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Biomedical subjects

M A Williams

Publications and source records attributed to M A Williams.

At least 109 records · Page 6Linked to original sources
PubMed1999

Prevalence of antibodies to Neospora sp. in horses from Alabama and characterisation of an isolate recovered from a naturally infected horse [corrected].

An IFAT was used to determine the prevalence of Neospora-specific IgG antibodies in serum from Alabama horses. Serum samples (n = 536) were from asymptomatic horses routinely submitted for equine infectious anaemia virus infection testing. We also subjected a 13-year-old horse with CNS disease to necropsy examination for isolation and in vitro cultivation of protozoal organisms. In antemortem tests, this horse was positive for antibodies to Neospora sp. in the IFAT and western immunoblot. Results of the prevalence survey indicated that IgG antibodies to Neospora were present in 62 (11.5%) of the 536 serum samples. Endpoint titres for the positive samples were 1:50 (35/6.5%), 1:100 (19/3.5%), 1:200 (7/1.3%) and 1:1600 (1/0.2%). Tachyzoites were first seen in cultured bovine turbinate cells 32 days after inoculation with spinal cord homogenates from the horse with CNS disease. Tachyzoites reacted with known N. caninum-positive serum from horses, cows, dogs and mice, but did not react with murine anti-Toxoplasma gondii or equine anti-Sarcocystis neurona serum. Ultrastructural features of tachyzoites and results of comparison of tachyzoite immunodominant proteins revealed that they were identical to those of N. hughesi, a species described recently from a naturally infected horse. The isolate recovered from the naturally infected horse in the present study (designated NA1) is thought to be an isolate of N. hughesi, although confirmation of this awaits additional molecular characterisation. These results provide some additional evidence that N. hughesi is a valid species and that Neospora infections in horses may occur in widely separated geographic regions of the United States.

Animals↗
PubMed1999

Plasma homocyst(e)ine concentrations in eclamptic and preeclamptic African women postpartum.

OBJECTIVE: To examine the relationship between plasma homocyst(e)ine and risk of eclampsia and preeclampsia among sub-Saharan African women who delivered at Harare Maternity Hospital in Zimbabwe. METHODS: We ran a hospital-based, case-control study at Harare Maternity Hospital, University of Zimbabwe, Harare, Zimbabwe comprising 33 pregnant women with eclampsia and 138 with preeclampsia. Controls were 185 normotensive pregnant women. Plasma was collected postpartum and homocyst(e)ine levels were measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Women with eclampsia or preeclampsia had significantly higher mean homocyst(e)ine levels than normotensive controls (12.54 or 12.77 micromol/L versus 9.93 micromol/L, respectively, P<.001). The odds ratio (OR) for eclampsia was 6.03 among women in the highest quartile of the control homocyst(e)ine distribution (median 13.9 micromol/L) compared with women in the lowest quartile (median 6.2 micromol/L). The corresponding OR for preeclampsia was 4.57. Nulliparas with elevated homocyst(e)ine had a 12.90 times higher risk of preeclampsia compared with multiparas without elevated homocyst(e)ine. CONCLUSION: Postpartum plasma homocyst(e)ine concentrations are higher among Zimbabwean women with eclampsia and preeclampsia compared with normotensive women.

Adolescent↗
PubMed1999

Leukemia cell differentiation: cellular and molecular interactions of retinoids and vitamin D.

1. The conventional approach to treatment of acute myeloid leukemia has been the use of chemotherapy, which although being cytotoxic to malignant clones, is also cytodestructive to normal cells. In addition, some leukemia cells develop resistance to chemotherapy and are therefore difficult to eradicate. 2. Differentiation therapy, whereby immature cells are induced to attain a mature phenotype by differentiation agents, has provided an alternative strategy in the treatment of hyperproliferative disorders. This has been highlighted by the use of all-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL). 3. Another differentiation agent, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), directs monocytic maturation of normal and leukemic cells. Cellular studies have revealed that combinations of vitamin D derivatives and retinoids such as ATRA and 9-cis retinoic acid (9-cis RA) exhibit cooperative effects on differentiation in established leukemia cell lines such as HL-60, U937, and NB4. Furthermore, vitamin D compounds, although not able to induce apoptosis when used alone, potentiate apoptosis induced by 9-cis RA in HL-60 cells and differentially regulate the expression of the apoptosis-related gene products bcl-2 and bax. The molecular mechanisms involved in regulating differentiation and apoptosis by these agents are mediated through the interactions of the nuclear receptors for vitamin D (VDR), ATRA (RAR), and 9-cis RA (RXR), which are able to form homo- or heterodimeric complexes and transcriptionally activate or repress target gene expression. 4. There is evidence to suggest that nitric oxide may also play a role in leukemic cell differentiation and that 1,25(OH)2D3 may influence endogenous nitric oxide production either by directly increasing tumor necrosis factor-alpha (TNF-alpha) or through a secondary mediator such as the C-type lectin CD23.

Acute Disease↗
PubMed1999

The incidence of gastric carcinoma in Asian migrants to the United States and their descendants.

OBJECTIVES: We examined the incidence of gastric carcinoma in Chinese, Japanese, and Filipino residents of the United States to obtain additional information about the etiology of this disease. METHODS: The age, race, and birthplace of residents of Hawaii, San Francisco/Oakland, and northwestern Washington who were diagnosed with gastric carcinoma during the period 1973-1986 were obtained from population-based registries, and a special tabulation from the 1980 Census was used to estimate the number of person-years at risk for each category of resident. RESULTS: The incidence of gastric carcinoma in Japanese-Americans was three to six times higher than that of US-born whites, with the highest rates occurring in those persons born in Japan. The rate in US-born Chinese and Chinese men who immigrated to the US was similar to that of whites, whereas the rate in Chinese female migrants was twice that of white American women. Filipino men, regardless of birthplace, were only at 60% the risk of US-born white men, while their female counterparts had a rate very similar to that of US-born white women. The high incidence observed among Japanese-Americans and Chinese female immigrants was largely restricted to sites other than the gastric cardia. CONCLUSIONS: Our findings suggest that dietary and other lifestyle differences between the different generations of Japanese-Americans, and between Japanese residents of the US and Japan may provide clues regarding the etiologies of stomach cancers that arise beyond the gastric cardia.

Adult↗
PubMed1999

Monocyte dysfunction in patients with multiple myeloma and lymphoplasmacytic disorders is related to serum paraprotein levels.

We have investigated monocyte function in 30 patients with lymphoplasmacytic disorders and in 21 age and sex matched normal controls. Marked abnormalities of all facets of monocyte function were demonstrated in six patients with multiple myeloma (MM) and a single patient with Waldenström's macroglobulinaemia (WM) plus significant paraproteinaemia. Serious infection occurred in three of these patients. An inverse relationship between the level of the serum paraprotein and impairment of monocyte phagocytosis plus killing of Candida albicans was observed. Crossover studies suggested that these abnormal findings were constitutive and not reversed by removal of the serum paraprotein. The data suggest that monocyte function is constitutively abnormal in patients with MM and can be further, but reversibly, inhibited by high paraprotein levels. Further research is required to confirm these findings, ascertain whether monocyte function can be normalized using chemotherapy or growth factors, and if so, whether their tumouricidal functions could be harnessed in the treatment of this currently incurable condition.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women.

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

Adipose Tissue↗
PubMed1999

The Washington State Intergenerational Study of Birth Outcomes: methodology and some comparisons of maternal birthweight and infant birthweight and gestation in four ethnic groups.

A statewide database of vital records and hospital discharge summaries of obstetric and neonatal admissions for Washington State in 1987-95 was linked to the birth certificates of mothers born in the state. A total of 46,000 births to mothers of four racial/ethnic groups were studied: Whites, African-Americans, Native Americans and Hispanics. For all four groups inverse associations were found between maternal birthweight and infant low birthweight and preterm birth. The birthweight distribution of African-American mothers was displaced markedly downwards compared with the Whites; this difference in maternal birthweight is offered as a partial explanation of the greater prevalence of suboptimal pregnancy outcomes in the former. In contrast, the maternal birthweight distributions of Whites, Native Americans and Hispanics are similar; differences in pregnancy outcomes are probably more related to maternal preconceptional and postnatal factors in these groups as well as differences in pregnancy-related factors. Mothers' birthweight may have clinical value in identifying high-risk pregnancies.

Adult↗
PubMed1999

A population-based cohort study of the relation between maternal birthweight and risk of gestational diabetes mellitus in four racial/ethnic groups.

Intrauterine growth retardation and low birthweight have been associated with an increased risk of insulin resistance and type II diabetes later in life. We hypothesised that maternal low birthweight is associated with an increased risk of gestational diabetes mellitus (GDM). Study subjects comprised women giving birth in Washington State between 1987 and 1995. Information for 21,528 births to non-Hispanic white women, 6359 to African-American women, 7456 to Native American women and 6496 to Hispanic women was available for analysis. All information was derived from statewide computerised vital records and hospital discharge summaries of obstetric and neonatal admissions with linkage to birth certificates of mothers. Maternal birthweight was collected from subjects' birth certificates. Information from both the birth certificates and the obstetric and neonatal admissions database was used to determine whether subjects developed GDM. Poisson regression models were estimated to calculate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for GDM by categories of maternal birthweight. The cumulative incidence of GDM among non-Hispanic white, African-American, Native American and Hispanic women was 2.8, 2.6, 2.7 and 3.0% respectively. After adjusting for maternal age, parity, cigarette smoking, history of chronic hypertension and participation in the Medicaid programme, non-Hispanic white women with a birthweight < 2000 g were 1.7 times more likely to have had their pregnancy complicated by GDM (RR = 1.7; 95% CI 0.8, 3.3) than those with a birthweight 3000-3999 g. The corresponding adjusted RRs for African-American, Native American, and Hispanic women were 2.8 [95% CI 1.2, 6.1], 3.1 [95% CI 1.2, 8.2] and 2.4 [95% CI 0.9, 6.0] respectively. Among African-American women, those with a birthweight > or = 4000 g also experienced a twofold increased risk of GDM (RR = 2.1; 95% CI 1.0, 4.1). This association of high birthweight and increased GDM risk was not found among women in the other three racial/ethnic groups. These findings suggest that individuals with low birthweight constitute a group at increased risk for GDM.

Adolescent↗
PubMed1999

Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia.

OBJECTIVE: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. STUDY DESIGN: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3, 042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels >/=5.5 micromol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3. 2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1. 1-9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1-14.1; p = 0.003). Women with a higher prepregnancy body mass index (>/=21.4 kg/m(2), or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4-32.1; p = 0.016). CONCLUSION: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.

Adult↗
PubMed1999

The utility of K-correction to adjust for a defensive response set on the MMPI.

This study examined the utility of the K-correction procedure to adjust for a defensive response set on the MMPI. The sample consisted of 61 patients with end-stage lung disease undergoing psychosocial evaluation for transplantation. Participants were separated into defensive and non-defensive groups using a median split on the K scale (defensive group T score 59) as the cutoff score. The MMPI was scored once in the standard manner and then rescored omitting all K-scale items from the clinical scales. As hypothesized, raw score analysis after omitting K-scale items showed the defensive group endorsed significantly fewer items on all five scales involving K-correction (Scales Hs, Pd, Pt, Sc, Ma). Analysis of K-corrected T scores on Scales Hs, Pd, Pt, and Sc using standard procedures showed a significant group difference only on Scale Hs with a higher T score found among the defensive group. The defensive and nondefensive groups were not significantly different in demographic, medical, or psychiatric characteristics suggesting that the tendency to respond in a defensive manner is the major characteristic that distinguishes the two groups. Taken together, these results provide support for the use of the K-correction procedure when examining MMPI clinical profiles among patients with end-stage pulmonary disease undergoing evaluation for transplantation.

Adaptation, Psychological↗
PubMed1999

Infusional paclitaxel and weekly vinorelbine chemotherapy with concurrent filgrastim for metastatic breast cancer: high complete response rate in a phase I-II study of doxorubicin-treated patients.

PURPOSE: We investigated 96-hour paclitaxel infusion combined with weekly (days eight and 15) vinorelbine as salvage therapy for metastatic breast cancer in anthracycline-exposed patients. All patients received scheduled support with granulocyte colony-stimulating factor (G-CSF; filgrastim). Tumor response, toxicity, time to progression (TTP), and survival were assessed. PATIENTS AND METHODS: This single-center nonrandomized trial enrolled 32 patients. Anthracycline exposure and subsequent progression were common to all patients. Paclitaxel and vinorelbine were escalated over three dosing levels, stratified by liver function. RESULTS: Seven patients (22%) achieved a complete response and nine patients achieved a partial response for an overall response rate of 50%. The median TTP was 6.1 months, and median survival time was 14.1 months. Dose-limiting toxicity was neutropenia, with dose delay or reduction in seven of 32 patients. Febrile neutropenia requiring hospitalization was uncommon (three of 32 patients; 9%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in two patients (6%), and 13 patients (41%) required RBC transfusions for anemia. Grade 3 nausea and vomiting was seen in one patient, who was found to be Addisonian. Despite potentially overlapping neurologic toxicities of the two agents, only two patients (6%) were removed from the study because of progressive peripheral neuropathy. CONCLUSION: Administration of 96-hour paclitaxel infusion and subsequent weekly vinorelbine with G-CSF support is well tolerated. The response rate, TTP, and survival data are encouraging for therapy given to anthracycline pretreated patients with metastatic breast cancer. If these results can be verified in multi-institution trials, this or a similar combination of drugs would merit investigation as first-line therapy in this patient population.

Adult↗
PubMed1999

The potential for monocyte-mediated immunotherapy during infection and malignancy--Part II: in vivo activation by exogenous cytokines and clinical applications.

The monocyte system exhibits a range of immunological mechanisms that may be harnessed for therapeutic effect against infection and malignancy. The advent of novel therapies aimed at treating infection and malignancy is complemented by a resurgence of clinical interest in immunotherapeutic programmes to treat diseases by modification or direct augmentation of host immunity. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma modulate the function of monocytes and have been used to experimentally probe the immunotherapeutic potential of monocytes against micro-organisms and malignancy. However, monocytes rarely act alone but communicate with other leukocytes involved in cell-mediated immunity. In particular monocytes cooperate with the T-helper (Th1 and Th2) sub-populations of peripheral lymphocytes. Moreover, sub-populations of monocytes, as identified by the co-expression of membrane-associated CD14 and CD16, have been shown to exist. At the preclinical level, this provides a unique opportunity to explore the effect of immunotherapeutic strategies on the function of monocyte sub-populations against infectious or malignant challenge and may allow immunotherapeutic strategies to be targeted towards specific monocyte sub-populations. Preclinical and clinical studies in human subjects suggest that GM-CSF and other cytokines such as IFN-gamma are the most promising biological response modifiers for augmenting monocyte-mediated immunity. In this review, the immunotherapeutic potential of the monocyte system will be discussed in the context of combating microbial and malignant disease.

Animals↗
PubMed1999

The potential for monocyte-mediated immunotherapy during infection and malignancy. Part I: apoptosis induction and cytotoxic mechanisms.

The mononuclear phagocyte system consists of peripheral blood monocytes and tissue macrophages that collectively play a major role in host immunity. Far from existing solely as phagocytic scavengers of cell debris and foreign matter, monocytes are highly active and responsive to inflammatory and immunological signals that activate their microbicidal and tumoricidal functions. Cytokines that are secreted as an integral component of the innate immune response such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and -IFN may directly activate the functions of the monocyte system. A key mediator of the effector functions of monocytes is tumour necrosis factor (TNF) which transduces its signals upon binding to specific transmembrane receptors. TNF is highly cytotoxic to micro-organisms and susceptible malignant cells and in most cases delivers its cytotoxic signal to tumour cells by highly regulated mechanisms of programmed cell death or apoptosis. We believe that the numerous functions of the monocyte system may be harnessed for therapeutic gain both in the context of microbiological infection and malignant disease. In this review, the mechanisms by which secreted and monocyte cell-membrane-associated TNF induce apoptosis will be discussed. In addition, the cell-associated and secretory immunological mechanisms employed by monocytes in host defence will be discussed in the context of the their ability to combat infection and neoplasia.

Animals↗
PubMed1999

Hepatitis B virus infection among pregnant women delivering at Harare Maternity Hospital, Harare Zimbabwe, 1996 to 1997.

OBJECTIVE: To determine the prevalence of hepatitis B virus (HBV) carrier and infectivity status among pregnant women delivering at Harare Maternity Hospital. DESIGN: A serological survey study of pregnant women admitted for labour and delivery. SETTING: Harare Maternity Hospital, Harare, Zimbabwe between June 1996 and June 1997. SUBJECTS: A random sample of 1,000 women, delivering at the hospital during the study period agreed to participate in the study. Serum samples were available for 984 women. MAIN OUTCOME MEASURES: HBV carriage status was determined by the presence of hepatitis B surface antigen (HBsAg) by enzyme immunoassay (EIA). Maternal HBV infectivity status was determined by testing all HBsAg positive women for the presence of hepatitis e surface antigen (HBeAg) using EIA. RESULTS: Overall 246 (25%) women were identified as carriers of HBV (95% confidence interval 22 to 28%). The frequency of HBV carriers did not vary with maternal age, parity or marital status. Only a positive prior history of spontaneous abortion was associated with an increased prevalence of HBV carriage status. Eight of the 246 (3.3%) women identified as HBV carriers tested positive for HBeAg. Hence, 0.8% of the entire study population was found to be at high risk of transmitting HBV to their newborns. CONCLUSIONS: Our results demonstrate a high prevalence of HBV carriage among women giving birth at Harare Maternity Hospital. None of the demographic variables studied were important predictors of HBV carriage status. The high carriage rate and low infectivity rates suggest that HBV infection is likely to be acquired by horizontal, rather than by vertical means of transmission. Given the scarcity of financial resources, routine testing of mothers for HBsAg may not be feasible. Our results suggest, however, that mass vaccination of all infants, irrespective of maternal HBV carriage status, may be the most effective approach to HBV prevention and control in Zimbabwe.

Adult↗