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Biomedical subjects

K Mohan

Publications and source records attributed to K Mohan.

At least 19 recordsLinked to original sources
PubMed1998

Interleukin-12 corrects severe anemia during blood-stage Plasmodium chabaudi AS in susceptible A/J mice.

The in vivo role of interleukin (IL)-12 in correcting anemia and the underlying defect in erythropoiesis in Plasmodium chabaudi AS-susceptible A/J mice was examined. Six daily intraperitoneal injections of 0.1 microg IL-12 in A/J mice, beginning on the day of infection, rapidly and significantly enhanced bone marrow and splenic erythropoiesis as demonstrated by marked increases in early and late committed erythroid progenitors, the erythroid burst (BFU-E) and colony-forming units (CFU-E), respectively, compared with control mice. The most dramatic effect of IL-12 treatment was a sevenfold increase in the number of splenic CFU-E on day 7 postinfection, compared with untreated, infected A/J mice. Treatment with IL-12 also caused significant increases in hematocrit levels, erythrocyte counts, percentage of reticulocytes, spleen cellularity, and frequencies of BFU-E and CFU-E in the bone marrow and spleen of A/J mice during infection. The frequency of BFU-E in the peripheral blood of these mice was also significantly increased, suggesting enhanced mobilization of precursor cells to the spleen as well as increased production of erythroid precursors in this organ. Consistent with previous observations using higher doses, 0.1 microg IL-12 administered daily for 6 days to normal A/J mice significantly decreased bone marrow erythropoiesis and significantly increased splenic erythropoiesis. However, the influence of IL-12 on erythropoiesis was much more pronounced during ongoing malaria infection. These results suggest a role for IL-12 during blood-stage malaria in not only enhancing the development of protective immunity but also in alleviating malaria-induced anemia by increasing the number of erythroid precursors and enhancing the expansion of committed erythroid progenitors.

Anemia↗
PubMed1997

Natural killer cell cytokine production, not cytotoxicity, contributes to resistance against blood-stage Plasmodium chabaudi AS infection.

Our recent study showed that IL-12 treatment of susceptible A/J mice induces Th1-mediated, protective immunity against lethal blood-stage Plasmodium chabaudi AS infection. To further understand the mechanism of this protection, we examined NK cell cytotoxic (NKCC) and cytokine secretory functions in untreated and IL-12-treated A/J mice, along with resistant C57BL/6 (B6) mice. Normal A/J mice receiving six daily doses of 0.1 microg IL-12 exhibited significant increases in NKCC in total spleen cell populations. Defective NKCC evident in vitro in enriched NK cells from infected A/J mice was corrected by addition of 10 ng/ml IL-12 and was comparable with that seen in B6 mice. In vivo and in vitro analyses revealed that enriched NK cells from day 6 infected A/J mice were defective not only in NKCC, but also in IFN-gamma, and to a certain extent, TNF-alpha secretion, which could also be corrected by IL-12 treatment. Depletion of NK cells from resistant B6 mice resulted in a more severe course of infection, while NK cell-depleted, IL-12-treated A/J mice had significantly higher parasitemia, as well as 100% mortality, suggesting the importance of NK cells in IL-12-mediated protection. NKCC-defective bg/bg mice produced optimum IFN-gamma and TNF-alpha and recovered from infection similar to bg/+ controls; in vivo depletion of these cytokines resulted in significantly higher parasitemia early in infection. Based on these results, we conclude that IFN-gamma, and possibly TNF-alpha, secretion by NK cells during early infection plays a major role in protective immunity to blood-stage malaria.

Adjuvants, Immunologic↗
PubMed1997

Phenotype and serotype of Pasteurella multocida isolates from diseases of dogs and cats in Zimbabwe.

A variety of disease manifestations, comprising skin bite wounds, pyothorax, respiratory and genitourinary tract infections, in 202 dogs and cats presented to the University Clinic, were investigated for the presence of Pasteurella multocida. Of these, 25-42% of various cases (69) were found to be infected with P. multocida. P. multocida-associated respiratory tract infections were more common than bite wounds or genitourinary tract infections. The regimen of treatment consisted of those antibiotics, sensitivity to which had been confirmed in vitro. Following detailed characterization of the isolates of P. multocida, in order to assign them to the reclassified taxa of Pasteurella, a preponderance of P. multocida subspecies multocida and septica were recorded. There did not appear to be a correlation between the reclassified taxa and their serotypes. Certain strains of different species or subspecies belonged to a common serotype and vice versa. However, the strains which were serotyped belonged to capsular type A, except for a solitary isolate from a cat which was capsular type D. Type D is known to cause atrophic rhinitis and does not appear to have been isolated either from a dog or a cat. Two strains, one from a dog and another from a cat, were identified as group EF-4 bacteria. This group of organisms has been incriminated in human wounds resulting from dog/cat bites, and has so far not been reported in Africa. Three different species, P. stomatis, P. dagmatis and P. multocida subspecies multocida were simultaneously isolated from a case of chronic bronchitis in a dog. There was no evidence of any relationship between disease manifestation in a host and the isolation of a particular taxon of Pasteurella, except that P. canis and Pasteurella taxon 16 were only isolated from dogs.

Animals↗
PubMed1997

Analysis of the maternal components of the AIDS clinical trial group 076 zidovudine regimen in the prevention of mother-to-infant transmission of human immunodeficiency virus type 1.

To gain insight into the protective effects of the three components of the zidovudine regimen used in AIDS Clinical Trial Group (ACTG) 076 on mother-to-infant transmission of human immunodeficiency virus (HIV) type 1, 188 zidovudine-treated women and their untreated infants from five HIV-1 obstetric centers were retrospectively studied. The overall rate of mother-to-infant transmission was 12.3% (95% confidence interval [CI], 7.9%-18.0%). When the 38 women with <200 CD4 cells/microL were excluded, the mother-to-infant transmission rate was 8.8% (95% CI, 4.6%-14.8%). This rate compares favorably with the 8.3% transmission in the zidovudine arm of the ACTG 076 study. Apart from low (<200/microL) maternal CD4 cells (P = .016), no factors, including the duration of zidovudine therapy during gestation and intravenous administration of zidovudine during labor, affected the rate of mother-to-infant transmission. These findings suggest that antenatal oral zidovudine may be as effective as antenatal oral plus intravenous zidovudine during labor and the three-component ACTG 076 regimen in decreasing mother-to-infant HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Mycoplasma crocodyli sp. nov., a new species from crocodiles.

Organisms with the typical characteristics of mycoplasmas were isolated from joints and lungs of crocodiles. The results of growth inhibition tests and immunobinding assays showed that the 24 mycoplasma strains isolated were identical and distinct from previously described Mycoplasma, Entomoplasma, Mesoplasma, and Acholeplasma species. These organisms represent a new species, for which the name Mycoplasma crocodyli is proposed. M. crocodyli ferments glucose and maltose, does not produce films and spots, does not hydrolyze arginine, esculin, and urea, reduces tetrazolium chloride, and possesses phosphatase activity. It lyses and adsorbs bovine, ovine, and rabbit erythrocytes. Cholesterol or serum is required for growth. The optimum growth temperature is 37 degrees C. The G + C content of the DNA is 27.6 mol%. This organism causes exudative polyarthritis in crocodiles. The type strain of M. crocodyli is strain MP145 (= ATCC 51981).

Alligators and Crocodiles↗
PubMed1997

Strains of Actinobacillus spp. from diseases of animals and ostriches in Zimbabwe.

Among the Actinobacillus spp. only A. lignieresii represents a homogenous and well studied taxon. However, haemolytic and non-haemolytic strains of A. equuli and A. suis are also isolated from a wide range of diseases in a variety of hosts. These isolates often pose problems in definitive identification. Consequently, several studies have been published, emphasizing the need for detailed studies to reclassify various members of this genus and also to assess their disease significance. We isolated 48 strains of Actinobacillus from clinical cases in horses, cattle, sheep, cat, pigs and ostrich. In order to investigate the association of various taxa of Actinobacillus in different pathological conditions in these hosts, the Zimbabwean isolates were characterized in detail and assigned to the recently described taxa of Actinobacillus. Representative strains of different taxa were also confirmed at the Department of Veterinary Microbiology, Frederiksburg C, Denmark. Of the 48 isolates, 22 were identified as A. lignieresii, 13 as A. equuli; 6 as A. suis, four as belonging to Taxon 11 and one as belonging to Taxon 9. These two taxa were recently described. Details of pathological conditions in the respective hosts and the significance of isolation, are discussed. We have reported for the first time isolation of A. lignieresii from a post-operative wound in a cat and there is also a first report of isolation from an ostrich. We considered A. equuli to be the primary cause of equine abortion and septicaemia, and Taxon 9 as causing "sleepy foal" disease. We did not encounter any case of "wooden tongue", but isolated A. lignieresii from cases of superficial lymphadenitis in cattle and sheep. This appears to be a first report of detailed descriptions of Zimbabwean strains of Actinobacillus spp.

Actinobacillus↗
PubMed1996

Diversity of energy-yielding substrates and metabolism in avian mycoplasmas.

The metabolism of organic substrates and production of H2O2, a potential pathogenicity factor, were studied in the type strains of fourteen avian Mycoplasma species, and in low-passage isolates of M. gallinarum, M. gallisepticum, M. iners and M. pullorum. Substrates were added to cell suspensions in Ringer or saline solution and oxygen uptake and/or change in pH monitored. The fermentative species could be sub-divided according to whether O2 uptake did (M. anatis, M. columborale, M. gallisepticum, M. imitans and M. iowae) or did not (M. gallinaceum, M. gallopavonis and M. pullorum) accompany glucose metabolism and the five non-fermentative, arginine-hydrolysing strains according to whether organic acids (lactate, 2-oxobutyrate, pyruvate) were (M. columbinasale, M. columbinum and M. gallinarum) or were not (M. iners and M. meleagridis) oxidized, Lysed cells of strains which consumed O2 during glucose or organic acid metabolism had relatively high NADH oxidase activity (170-950 nmol min-1 mg cell protein-1) and produced 0.02-0.36 mol H2O2 per mol O2 consumed during NADH oxidation. In contrast, strains which did not oxidize organic acids or consume O2 during glucose or organic acid metabolism possessed low NADH oxidase activity (< or = 20 nmol min-1 mg cell protein-1). All arginine-hydrolysing species showed a high affinity (Km value 1-3 microM) towards arginine. The fermentative species similarly showed a high affinity (Km value 2-5 microM) towards glucose, but used only a small number of additional sugars at detectable rates. All M. pullorum strains metabolized sucrose (Km < or = 3 microM). The type-strains of M. gallisepticum and M. imitans were biochemically similar and had high affinities for fructose and mannose. A number of low-passage avain isolates, but none of the type strains, metabolized glycerol and, in lysed cells, oxidized L-alpha-glycerophosphate (GP) with the production of 1 mol H2O2 per mol GP.

Animals↗
PubMed1996

Outbreak of meningitis in weaner pigs caused by unidentified asaccharolytic gram-negative bacterium.

Several organisms are known to cause outbreaks of meningitis in pigs, with Haemophilus species being the most frequently implicated. We report such an outbreak in which necropsied pigs manifested an unusual combination of meningitis, tracheitis, and bronchitis. The causative agent appeared to be an asaccharolytic gram-negative nonfermentative bacterium whose classification has yet to be determined. The organism was isolated from the brain and was extremely capnophilic, growing in air only after several serial subcultures.

Animals↗
PubMed1996

Brucellosis surveillance and control in Zimbabwe: bacteriological and serological investigation in dairy herds.

Brucellosis in dairy cattle is endemic in Zimbabwe. The prevalence continues to be monitored intensively. Only milk and serum samples are routinely screened. Attempts to culture Brucella spp. from clinical specimens are seldom made. Consequently, incidence of various Brucella spp. within Zimbabwe is virtually unknown, despite the high serepositivity reported. This information is paramount in understanding the transmission cycle and is also significant to public health; particularly as B melitensis infects humans more often than do the other brucellae. This paper describes the results of bacteriological and serological investigations of brucellosis in a dairy from near Bulawayo. The said farm was selected for the present pilot study because of the high incidence of reported abortion. The milk ring test was employed to test the bulk pooled milk samples once a month for 14 months. The test was recorded highly positive on all 14 occasions. To locate reactors, milk samples from 36 individual cows were similarly tested. Of these, 21 (almost 59%) were found to be reacting positively. One hundred and seventy-seven animals were marked for serotesting. Of these 40 (approximately 25%) showed quite high serum titres (> 1:360) in both the STT and the Rosebengal test. The farmer was advised to havet all abortions full investigated. However, all the clinical material from cases of abortion, except one, were received in an advanced state of putrefaction. From this, Brucella was isolated on culture from stomach contents and cotyledons. The isolates from both the sites were characterized in detail, employing dye inhibition, phagetyping; the oxidative metabolic test and agglutination with monospecific sera. Both the isolates belonged to B. abortus biovar I, which was confirmed by the Central Veterinary Research Laboratory, Weybridge. The significance of isolation and the need to intensify similar studies have been discussed.

Animals↗
PubMed1995

Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane damage and red cell loss during malaria.

The role of Plasmodium falciparum and blood monocytes in the erythrocyte damage and pathogenesis of anemia has been investigated using two strains of the parasite; one laboratory-established strain (FSJ-M) and one wild, fresh, clinical isolate (PfPGI). Peripheral blood monocyte-induced growth inhibition of the parasites, erythrocyte membrane lipid peroxidation as seen by the formation of lipid peroxide products, and sensitivity to peroxide hemolysis at atmospheric oxygen were evaluated. The growth inhibition of FSJ-M by activated blood monocytes was greater than that of PfPGI. The extent of lipid peroxidation and sensitivity to hemolysis increased significantly as the parasites matured. These adverse effects were more marked following exposure to activated monocytes, especially in synchronized, parasitized RBCs. In addition, uninfected erythrocytes within the PfPGI parasite culture revealed a significant increase in the lipid peroxide formation (P < 0.01) and susceptibility to lysis (P < 0.05) under similar oxidant stress induced by monocytes from normal healthy donors. Furthermore, there was a direct correlation between membrane lipid peroxidation and peroxide hemolysis, both before and after monocyte exposure, suggesting a primary role of membrane peroxidation in red cell lysis. The contribution of intraerythrocytic parasites and nonspecific activation of blood monocytes in the pathophysiology of erythrocyte damage and anemia of P. falciparum infection is discussed.

Adult↗
PubMed1995

Mycoplasma-associated polyarthritis in farmed crocodiles (Crocodylus niloticus) in Zimbabwe.

Outbreaks of polyarthritis in farmed crocodiles (Crocodylus niloticus) on five farms in Zimbabwe are described. Cases were reported only among the rearing stock aged 1-3 years. No breeding stock suffered. Morbidity was about 10% and the mortality even lower. All the sick animals consistently displayed swollen limb joints as well as progressive lameness and paresis. The synovial structures in subacute cases contained mycoplasmas and excess turbid mucus which, at a later stage of the disease, became yellowish, inspissated and sterile. Cellular changes in the joint capsule included oedema, necrosis of the superficial layers of membrane, lymphocytic infiltration and fibrosis. Evidence of pneumonia was observed only at necropsies. Fifteen isolates of Mycoplasma were cultured from the clinical specimens collected from the four sick and three dead crocodiles. The affected joints of all these animals yielded Mycoplasma in pure culture, but the culture from lungs yielded post-mortem invaders also. The sick animals were treated with a single intramuscular injection of long-acting tetracycline (10 mg/kg), and oxytetracycline mixed in feed at 550 mg/kg was fed for 10 d. The treatment appeared to be effective in ameliorating the clinical signs, but in some cases inflammatory swelling persisted. All 15 the isolates conformed to the characteristics of the genus Mycoplasma, and were serologically indistinguishable in growth-inhibition (Gl) tests. Although these isolates shared the main biochemical characteristics of Mycoplasma capricolum, they differed serologically. Also goats were refractory to experimental infection with crocodile strains. In crocodile yearlings, however, the disease was reproduced with an isolate from one of the affected farms. The source of infection remained elusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Alligators and Crocodiles↗
PubMed1994

Phenotypic characterization of Zimbabwean isolates of Pasteurella multocida.

The phenotypic characteristics of 60 Zimbabwean isolates of Pasteurella multocida sensu stricto, from disease syndromes in different host species were studied. A number of representative strains were also serotyped. Consistent results were obtained in the tests for; catalase, oxidase, urease, indole, acid in glucose, inositol, salicin and sucrose. There was no obvious relationship between serotype, host or disease and the pattern of utilization of certain substrates by an isolate. This has been discussed in the context of recent proposals to reclassify Pasteurella and P. multocida on genotypic and phenotypic studies. It is suggested that notwithstanding the relevance of genetic studies in circumscribing P. multocida, the phenotype and disease significance of the taxon should not be ignored. A case of bronchitis in a dog which was simultaneously colonized by three different strains of Pasteurella is described. Also septicaemic pasteurellosis in a Nile crocodile (Crocodylus niloticus) is reported and for the first time prevalence of various serotypes in pasteurellosis of animals in Zimbabwe.

Alligators and Crocodiles↗
PubMed1994

Plasmodium falciparum and blood monocyte induced abnormalities in human erythrocyte cation homeostasis.

The role of Plasmodium falciparum and activated blood monocytes in bringing about erythrocyte membrane lipid peroxidation and in altering the enzyme activity associated with Ca2+ and K+ efflux was studied. An attempt was made to investigate the role of parasite and monocyte-mediated reactive oxygen species (ROS) in inhibiting Ca(2+)-Mg2+ ATPase and Na(+)-K+ ATPase in order to find out the cause of reported high intra-erythrocytic calcium and depleted potassium levels in parasitized erythrocytes (PRBC). The PRBC showed enhanced lipid peroxidation as indicated by increased malonyldialdehyde (MDA) formation which coincided with the maturity of the parasite. This was further enhanced following exposure of PRBC to activated blood monocytes. The Ca(2+)-Mg2+ ATPase activity was decreased as the parasite matured and was further hampered significantly in mature parasite-infected red cells exposed to activated blood monocytes. There was a good negative correlation between MDA formation and Ca(2+)-efflux from red blood cells suggesting the negative influence of ROS on Ca(2+)-efflux. The Na(+)-K+ ATPase activity did not reveal any significant change, both during parasite maturation as well as upon exposure to ROS from activated monocytes. We therefore suggest that inhibition of Ca(2+)-efflux and the resulting increased cytosolic Ca2+ in PRBC might have a role in structural and functional abnormalities of red blood cell, thus enhancing the red cell loss during P. falciparum infection.

Animals↗
PubMed1994

Increased glutathione cycling and vitamin E of P. falciparum infected erythrocytes fail to prevent spontaneous haemolysis.

In an attempt to understand the pathogenesis of anaemia in Plasmodium falciparum infection, the status of erythrocyte glutathione and vitamin E content in relation to the susceptibility of infected red cells to peroxide haemolysis was examined. Synchronized cultures of the parasite with either ring-, trophozoite or schizont-infected red cells showed a gradual increase in the reduced glutathione content which was significantly higher (p < 0.05) in schizont-infected cells. Trophozoite-infected cells revealed significant increase in oxidized glutathione (p < 0.01) suggesting an increase in glutathione utilization during active erythrocytic schizogony of the parasites. The membrane antioxidant vitamin E also showed an increased accumulation in trophozoite- and schizont-infected red cells (p < 0.05) but not in the uninfected or ring-infected erythrocytes. Despite a favourable change in these antioxidants, the infected as well as uninfected red cells from parasite cultures showed enhanced peroxide haemolysis (uninfected, p < 0.05; ring-rich, p < 0.05, trophozoite- and schizont-rich, p < 0.001). The study provided direct evidence for enhanced susceptibility of red cells to lysis, including those of uninfected cells exposed to parasite products. This might explain the cause for much higher red cell loss and anaemia during P. falciparum infection than all the infected cells put together.

Animals↗
PubMed1993

Effect of nifedipine on oxidative damage of erythrocytes in Plasmodium berghei-infected mice.

It is known that the calcium channel blocker (CCB), nifedipine, can inhibit phagocyte oxidative burst in Plasmodium berghei-infected mice. The extent of immunopathological changes as seen by the course of infection and membrane lipid peroxidation in nifedipine-treated mice was examined in comparison with untreated mice at different parasite loads. The glutathione antioxidant system was also studied in these animals to assess its capacity to neutralize reactive oxygen species (ROS) in infected erythrocytes. The survival period of nifedipine-treated, infected mice decreased significantly. It was observed that the accumulation of reduced glutathione was greater and the decrease in glutathione peroxidase activity was less marked in drug-treated animals, suggesting better protection of the parasites against oxidative injury. The accumulation of the lipid peroxidation product, malonyldialdehyde was significantly lower in nifedipine-treated animals at all parasitemia levels studied, indicating decreased ROS generation and parasite damage. These observations reveal the shortcomings of using CCB to reverse the chloroquine resistance in malaria as this would minimize oxidative damage of parasitized red cells and phagocyte-mediated parasite killing.

Animals↗
PubMed1993

Altered course of Plasmodium berghei infection by nifedipine treatment.

The effect of nifedipine (a calcium channel blocker) on the course of P. berghei infection was examined. It was observed that mice receiving a daily dose of 0.015 mg/kg of nifedipine had significantly shorter prepatent, patent and survival periods as compared to untreated P. berghei-infected animals (p < 0.001). This shows that the calcium channel blockers, in addition to possessing the property of reversing drug resistance during combined therapy with chloroquine, may also alter the pathophysiology of malaria infection. The decreased resistance of the host to the invading parasite suggests that the effect of CCB on the host-parasite interaction in human malaria needs to be investigated further before CCB can be used in combination with chloroquine for the treatment of chloroquine-resistant malaria or for chemoprophylaxis.

Animals↗
PubMed1993

Generation of reactive oxygen species by blood monocytes during acute Plasmodium knowlesi infection in rhesus monkeys.

The status and kinetics of monocyte activation during acute P. knowlesi infection was investigated by latex-induced, luminol-dependent chemiluminescence (CL) response. The contribution of various reactive oxygen species (ROS) to CL response was estimated before infection and at peak parasitaemia (day 7 post infection) by using scavengers of ROS (benzoate, catalase and superoxide dismutase). The chemiluminescence index (CLI) was not found to be significantly different from controls on day 2 postinfection, but was significantly higher on days 5 and 7 postinfection. Hydroxyl radical (OH.) production was considerably elevated, whereas superoxide anion (O2-.) and hydrogen peroxide (H2O2) production dropped following infection. These changes in generation of ROS are discussed in relation to the progression of parasitaemia to high levels, immunopathology and immunosuppression during acute P. knowlesi infection.

Animals↗