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J Scholes

Publications and source records attributed to J Scholes.

17 recordsLinked to original sources

Diversity amongst the microglia in growing and regenerating fish CNS: immunohistochemical characterization using FL.1, an anti-macrophage monoclonal antibody.

We have immunohistochemically characterized the forms and distribution of microglia--the macrophages of the CNS--in fish, using a new monoclonal antibody (mAb), FL.1. This mAb specifically reacts with resident macrophages throughout the body in Oreochromine fish, including Kuppfer cells, gut-associated myeloid cells, and peritoneal macrophages, as well as with microglia, but circulating monocytes are not labelled with FL.1. The FL.1-epitope, which is lost following treatment with reducing agents, has an extracellular location and is associated with three integral membrane glycoprotein variants. FL.1-staining shows that microglia are extremely abundant throughout the fish CNS. For example, they comprise a third of the glia in the optic nerve, and 30% of all cells, including neurons, in the spinal cord, i.e., fish have about tenfold more microglia than mammals. Two forms of FL.1-positive microglia are predominant in fish, one resembling their mammalian counterparts, but less ramified, and the other comprising smaller rounded cells with very little cytoplasm, which are most numerous in the ependymal region of the optic tectum. Apart from the conventional microglia, the optic nerves also contain large lipid-laden macrophages which comprise a third form of FL.1-positive cell in the CNS. Fish optic nerves contain astrocytes of a distinct type which form reticular networks, but lack connections to capillaries (Maggs and Scholes, J. Neurosci. 1990;10:1600-1614). The co-distribution of foamy macrophages may have a metabolic role that is performed by ordinary astrocytes elsewhere in the CNS. An antiserum against the beta 2 subunit of the human leukocyte integrins (Kishimoto et al., Cell 1987a; 50:193-202) was found selectively to recognize the foamy macrophages in Oreochromis. Following lesion to the optic nerve, FL.1-labelling shows that microglia proliferate throughout the visual pathway. In the optic tectum, the additional FL.1-positive cells are concentrated in the vicinity of degenerating retinal axons and their terminals. Most of the microglia in the injured optic nerve have amoeboid morphologies, and the foamy macrophages become depleted.

Animals

Epididymal metastasis from prostatic adenocarcinoma mimicking adenomatoid tumor.

A case of epididymal metastasis from prostatic carcinoma is presented. The initial histologic findings were suggestive of adenomatoid tumor, but a diagnosis of metastatic adenocarcinoma of prostatic origin has been established by prostatic acid phosphatase and prostate-specific antigen immunoperoxidase staining.

Acid Phosphatase

Reticular astrocytes in the fish optic nerve: macroglia with epithelial characteristics form an axially repeated lacework pattern, to which nodes of Ranvier are apposed.

Astroglia in lower vertebrate optic nerves are unusual: as shown recently (Giordano et al., 1989; Rungger-Brändle et al., 1989), they express abundant Type II cytokeratin, not glial fibrillary acidic protein (GFAP), the cytoskeletal marker for astrocytes elsewhere. To determine the implications for the glial cells of these epithelial-type cytoskeletons, which are linked up by desmosomal junctions, we analyzed the tissue patterning of fish optic nerve astroglia, which we term reticular astrocytes on account of their uniquely specialized arrangement. The processes of the reticular astrocytes fasciculate extensively with one another in a pattern stabilized by the desmosomes, forming a network laid out in thin planar sheets, or partitions. These are arranged transversely, that is at right angles to the optic fibers and are repeated at regular intervals of about 15 microns longitudinally throughout the optic nerve. They merge periodically forming a 3-dimensional framework whose pattern we speculate provides a flexible tissue skeleton for the optic nerve, capable of accommodating eye movements. Virtually all fibers in mature regions of the optic nerve are myelinated, and we show that nodes of Ranvier mostly occur in register with the partitions, displaying perinodal astrocytic associations resembling those found at CNS nodes in mammals. This clustering may account for the unexpectedly high observed incidence of neighbor pairs of nodes. Among other peculiarities associated with the reticular astrocytic network, one is that up to 20% of all cells comprise foamy macrophages not found elsewhere in the CNS.

Animals

Effects of calcium and bile acid feeding on colon tumors in the rat.

The hypothesis that dietary calcium alters the incidence of colorectal neoplasms was examined in an established model of carcinogenesis. Male Fischer 344 rats (28 days old) were quarantined for 2 weeks. All animals were fed the basal diet (AIN-76) supplemented with cholic acid (0.2%) and/or calcium (1.6%, corresponding to a 3-fold increase above that of the basal diet). N-Methyl-N-nitrosourea (MNU) (2 mg/dose) or saline (control) was given intrarectally to all animals on days 1 and 4 of the experiment. Groups 1-8 were fed the experimental diets concurrently with the first dose of MNU, while groups 9 and 10 were fed the diets 2 weeks prior to MNU (or saline). All animals were sacrificed after 28 weeks. No tumors were observed in the groups given saline (groups 1, 3, 5, 7, and 9). In groups receiving MNU, the addition of cholic acid to the diet (group 4) caused a significant increase in tumors (80% versus 55%), tumors/animal ratio (2.24 versus 0.75), and tumors/tumor-bearing animal ratio (2.80 versus 1.36), group 4 versus group 2, respectively. Increased dietary calcium did not inhibit tumor formation; 68% of animals in groups 6 and 10 had tumors. The combination of dietary cholic acid and calcium (group 8) gave a tumor incidence similar to cholic acid (group 4) alone (72% versus 80%, 2.00 versus 2.24 tumors/animal; 2.77 versus 2.80 tumors/tumor-bearing animal). Most tumors were adenomatous polyps but carcinomas in situ and invasive carcinomas were also present; dietary calcium reduced the number of invasive carcinomas (group 6 versus group 2, P less than 0.04).

Adenocarcinoma

Massive thymic hyperplasia in an adolescent.

Massive thymic hyperplasia (weight, greater than 100 gm) is a rare lesion in adolescents, and most of the anterior mediastinal masses are true neoplasms. We present a case of massive thymic hyperplasia, in which a 680-gm thymus was resected from a 15-year-old boy. We also present the computed tomographic scan appearance of this lesion, which differed from that previously described, and correlate the histological and radiological findings.

Adolescent

Recurrent IgA nephropathy in living-related donor transplantation: recurrence or transmission of familial disease?

We describe a patient who developed terminal renal failure of two HLA-identical renal allografts due to crescentic IgA nephropathy. The first graft contained IgA deposits at the time of donation, suggesting that transmission of IgA deposits may have contributed to the nephritis of the first allograft. The second graft was free of IgA deposits at the time of donation, but the recipient developed a similar, rapidly progressive nephritis. This case points up the malignant potential of IgA nephropathy and the complex nature of transplant planning for patients with end-stage renal disease (ESRD) secondary to IgA nephropathy. Living-related donor (LRD) transplants seem to be associated with a higher rate of recurrence than cadaveric grafts. This higher rate may partly reflect the inadvertent transmission of subclinical IgA deposits from donor to recipient and a genetic susceptibility of certain HLA types (specifically B35 and DR4) to recurrent disease. Cadaveric transplants may be preferable in the setting of high-risk HLA types or familial patterns of IgA nephropathy.

Adult

An unusual presentation of colon cancer.

A rare case of asymptomatic cancer of the ascending colon presenting as a subcutaneous groin mass is reported. At the time of right hemicolectomy with resection of the groin mass there was no sign of incontinuity spread or lymph blockage. Sequential determination of carcinoembryonic antigen levels (CEA) in serum reflected the reduction in tumor mass after surgery as well as subsequent recurrences of disease in the groin and in the lung after 2 years. Immunoperoxidase staining of the primary tumor and the metastases showed strong positivity for CEA confirming the origin of the serum CEA. There have been no signs of liver involvement. The route of spread of this unusual metastasis is not known.

Adenocarcinoma

Glial domains and nerve fiber patterns in the fish retinotectal pathway.

Optic nerve fibers run parallel from the retina as far as the optic tract in fish, then suddenly criss-cross into a new pattern matching the tectal map. This change coincides with a unique demarcation between two astroglial territories in the retinotectal pathway, located where the optic chiasm occurs in other vertebrates, which we defined using antibodies directed against intermediate filaments (IF). We found that astroglia in optic nerve territory express an Mr 56,000 IF polypeptide, band 3, which we identify as the fish equivalent of vimentin in mammals. These astrocytic cells lack glial fibrillary acidic protein (GFAP; cf. Dahl and Bignami, 1973). Conversely, glia in brain territory, that is, in the optic tract and elsewhere in the CNS, lack the fish vimentin, but express GFAP. By electron microscopy, we obtained evidence that new retinal axons extend swiftly through the growing optic nerve, where they are tightly shepherded into a narrow track by newly differentiating glial cells, positive for the fish vimentin. In the GFAP-positive glial territory of the optic tract, by contrast, growing axons are slowed down and probably branch. We suggest that this allows them to fasciculate accurately with older fibers and thereby propagate a tectotopic pattern established by pioneer axons in the embryo.

Animals

Amyloidosis in chronic heroin addicts with the nephrotic syndrome.

Four chronic heroin addicts had renal amyloidosis and the nephrotic syndrome. Amyloidosis had the secondary type of tissue distribution and developed after many years of addiction. That chronic immunologic stimulation by one or more exogenous antigens or multiple acute inflammatory episodes were important factors in the pathogenesis of amyloidosis in these patients is postulated. Amyloidosis, although uncommon, must be considered among the different types of renal involvement that are known to occur in drug addicts, especially those with the nephrotic syndrome, and amyloid should be specifically searched for in their renal biopsies.

Adult

An improved procedure for purifying RNA tumor viruses from malignant tissue.

A convenient method for purifying RNA tumor viruses is described. Viruses banded in isopycnic gradients are contaminated with membranes that can be removed by velocity sedimentation in glycerol gradients. On sodium dodecyl sulfate (SDS) gel electrophoresis, the particles purified by these procedures from mouse mammary tumor tissue show protein profiles typical of those observed with virus purified from milk.

Animals

The design of the optic nerve in fish.

Fish have large eyes, with short optic nerves that are continually flexed by compensatory eye movements during swimming. Here, I review the tissue construction of the fish optic nerve, to see how the glia and axons are adapted to withstand these mechanical stresses, which are not normally encountered by CNS tissue within the skull. As in other lower vertebrates, the optic nerve astrocytes are highly unusual: their intermediate filaments are composed of cytokeratins (Giordano et al., 1989), not GFAP. Their processes are linked together by desmosomes, forming thin transverse lace-like partitions, placed at quasi-regular intervals longitudinally (Maggs & Scholes, 1990). This accordion-like arrangement is interpreted as providing a flexible tissue-skeleton for the optic nerve. A new observation is that the optic axons run in coherent parallel waves. This pattern, which is complementary to that of the astroglia, reversibly accommodates limited axial stretches. The waves are equivalent to those underlying the optical banding of Fontana (1781) in peripheral nerves, but wavelength (30 microns) and amplitude (5 microns) are about an order of magnitude less, reflecting the much smaller average size of the optic axons. The pattern also occurs in mammals, and may be restricted to the visual pathway: if present elsewhere in the CNS, nerve-fiber waves are inconspicuous at best. In fish, the astroglial partitions occur in register with the waves, suggesting that steric interactions between developing axons and glia may help to establish, or stabilize, the regular longitudinal spacing. This may have functional as well as mechanical implications, since the astrocytes form perinodal associations and their pattern is one which strongly clusters the nodes of Ranvier.

Animals