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S J Johnson

Publications and source records attributed to S J Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Post-infantile giant cell hepatitis: histological and immunohistochemical study.

AIM: To determine the composition of the inflammatory infiltrate and to check for the presence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in nine cases of post-infantile giant cell hepatitis. METHODS: The clinical, serological, and histological features of the nine cases were reviewed. Immunohistochemistry was used on liver biopsy specimens from six cases to: (i) characterise the lymphocytic infiltrate; (ii) assess the monocyte/macrophage response; (iii) detect "activated" perisinusoidal cells; and (iv) detect CMV and EBV antigens. Electron microscopic examination was carried out in two cases. RESULTS: Four patients had serological features suggestive of autoimmune chronic active hepatitis; in the other five cases the aetiology was obscure. Two patients presented with neurological symptoms. Hepatitis resolved completely in one patient; two patients showed clinical improvement; and one remained stable. Cirrhosis developed in three patients, one of whom proceeded to liver transplantation, and three patients died. Portal inflammation was present in all cases and lymphocytic piecemeal necrosis in eight cases, but intra-acinar inflammation associated with hepatocyte necrosis was observed in only five cases. The inflammatory infiltrate was composed predominantly of T lymphocytes; an increase in monocyte/macrophage cells was also observed. Mallory bodies, often with associated neutrophilic infiltrate, were present in four cases, and bilirubinostasis was a feature in four cases. "Activated" perisinusoidal cells were present, especially in relation to areas of inflammation, necrosis, and fibrosis. There was severe fibrosis or cirrhosis in five cases. Paramyxoviral nucleocapsids were not seen in the two cases examined ultrastructurally. CONCLUSIONS: Post-infantile giant cell hepatitis should be viewed as a heterogeneous clinical and aetiological entity encompassing cases of hepatitis with extensive giant cell hepatocyte transformation.

Adult↗
PubMed1994

GME financing: a well-kept secret.

Comprehensive healthcare reform depends on our ability to educate more primary care providers and reduce the oversupply of specialists and subspecialists. However, significant financial incentives exist, hidden within the Federal reimbursement system to fuel continued growth of highly specialized physicians, undermining efforts to educate primary care practitioners. If Medicare cannot correct this situation, perhaps the government should redirect GME funds to educate nurse practitioners.

Education, Medical, Graduate↗
PubMed1993

Clinical pathology of Australian bluetongue virus serotype 16 infection in merino sheep.

Viraemic blood from an ox naturally infected with Australian bluetongue (BLU) virus serotype 16 was passaged twice in sheep. Twelve 2- to 4-years-old Merino ewes, negative in a bluetongue agar gel immunodiffusion test, were inoculated with viraemic blood from the second sheep passage. They were examined for 18 days and compared with a control group. Significant changes in haematological measurements, namely packed cell volume, total white cell count and lymphocyte count, and in plasma enzyme concentrations, namely aspartate transaminase and creatine kinase, occurred in the infected sheep. All infected sheep became sick. The antibody response, and clinical and necropsy findings were consistent with other reports of mild to moderate disease with Australian BLU serotypes.

Animals↗
PubMed1993

In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury.

We investigated the response of macrophages and perisinusoidal (Ito) cells (PSCs) during the development of secondary biliary cirrhosis after ligation and division of the common bile duct. Liver tissue was obtained from three groups of male Wistar rats: 1) untreated controls (n = 3); 2) common bile duct-ligated (CBDL) animals (n = 15); and 3) sham-operated controls (n = 15). Material from animal groups 2 and 3 was obtained on days 3, 7, 14, 21, and 28 after operation; in all animals 5-bromo-2-deoxyuridine was administered intraperitoneally before death. Monocytes and macrophages were detected using the monoclonal antibody ED1 and tissue macrophages using the antibody ED2. Cell proliferation within the macrophage population was demonstrated by double labeling for ED2 and incorporated 5-bromo-2-deoxyuridine. PSCs were demonstrated in tissue sections by immunolocalization of desmin; proliferating PSCs were identified by double labeling for desmin and incorporated 5-bromo-2-deoxyuridine. Evidence of phenotypic modulation of PSCs was sought using anti-alpha-smooth muscle actin (alpha-SMA) antibody. Increased numbers of ED1- and ED2-positive cells were seen in CBDL animals at all time points. Local proliferation of macrophages could be identified and reached a peak at day 3, thereafter falling toward control values. Compared with those of controls, livers of CBDL animals showed increased numbers of desmin-positive PSCs in periportal zones from day 3 on, reaching a peak at day 14 (127.8 +/- 10.99 cells/0.635 mm2) and followed by a plateau. PSC proliferation peaked at days 3 and 7 (labeling indices 11.2% and 11.2%, respectively) and thereafter fell toward control values; no expansion of the PSC population was seen in sham-operated rats. Increased alpha-SMA-positive cells were also noted from day 3, with a peak at day 21 (231.1 +/- 11.52 cells/0.635 mm2) and followed by a plateau. En face labeling experiments in days 14, 21, and 28 CBDL animals showed cells co-expressing alpha-SMA and desmin and cells expressing alpha-SMA alone. These results indicate that in response to chronic cholestatic liver injury, PSCs proliferate and undergo phenotypic modulation toward "myofibroblast-like" cells. The kinetics of the response are similar to those of the ED2-positive cell population in keeping with a hypothesis that PSC proliferation and activation may be mediated by factors released by macrophages in response to various forms of liver injury. We conclude that the responses of macrophages and PSCs to cholestatic injury are similar to those after toxin-induced hepatocyte necrosis.

Actins↗
PubMed1992

Macrophage and perisinusoidal cell kinetics in acute liver injury.

Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.

Animals↗
PubMed1992

Immunolocalization of proliferating perisinusoidal cells in rat liver.

There is now substantial evidence that perisinusoidal (Ito or fat-storing) cells are the principal source of extracellular matrix proteins during hepatic fibrogenesis. In rat liver these cells express the intermediate filament protein desmin; this is now widely used as an immunohistochemical marker for these cells. It has been shown that in experimental models of acute and chronic liver injury there is an increase in the number of desmin-positive perisinusoidal cells prior to the deposition of matrix proteins; however, these studies have failed to establish whether local proliferation is involved in this expansion of the desmin-positive perisinusoidal cell population. In order to investigate the kinetics of the perisinusoidal cell response, we have developed a novel double-labelling immunohistochemical technique for the simultaneous demonstration of desmin and incorporated bromodeoxyuridine in proliferating perisinusoidal cells in sections of fixed paraffin-embedded rat liver. Application of this technique to a model of acute liver injury (single dose carbon tetrachloride by gavage) has shown that expansion of the perisinusoidal cell population is contributed to by local proliferation, with a labelling index of 18.7% 2 days following injury.

Animals↗
PubMed1992

Phenotypic modulation of perisinusoidal cells following acute liver injury: a quantitative analysis.

Expression of the alpha-(smooth muscle) isoform of actin (alpha-SMA) by non-parenchymal cells in rat liver was studied following induction of acute liver injury using a single sublethal dose of carbon tetrachloride (CCl4). In normal liver, alpha-SMA immunoreactivity was identified in the smooth muscle cells of hepatic arteries and in the walls of portal and hepatic vein branches. Occasional alpha-SMA-containing stellate shaped cells were found in acinar zone 3 but most perisinusoidal cells (PSCs) did not express this protein. In CCl4-treated animals, there was an increase in the number of immunoreactive cells in perivenular zones, reaching a peak at day 3 following exposure to the toxin. These cells were morphologically identical to desmin-positive PSCs and the kinetics of the responses of alpha-SMA-positive and desmin-positive cells were similar. In en face labelling experiments, evidence of co-expression of alpha-SMA and desmin by non-parenchymal cells was obtained, although some desmin-positive PSCs did not appear to express alpha-SMA. These results suggest that PSCs rapidly undergo phenotypic modulation in response to acute liver injury with acquisition of alpha-SMA expression. It is proposed that these phenotypic changes coincide with functional alterations, such activated 'myofibroblast-like' cells being responsible for the enhanced matrix protein synthesis necessary for tissue repair.

Actins↗
PubMed1991

Coupling of spectrin and polylysine to phospholipid monolayers studied by specular reflection of neutrons.

The technique of specular reflection of neutrons is applied for the first time to study the charge-dependent interaction of the protein spectrin and the polypeptide poly-L-lysine with model phospholipid monolayers in the condensed phase state. We first established the structure of a pure monolayer of dimyristolyphosphatidylcholine (DMPC) in both the expanded and condensed fluid phase states without protein in the subphase. The thickness of the hydrocarbon chains increases from 11.4 +/- 1.5 A in the expanded state to 15.8 +/- 1.5 A in the condensed state, whereas the head group region is approximately 10 A thick for both phase states. When spectrin is present in the subphase, the dimensions of DMPC in the condensed state are not significantly affected, but there is approximately 0.09 volume fraction spectrin in the head group region. Lipid-spectrin coupling is enhanced by electrostatic interaction, as the volume fraction of spectrin in the head group region increases to 0.22 in a mixed monolayer of DMPC and negatively charged dimyristolyphosphatidylglycerol in the condensed state. In contrast to spectrin, polylysine does not penetrate the head group region, but forms a layer electrostatically adsorbed to the charged head groups.

Biophysical Phenomena↗
PubMed1991

Structure of an adsorbed dimyristoylphosphatidylcholine bilayer measured with specular reflection of neutrons.

Using specular reflection of neutrons, we investigate for the first time the structure of a single dimyristoylphosphatidylcholine bilayer adsorbed to a planar quartz surface in an aqueous environment. We demonstrate that the bilayer is strongly adsorbed to the quartz surface and is stable to phase state changes as well as exchange of the bulk aqueous phase. Our results show that the main phase transition is between the L alpha phase and the metastable L beta'* phase, with formation of the P beta' ripple phase prevented by lateral stress on the adsorbed bilayer. By performing contrast variation experiments, we are able to elucidate substantial detail in the interfacial structure. We measure a bilayer thickness of 43.0 +/- 1.5 A in the L alpha phase (T = 31 degrees C) and 46.0 +/- 1.5 A in the L beta'* phase (T = 20 degrees C). The polar head group is 8.0 +/- 1.5 A thick in the L alpha phase. The water layer between the quartz and bilayer is 30 +/- 10 A for the lipid in both the L alpha and L'* phase. Our results agree well with those previously reported from experiments using lipid vesicles and monolayers, thus establishing the feasibility of our experimental methods.

Dimyristoylphosphatidylcholine↗
PubMed1988

Differentiation-inducing factor from the slime mould Dictyostelium discoideum and its analogues. Synthesis, structure and biological activity.

Previous work has led to the identification of a novel class of effector molecules [DIFs (differentiation-inducing factors) 1-3] released from the slime mould Dictyostelium discoideum. These substances induce stalk-cell differentiation in Dictyostelium discoideum and are thought to act as morphogens in the generation of the prestalk/prespore pattern during development. The DIFs are phenylalkan-1-ones, with chloro, hydroxy and methoxy substitution on the benzene ring. DIFs 1-3 and a number of their analogues have been synthesized by using a simple two-step procedure, and each analogue has been characterized by m.s., u.v. and n.m.r. spectroscopy. The crystal structure of synthetic DIF-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one, was investigated. The specific biological activity of each analogue was determined in a bioassay, where isolated Dictyostelium amoebae are induced to differentiate into stalk cells. The major biologically active substance, DIF-1, caused 50% stalk-cell differentiation at 1.8 x 10(-10) M; the C4 alkyl homologue (DIF-2) and C6 homologue possessed 40 and 16% of the activity of DIF-1 respectively. Further increase or decrease in the alkyl chain length resulted in a marked decrease in specific activity. The pattern of substitution on the benzene ring is a major determinant of bioactivity, since the specific activities of the 2,4-dihydroxy-6-methoxy and trihydroxy analogues were less than 1% of that of DIF-1. Substitution of bromine in DIF-1 had little effect on bioactivity; in contrast the activity of monochloro-DIF-1 (DIF-3) was diminished. There was no evidence for antagonism or synergy between DIF-1 and any of its analogues. This series of analogues will facilitate further studies in the biological effects and mode of action of DIF-1.

Cell Differentiation↗
PubMed1988

Isolation and characterisation of glutamate receptor antagonists from venoms of orb-web spiders.

Two distinct families of low-molecular-weight toxins (argiotoxins) have been isolated from the venom of the orb-web spider. Argiope trifasciata. The toxins have been purified to homogeneity and characterised by spectroscopic, mass spectrometric and microchemical analysis. The major biologically active member of the first family of toxins is 2,4-dihydroxyphenylacetyl-asparagine linked through a C11-tetra-amine to N-terminal arginine; other members of this family are methylene homologues. The second family of toxins possesses an indolic group in place of the 2,4-dihydroxyphenyl chromophore. The toxins act as non-competitive inhibitors at quisqualate-type glutamatergic receptors on a metathoracic retractor unguis nerve-muscle preparation of Schistocerca gregaria. The loss of the N-terminal arginine reduces biological activity of the first family of toxins, but not of the second. The nature of the polyamine appears to be less important, perhaps acting as a spacer between the cationic arginine and the more hydrophobic aromatic tail of the toxins.

Animals↗
PubMed1988

Prevalence of stephanofilariasis in young Bos indicus cattle in northern Australia.

Four consecutive annual calf crops of known genotype from a single property in northern Australia were examined for the presence of stephanofilarial lesions. The animals ranged in age from 60 to 348 days at the time of examination. Initial lesions of stephanofilariasis developed adjacent to the medial canthi of the eyes; animals as young as 69 days of age were found infected. In all years, prevalence of lesions increased with age for all genotypes, and was significantly lower in genotypes with higher Bos indicus content (P less than 0.01). Males had a higher prevalence of lesions than females in only one year, and in two of the years, dark-coloured animals had a higher prevalence of lesions than light-coloured ones.

Animals↗
PubMed1986

Prevalence of sensorineural hearing loss in premature and sick term infants with perinatally acquired cytomegalovirus infection.

Audiologic follow-up was obtained on 40 premature or sick term infants with perinatally acquired cytomegalovirus (CMV) infection and on 40 prospectively matched control subjects. Final evaluation was postponed until 3 years of age to assess any long-term hearing sequelae of perinatal CMV infection in this population, and to obtain reasonably complete audiometric results. One experimental subject had a bilateral sensorineural hearing loss above 4000 Hz. Four control subjects had sensorineural hearing losses, three requiring binaural hearing aids. The prevalence of confirmed hearing loss requiring amplification (3.75%) in this study group was consistent with that observed in all graduates of the Intensive Care Nursery who were considered at risk for hearing loss in the same time period (4.2%). These data suggest that perinatally acquired CMV infection is not associated with significant sensorineural hearing loss in premature or full term infants through age 3.

Cytomegalovirus Infections↗
PubMed1986

The distribution and prevalence of stephanofilariasis in cattle in Queensland.

A total of 10,543 cattle from 1,386 farms throughout Queensland was examined at abattoirs and the presence of stephanofilarial lesions was related to property of origin, sex, breed, and age of the slaughtered cattle and season of slaughter. The mean prevalence was 38% and within the infected area this varied from less than 5% in south east Queensland to 95% on Cape York Peninsula. The prevalence of lesions was higher in bulls than in steers [corrected] and was least in cows [corrected]. Bos indicus animals had a lower prevalence than B. taurus. Prevalence increased with age. The distribution of the disease closely matched that of the buffalo fly, Haematobia irritans exigua.

Animals↗
PubMed1985

Sequelae of acquired cytomegalovirus infection in premature and sick term infants.

To assess the risk of long-term sequelae after acquired cytomegalovirus (CMV) infection in premature and sick term infants, 55 CMV infected patients were matched prospectively with 55 control patients and these matched pairs were evaluated at 3 years of age. Sensorineural hearing losses were present in four of 43 CMV infected patients (all mild-moderate) and in two of 43 controls (one severe). The incidence of neurologic sequelae was not increased in CMV infected patients with birth weight greater than 2000 gm. Among patients with birth weight less than 2001 gm, moderately abnormal EEGs were found in four (17%) of 23 CMV infected patients and in one (4%) of 23 controls, and severe handicaps occurred in four (14%) of 29 CMV infected patients and in two (7%) of 29 controls. Severe handicaps in premature infants were significantly (P less than 0.05) associated with early onset of CMV excretion (less than 8 weeks of age) and severe cardiopulmonary disease. Among the premature infants who were documented early excretors, three of 13 had severe neuromuscular impairment, four of 13 had severe handicaps (DQ less than 70, severe neuromuscular impairment, or profound loss of vision or hearing), and an additional four had DQs of 70 to 79. Among their matched control subjects, none of 13 had severe neuromuscular impairment, two of 13 had severe handicaps, and an additional two had DQs between 70 and 79. None of the premature infants who were documented late excretors (greater than or equal to 8 weeks of age) had any neurologic sequelae. The risk of neurologic sequelae and handicap may be increased in premature infants with onset of CMV excretion in the first 2 months of life.

Cytomegalovirus Infections↗
PubMed1985

Asbestos disease in family contacts of shipyard workers.

Radiologic signs of pulmonary asbestos disease were found in 11.3 per cent of 274 wives of shipyard workers who were 20 or more years from initial hiring-on in shipyards in Los Angeles County. Asbestosis was also found in 7.6 per cent of 79 sons and 2.1 per cent of 140 daughters of these workers. The wives, sons, and daughters were without occupational exposure. Comparable radiographic signs were not found in comparison groups. It is probable that asbestos exposure in the household places these family members at risk for mesothelioma and lung cancer.

Adolescent↗