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Biomedical subjects

R M Williams

Publications and source records attributed to R M Williams.

At least 145 records · Page 8Linked to original sources
PubMed1985

111Indium-labelled lymphocytes do not image or label the pancreas of the BB/W rat.

Autologous transfusions of 111indium-labelled peripheral blood lymphocytes reportedly image the pancreas of patients with Type 1 (insulin-dependent) diabetes at the time of onset. We attempted to apply this technique to the spontaneously diabetic BB/W rat. First, acutely diabetic BB/W rats, diabetes-prone BB/W rats, diabetes-resistant W-line BB/W rats, and Wistar Furth rats were given autologous transfusions of labelled peripheral blood lymphocytes. Radioactivity recovered from the pancreas was similar in all groups. No correlation was found between the intensity of imaging and the presence or intensity of insulitis. To decrease non-specific intravascular radioactivity, acutely diabetic, diabetes-prone, and W-line rats were perfused 48 h after autologous transfusion of labelled lymphocytes. Again, the intensity of recovered activity was similar in all groups, using both macroautoradiography and numerical counting techniques. A second set of experiments studied diabetes and insulitis induced by passive transfer of concanavalin A-treated splenic lymphocytes from acutely diabetic donors. Activated lymphocytes were labelled with 111Indium and given to groups of diabetes-prone and diabetes-resistant rats. There were no differences in pancreatic localization 72-96 h after injection. Groups of diabetes-prone and diabetes-resistant rats were also given concanavalin A-activated lymphocytes and then challenged 2-10 days later with autologous transfusions of labelled peripheral blood lymphocytes. Again, no differences in organ labelling or imaging were detected. We conclude that the autologous transfusions of 111indium-labelled lymphocytes do not label or image the pancreas of the BB/W rat.

Acute Disease↗
PubMed1985

Synthesis and antimicrobial evaluation of bicyclomycin analogues.

The synthesis and antimicrobial evaluation of novel bicyclomycin analogues are described. The series of analogues were prepared from the basic 8,10-diaza-2-oxabicyclo[4.2.2]decane-7,9-dione, 7,9-diaza-2-oxabicyclo[3.2.2]nonane-6,8-dione 8,10-diaza-5-methylene-2-oxabicyclo[4.2.2]decane-7,9-dione and 7,9-diaza-4-methylene-2-oxabicyclo[3.2.2]nonane-6,8-dione nuclei. For compounds where R1 = p-methoxybenzyl, deprotection of the lipophilic amides with ceric ammonium nitrate affords the corresponding lipophobic free amides. The basic bicyclic nucleus of bicyclomycin (8h, R1 = R2 = R3 = R4 = H) has been synthesized for the first time as well as increasingly more complex congeners bearing the C-6 OH, 5-methylene; C-1'-C-3' trihydroxyisobutyl group. In general, it has been found that the bicyclic nucleus of bicyclomycin is devoid of antimicrobial activity, the entire structure of bicyclomycin being generally obligate for activity. In one instance, the racemic analogue 10c (R1 = CH2Ph, R2 = OH, R3 = H) showed interesting antimicrobial activity against several Gram-positive organisms; the minimum inhibitory concentrations were of the same order of magnitude as bicyclomycin displays toward Gram-negative organisms. Totally synthetic (+/-)-bicyclomycin was half as active as the natural antibiotic. The design, synthesis, and antimicrobial activity (and/or lack thereof) of bicyclomycin and the analogues are discussed in the context of a proposed chemical mechanism of action.

Anti-Bacterial Agents↗
PubMed1985

Passive transfer of diabetes from BB/W to Wistar-Furth rats.

Autoimmune diabetes can be transferred to young, diabetes prone BB/W rats by injecting them intravenously with concanavalin A (Con A)-treated spleen cells from acute diabetic BB/W donors. This study describes the transfer of diabetes to the normal Wistar-Furth strain of rats using a similar procedure. For the successful transfer of diabetes it was necessary to immunosuppress recipient animals with a single intraperitoneal injection of cyclophosphamide 24-48 h before administering Con A-stimulated spleen cells from acute diabetic BB/W rats. Of 68 Wistar-Furth rats in immunosuppressed with a dose of 100-150 mg cyclophosphamide/kg body wt, 10 (15%) became diabetic. None of the control rats receiving either Con A-stimulated Wistar-Furth spleen cells (n = 28), freshly isolated BB/W spleen cells (n = 14), or fresh RPMI medium (n = 11) became diabetic. These data indicate that diabetes can be transferred from BB/W to Wistar-Furth rats. In addition, they support the hypothesis that cell-mediated immune processes are involved in the development of insulin-dependent diabetes and rule out any absolute requirement for BB-derived genes in the target pancreatic beta cells.

Animals↗
PubMed1984

Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses.

The BB rat develops a syndrome of autoimmune diabetes similar to Type I diabetes of man. It also has a severe T cell lymphopenia. As part of an ongoing breeding program to transfer the diabetogenic genes of the BB rat onto inbred rat strain backgrounds, diabetic animals were used in a backcross (BC)- intercross (IC)-backcross breeding scheme with Brown Norway (BN), Lewis (L), and Wistar-Furth (WF) inbred rats. We have used monoclonal antibodies to analyze both lymphopenia and major histocompatibility (MHC) antigens (the RT1 locus in the rat) in relation to the development of diabetes. To examine T cell subsets we used a panel of monoclonal antibodies, in particular W3/25 and OX19 , which discriminate the abnormal phenotype better than W3/13. In our breeding program, at least two independent genes or gene complexes are required for the expression of diabetes. One gene determines the lymphopenia, is inherited by simple autosomal recessive genetics and is not linked to the MHC. The second gene is linked to the MHC. Both genes are necessary, but neither gene is sufficient by itself for the development of diabetes.

Animals↗
PubMed1984

Immune response to the H-X antigen on P815-X2. I. Recombinant inbred strain analysis and lack of effect of castration.

In a preceding report, the detection of an H-2-linked immune response to the H-Xd antigen on the P815-X2 mastocytoma was demonstrated by the significantly increased survival of (C57BL/6 X DBA/2)F1 (B6D2F1) male hybrids (H-Xb) compared with female siblings (H-Xb/H-Xd) after injection with the histocompatible tumor (H-Xd). This interpretation was supported by the absence of this sex effect in reciprocal D2B6F1 hybrids (H-Xd and H-Xd/H-Xb). Additional findings presented in this paper support the conclusion that this sex effect is due to a true immunological response to H-Xd: (a) Reciprocal (DBA/2 X C57BL/6 H-2 mutant)F1 hybrids, as well as D2B6F1, failed to exhibit the sex effect: (b) the demonstration of the sex effect in (BALB/c X DBA/2)F1 and (BALB/c-H-2dm2 X DBA/2)F1 hybrids and in (C57BL/10 X DBA/2)F1 hybrids was consistent with the known H-X incompatibilities between the strains BALB/c and DBA/2 and C57BL/10 and DBA/2, respectively, previously demonstrated by skin grafting; and (c) the sex effect was not abrogated by castration of male B6D2F1 hybrids. Variability in the presence or absence of the sex effect was observed in various [recombinant inbred (RI) X DBA/2]F1 hybrids and may be attributed to the influence of a regulatory non-H-2 gene which is closely linked to the gene coding for mouse kidney-androgen-regulated protein (KAP) but androgen-independent, or to variability in inheritance of the H-Xb allele among the RI lines. It is proposed that the P815-X2 model may be utilized to type RI lines derived from a cross between C57BL/6 and DBA/2 for their H-X genotypes.

Animals↗
PubMed1984

Relationship between subjective self-report of cognitive dysfunction and objective information-processing performance in a group of hospitalized schizophrenic patients.

This study examines the relationships between subjective self-report of cognitive difficulties associated with schizophrenia and performance parameters of an objective choice reaction time task. The predicted relationships did not emerge and the results are discussed with regard to the methodological difficulties of measuring self-report and the features of the CRT task used. One positive finding was the significant relationship between chronicity of illness and the CRT measures.

Adolescent↗
PubMed1984

HLA antigens in Guillain-Barré syndrome.

We compared Guillain-Barré syndrome (GBS) cases reported from cities in the United States in 1976-1977 with spouse or associate controls to detect possible HLA associations. HLA-A11 was somewhat less common among 92 cases than among 100 controls (p = 0.04). The 38 patients and 42 controls vaccinated against A/NJ/76 differed slightly in overall distribution of B locus antigens (p = 0.06), but the individual HLA-B antigen associations were more easily explained by chance. The 54 unvaccinated cases showed no apparent relation to HLA type. These findings should encourage further immunogenetic study of etiologically related GBS cases.

Adolescent↗
PubMed1983

H-2-linked resistance to mastocytoma in male mice: immune response to a histocompatibility antigen on the X chromosome.

Male hybrids from a cross between female mice of strain C57BL/6Kh and males of strain DBA/2J lived longer after injection of P815 mastocytoma cells of DBA/2 origin than did their female siblings. Responses to the histocompatibility antigen on the X chromosome of the DBA/2 strain may be involved in resistance to the tumor. When the female parent was replaced with a C57BL/6Kh carrying one of several mutations in the H-2 region, this sex effect disappeared in some of the hybrid combinations. Thus, the H-2 complex appears to be involved in the regulation of the immune response to the X-linked histocompatibility antigen in this tumor model.

Animals↗
PubMed1983

Passive transfer of diabetes in the BB/W rat.

Severe diabetes with insulitis was produced in young diabetes-prone BB/W rats by passive transfer of concanavalin A-treated spleen cells from BB/W animals with acute diabetes. Spleen cells alone or in combination with lymph node cells were active in transferring disease.

Animals↗
PubMed1983

Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: immunological studies in rabbits.

A chronic experimental allergic encephalomyelitis (EAE) has been produced in rabbits sensitized with bovine white matter proteolipid apoprotein. Eleven of 12 animals developed clinical disease one to six months after immunization with a single dose of the apoprotein. The clinical course was characterized by posterior ataxia, flaccid paralysis progressing to spastic paralysis, and incontinence. Spontaneous relapses and remissions were observed in 3 rabbits. Histologically, acute and chronic encephalomyelitis accompanied by primary demyelination were observed. Serum antibody production, assayed by both an enzyme-linked immunosorbent assay and an electroblot procedure, did not correlate with either the clinical course or the histopathological findings. Delayed hypersensitivity to proteolipid apoprotein was observed in all rabbits prior to the onset of clinical signs. The data suggest that lymphocytes specifically sensitized to the proteolipid may be involved in the pathogenesis of the demyelination in chronic EAE.

Animals↗
PubMed1983

H-2 gene control of resistance to P815-X2 mastocytoma.

Some, but not all, mutations at H-2 loci can alter, in either direction, histocompatible tumor resistance in the model system of P815-X2 mastocytoma (DBA/2 origin) transplanted into DBA/2J or (C57BL/6 X DBA/2J)F1 mice. This hybrid effect has been shown previously to depend on the immune system. We have examined eight mutants at H-2Kb (bm1, bm4, bm6, bm7, bm8, bm10, bm11, and bm16, two at H-2Db (bm13 and bm14), and one I-Ab mutant (bm12). When one parent is an H-2b mutant (C57BL/6 mutant), the hybrid progeny (C57BL/6 mutant X DBA/2J)F1 may have increased (bm7 and bm8) or decreased (bm10, bm11, bm12, and bm16) survival times when compared to C57BL/6 X DBA/2J)F1 controls. Hybrids from bm1, bm4, bm6 (all H-2Kb), and bm13 and bm14 (both H-2Db) mutants showed no differences in survival. Several of the mutant molecules differ from those of the parental strain by only one or two amino acids. Apparently, these small changes in H-2 antigens are capable of altering resistance to a histocompatible tumor to produce an immune response gene-like effect. The availability of H-2 mutant strains and detailed data on the molecular nature of the gene products make the model presented in this report a particularly useful system to study.

Alleles↗
PubMed1983

Acute hemorrhagic obstructive uropathy as a complication of experimental autoimmune encephalomyelitis.

During studies related to immunoregulation in experimental allergic encephalomyelitis (EAE) in rats, acute hemorrhagic obstructive uropathy developed as an unexpected complication. The urinary retention was attributed to mucous plugs tightly impacted into the bladder neck. Although mucous plugs commonly are detected in the bladders of healthy adult rats, they could create a serious complication when impacted into the outflow tract as the result of malfunctioning sphincter actions by EAE-induced spinal cord injury.

Acute Disease↗
PubMed1982

Fractures of the hand associated with riding the mechanical bull.

Presented are the cases of four patients who sustained similar dominant hand injuries while riding a mechanical bull apparatus. The injuries included fractures of the second metacarpals as well as of the index finger phalanges. The mechanism of injury in each case occurred not from striking or catching the injured hand on the bull or by falling off the apparatus, but secondary to the extreme torque forces applied to the extremity during the severe gyrations.

Adult↗