Scaling Laws for Branching Vessels of Human Cerebral Cortex

Objective: Vascular architecture, particularly of cerebral microvessels, has profound implications for both health and disease in a variety of areas, such as neuroimaging, angiogenesis and development, Alzheimer's disease, and vascular tumors. We analyzed the architecture of tree‐like vessels of the human cerebral cortex. Methods: Digital three‐dimensional images of the microvascular network were obtained from thick sections of India ink–injected human brain by confocal laser microscopy covering a large zone of secondary cortex. A novel segmentation method was used to extract the skeleton and measure the diameter at every vertex. Results: In this paper, we focus on the topology of the cortical tree‐like vessels. Using stem‐crown decomposition, power‐scaling laws were shown to govern the relationships between integrated parameters, such as the distal cumulative length, volume, or normalized flow. This led us toward an experimental confirmation of the allometric equation between mass and metabolic rate. Inversely, the power‐law model did not match the relationships between local parameters, such as diameter, and integrated ones. As a consequence, Murray's law did not appropriately model the architecture of cerebrovascular bifurcations. Conclusions: This study provides a unique, large database and mathematical characterization that may prove valuable for modeling the cerebral.     

Hodgkin''s disease presenting with the histological features of Castleman''s disease

Three cases are reported in which an initial diagnosis of the plasma cell variant of Castleman's disease was made, but in which a second lymph node biopsy within a year showed evidence of Hodgkin's disease. Review of the initial biopsy indicated that atypical CD15 and CD30 positive cells were present in the initial biopsy. This illustrates the difficulty in making the diagnosis of Castleman's disease and suggests that the lymphoid reaction to the presence of Hodgkin's disease may result in similar histological appearances. The need for re-evaluation of the diagnosis of Castleman's disease in the face of persistent or recurrent disease is stressed.     

LOCALLY RECURRENT PROSTATE TUMORS FOLLOWING EITHER RADIATION THERAPY OR RADICAL PROSTATECTOMY HAVE CHANGES IN KI-67 LABELING INDEX, P53 AND BCL-2 IMMUNOREACTIVITY

Purpose

We compare the biological phenotype of recurrent prostatic tumors after definitive local therapy (radiation or radical prostatectomy) with that of the same tumors before treatment.

Materials and Methods

Cellular proliferation (Ki-67 labeling index), p53 nuclear reactivity and bcl-2 immunoreactivity were determined in pretreatment and posttreatment tumor specimens from 13 patients with local tumor recurrence following radiation, and in 18 patients with local tumor recurrence following radical prostatectomy.

Results

Mean Ki-67 labeling index increased approximately 2-fold in locally recurrent tumors after radiation (10.5 versus 5.6%, p = 0.0008) or surgery (6.0 versus 3.2%, p = 0.0025) when compared with pretreatment tumors. We noted p53 nuclear reactivity in a significantly higher proportion of recurrences than in pretreatment tumors following radiation (54 versus 8%, p = 0.032) and surgery (39 versus 5%, p = 0.022). Although bcl-2 immunoreactivity was also seen in a higher proportion of recurrent tumors, this difference did not reach statistical significance for either radiation or surgery.

Conclusions

Recurrent tumors following either radiation or surgery differ significantly from the corresponding pretreatment tumors with respect to cellular proliferation and p53 nuclear reactivity.     

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Proteins secreted across the cell wall of mycobacteria are important antigens recognized early in the host response to mycobacterial infection. MPT64 is a 23-kD secreted protein restricted to members of the Mycobacterium tuberculosis complex which elicits T cell responses and cutaneous DTH reactions in Myco. tuberculosis-infected animals. Patients with tuberculosis and their tuberculin-positive contacts respond to the protein, but recipients of bacille Calmette–Guérin (BCG) vaccine strains lacking the mpt64 gene do not. In the present study, we describe the development of a unique recombinant mycobacterial vector which secretes the encoded Myco. tuberculosis protein MPT64 at high levels into the culture filtrate, from which the protein is isolated by a single-step affinity chromatographic step. The purified protein was recognized by both polyclonal and monoclonal anti-MPT64 antibodies. The T cell reactivity of the protein was confirmed by its ability to stimulate human anti-rMPB64 T cell lines. The Myco. smegmatis recombinant MPT64 protein was superior to the Escherichia coli rMPB64 protein, which has identical amino acid sequence, in eliciting cutaneous DTH reactions in guinea pigs sensitized with Myco. tuberculosis. Animals sensitized with BCG strains lacking the mpb64 gene failed to respond to MPT64. Similarly, interferon-gamma (IFN-γ) responses in tuberculosis patients and their contacts were higher to the Myco. smegmatis form of the protein. The potential of this form of the Myco. tuberculosis MPT64 protein as a skin test reagent for tuberculosis is discussed.     

Immunolocalization of cytokines to mast cells in normal and allergic conjunctiva

Background Recently, the potential role of mast cells in allergic reactions has been extended by the discovery that these cells synthesize, store and secrete multifunctional cytokines. Seasonal allergic conjunctivitis is characterized as an immediate hypersensitivity reaction, in which allergen binds to specitic IgE on mast cells, leading to release of preformed and newly synthesized inflammatory mediators. Objective In this study we aimed to localize the cytokines IL-4, IL-5, IL-6, IL-8 and TNFα to conjunctival mast cells and lo examine the relationship between mast cell-associated ctokines and allergic conjunctivitis. Methods Immunobistochemistry was perfonned on serial sections of conjunctival biopsies from patients with seasonal allergic conjunctivitis, in and out of tbe hay fever season, as well as from non-allergic volunteers. Results IL-4, IL-5, IL-6 and TNFα were localized to mast cells in normal and allergic conjunctiva. IL-8 was localized to mast cells in two patients with seasonal allergic conjunctivitis, one during and the other outside the pollen season. Using the monoclonal antibody 3H4, which identifies the secreted form of IL-4, biopsies frotn patients with active seasonal allergic conjunctivitis contained a significantly bigher proportion of mast cells positive for IL-4. than those from out-of-season patients (P= < 0.016). There was no difference between the two groups in the number of mast cells immunostained by the antibody 4D9 which identifies the stored form of IL-4. Conclusions These results suggest that conjunctival mast cells can store a range of multifunctional cytokines and release IL-4 during active disease, which may give them an important role in upregulating allergic inflamtnation in the conjunctiva.     

Excess Hemolysis in Subjects with Severe Iron Deficiency Anemia Associated and Nonassociated with Hookworm Infection

An excess hemolysis was found in subjects with iron deficiency anemia associated with hookworm infection. Red cell survival, measured with Cr⁵¹ andDFP³² in the subjects before deworming, showed a marked disproportionbetween the decrease of the survival and the amount of daily intestinal bloodloss in most cases. Excess of hemolysis was still present after more than 90 percent of the parasites were removed. Red cell survival became normal aftercorrection of anemia through iron treatment. Excess of hemolysis was alsopresent in noninfected subjects with iron deficiency anemia due to othercauses.

The reduction in the survival of the erythrocytes from infected subjectstransfused into normal recipients shows that the hemolytic process is due toan intrinsic defect of the red cells. The low values of hemoglobinemia andthe presence of haptoglobins in the plasma indicate that hemoglobin has notbeen liberated in excess intravascularly. Finally, the fact that the red cellsfrom an infected patient taken after deworming survived normally in splenectomized recipients indicates that the spleen is probably the principal siteof the red cell destruction. The clinical and autopsy findings suggest thatsplenic function is not pathologically increased, but rather that this organ isacting physiologically at a more rapid rate, "culling" the abnormal circulatingred cells and thus leading to a decrease in red cell survival.

The studies presented here also indicate that the hookworm infection perse does not induce hemolysis.

Submitted on January 13, 1964 Accepted on April 24, 1964