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Biomedical subjects

A L Richards

Publications and source records attributed to A L Richards.

At least 37 records · Page 2Linked to original sources
PubMed1996

Assessment of arthropod vectors of infectious diseases in areas of U.S. troop deployment in the Persian Gulf.

Beginning in August 1990, approximately 800,000 coalition troops were deployed to the Persian Gulf during Operations Desert Shield and Desert Storm. There was substantial concern about arthropod-borne diseases, particularly sand fly fever and cutaneous leishmaniasis, because of high morbidity rates in the Persian Gulf during World War II (WWII). In sharp contrast to WWII, there was no report of sand fly fever among coalition forces and only 31 cases of leishmaniasis among 697,000 U.S. troops. To further evaluate the risk of arthropod-borne diseases, an entomologic survey was conducted in 12 areas of Kuwait and Saudi Arabia. A total of 1,556 arthropods was collected during four survey periods in 1992. The suspected vectors of cutaneous Leishmania major infection, sand fly fever, West Nile fever, Rift Valley fever, and Crimean-Congo hemorrhagic fever were identified; however, there was no evidence of arboviruses or Leishmania among collected specimens nor from 51 trapped rodents. There are several possible reasons for the low risk of arthropod-borne infectious diseases among Desert Shield/Storm troops in an area where suspected vectors frequently were found: the use of insecticides and repellents, and the deployment of most ground troops to the open desert during the cooler, winter period--conditions least favorable for the transmission of arthropod-borne diseases.

Animals↗
PubMed1996

A non-invasive assessment of hepatitis B virus carrier status using saliva samples.

A non-invasive testing method to determine hepatitis B virus (HBV) carrier status in pregnant women was evaluated. Paired serum and saliva samples were collected and assessment of hepatitis B markers were performed. Of the 502 women enrolled, 5.6% (28/502) of their sera were found to be positive for HBV surface antigen (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the saliva reactive samples were matched to the serum reactive samples (50% sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were non-reactive for HBeAg. This report found a non-invasive saliva testing method to be a possible alternative approach for determining chronic HBV carrier status if the sensitivity of the test can be improved.

Carrier State↗
PubMed1996

Anthelminthic treatment raises plasma iron levels but does not decrease the acute-phase response in Jakarta school children.

The study was conducted to investigate the impact of intestinal helminthiasis and treatment on iron status and acute phase response (APR) among urban Indonesian primary school children, aged 8-11 years old. The prevalence of helminthiasis among these children was; Ascaris lumbricoides, 81.6%; Trichuris trichiura, 88.3%; and mixed infection of A. lumbricoides and T. trichiura, 70.0%. Of 120 children enrolled in the investigation, 59 received a single 400 mg dose of albendazole, and 61 received a placebo. Ten days following treatment, the prevalence of ascariasis and trichuriasis in the treatment group diminished to 0% and 27%, respectively, and in the placebo group to 63.9% and 68.9%. Plasma iron, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) concentrations were determined prior to the intervention and 10 days after. Plasma iron concentrations and WBC count rose in the treatment group (p=< or =0.05) when compared to baseline status. Increases in hemoglobin concentrations observed in the treatment group 10 days post-treatment were not statistically significant. CRP, IL-1, IL-6 and TNF were found to be within normal limits for both groups both before and after treatment. ESR increased significantly in both treatment and placebo groups when compared the rates measured before treatment. These findings show that treatment with albendazole is associated not only with a decreased worm burden in school children, but also a rise in plasma iron.

Acute-Phase Reaction↗
PubMed1995

Randomised placebo-controlled trial of primaquine for prophylaxis of falciparum and vivax malaria.

Drug resistance has made malaria prevention difficult and the new agents are too expensive for widespread use. Primaquine, an established drug for treatment, is potentially useful for prevention. Malaria prophylaxis with primaquine was evaluated in Irian Jaya during one year in Javanese men who were not deficient in glucose-6-phosphate dehydrogenase (G-6-PD). 126 volunteers were randomised to receive 0.5 mg/kg primaquine base or placebo daily (double-blinded), or 300 mg chloroquine base weekly (open). The protective efficacy of primaquine relative to placebo was 94.5% (95% confidence interval 57-99) for Plasmodium falciparum and 90.4% (95% CI 58-98) for P vivax. Attack rates for either parasite did not differ significantly between the chloroquine and placebo groups. Incidence density of physical complaints not associated with parasitaemia was low (17-18 complaints/person-year) and was about the same in all groups except for cough, which was increased in the primaquine group. Complete blood counts were normal and no evidence of hepatic or renal dysfunction was found with primaquine. However, at 50 weeks the primaquine group had a mean methaemoglobin of 5.8% (range 1.4-13%), which declined by half within 7 days of ending prophylaxis. When used daily for one year by men with normal G-6-PD activity, primaquine was well tolerated and effective for prevention of malaria.

Adolescent↗
PubMed1994

Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets.

A novel lipid-dependent protein kinase in human platelets was partially purified and characterized. This enzyme was calcium-independent and was selective for phosphatidic acid as a cofactor/activator with initial activation observed at approximately 2 mol % and peak activity achieved at 4 mol % phosphatidic acid. In the presence of phosphatidylserine, enzyme activation was observed with concentrations of phosphatidic acid as low as 0.5 mol % with peak activity at 2 mol %. Other anionic phospholipids also activated the enzyme but to a lesser extent and with less potency. Enzyme activity was independent of diacylglycerol or phorbol esters and the enzyme did not bind [3H]phorbol dibutyrate. In a soluble protein kinase assay, the enzyme was activated by cis-unsaturated fatty acids with maximum activation occurring at 5-10 microM sodium oleate. Western blot analysis showed that this enzyme did not cross-react immunologically with antibodies raised against the currently identified isoenzymes of protein kinase C. A number of additional biochemical criteria distinguished this enzyme from known isoenzymes of protein kinase C. These biochemical and immunologic data define a novel lipid-dependent protein kinase in human platelets. The role of this enzyme in signal transduction as a phosphatidic acid-activated enzyme and as a possible target for cis-unsaturated fatty acids is discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Acute sporadic hepatitis E in Kuwait.

Fifty-seven adult patients with acute hepatitis and 34 comparison patients without liver disease were evaluated using a newly developed Western blot assay for IgM antibody to hepatitis E virus. The mean age of patients with hepatitis was 32 years (range, 18-55 years); 88% were male. Among patients with acute hepatitis, hepatitis A (anti-HAV IgM positive) was diagnosed in two (4%), hepatitis B (anti-HBc IgM positive) in three (5%), and hepatitis E (anti-HEV IgM positive) in 34 (60%). One hepatitis patient had CMV IgM, another had EBV IgM, and 16 others (28%) were negative for all serologic markers of acute viral hepatitis. No patient with acute hepatitis A or B and none of the comparison patients without acute hepatitis had anti-HEV IgM. All but one case of acute hepatitis E were found among expatriates of Asian origin, and acute hepatitis E was associated significantly with recent travel to the Indian subcontinent. These data suggest that acute hepatitis E is common among foreign workers in Kuwait but that little HEV transmission is occurring directly in Kuwait.

Acute Disease↗
PubMed1994

Laboratory and field trials of four repellents with Culex pipiens (Diptera: Culicidae).

During Operation "Desert Shield," 16 volunteers field-tested four insect repellents (deet, the lactone CIC-4, and the piperidine compounds AI3-37220 and AI3-35765) against biting mosquitoes at King Fahd Airport, Eastern Province, Saudi Arabia. CIC-4 and AI3-37220 (25% wt/vol) provided effective (> 90%) protection against bites for 4 h. Deet and AI3-35765 protected for only 2 h. The compounds subsequently were evaluated for repellency against laboratory-reared Culex pipiens L. CIC-4 was more effective than deet, AI3-37220, or AI3-35765 at the ED50 but not at the ED95 level in initial sensitivity tests using human volunteers. At the ED95 level, deet provided significantly better protection than either piperidine compound. In laboratory duration tests, AI3-37220 provided 8 h of effective (> 90%) protection against Cx. pipiens bites, deet and AI3-35765 7 h of protection, and CIC-4 2 h of protection.

Animals↗
PubMed1993

Respiratory disease among military personnel in Saudi Arabia during Operation Desert Shield.

OBJECTIVES: The purpose of this study was to determine whether respiratory disease due to crowded living conditions and high levels of suspended and blowing sand had a major adverse impact on US military personnel during Operation Desert Shield. METHODS: A questionnaire survey was administered to 2598 combat troops stationed in Northeast Saudi Arabia for a mean of 102 days. Samples of surface sand from seven different locations were analyzed by scanning electron microscopy and x-ray diffraction. RESULTS: Among surveyed troops, 34.4% reported a sore throat, 43.1% complained of a cough, 15.4% complained of chronic rhinorrhea, and 1.8% were unable to perform their routine duties because of upper respiratory symptoms. Evaluation of sleeping accommodations indicated that complaints of a sore throat and cough were most closely associated with sleeping in air-conditioned buildings; in contrast, complaints of rhinorrhea were associated with exposure to the outdoor environment while living in tents. Sand samples consisted mostly of quartz, with just 0.21% by weight of respirable size (< 10 microns in diameter). CONCLUSIONS: These findings indicate that upper respiratory complaints were frequent among Operation Desert Shield troops and were related both to the troops' housing and to their exposure to the outside environment.

Adolescent↗
PubMed1991

Selective inhibition of natural killer but not natural cytotoxic activity in a cloned cell line by delta-9-tetrahydrocannabinol.

Natural killer (NK) and natural cytotoxic (NC) activities are spontaneously generated against certain tumors in vitro and their contribution to tumor immunity is being extensively investigated. We report here that the interleukin-2 (IL-2)-dependent murine cell line, NKB61A2, which we recently found to express both NK and NC functions, can be modulated selectively by 9 delta-tetrahydrocannabinol (THC). THC, a major psychoactive metabolite of marijuana, could significantly inhibit NK activity without altering NC activity in NKB61A2 cells. Inhibition of NK function occurred at a post-binding stage because effector/target conjugation was unaffected by THC. With regard to NC function, neither the cytotoxic activity of the cells nor release of tumor necrosis factor was interrupted by THC. Therefore, THC may provide a useful tool for dissociating the mechanism of NK and NC activities within a single population of cells.

Animals↗
PubMed1991

Ethnic comparison of haloperidol and reduced haloperidol plasma levels: Taiwan Chinese versus American non-Chinese.

Steady-state haloperidol (HAL) and reduced HAL (RHAL) plasma levels were measured in Chinese and non-Chinese schizophrenic patients. The patients (n = 38) were matched according to age (+/- 1 yr) and by HAL dose. In general, Chinese patients had higher mean plasma HAL levels and lower RHAL/HAL ratios compared to non-Chinese patients (23.6 +/- 14.9 ng/ml versus 17.1 +/- 10.1 ng/ml, p less than 0.05; 0.52 +/- 0.44 versus 0.82 +/- 0.62, p less than 0.05). Six groups were formed according to HAL dose (number per group): 10 mg/day (6); 20 (11); 30 (11); 40 (4); 50 (3); and 60 (3). No significant differences were found in age, weight and dose/weight. In each dose group, HAL plasma levels were generally higher in the Chinese patients than in the non-Chinese patients, though significance was only detected in the 30 mg group (26.1 +/- 7.0 ng/ml versus 18.5 +/- 5.1 ng/ml, p = 0.035) and a slight trend in the 40 mg group (36.0 +/- 15.0 ng/ml versus 23.5 +/- 10.4 ng/ml, p = 0.074). RHAL/HAL ratios were generally lower in the Chinese patients than in the non-Chinese patients, with a strong trend toward the significance level in the 20 mg and 30 mg groups (0.22 +/- 0.13 versus 0.58 +/- 0.57, p = 0.066 and 0.43 +/- 0.26 versus 0.71 +/- 0.34, p = 0.062). This study further suggests the possibility of different metabolic rates between Chinese and non-Chinese patients. Possible differences in the enzyme systems which relate to the metabolism of HAL and RHAL between Chinese and non-Chinese populations are discussed.

Adult↗
PubMed1990

Calcium-dependent natural killer and calcium-independent natural cytotoxic activities in an IL-2-dependent killer cell line.

Using a cloned murine cell line, NKB61A2, that concomitantly exhibits both NK and natural cytotoxic (NC) activities, we investigated the biochemical mechanisms involved in natural cell mediated cytotoxicity against NK-sensitive YAC-1 tumor cells and against the NC-sensitive WEHI-164 tumor cells. Recent reports have suggested that target cell lysis by cytotoxic lymphocytes occurs by either a calcium dependent and/or a calcium-independent mechanism(s). To determine the role of calcium in NK and NC activities of the NKB61A2 cell line, we evaluated the effect of: 1) extracellular Ca2+ depletion by the divalent cation chelator, EGTA, 2) Ca2+ influx blockade by the Ca2+ channel blocker verapamil, and 3) blocking of intracellular Ca2+ mobilization by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8). We found that EGTA, verapamil, and TMB-8 were all capable of inhibiting NK activity, but they had little effect on NC activity of the NKB61A2 cells. Using 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide which are inhibitors of protein kinase C and calmodulin respectively, we determined that protein kinase C and calmodulin do play a role in the NK activity of NKB61A2 cells. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and N-(6-aminohexyl)-5-chloro-1-naphthalanesulfonamide, similar to Verapamil and TMB-8, had no effect on NC activity. Thus, the data indicate that the NK activity of NKB61A2 cells is calcium dependent whereas NC activity is not. These results may explain the disparate reports seen in the literature of calcium-dependent and -independent lysis of tumor cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Haloperidol and reduced haloperidol plasma levels in Chinese vs. non-Chinese psychiatric patients.

Haloperidol and reduced haloperidol plasma concentrations were measured in age-matched Chinese and non-Chinese patients (n = 32). Steady-state plasma concentrations were obtained 10-12 hours after the bedtime dose. Haloperidol and reduced haloperidol concentrations were measured by liquid chromatography and radioimmunoassay. Haloperidol plasma concentrations did not significantly differ between the populations, but reduced haloperidol levels were 3 times greater in non-Chinese patients than in Chinese patients. The incidence of extrapyramidal side effects was higher in Chinese patients (18 vs. 10), while non-Chinese patients with extrapyramidal symptoms had higher reduced haloperidol plasma levels. Logistic regression analysis revealed that ethnicity and reduced haloperidol/haloperidol ratios were important variables in predicting extrapyramidal symptoms. These results suggest that the metabolism and disposition of haloperidol and reduced haloperidol could differ among ethnic populations.

Adult↗
PubMed1989

Natural cytotoxic activity in a cloned natural killer cell line is mediated by tumor necrosis factor.

The interleukin-2-dependent mouse natural killer (NK) cell line NKB61A2 concomitantly exhibits NK and natural cytotoxic (NC) activities. This was determined by the cells' ability to lyse both the NK-sensitive YAC-1 lymphoma and the NC-sensitive WEHI-164 fibrosarcoma cell lines in a 4- and 18-hour 51Cr release assay, respectively. Cell-free supernatant from NKB61A2 cells grown in culture for 48 h had substantial lytic activity against WEHI-164. The mouse mast cell line PT18-A17 and the rat basophilic leukemia cell line RBL-2H3, which both express NC activity, also produced a soluble factor during culture which lysed WEHI-164 cells. This activity was increased in the basophilic/mast cells by crossbridging the surface IgE receptors. Similar results were obtained by triggering the basophilic NC cells with the calcium ionophore ionomycin and the tumor promoter phorbol-12-myristate-13-acetate (PMA). Such triggering of NKB61A2 cells, however, did not significantly increase their NC activity. Interestingly, both ionomycin and PMA had an inhibitory effect on the NK activity of NKB61A2. Recently it has been found that tumor necrosis factor (TNF) is a major mediator of NC activity. To determine if the soluble factor responsible for the NC activity of the NK clone was related to TNF, a rabbit polyclonal antiserum to mouse TNF was tested against the cell-free culture medium of NKB61A2, PT18-A17, RBL-2H3 and murine recombinant TNF (Mu-rTNF). The lytic activity of the culture medium from all these cells and the Mu-rTNF control was abrogated by this antibody. These data suggest that the murine cell line NKB61A2 has both NK and NC activities and that the NC activity is due to a factor immunologically similar to TNF. In addition, the enhancement of NC activity in the NK cell line is apparently under control by a separate pathway, different from that in the basophilic cells.

Antibodies, Monoclonal↗
PubMed1988

Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes.

Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from NK cells by certain tumor cells. Sendai virus has also been reported to induce TNF from macrophages. We report here that an opportunistic fungi, Candida albicans, can also induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes (LGL) which mediate NK function. Incubation of monocytes of LGL with C. albicans for 8 h was sufficient for detection of TNF release and peak induction was observed at 24 h. Induction of TNF from LGL did not require the participation of monocytes or T cells because treatment of the LGL with CD14 or CD15 to eliminate contaminating monocytes and CD3, CD4, or CD8 to eliminate contaminating T cells did not decrease the level of TNF produced from the treated LGL. Small T cells recovered from the denser fractions of the Percoll gradient had no ability to produce TNF, even when 10% monocytes were added to the T cells to provide accessory function. The phenotype of the TNF-producing LGL was CD2+, CD11+, CD16+, NKH1+, LEU7-. The TNF produced by both monocytes and LGL was neutralized by specific monoclonal and polyclonal anti-TNF but not by monoclonal antilymphotoxin. These results indicate that TNF production is a normal response of monocytes and LGL to stimulation by fungi such as C. albicans and that the release of TNF may be related to its ability to activate effector function to control Candida growth, which we have shown earlier for neutrophils with TNF.

Antibodies, Monoclonal↗
PubMed1988

Natural cytotoxic cell-specific cytotoxic factor produced by IL-3-dependent basophilic/mast cells. Relationship to TNF.

The murine IL-3-dependent mast cell line, PT18-A17, and the rat basophilic leukemia cell line, RBL-2H3, were found to mediate natural cytotoxic (NC) activity via the release of a soluble factor which specifically lysed NC-sensitive WEHI-164 but not NK-sensitive YAC-1 tumor cells. The release of this NC cell-specific cytotoxic factor was enhanced by triggering of both types of cells via IgE receptor bridging. This factor had activity on TNF-sensitive but not TNF-resistant cell lines and could be neutralized by two independently produced polyclonal anti-mouse TNF antisera. It was not neutralized by antibodies against mouse IFN-alpha/beta or IFN-gamma. Moreover, it was not neutralized by a monoclonal or a polyclonal anti-human TNF, demonstrating that the rodent TNF differed antigenically from human TNF. These results indicate that the cytotoxic factor released from a murine IL-3-dependent mast cell line and from a rat basophilic leukemia cell line is immunologically and functionally related to murine TNF.

Animals↗