Biomedical subjects

A R Freedman

Publications and source records attributed to A R Freedman.

11 recordsLinked to original sources

PubMed1992

Cellular distribution of nuclear factor kappa B binding activity in rat liver.

The cellular localization of nuclear factor kappa B (NF-kappa B) binding activity in rat liver has been investigated using electrophoretic mobility shift assay on extracts of highly purified hepatocytes and Kupffer cells obtained from liver perfused in vivo with collagenase. Constitutive NF-kappa B binding activity was demonstrated in nuclear extracts of control Kupffer cells, and this was not apparently influenced by injection of lipopolysaccharide (LPS) into rats 24 h before perfusion. In contrast, little nuclear NF-kappa B binding activity was present in hepatocytes from control animals, although there was detectable inactive, inhibitor-bound, NF-kappa B in the cytoplasm. However, nuclear NF-kappa B binding activity was increased in hepatocytes from LPS-treated animals and after in vitro culture of control rat hepatocytes. Thus NF-kappa B binding activity has been demonstrated in highly purified hepatocytes and appears to be inducible both in vivo and in vitro. These findings support a role for NF-kappa B in hepatocyte gene regulation which may be important in the modulation of the hepatic acute phase response.

Animals↗

PubMed1992

Diffuse tuberculous parotitis.

Parenchymatous parotid tuberculosis diffusely affecting the entire gland is very rare. We present a case, associated with a primary pulmonary focus, that was confirmed after positive identification of alcohol and acid-fast bacilli in gastric washings. Both sites of infection resolved with quadruple anti-tuberculous chemotherapy.

Adult↗

PubMed1992

Giardia lamblia as an intestinal pathogen.

Giardia lamblia are protozoan parasites which cause human intestinal disease. The life cycle has a multiplying intraduodenal trophozoite and an excreted cyst. Infection occurs after cyst ingestion from faecally contaminated water or by direct faecal-oral transmission in situations of poor sanitary standards, but the zoonotic nature of giardiasis is debated. The pathophysiology may arise from enzyme or active transport deficiencies, synergy with intestinal bacteria or an immunopathological process. Diagnosis is made by microscopic identification of cysts or trophozoites in small bowel samples or faeces. Symptoms are acute with diarrhoea (without blood), abdominal cramps, bloating and flatulence. The treatment of choice is either metronidazole or tinidazole. No vaccine or drug prophylaxis exists, and measures to avoid cyst ingestion should be undertaken.

Animals↗

PubMed1991

Human immunodeficiency virus infection of eosinophils in human bone marrow cultures.

Normal human bone marrow, cultured in vitro with interleukin 5 to promote eosinophil production and maturation, was inoculated with cell-free isolates of human immunodeficiency virus type 1 (HIV-1). CD4 expression by eosinophil precursors, determined by immunocytochemistry, was found to be greatest early in their maturation with a rapid decline after 28 d in culture. Productive HIV infection of eosinophil precursors was detected 14 d after inoculation, by a combination of immunostaining for HIV-1 p24 and gp41/160 and in situ hybridization for viral RNA, together with assay of culture supernatants for p24 antigen and reverse transcriptase activity. Thus, eosinophils are susceptible to productive HIV-1 infection in vitro and may be an important reservoir for the virus in vivo.

Bone Marrow↗

PubMed1990

Detection and estimation of the barley prolamin content of beer and malt to assess their suitability for patients with coeliac disease.

Malt, lager, brown ale, bitter and stout were assessed for their barley prolamin (hordein) content. Monoclonal antibody immunoperoxidase staining of electrophoretically separated samples of beer revealed the presence of immunoreactive hordein. Polyclonal antibody based enzyme linked immunosorbant assays (ELISAs) revealed 1.6 mg of hordein per gram of malt and 1.5 mg per pint in the beers. Patients with coeliac disease should avoid ingestion of beer and foods that contain malt since they contain quantifiable amounts of hordein that is known to exacerbate the condition.

Alkaline Phosphatase↗

PubMed1990

Q fever encephalitis.

Encephalitis is a rare but documented complication of acute Q fever. We report here the case of a 48-year-old lady who presented with an acute illness characterised by influenza-like symptoms, pneumonia and neurological disturbance but in whom the serology was suggestive of chronic rather than acute Q fever.

Canada↗

PubMed1989

The production and characterisation of monoclonal antibodies to wheat gliadin peptides.

BALB/c mice maintained on a gluten-free diet were immunised with Frazer's Fraction III (FFIII, a peptic tryptic digest of wheat gluten that exacerbates coeliac disease) in order to overcome oral tolerance. A control group was maintained on normal diet. Serum antibody titres to FFIII were higher in the mice on a gluten-free diet (P less than 0.05). Three monoclonal antibodies to FFIII were produced from splenocytes obtained from mice maintained on a gluten-free diet. The antibodies were characterised by ELISA, immunodot assay and immunoblotting with prolamins from cereals toxic to coeliac patients (wheat, rye, barley, oats) and the non-toxic prolamins from maize and rice. The binding characteristics of the three antibodies to the cereal prolamins were different, implying that the antibodies recognise different cereal protein epitopes. Immunoblotting revealed FFIII to be comprised of antigenically dissimilar peptides.

Antibodies, Monoclonal↗

PubMed1989

Early biochemical responses of the small intestine of coeliac patients to wheat gluten.

The pathogenesis of coeliac disease has been investigated by studying the response of small intestinal hydrolases in patients with coeliac disease subject to gluten challenge. Small intestinal biopsies taken before and two and a half hours after a gluten challenge in five patients with coeliac disease who had been maintained on a gluten free diet were examined by a combination of electron and light microscopy, organ culture, pulse chase biosynthetic labelling, SDS-PAGE and autoradiography. Before the challenge, the small intestinal biopsies showed nearly normal morphology. Two and a half hours after the challenge there was deterioration in villus architecture, distortion of microvillus structure, disorganisation of the intermicrovillus pit region, an increase in lysosome like bodies in the apical cytoplasm of the luminal enterocytes and pronounced hypertrophy of the rough endoplasmic reticulum of these cells. SDS-PAGE of small intestinal biopsies from four treated coeliac patients before gluten challenge revealed normal microvillus membrane and hydrolase composition. There was a generalised reduction but no specific alteration in the pattern of polypeptide synthesis in the mucosa of the small intestine in these subjects two and a half hours after the gluten challenge. These results suggest that the generalised reduction in small intestinal brush border enzymes in coeliac patients is not the primary pathogenetic mechanism and represents a secondary effect.

Adult↗

PubMed1989

Gliadin antibody production by small intestinal lymphocytes from patients with coeliac disease.

Small intestinal lymphocytes (SIL) were isolated from jejunal biopsies from 9 non-coeliac controls, 6 treated and 5 untreated coeliac patients. Six-day cell culture supernatants were assayed for total IgG, IgM and IgA and specific anti-casein and anti-gliadin antibodies by ELISA. SIL from the untreated patients secreted more total IgM and IgA than SIL from the treated patients and more total IgG, IgM and IgA than SIL from the controls. The untreated patients' cells secreted more specific anti-gliadin IgA than those from the treated patients and more anti-gliadin IgG, IgM and IgA than the controls. SIL from the untreated group released more anti-casein IgM than those from either the treated or control groups. There were no differences in total immunoglobulin, or specific anti-casein or anti-gliadin antibody secretion by SIL from the treated and control groups. Comparison of immunoglobulin release from cells lysed prior to culture and that secreted both after 30-min and 6-day cultures showed that the majority of immunoglobulin had been synthesised in vitro and could not be accounted for by carry-over.

Antibody Formation↗

PubMed1988

Western immunoblotting of cereal proteins with monoclonal antibodies to wheat gliadin to investigate coeliac disease.

Western immunoblotting was used to investigate the binding of two monoclonal antibodies raised against unfractionated wheat gliadin to different cereal protein fractions separated by SDS-PAGE. Our results confirm the presence of considerable epitope sharing between the gliadin subfractions as well as barley and rye prolamins; however, there was less binding of these antibodies to bands present in oat avenins and maize zeins. The pattern of binding of one of these two antibodies to different cereal prolamins as well as to Frazer's fraction III corresponds closely to the known toxicity of these proteins to patients with coeliac disease.

Antibodies, Monoclonal↗

PubMed1978

Primate mesenteric blood flow. Effects of vasopressin and its route of delivery.

The effects of vasopressin on blood flow in the superior mesenteric artery and on mean arterial pressure and portal venous pressure were measured in 7 rhesus monkeys. Vasopressin was injected, as either a bolus, or infused both intravenously and intraarterially to assess the influence of the route of administration upon hemodynamic responses. Dose-dependent decreases in superior mesenteric arterial flow were observed during both intraarterial and intravenous injections of vasopressin. No statistically significant differences between the two routes of administration, the decrease in flow, and changes in pressure were observed. Based upon these observations, one might anticipate that intravenously administered vasopressin will be as effective as intraarterially administered vasopressin in reducing mesenteric blood flow, and thus portal venous pressure, in man.

Animals↗