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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 181 records · Page 10Linked to original sources

Neurosyphilis revisited. A contemporary wolf in sheep's clothing?

Neurosyphilis has become an uncommon clinical problem, for primary and secondary infections are usually recognised and treated early and successfully. However, patients occasionally receive no treatment for their acute infections--usually because they fail to seek advice--or may receive inadequate therapy when prescribed oral penicillin for other infections. The natural course of the disease is thus influenced, but the syphilis is not cured. Variegated clinical presentations of late disease arise and may make objective diagnosis difficult, especially when this occurs in a clinical setting where neurosyphilis may not be entertained in the initial diagnostic deliberations. Details of three such patients, seen during the last five years in the Aberdeen hospitals, are described--and highlight the range and diversity of clinical presentations which may occur, and typify the problem of making a firm diagnosis while the condition is still potentially curable.

Adult↗

Expression and cellular compartmentalization of a herpes simplex virus type 2 protein (ICP 10) in productively infected and cervical tumor cells.

Antiserum to ICP 10, a herpes simplex virus type 2 (HSV-2) protein that is expressed in cells neoplastically transformed by viral DNA sequences within the Bgl II/Hpa I CD fragment, specifically precipitates the ICP 10 protein from HSV-2 infected cells and stains cells infected with HSV-2 for 4 to 16 hrs by indirect immunofluorescence. At 4 hr post infection (p.i.), the staining is primarily perinuclear, while at 16 hr p.i., it is cytoplasmic and intranuclear. Compartmentalization studies indicate that the 35S-[L]-methionine labeled ICP 10 is detectable in both the cytoplasmic and nuclear fractions early and late in infection. However, in its phosphorylated form, ICP 10 is undetectable in the nuclear fraction late in the viral reproductive cycle. Anti-ICP 10 serum stains a high (75%-83%) proportion of cervical tissue with pathological findings of dysplasia or carcinoma, as well as atypical exfoliated cells from these patients. Cervical tumor tissue from 4 of 12 patients also stains with antiserum to another purified viral protein complex designated ICP 12/14. In the majority of atypical cells with mild or moderate changes, ICP 10 localizes in the cytoplasm, while the majority of atypical cells with severe changes also display nuclear staining with anti-ICP 10 serum. While exfoliated atypical cells from 60% of patients with dysplasia are positive for ICP 10, those from only one half of these patients stain also with anti-ICP 12/14 serum and this staining is strictly cytoplasmic. Atypical cells from three patients in these series stain with the anti-HSV-2 serum but are negative for both ICP 10 and ICP 12/14. Exfoliated atypical cells from patients with CIS or invasive cancer stain equally well with all three antisera.

Antigens, Viral, Tumor↗

Chronic or fatal Q-fever infection: a review of 16 patients seen in North-East Scotland (1967-80).

Sixteen patients with serologically proven Q-fever infection are reviewed. Fifteen had significantly raised antibody titres to both phase I and phase II Coxiella burneti antigens, indicating persistent or chronic infection. One patient, a premature infant who died, had raised phase II titres only, but is included together with the mother who had chronic Q-fever and was the presumed source of infection. Chronic Q-fever infection has previously been regarded as virtually synonymous with Q-fever endocarditis, but only seven of the patients in this survey had evidence of valvular endocarditis. In those who did, the infection had arisen on prosthetic valves or those affected by rheumatic or syphilitic heart disease. One patient had inexorably progressive destruction of an infected congenitally bicuspid aortic valve. Eight patients had infections associated with extra-valvular sites and several of these associations have not been previously described. These include extreme prematurity with perinatal death, possibly following transplacental infection, the sudden infant death syndrome (SIDS), multiple lower limb emboli from endocarditis of an abdominal aortic dacron graft, and colonization of ventricular endocardium following left ventricular myotomy/sub-aortic diaphragm resection. The current concept that chronic Q-fever is invariably associated with endocarditis is therefore untenable and the indications for phase I antibody screening should be extended to include patients other than those under investigation for 'culture-negative' endocarditis, for example those with unusual osteomyelitis of vertebrae.

Adult↗

Metabolism of bis(2-chloroethyl)ether and bis(2-chloroisopropyl)ether in the rat.

Male rats were given single peroral doses of bis(1-14C-2-chloroethyl)ether ([1-14C]BCEE) (40 mg/kg) and of bis(1-14C-2-chloroisopropyl)ether ([1-14C]BCIE) (90 mg/kg). Excretion of 14CO2 and urinary 14C was followed for 48 hr. The time required to eliminate one half of the dose was 12 hr for [1-14C]BCEE and 19 hr for [1-14C]BCIE. In the case of [1-14C]BCEE, expired 14CO2 accounted for 11.5 +/- 5.6(SD)% of the dose, urinary 14C accounted for 64.7 +/- 14.8%, and 2.4 +/- 1.3% was found in the feces. The figures for [1-14C]BCIE were 20.3 +/- 9.4% expired as 14CO2, 47.5 +/- 8.1% as urinary 14C, and 3.8 +/- 0.3% as fecal 14C. Thiodiglycolic acid (TDGA) accounted for roughly 75% of the total urinary 14C collected after the [1-14C]BCEE dose. Lesser metabolites of BCEE were 2-chloroethoxyacetic acid (CEAA) (5%), and N-acetyl-S-[2-(2-chloroethoxy)ethyl]-L-cysteine (ACEEC) (7%). Metabolites of [1-14C]BCIE identified in rat urine were 2-(2-chloro-1-methylethoxy)propanoic acid (CMEPA), roughly 36% of the total urinary 14C, and N-acetyl-S-(2-hydroxypropyl)-L-cysteine (AHPC) at 19%.

Animals↗

Technique for making a template for temporary restorations.

A fast, accurate, and simple technique for fabricating custom templates used to construct customized acrylic resin temporary crowns and fixed partial dentures has been presented. Acrylic resins are used directly on the diagnostic cast to restore single tooth contours, secure pontics to the cast, and to contour edentulous areas. Duplicate casts and impressions are not needed. Acrylic resins prove superior to wax and other materials for constructing custom templates because they will not distort or melt under the heat and pressure of the thermal vacuum machine. Thus, the template is accurate and free of melted residue on the inner template surface.

Acrylic Resins↗

Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients.

Cortical biopsies were taken from the frontal lobe of 25 patients with presenile dementia. Choline acetyltransferase (ChAT) activity, and in some specimens the high affinity uptake of choline, was used to estimate loss of cholinergic nerve terminals. Of the 15 samples with varying degrees of histological evidence of Alzheimer's disease (AD) 14 were from clinically suspected examples of the disease. There was significant loss of ChAT in 10 of the 15 compared with control and the mean activity was also highly significantly reduced (to 41% of control). The deficit was found in patients examined within a year of onset of symptoms. In 6 biopsies from clinically suspected cases of AD without diagnostic histological features there was loss of activity in only one, subsequently shown to have Jakob-Creutzfeldt disease. The remaining samples were two of vascular dementia (no loss of ChAT), one probable disorder of white matter (no loss of activity) and one undiagnosed disorder (with loss of ChAT activity). Thus most patients without histologically demonstrated AD had no evidence of a presynaptic cholinergic defect. It was concluded that suspected cases of AD particularly suitable for putative cholinergic therapy were those with an onset of the disease at 55 to 65 and an absence of family history.

Aged↗

Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities.

We have examined the choline acetyltransferase [CAT] activity in autopsy samples of frontal and temporal lobe cortex from 47 patients (31 with Alzheimer's disease, 4 with dementia due to cerebrovascular disease and 12 undemented controls) and compared it with the severity of dementia during life and with the numbers of argyrophilic plaques and neurofibrillary tangles in the corresponding areas of cortex in the contralateral cerebral hemisphere. CAT activity was significantly reduced, most severely in the temporal lobe, in patients with Alzheimer's disease but not in patients with a cerebrovascular cause for their dementia, and CAT activity showed no significant reduction with age in the undemented control patients. In the patients with Alzheimer's disease the reduction in CAT activity was significantly correlated with the severity of dementia and with the numbers of neurofibrillary tangles, but not argyrophilic plaques, present in the corresponding contralateral cortex.

Aged↗

Effect of benzodiazepines on cyclic GMP formation in rat cerebellar slices.

Cyclic 3',5' guanosine monophosphate (cGMP) levels, stimulated in brain slices by ouabain, potassium, and sodium azide depolarization, have been found to be inhibited in a dose-dependent fashion by both behaviorally active and inactive benzodiazepines. ED50's for these benzodiazepines bear no relation to potencies established from receptor membrane binding studies; however, these values do correspond to ED50's calculated for several known membrane stabilizing agents tested in this system. The concentration of [3H]flunitrazepam necessary to saturate the benzodiazepine receptor in identical slice preparations is considerably lower than that needed to initiate inhibition of depolarization-induced cGMP stimulation. Some of the reported in vivo actions of benzodiazepines on cGMP formation may be the result of membrane stabilizing actions of the benzodiazepines or mediated indirectly.

Animals↗

An unusual karyotype in preleukemia.

A case of a myeloproliferative disorder classified as preleukemia is described in which the patient developed a single, complicated, abnormal karyotype in 100% of the bone marrow cells (45, XY, -2, -5, -7, -8, -11, -12, -13, -14, + t(2;5), +t(11;12), +t(16;17), +17, plus three or four dicentric markers). The possible significance of these unusual, if not unique, chromosome changes is discussed in relation to hematologic and clinical findings and with particular reference to the existing nonrandom patterns of chromosome changes in myeloproliferative disorders and acute nonlymphoblastic leukemias.

Aged↗

Stage specific protein and nucleic acid synthesis during the asexual cycle of the rodent malaria Plasmodium chabaudi.

The asexual, intraerythrocytic stage of Plasmodium chabaudi develops synchronously in CBA mice. This in vivo synchrony has been exploited in in vitro pulse-labelling experiments to investigate the stage specificity of macromolecular synthesis by malaria parasites. Groups of mice were infected on day 0 with P. chabaudi and on day 3, individual mice were killed at three hour intervals, and the parasitised blood labelled in vitro for 2 h with radioactive precursors of protein or nucleic acid synthesis. By taking 11 samples covering one and one-third parasite division cycles, it was shown that the synthesis of many parasite polypeptides was restricted to defined morphological stages of parasite development. Other polypeptides were synthesised more or less continuously during the growth cycle. The synthesis of at least 6 polypeptides was confined to schizont or merozoite differentiation. RNA synthesis was shown to increase in rate steadily during parasite growth and to fall sharply during merozoite invasion. Approximately 40% of DNA synthesis was shown to occur during trophozoite growth, but the majority (60%) was confined to a short 4-6 h period at or just before schizogony.

Animals↗

Identification of a schizont- and species-specific surface glycoprotein on erythrocytes infected with rodent malarias.

Erythrocytes infected with mature trophozoites of Plasmodium chabaudi and reticulocytes infected with P. berghei were labelled metabolically in vitro with [35S]methionine. The labelled cells were incubated with normal and immune serum and washed to remove unbound antibody. Solubilisation of the antibody-coated cells in detergent was followed by co-precipitation of antibody/antigen complexes and analysis of the immunoprecipitates by SDS-PAGE and fluorography. One major parasite polypeptide of 250 000 daltons was found to be exposed to antibody in both species. A labelled band of the same molecular weight could be identified by immunoprecipitation and SDS-PAGE analysis of P. chabaudi-infected cells that had been surface-labelled with periodate/NaB3H4. This molecule also incorporated [3H]glucosamine in short term cultures of mature parasitised erythrocytes. The results suggest that a 250 000 dalton glycoprotein which is synthesised only by late trophozoites or schizonts is exposed either on the surface of the infected erythrocyte, the surface of the merozoite, or both. Furthermore, the exposed portion of the molecule was not immunologically cross-reactive in the two Plasmodium species, but some cross reaction was detectable in total parasite lysates. The significance of these findings to protective immunity is discussed.

Animals↗

Fatal Salmonella septicaemia with disseminated intravascular coagulation and renal failure.

Four elderly patients with salmonella septicaemia complicated by irreversible endotoxic shock and acute renal failure are described. The organism isolated from three of the patients with Salmonella typhimurium, which is not usually invasive; the fourth patient was infected with S. abony. The factors associated with the severe systemic infections are discussed. Clinical and haematological findings suggested disseminated intravascular coagulation, and this was subsequently confirmed histologically in each patient by the identification of haematoxylinophil bodies in the pulmonary and renal microcirculations.

Acute Kidney Injury↗

Monoclonal antibodies that protect in vivo against Plasmodium chabaudi recognize a 250,000-dalton parasite polypeptide.

Twenty monoclonal antibodies have been prepared to the erythrocytes from CBA/Ca mice infected with the rodent malaria Plasmodium chabaudi. By immunofluorescence, 15 of these antibodies recognized parasite antigens expressed only during the development of mature trophozoites to schizonts and merozoites, 2 recognized parasite antigens that were expressed throughout most of the intraerythrocytic cycle, and 3 recognized the membranes of all infected and uninfected erythrocytes. By immunoprecipitation of [35S]methionine-labeled, parasitized erythrocytes, parasite antigens recognized by all of the antiparasite antibodies were characterized. Eleven precipitated a 250,000-dalton parasite polypeptide which was synthesized and expressed late in the intraerythrocytic cell cycle and which appeared to be the major coat protein of the merozoites. In passive protection experiments, transfer of hyperimmune serum before infection with the parasite resulted in a delay in the rise of parasitemia, reduction in peak parasitemias, and a delay in the clearance of the parasitemia. Two monoclonal antibodies to the 250,000-dalton polypeptide had a similar but not as marked effect on parasitemia when given as a single dose before infection. When mixed and administered throughout the course of infection, their effects were greater. They had no influence on the course of Plasmodium berghei KSP11 parasitemia. Monoclonal antibodies to other parasite antigens and normal erythrocyte antigens failed to have a significant and reproducible effect on P. chabaudi parasitemia. The results suggest that this 250,000-dalton malaria parasite antigen may be important in the induction and expression of antibody-mediated immunity to malaria.

Animals↗