The blood/brain barrier prevents the passive diffusion of proteins and metabolites from cerebral blood vessels into tissue spaces around neuronal and glial cells. To provide nutrients for these cells, transport mechanisms must exist and indeed have been demonstrated for metabolites. We now show that monoclonal antibodies against rat and human transferrin receptors label blood capillaries in the brain but not in other tissues. In the rat this labelling occurs after injection of antibody into the blood, thus the receptors seem to be accessible at the endothelial surface. It is possible that transferrin receptors are expressed on these cells to allow transport of transferrin (and thus iron) into brain tissues.

Transferrin receptor on endothelium of brain capillaries

Relaxation of the smooth muscle of the corpora cavernosa of the penis is necessary for penile erection. To determine the relation of impaired relaxation to impotence in diabetic patients, we performed an in vitro examination of corpus cavernosum tissue obtained at the time of implantation of a penile prosthesis in 21 diabetic and 42 nondiabetic men with impotence. Contraction was induced in isolated strips of corporal smooth muscle by norepinephrine; then relaxation was assessed with electrical stimulation of autonomie nerves and with the administration of three agents: acetylcholine, which is known to be mediated by endothelium-derived relaxing factor; papaverine; and sodium nitroprusside. The latter two act directly on smooth muscle (i.e., they are endothelium-independent). Autonomically mediated relaxation with electrical stimulation was less pronounced in the smooth muscle from diabetic men (n = 18) than in the smooth muscle from nondiabetic men (n = 24; P = 0.001). The degree of impairment i...

Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence.

Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell–mediated therapies.

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Identification of a novel population of muscle stem cells in mice potential for muscle regeneration

Toxicological profile for arsenic

Abundant evidence has shown that tumor growth and metastasis are dependent upon tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within the tumor. Until TA occurs, tumors grow no larger than 2–4 mm in diameter. Also, TA is necessary at the beginning and at the end of the metastatic cascade of events. Thus, it seems reasonable that increasing intratumoral microvascular density (iMVD) might correlate with greater tumor aggressiveness, such as a higher frequency of metastases and/or decreased survival. Indeed, in 1991 my colleagues and I reported a statistically significant association between greater incidence of metastases in patients with breast carcinoma and increasing iMVD. Microvessel density was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density (neovascular “hot spot”). This was done after endothelial cells, lining the microvessels, had been highlighted with anti-factor VIII-related antigen/von Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti-CD31, have shown that the association of greater tumor aggressiveness with increasing iMVD exists not only in breast carcinoma, but also in other solid tumors. This article reviews the methods of highlighting intratumoral vessels and describes the techniques for counting these vessels for assessing iMVD.

Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors.

Using an immunoperoxidase method, factor VIII-related antigen was localized in vascular endothelial cells. This method provides a marker for endothelial cells at the tissue level and may be used to confirm the vascular nature of a variety of hyperplastic and neoplastic lesions of skin, soft tissues, and other locations.

Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method.

Immunohistochemical staining for factor VIII-related antigen (FVIII-RAG) with the peroxidase-antiperoxidase technic was used as a marker for endothelial cells in a variety of nevoid, reactive, and malignant vascular cutaneous proliferations. The endothelial cells of small normal cutaneous vessels gave the strongest reaction. The cells of hemangioma and angiokeratoma generally were stained, but with less consistency. In lymphangioma, pyogenic granuloma, and pigmented purpuric dermatosis, positivity was either patchy or of lesser intensity. Numerous strongly positive endothelial cells lining well-formed blood vessels were present in lesions of Kaposi's sarcoma, but the proliferating spindle cells forming "vascular slits" were uniformly negative. The cells of angiosarcoma were essentially negative, except for isolated elements in the better-differentiated areas. Plasma was also strongly positive; this may aid in distinguishing vascular from lymphatic channels. Anti-FVIII-RAG immunoperoxidase staining is a helpful aid in evaluating cutaneous vascular proliferations.

Immunohistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature.

In 20 000 consecutive skin biopsies we found 35 cutaneous osteomas Ten were primary while 25 appeared secondary to another abnormality Associated with ossification were Malherbe's calcifying epithelioma, basal cell carcinoma, nevus cell nevus, appendageal and fibrous proliferations, inflammation, trauma, and calcification Cutaneous bone formation appears to be either a hamartomatous or metaplastic phenomenon

Cutaneous osteomas: a clinical and histopathologic review.

An elevated sister chromatid exchange (SCE) rate was found in the lymphocytes of six patients treated with arsenic. All had stigmata of arsenic use as well as biopsy-proven skin cancers. The arsenic exposed patients had a mean of 14.00 SCE/mitosis while 44 normal controls had a mean of 5.8 SCE/mitosis. Chromosome breakage analysis revealed no difference between the two groups. SCE rate has been shown to be elevated in a variety of systems where cell cultures or experimental animals were exposed to known mutagens and carcinogens. We suggest that the relationship carcinogen exposure-elevated SCE rate-cancer may also be valid in humans treated with arsenic.

Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic

Histiocytosis X, multicentric reticulohistiocytosis, juvenile xanthogranuloma, the "fibrous" type of dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma are all characterized by dermal and/or subcutaneous infiltrates composed at least partially of cells having morphologic features suggestive of histiocytes. Paraffin-embedded tissues representing these conditions were stained for lysozyme (muramidase) with a peroxidase-antiperoxidase technic. The cells of juvenile xanthogranuloma were rich in lysozyme. Some of the cells of histiocytosis X showed a positive pattern, and the cells of the other three conditions were essentially negative. This study confirmed the histiocytic nature of juvenile xanthogranuloma and multicentric reticulohistiocytosis, supported the interpretation that there is a histiocytic component in the lesions of histiocytosis X, and cast some doubt on the alleged histiocytic nature of "fibrous" dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma.

Walter H. C. Burgdorf

Papers

Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method.

Immunohistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature.

Cutaneous osteomas: a clinical and histopathologic review.

Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic

Immunohistochemical identification of lysozyme in cutaneous lesions of alleged histiocytic nature.