PubMed Health⌕ Search

Biomedical subjects

K Knox

Publications and source records attributed to K Knox.

At least 19 recordsLinked to original sources
PubMed1995

Plasmodium berghei infection: dichloroacetate improves survival in rats with lactic acidosis.

The kinetics of Plasmodium berghei infection and the development of lactic acidosis, hypoglycemia, and anemia were defined in young Wistar rats. This model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroacetate, a treatment for lactic acidosis, prolonged survival in rats receiving a single antimalarial dose of quinine (20 mg/kg). Rats with hyperlactatemia (lactate > 5 mmol/liter, N = 183) were randomized to receive either dichloroacetate (100 mg/kg, N = 99) or saline (N = 84) and were monitored for outcome (survival or death) for 50 hr. Logistic regression modeling adjusting for baseline venous lactate concentration demonstrated that dichloroacetate increases survival rates in rats with venous lactate concentrations between 5 and 8.9 mmol/liter (odds ratio > 2.2, P < 0.021). This is the first demonstration that specific intervention to treat lactic acidosis can prolong survival and suggests that dichloroacetate may be useful as adjunctive therapy in the management of lactic acidosis complicating severe falciparum malaria.

Acidosis, Lactic↗
PubMed1993

Stimulation of tyrosine phosphorylation without inositol lipid hydrolysis in human B lymphocytes on engaging CD72.

Occupancy of CD72 on resting tonsillar B cells by monoclonal antibodies (mAb) promotes entry into the G1 phase of the cell cycle with an accompanying increase in MHC Class II expression and provides a co-stimulus to immobilized anti-mu for driving DNA synthesis. We now report that engagement of CD72 by mAb stimulates tyrosine phosphorylation in B cells with a peak of activity seen at 5-10 min. Two major substrates of 29 and 57 kDa showed a basal level of phosphorylation which increased with time, while a 40 kDa protein and several other minor components were phosphorylated de novo on the addition of mAb to CD72. Inositol lipid hydrolysis was found to be unperturbed, although a shallow rise in the basal level of intracellular free Ca2+ was provoked on engaging CD72. Receptor cross-linking was not a requirement for signaling human B cells through CD72: simple occupancy by univalent antibody was sufficient both to trigger the rise in basal [Ca2+]i and to promote DNA synthesis.

Antigens, CD↗
PubMed1993

Regulation of survival in normal and neoplastic B lymphocytes.

The regulation of survival is clearly a vital component in deciding the fate of normal and malignant cells. In cell populations subject to selection through apoptosis, dysregulation of this mechanism could disrupt homeostasis with the potential overproduction of affected clones. Germinal centres are the sites of such selection for B cells proliferating in response to T-dependent antigen: two tumours arising at these sites--Burkitt lymphoma (BL) and follicular centre cell (FCC) lymphoma--show aberrations in their capacity to undergo programmed cell death (PCD). Here, we summarize present knowledge on the factors, both extra- and intracellular, which regulate survival in normal and malignant B cells arising in germinal centres.

Antigens, CD↗
PubMed1993

Aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection.

Aerosol vaccination is used effectively to immunize poultry against Newcastle disease, but to the authors' knowledge, this vaccination procedure is not well studied in other species. The efficacy of IM and aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection was evaluated. Twenty-one pigs from a Mycoplasma-free herd were randomly allotted by litter and body weight into 3 groups. One group was given aerosolized phosphate-buffered saline solution (PBSS) by inhalation. The second group (AERO) was given aerosolized M hyopneumoniae vaccine by inhalation. The third group (IM) was given the same vaccine by IM injection. Vaccination by IM administration was repeated once, and aerosol vaccination was repeated twice at 2-week intervals. Two weeks after the last vaccination, all pigs were intratracheally challenge-exposed with 3 ml of broth culture containing 10(7) color-changing units (CCU) of a low-passage strain of virulent M hyopneumoniae. Pigs were observed daily for coughing. Four weeks after challenge exposure, all pigs were necropsied. Percentage of lung affected by gross pneumonia was measured, bronchioalveolar lavage fluid (BALF) cells were counted, and quantitative culture for mycoplasmas was performed on lung sections. Additionally, M hyopneumoniae-specific antibodies were measured in prevaccination, postvaccination, and postchallenge-exposure serum and BALF by use of indirect ELISA. Mean prevalence of persistent coughing in pigs of the AERO group (4.6 d/pig) was not different from that in pigs of the PBSS group (3.7 d/pig). Prevalence of coughing in IM vaccinated pigs (1.0 d/pig) was lower (P < 0.05) than that in pigs of the PBSS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Factors modifying survival pathways of germinal center B cells. Glucocorticoids and transforming growth factor-beta, but not cyclosporin A or anti-CD19, block surface immunoglobulin-mediated rescue from apoptosis.

The tendency for germinal center (GC) B cells to enter apoptosis is suppressed on engaging antigen receptor with immobilized anti-immunoglobulin; cross-linking of surface CD40 by monoclonal antibodies provides an additional signal for rescuing GC cells from programmed death. These observations are believed to reflect events that, in vivo, would allow for the selection of centrocytes which have undergone somatic mutation on Ig V-region genes to generate antigen receptor of high affinity. The purpose of the present study was to identify factors capable of modifying the survival pathways of GC cells. Transforming growth factor-beta, at an optimal concentration of 1 ng/ml, was found to inhibit surface immunoglobulin (sIg)-mediated rescue of GC cells but had no influence on survival promoted through CD40. Both routes of rescue were blocked by the glucocorticoid prednisolone at pharmacological concentrations (ID50 = 10(-7) M). Cyclosporin A, an antagonist of sIg-mediated signaling in resting B cells, failed to block rescue of GC cells through either of the receptor-activated pathways. Antibody to CD19--which also suppresses the activation of resting B cells--not only left GC cell rescue undiminished, but rather provided a modest survival signal of its own; interferon-alpha behaved similarly while interferon-gamma failed to influence GC cell survival in either direction.

Antibodies↗
PubMed1992

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections↗
PubMed1991

Inhibition of influenza virus formation by a peptide that corresponds to sequences in the cytoplasmic domain of the hemagglutinin.

A decapeptide with a sequence corresponding to the cytoplasmic domain of the influenza virus hemagglutinin inhibited the release of virus particles and infectious virions when added to infected cultured cells for a 2-hr period during a one-cycle growth. Inhibition was dose-dependent in the range of 50 to 250 micrograms/ml. The peptide did not affect formation of intracellular virus-specific proteins or assembly of nucleocapsids and did not inhibit replication of two unrelated enveloped RNA viruses, Sindbis virus and vesicular stomatitis virus. Peptides of similar size but different in sequence were ineffective. We postulate that this peptide acts as a competitive inhibitor for virus-specific protein-protein interactions between the hemagglutinin and the matrix protein or nucleocapsid during virus assembly. These data offer an approach to the development of antiviral drugs based on virus specific activities.

Amino Acid Sequence↗
PubMed1987

Toxicosis in newborn pigs associated with cutaneous application of an aerosol spray containing chlorpyrifos.

Weakness, lethargy, ataxia, lateral recumbency, limb paddling, tremors, salivation, and diarrhea were observed in newborn pigs on a commercial swine farm. Many pigs became moribund and died. All had been treated with an aerosol wound spray containing 2.5% chlorpyrifos. A controlled study was undertaken to determine whether the aerosol spray was the cause of these clinical signs. Pigs exposed to aerosol spray containing 2.5% chlorpyrifos at 3 hours (n = 4) and 6 hours (n = 3) after birth developed clinical signs similar to those on the farm; none survived. Pigs exposed at 24 hours (n = 5) after birth developed clinical signs consistent with those that had developed in pigs on the farm; 3 died and 2 survived. Of 3 pigs exposed to the same spray at 36 hours after birth, 1 developed tremors 7.5 hours later and diarrhea 9 hours later, then returned to normal.

Aerosols↗
PubMed1987

Lung cancer mortality in workers exposed to sulfuric acid mist and other acid mists.

Mortality patterns were studied in 1,165 workers exposed to sulfuric acid mist and other acid mists (primarily hydrochloric acid mist) in steel-pickling operations. Standardized mortality ratio (SMR) analysis of the full "any acid exposure" cohort (n = 1,165), with the use of U.S. death rates as a standard, showed that lung cancer was significantly elevated, with a mortality ratio of 1.64 [95% confidence interval (CI) = 1.14-2.28, based on 35 observed deaths]. The lung cancer mortality ratio for workers exposed only to sulfuric acid (n = 722) was lower (SMR = 1.39), but further restriction to the time 20 years and more from first employment in a job with probable daily sulfuric acid exposure (approximately equal to 0.2 mg/m3) yielded a mortality ratio of 1.93 (95% CI = 1.10-3.13). An excess lung cancer risk was also seen in workers exposed to acids other than sulfuric acid (SMR = 2.24; 95% CI = 1.02-2.46). When comparison was made to other steel workers (rather than to the U.S. general population) to control for socioeconomic and life-style factors such as smoking, the largest lung cancer excess was again seen in workers exposed to acids other than sulfuric acid (SMR = 2.00; 95% CI = 1.06-3.78). Adjustment for potential differences in smoking habits showed that increased smoking was unlikely to have entirely explained the increased risk. Mortality from causes of death other than lung cancer was unremarkable, with the exception of significantly low rates for deaths due to digestive system diseases.

Adolescent↗
PubMed1985

Effects of flunixin meglumine on blood pressure and fluid compartment volume changes in ponies given endotoxin.

A study was conducted to determine whether body fluids undergo a net shift from one compartment to another during endotoxin-induced shock in the pony, and whether flunixin meglumine alters these endotoxin-induced changes in the volumes of body fluid compartments. Total blood, RBC, and plasma volumes were determined, using 51Cr-labeled RBC and PCV that were corrected for trapped plasma. Total body water was measured by distribution of 3HOH. Arterial blood pressure was measured directly, using a blood pressure transducer. Treatment (flunixin meglumine, 1.1 mg/kg of body weight) was given to 6 of the 12 ponies 1 minute before an IV injection of Escherichia coli endotoxin (100 micrograms/kg of body weight, LD100). The PCV and RBC volume increased in both groups; however, the hemoconcentration was less in flunixin meglumine-treated ponies. In nontreated ponies, total blood volume and plasma volume decreased significantly during the first hour after endotoxin administration. In treated ponies, total blood volume did not vary significantly, and plasma volume decreased only slightly. In both groups, the increase in PCV was apparently due to splenic contraction, which increased the number of circulating RBC. Hemoconcentration was further increased in nontreated ponies by the loss of plasma into the interstitial space. Flunixin meglumine reduced plasma loss, minimized hemoconcentration, and maintained normal blood volume. Total body water remained constant in treated and nontreated ponies.

Animals↗
PubMed1984

Development of home orientation in offspring of protein-restricted cats.

The development of home orientation was evaluated in 2-14-day-old kittens nursing from mothers fed a protein-restricted or control diet during late gestation and lactation. Although restricted kittens remained in the home when placed in it, their ability to return to the home was delayed when they were removed from it. Restricted kittens also exhibited aberrant locomotor development and an increased frequency of loss of balance (upsets) en route to the home. During postnatal Week 1, vocalization frequency, an index of kitten disturbance when outside the home, was increased in restricted kittens tested in the home, and in adjacent and diagonal corners. Restricted kittens persisted in vocalizing more frequently than controls in home and adjacent corner tests during Week 2. Taken together, these data suggest that maternal protein restriction during late gestation and lactation disrupts the development of home orientation behavior by impairing locomotor function and increasing emotional responsiveness.

Animals↗