and previous quantitative morphological and physiological studies (electronic and dye coupling) demonstrate that there is limited coupling between cz epithelial cells and underlying elongating fibers. Furthermore, the absence of gap junctional plaques in cz EFI freeze-fracture replicas and either pentalaminar or septalaminar profiles in correlative thin-sections, suggests that this limited coupling could be mediated via isolated gap junction channels. However, the results of this and previous quantitative studies further show that a greater degree of coupling exists across the pgz, gz and tz regions of the EFI and that this coupling is likely to be mediated by gap junction plaques. Finally, this and other studies continue to demonstrate that transcytotic processes play a role in lens physiology at the EFI.

Animals↗
PubMed1994

Long term follow-up of dermofasciectomy for Dupuytren's contracture.

During the 4-year period 1980-1983, we carried out 338 operations for Dupuytren's disease of the hand. Of these 46 (13.6%) had a dermofasciectomy and skin graft for recurrent disease. In this sub-group, 34 patients (10.1%) were operated on by the same senior surgeon (H.G.B.). Only these cases were included in this study. Average follow-up was 100 months (range 80-120 months). It was found that graft durability was good, there was no clinical evidence of recurrence beneath grafts, contracture did not exceed 15 degrees at any joint and two point discrimination in the graft was equal to, or better than, 12 mm in the palm and 8 mm in the digit.

Adult↗
PubMed1994

Intercellular communication between epithelial and fiber cells of the eye lens.

Results of electrical, dye-coupling and morphological studies have previously suggested that gap junctions mediate communication between the anterior epithelium of the lens and the underlying lens fiber cells. This connection is believed to permit 'metabolic cooperation' between these dissimilar cell types and may be of particular importance to the fiber cells, which are thought incapable of autonomous ionic homeostasis. We reinvestigated the nature of the connection between epithelial and fiber cells of the embryonic chicken lens using fluorescence confocal microscopy and freeze-fracture analysis. In contrast to earlier studies, our data provided no support for gap-junction-mediated transport from the lens epithelium to the fibers. Fluorescent dyes loaded biochemically into the lens epithelium were retained there for more than one hour. There was a decrease in epithelial fluorescence over this period, but this was not accompanied by an increase in fiber cell fluorescence. Diffusional modeling suggested that these data were inconsistent with the presence of extensive epithelium-fiber cell coupling, even if the observed decrease in epithelial fluorescence was attributed exclusively to the diffusion of dye into the fiber mass via gap junctions. Furthermore, the rate of loss of fluorescence from isolated epithelia was indistinguishable from that measured in whole lenses, suggesting that decreased epithelial fluorescence resulted from photobleaching and leakage of dye rather than diffusion, via gap junctions, into the fibers. Analysis of freeze-fracture replicas of plasma membranes at the epithelial-fiber cell interface failed to reveal evidence of gap-junction plaques, although evidence of endocytosis was abundant. These studies were done under conditions where the location of the fracture plane was unambiguous and where gap junctions could be observed in the lateral membranes of neighboring epithelial and fiber cells. Paradoxically, tracer molecules injected into the fiber mass were able to pass into the epithelium via a pathway that was not blocked by incubation at 4 degrees C or by treatment with octanol and which excluded large (approximately 10 kDa) molecular mass tracers. Together with previous measurements of electrical coupling between fiber cells and epithelial cells, these data indicate the presence of a low-resistance pathway connecting these cell types that is not mediated by classical gap junctions.

Animals↗
PubMed1993

Commitment to a world without cancer.

The author is a layperson, health educator, and political oncologist who is, in addition to her work at the cancer center at UCLA, a long-time volunteer with the American Cancer Society. She has served the National Cancer Institute as a member of the National Cancer Advisory Board and is currently a member of its Board of Scientific Counselors, Division of Cancer Control. In these various roles she was part of the lay leadership that influenced and cooperated with the Nixon administration in its efforts to pass the National Cancer Act of 1971. She has participated continually in the implementation of the National Cancer Program and Act since 1971. This essay reviews the history of our nation's support of cancer research, commencing with the founding of the American Cancer Society. It considers the factors that led to the passage of the National Cancer Act in 1971. It then comments on the interaction between universities, the National Cancer Institute, and the Cancer Act, which has produced the "cancer business" that has come of age since the Cancer Act was passed. This commentary does not review the advances made in research and clinical practice as a result of the passage of the National Cancer Act of 1971. Others, better qualified, will do that in this journal and in other publications as well. These views are concerned with the process, the systems, and ancillary activities that have developed as a consequence of the national will to conquer cancer. They are meant to highlight several portions of the whole. The "seeds" of cancer consciousness sown early by the American Cancer Society and those so firmly planted in research and in the creation of a national network of researchers, patient care institutions, and information systems by the National Cancer Institute and the National Cancer Program Plan and Act of 1971 have reaped a harvest of independent programs and even businesses that have given substance to the hopes of those seeking to achieve a world without cancer.

American Cancer Society↗
PubMed1992

Vocational rehabilitation of cancer patients.

Indeed, cancer patients do face job discrimination. Empirical studies have shown evidences of personnel selection bias and many other work-related problems. Laws and legislation are good tools but are not the answers to most of the problems. A competent multidisciplinary rehabilitation team, a well-educated general public and employers, together with empowered cancer patients can do more towards eliminating destructive road blocks to the employment of the employable. This takes time and initially may be costly for all concerned. However, evidence has shown that the cost of closed cancer rehabilitation cases is the lowest per case for all occupational disabilities including tuberculosis, diabetes, mental disorders, heart disease, and orthopedic problems. In short, we dare not forget the simple truth put forth by Harold Dodds that "No, work is not an ethical duty imposed on us from without by a misguided and outmoded Puritan morality; it is a manifestation of man's deepest desire that the days of his life shall have significance." Cancer patients living with cancer desire significance to their days to the same degree that those of us who are healthy and well desire and need it.

Employment↗
PubMed1991

Patient issues in breast reconstruction.

Breast reconstruction is not a new idea. Techniques have been developing since the late 1800s. The state of the art is such that the knowledge of its availability and success has significant effect on the willingness of women to seek earlier diagnosis and treatment. However, reconstruction is not for everyone. This paper examines the issues about knowledge, attitudes, and practices that either result in electing for or against reconstruction. Some issues involved are financial, others have to do with cosmetic appearance, and still others involve the medical and psychological affects. Identifying and understanding the issues from the point of view of the patient is important in providing support for the patient with breast cancer.

Breast Neoplasms↗
PubMed1990

Dermal eccrine cylindroma (turban tumour).

Dermal eccrine cylindroma, or turban tumour, is a rare benign tumour of the eccrine sweat glands. Despite its histologically benign behaviour, the disease process is distressing for the patients. We present our experience of this condition, with a review of the literature, and recommend a treatment protocol for the disease.

Adult↗
PubMed1990

Perceptions of the autopsy: views from the lay public and program proposals.

The autopsy has historically served as a critical research and teaching tool in medicine as well as a means to ensure control over the quality of health care. In recent years, however, the autopsy has lost favor among the public and fallen into disuse within the medical community. This paper offers some insights into the reasons behind the decline of the autopsy as viewed by the lay public. Programs to help revitalize use of the autopsy are suggested.

Autopsy↗
PubMed1990

Ultrastructural, biochemical, and immunologic evidence of receptor-mediated endocytosis in the crystalline lens.

The lens epithelium is essentially the basal layer of the crystalline lens of the eye, an uncommon stratified epithelium. Ions and metabolites present in the aqueous humor gain access to the lens epithelium by diffusion through the lens capsule (the basement membrane of the lens epithelium). Then, it is presumed, the underlying lens fiber cells obtain necessary ions, metabolites, and nutrients through gap junctions conjoining the apical surfaces of the lens epithelial cells from the basal layer with the apical surfaces of elongating fiber cells from upper strata. In this report, correlative morphologic, biochemical, and immunochemical evidence is presented that both lens epithelial and fiber cells use endocytotic and/or transcytotic processes rather than being solely dependent on gap junctions for metabolic cooperation. Freeze-fracture analysis of the apicoapical interface between lens epithelial and elongating fiber cells (epithelial-fiber cell interface [EFI]) revealed protrusions and pits of two distinct sizes (average diameters, 46 and 126 nm). Gap junctions with tight particle packing were only rarely observed at the EFI. Gap junctions with loose particle packing were never observed at the EFI. "Orthogonal arrays" of intramembrane particles (OAPs) were not uncommon at the EFI. Thin-sections taken perpendicular to the EFI confirmed the existence of micropinocytotic and clathrin-coated vesicles in both lens epithelial and elongating fiber cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of separate preparations of lens epithelial and fiber cells, specifically enriched for clathrin-coated vesicles, showed a 180-kD protein. Western blot analysis of this protein revealed selective cross-reactivity with polyclonal anticlathrin antibodies. These results strongly suggest that transcytotic processes provide a primary route for the entry and egress of macromolecules in the lens.

Animals↗