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Biomedical subjects

R M Williams

Publications and source records attributed to R M Williams.

At least 163 records · Page 9Linked to original sources

Chronic experimental allergic encephalomyelitis induced in rabbits with bovine white matter proteolipid apoprotein.

A chronic, progressive form of experimental allergic encephalomyelitis was produced by immunization of rabbits with bovine brain white matter proteolipid apoprotein. Clinical signs appeared 4 to 13 months after sensitization, and were characterized by ataxia and limb paresis which progressed to flaccid paralysis and incontinence. Light and electron microscopic observations showed both acute and chronic nonsuppurative myelitis or encephalomyelitis accompanied by primary demyelination. Myelin damage was most evident in the spinal cord but was also present in the optic nerve and brain. The neuropathology was consistent with lesions of chronic experimental allergic encephalomyelitis produced by central nervous system tissue, and resembled lesions of multiple sclerosis as well. These observations suggest that protein may be involved in the pathophysiology of demyelinating diseases. A mechanism for the chronic course of the disease is discussed.

Animals↗

Spontaneous autoimmune diabetes mellitus in the BB rat.

The BioBreeding Rat is a recently discovered model of spontaneous diabetes mellitus. Studies to date have revealed the following characteristics of the syndrome: genetic predisposition, equal frequency and severity among males and females, absence of obesity, life sustaining requirement for insulin therapy, lymphocytic insulitis with destruction of pancreatic beta-cells, lymphocytic thyroiditis and the presence of autoantibodies to smooth muscle, thyroid colloid and other cellular antigens. Animals raised in a germ-free environment evidence diabetes with equal frequency and severity. Support for a cell-mediated autoimmune pathogenesis of the diabetic syndrome is derived from the following experiments: administration of antiserum to rat lymphocytes prevents diabetes in susceptible animals and normalizes plasma glucose levels in 36% of diabetic rats; neonatal thymectomy almost completely prevents the occurrence of diabetes. Although the BB rat may not be an appropriate model for studying the vascular complications of diabetes, peripheral nerve functional and ultrastructural defects have been reported and renal glomerular immuneglobulin deposits have been observed in long-term diabetic animals.

Animals↗

La Crosse virus infection and disease in western North Carolina.

Active surveillance for La Crosse infection from 1977 to 1979 revealed 12 laboratory documented cases in children from the Cherokee reservation and nearby areas of western North Carolina. The annual rate of hospitalization with La Crosse virus was isolated from two of 34 pools of male and one of 34 pools of female Aedes triseriatus mosquitoes reared from larvae collected around the residences of reservation children who had been hospitalized with encephalitis. The occurrence of the recent cases, the history of cases in 1964 and 1965, and the demonstration of antibodies to La Crosse virus in sera from second grade children collected in 1968 (2%), in 1978 (4.5%), and in high school students in 1979 (11.3%), indicate that La Crosse has persisted in the Cherokee area for at least 15 years. La Crosse infection is infrequently reported from the southeast, but this may reflect inactive surveillance. More frequent testing would reveal whether La Crosse is a significant health problem in other areas of the southeast.

Aedes↗

Histiocytic sarcoma of the scrotum in a rat.

A 225-day-old male fourth generation rat from a developing recombinant inbred line (Lewis x Brown Norway) had a bilaterally symmetrical enlargement of the scrotum. Palpation indicated the presence of a firm lobulated mass extending from the tip of the scrotum to the abdominal wall. Bilateral nodular masses totally occupied the scrotal sacs, surrounded the testicles, and extended along the spermatic cords into the abdominal cavity. Tumor nodules also were present in the intestinal mesentery, omentum, mesenteric lymph nodes, pancreas, and lung. Histologically, the neoplasm presented a spectrum of characteristics varying from that of a granuloma with giant cells to a diffuse proliferation of spindle-shaped mononuclear cells.

Animals↗

An ultrastructural study of a jejunal inflammatory fibroid polyp.

Ultrastructural appearances of a small intestinal inflammatory fibroid polyp are reported. There is a vascular scaffolding, with interstices which contain regular and fibrous long-spacing type collagen, condensed lamellar basement membrane fibroblasts, basophils, some eosinophils and histiocytes. In addition other cells less easily characterized but believed to be of an endothelial and primitive mesenchymal cell nature are recognized. Possible origins of the polyp are considered.

Female↗

Homozygosity at the major histocompatibility complex is required for optimal immunogenicity of bone marrow cell allografts in irradiated rats.

Hemopoietic histocompatibility (Hh) Genes associated with the H-2 region control the antigenicity of hemopoietic cell grafts in the mouse. We have tested for similar genes in rats. Wistar Furth (WF, RTlu) or Lewis (LEW RTl1) bone marrow cell grafts did not proliferate in spleens of lethally irradiated (WFxLEW) F1 hybrid rats as assessed by measuring the incorporation of 5-iodo-2' deoxyuridine - 125I (IUdR) into recipient spleens 5 days after transplantation. In contrast, (WFxLEW) F1 hybrid marrow cells grew well in both WF and LEW parental strain hosts. (WFxLEW) F1 or (WFxLEW) F1 hybrid rats were backcrossed to WF parental strain rats to produce progeny, either homozygous, or heterozygous for the MHC. The RTl type of 46 individual backcross progeny was determined using a 5 day mixed-lymphocyte reaction (MLR). Correlation between RTl type and growth of marrow grafts of individual backcross rats were determined by using each rat as a bone marrow donor for irradiated LEW hosts. Marrow grafts from rats heterozygous for RTl were accepted in all 25 cases, whereas, grafts from 19 to 21 homozygous donors were rejected by the LEW hosts. Thus, homozygosity, for Hh determinants in or near the RTl region appears to be necessary for optimal immunogenicity of bone marrow allografts.

Animals↗

EAE in rat bone marrow chimeras: analysis of the cellular mechanism of BN resistance.

Unlike Lewis strain, BN rats do not develop EAE when given 10 microgram GPBP + CFA. Their resistance is mediated via the MHC-linked gene Ir-EAE-. The cellular mechanism of BN resistance can be probed using bone marrow chimeras between susceptible LBNF1 strain and BN. F1 leads to BN chimeras can develop EAE when actively sensitized with GPBP + CFA, but are markedly more resistant than F1 leads to F1. By contrast, F1 leads to BN chimeras are highly susceptible to passively transferred EAE from an F1 donor. F1 rats reconstituted with BN bone marrow, i.e., BN leads to F1 chimeras, are completely resistant to EAE induced by active sensitization, but they too are susceptible to passively transferred EAE. We argue that Ir-EAE- blocks the development of T cells reactive to self myelin, and that this occurs at the level of macrophage presentation of antigen to the T cell. Suppressor mechanisms do not appear to play a major role.

Animals↗

In vivo demyelination by antimyelin antibodies.

Central nervous system (CNS) myelin-specific antiserum was capable of initiating primary demyelination within 24 h following injection into the dorsal column of guinea pig spinal cord. Control serum injected in the same manner did not produce demyelination. The demyelinating lesions occurred as focal linear plaques of completely denuded intact axons surrounded by partially demyelinated and myelinated normal axons. Antiserum-mediated demyelination was followed by mononuclear cell infiltration 7-10 days later. Ultrastructural examination revealed vesiculation of myelin followed by cleavage of myelin lamellae at the intraperiod line. Remyelination began between 7 and 10 days following injection and correlated well with clinical evidence of recovery. The results of this study point to the importance of circulating antimyelin antibodies in the pathogenesis of demyelinating encephalitis. The model represents an in vivo approach to the study of the pathogenesis of immune-mediated myelinolysis in demyelinating disorders like multiple sclerosis (MS), subacute sclerosing panencephalitis (SSPE), and canine distemper encephalitis (CDE).

Animals↗

A study of the benefits and acceptability of ambulation in spontaneous labour.

A prospective study of 300 consecutive deliveries has been made to assess the benefits and acceptability of ambulation during spontaneous labour. Ambulation during the first stage occurred in 48 patients with 55 non-ambulant patients acting as controls. No difference in the length of first or second stage, incidence of fetal distress or mode of delivery was observed. In spite of the lack of apparent advantage to the fetal condition, ambulation was acceptable to both patients and nursing staff and should not be discouraged.

Adolescent↗

Congenital convex pes valgus: results of an early comprehensive release and a review of congenital vertical talus at Richmond Crippled Children's Hospital and the University of Alabama in Birmingham.

Nineteen patients with 28 feet with congenital vertical talus were reviewed. The male to female ratio was equal, and associated congenital abnormalities were found in 15 of the 19 patients. No genetic pattern was established. Fifteen of the 16 surgically corrected feet were reevaluated, with an average follow-up of 60 months. Ten of the 15 feet were found to be in the good to excellent category, and five were rated poor. Twelve of 12 feet treated by cast correction were poor. Poor prognostic signs include late age of surgical correction, associated arthrogryposis and cerebral palsy, and an increased space between the calcaneus and cuboid. Best results occurred in those patients who had early surgical correction, after 4 to 6 months of serial casting, using magnification. Surgical technique which yielded the best results involved total release of the talus from the posterior, medial, and lateral approach, with reduction of the talocalcaneal as well as the talonavicular joints with multiple pin fixation. Lengthening of the Achilles tendon, extensor tendons, and peroneal tendons and transfer of the anterior tibialis to the navicular are recommended. Navicular excision was not found to be necessary. Surgical results in those patients over 3 1/2 years of age were found to be poor, and these individuals were considered for salvage procedures using a subtalar extra articular arthrodesis, excision of the navicular, or triple arthrodesis, depending on age.

Casts, Surgical↗

Linkage of severity of experimental allergic encephalomyelitis to the rat major histocompatibility locus.

The incidence of EAE is determined by Ir-EAE, a gene linked to the rat MHC. EAE severity can be assessed by quantitative clinical and pathologic measures. Using these measures, one can say that disease severity in LBNF1 is approximately one-tenth that in Lewis. Analysis of LBNF2, LBC, BNBC, and parental Lewis strain reveals that severity is primarily a function of dose of Lewis MHC alleles. Non-MHC genes have a small but discernable effect.

Animals↗