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Biomedical subjects

W D Johnson

Publications and source records attributed to W D Johnson.

At least 145 records · Page 8Linked to original sources

Evaluation of T-cell subsets in the lesion infiltrates of human cutaneous and mucocutaneous leishmaniasis.

We have characterized the T-lymphocytes in the skin lesions of 10 patients with cutaneous leishmaniasis and in the nasal lesions of seven patients with mucosal leishmaniasis, with the immunoperoxidase and monoclonal antibody techniques. There was predominance of cells with helper phenotype (Leu 3A+ 3B) over suppressor phenotype (Leu 2a) in the lesions of both groups. The helper/suppressor (H/S) ratio in the skin lesions was 1.6 +/- 0.5 and in the nasal lesions of mucosal leishmaniasis was 1.7 +/- 0.8. The H/S ratios in the peripheral blood of patients with cutaneous leishmaniasis (2.1 +/- 0.8) and in patients with mucosal leishmaniasis (1.6 +/- 0.8) were comparable and similar to the ratios in the skin and nasal biopsies. The percentage of T-cells and macrophages expressing the Dr antigen in the cutaneous group (69.5 +/- 13.7) was not significantly different from the mucosal patients (90.3 +/- 5.7). We conclude that the immunopathology of the skin lesions in cutaneous leishmaniasis is similar to the nasal lesions of mucosal leishmaniasis.

Adolescent↗

Cryptosporidiosis in Haitian children.

We used a modified acid-fast stain to detect Cryptosporidium oocysts in unconcentrated stools from 824 Haitian children less than 2 years of age with acute diarrhea. Oocysts were identified in stools from 17.5% of 291 children seen at a rural dispensary and in 16.3% of stools from 533 children in an urban hospital. Children with cryptosporidiosis were identified throughout a 22-month period from October 1982 to July 1984, without seasonal predilection. Cryptosporidiosis was twice as common in infants greater than 6 months of age than in younger infants. Cryptosporidium oocysts were rarely found in stools of infants receiving only breast milk. The clinical presentation of children with cryptosporidiosis was similar to other patients with diarrhea who did not have cryptosporidiosis. No asymptomatic Cryptosporidium infections were detected among 71 family members of 31 children with cryptosporidiosis. Three of the 71 family members less than 3 years of age were found to have diarrhea and Cryptosporidium oocysts. In follow-up studies of 31 patients, oocysts persisted in stools for a mean of 14 days (range 5-31 days). Duration of oocyst excretion was directly correlated with duration of diarrhea. These findings suggest that Cryptosporidium is an important cause of acute self-limited diarrheal illness to Haitian children.

Breast Feeding↗

Clinical manifestations and therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome.

Isospora belli has recently been recognized as an opportunistic protozoan pathogen in patients with the acquired immunodeficiency syndrome (AIDS). Although I. belli rarely causes diarrhea in patients with AIDS in the United States, we have documented isosporiasis in 15 percent (20 of 131) of such patients in Haiti. The infection was associated with chronic watery diarrhea and weight loss that was clinically indistinguishable from disease caused by the related coccidia cryptosporidium. No demographic or laboratory data distinguished the patients with AIDS and isosporiasis from those with either cryptosporidiosis or other opportunistic infections. Neither I. belli nor cryptosporidium was detected in stool samples from 170 healthy siblings, friends, and spouses of the patients with AIDS. In all patients with isosporiasis, diarrhea stopped within two days of the beginning of treatment with oral trimethoprim-sulfamethoxazole. Recurrent symptomatic isosporiasis developed in 47 percent of the patients, but it also responded promptly to therapy with trimethoprim-sulfamethoxazole. We conclude that isosporiasis is common in Haitian patients with AIDS, and that it responds to therapy with trimethoprim-sulfamethoxazole but is associated with a high rate of recurrence.

Acquired Immunodeficiency Syndrome↗

Hepatic peroxisomal changes induced by a tetrazole-substituted alkoxyacetophenone in rats and comparison with other species.

Previous work in this laboratory indicated that compound LY171883, a tetrazole-substituted alkoxyacetophenone with leukotriene D4 antagonist activity, caused dose-related hepatomegaly in rodents without other histological evidence of liver toxicity. In the present studies, administration of LY171883 at dietary concentrations of 0.25 or 0.50% to rats for 2 weeks increased peroxisomal beta-oxidation, catalase activity, and peroxisome volume fraction in the liver. The effects were dose-related and corresponded with increases in liver weight. Dietary concentrations of 0.05 and 0.1% LY171883 did not significantly alter peroxisome morphology, enzyme activity, or liver weight. Serum triglycerides were lowered equivalently by all four dietary concentrations of LY171883, indicating that the hypotriglyceridemia was dissociated from induction of peroxisomal beta-oxidation. The hepatic effects in rats reversed within 16 days after discontinuing treatment with LY171883. Liver weight and peroxisomal enzyme activities were increased in mice by LY171883 in a manner comparable to that observed in rats, whereas hamsters were less responsive. In guinea pigs there was a minor increase in beta-oxidation at a toxic dose of LY171883, but no change in catalase or liver weight. Neither hepatomegaly nor induction of peroxisomal enzymes occurred in beagle dogs or rhesus monkeys given LY171883. Since the hepatic effects of LY171883 in rats are not observed in higher species at a significant multiple of the anticipated clinical dose, it is unlikely that such effects will occur in humans.

Acetophenones↗

Typhoid fever: successful therapy with cefoperazone.

We compared cefoperazone with chloramphenicol in a randomized trial involving the treatment of 25 children with severe typhoid fever. The clinical characteristics of the two treatment groups were comparable on entry into the study. Four patients died (three receiving chloramphenicol, one cefoperazone), and an additional two patients received dexamethasone (one per group). Excluding these six patients, the response of the cefoperazone group was comparable or superior to that of the chloramphenicol group in terms of the number of days from initiation of therapy to becoming afebrile (P less than .055) and the number of days until negative blood cultures were obtained (P less than .19). There were no relapses or treatment failures in either group. We conclude that cefoperazone is as effective as chloramphenicol in the treatment of severe typhoid fever.

Adolescent↗

A prospective study of visceral leishmaniasis in an endemic area of Brazil.

The epidemiology, clinical patterns, and risk factors for visceral leishmaniasis were prospectively studied in an endemic area of Brazil. The prevalence of disease was 3.1% for children less than 15 years of age, and the annual incidence was 4.3 cases per 1,000 children. The number of children with disease fluctuated yearly and seasonally, and distribution of the disease varied within the endemic area. Risk factors included young age (median, three years) and malnutrition before the onset of disease. Intestinal parasitism, recent migration into the area, and house location within the area did not influence the progression of infection to disease. Serological testing indicated that 7.5% of children were infected with Leishmania each year and that the ratio of disease to infection was 1:18.5 for the whole area and 1:6.5 for the section with the highest prevalence of disease. Early diagnosis and therapy altered clinical patterns of the disease.

Adolescent↗

New perspectives on a subclinical form of visceral leishmaniasis.

During an epidemiological study of visceral leishmaniasis in an endemic region of Brazil, new perspectives emerged on a subclinical form of the disease. A group of 86 children with antibody to Leishmania were identified. None of these children had a history of leishmaniasis. The children were segregated into four groups: One group remained asymptomatic (n = 20), whereas another developed classic kala-azar within weeks of the index serology (n = 15). The remaining 51 patients initially had subclinical disease; 13 (25%) of these patients progressed to classic kala-azar (mean, five months). The others (75%) resolved their illness after a prolonged period (mean, 35 months). The initial illness in the subclinical group was characterized by hepatomegaly, frequent splenomegaly, intermittent cough, diarrhea, and low-grade fever. Malaise and poor weight gain were common. Giemsa-stained smears and cultures of bone marrow aspirates were usually negative for Leishmania in the absence of symptoms of classic kala-azar.

Antibodies↗

Risk factors associated with AIDS in Haiti.

A total of 121 acquired immunodeficiency syndrome (AIDS) patients diagnosed in Haiti were studied between June 1979 and December 1983. Risk factors were identified in 65% of 34 patients evaluated in a standardized manner since July 1983 and included: bisexuality, 38%; blood transfusion, 21%; and intravenous drug abuse or a spouse with AIDS, 6%. These risk factors were reported by only 20% of the 85 patients studied between June 1979 and June 1983. AIDS patients also reported more frequent parenteral injections prior to the onset of their illness than control subjects (e.g., siblings, friends, sexual partners). Heterosexual activity among female AIDS patients was also greater than in their female controls. It was concluded that, in contrast to the experience reported among Haitians with AIDS in the USA, risk factors are present among most patients with AIDS in Haiti.

Acquired Immunodeficiency Syndrome↗

Combined valve replacement and coronary bypass surgery. Results in 127 operations stratified by surgical risk factors.

The results of 127 operations with both valve replacement and coronary bypass were compared with all 5,053 operations involving coronary bypass performed from August 1972 through June 1985. Both groups were stratified by the number of risk factors (age over 70 years, bad ventricle, extensive endarterectomy, and reoperation). Compared with all bypass operations, valve replacement had no effect on surgical mortality except in the group at highest risk. Conversely, valve replacement was associated with reduced late survival in all but those at highest risk. Results with tissue valves were better than with mechanical, but statistical significance was lacking. Relief of angina was equal. Ischemic mitral insufficiency continues to be the greatest challenge, with 46 percent five-year survival. We conclude that combined valve replacement and bypass surgery can be performed successfully, even in the patients at higher risk; however, this operation should be performed only by teams with demonstrated success in surgically treating advanced coronary artery disease.

Adult↗

Selection of a skin test antigen for American visceral leishmaniasis.

Studies were designed to examine skin test responses to leishmanial antigens in American visceral leishmaniasis (AVL) in Brazil. We found that after recovery from AVL, patients had positive delayed hypersensitivity reactions to Leishmania. Different amounts of a soluble extract obtained from Leishmania donovani chagasi promastigotes were compared with whole L. d. chagasi promastigotes in persons with past AVL. The most effective soluble preparations tested contained 25 and 50 micrograms leishmanial protein. These produced positive responses in 95%-100% of the individuals with past AVL. The 25 micrograms protein dose was used in further studies. This preparation produced no positive responses in either normal controls, tuberculosis patients, or schistosomiasis patients, and less than 5% positive responses in persons with Chagas' disease. The same amount of soluble extract prepared from L. mexicana amazonensis produced 82% positive skin test responses in persons with past AVL. When persons living in an area endemic for AVL were skin tested with the 25 micrograms preparation of L. d. chagasi extract, 34.1% yielded positive tests with a low number of positive responses in young children and 48% positive in adults. Only 3.1% of the population studied had a history of AVL. We have found that positive delayed hypersensitivity response to a soluble Leishmania extract is a sensitive and specific indicator of previous infection with AVL.

Adolescent↗

Characterization of liver enlargement induced by compound LY171883 in rats.

Compound LY171883 caused dose-related and reversible hepatomegaly in male Fischer 344 rats. Histological examination revealed hepatocellular hypertrophy with no other evidence of liver disease. There were only minor changes in serum glucose, total bilirubin, alkaline phosphatase, and alanine transaminase which were generally unrelated to dose and dissociable from the hepatomegaly. Total liver DNA increased but the DNA concentration decreased, indicating that liver growth involved a combination of hypertrophy and hyperplasia. Total liver protein and RNA increased. Hepatic mitochondrial protein content increased but cytochrome oxidase activity was not changed. There were minor changes in mitochondrial respiratory parameters; however, all the values were in the normal range and there was no indication of mitochondrial toxicity. Microsomal protein, drug-metabolizing activity, and cytochrome P-450 increased, but glucose-6-phosphatase activity was not changed. The induction of drug-metabolizing enzymes and absence of toxicity were evidence that the hepatomegaly was an adaptation to an increased functional load in the liver. An increase in catalase activity suggested that the response may have also involved peroxisomes. In addition to rats, LY171883 administration caused hepatomegaly in mice and hamsters at daily exposures exceeding 100 mg/kg. The response was not observed in guinea pigs, beagle dogs, or rhesus monkeys given maximum tolerated doses, indicating LY171883-induced hepatomegaly is not a response common to all species. The doses required to elicit hepatomegaly greatly exceeded doses that produce pharmacological efficacy in animals and those that are expected to be used clinically. Since humans will not receive doses comparable to those given rodents, and considering that the primate species tested did not experience hepatomegaly, it is unlikely that the effect observed in rodents can be extrapolated to humans.

Acetophenones↗

Trace element concentrations in hair from autistic children.

The concentrations of 14 elements were determined in scalp hair samples from control, autistic and autistic-like children. Significant differences were noted between normal males and females for calcium, magnesium and mercury. The autistic population had significantly lower levels of calcium, magnesium, copper, manganese and chromium and higher levels of lithium as compared to sex- and age-matched controls. Children with autistic features (autistic-like), classified as having childhood-onset pervasive disorder, had lower levels of magnesium, cadmium, cobalt and manganese as compared to controls. Discriminant function analysis using the 14 trace elements correctly classified 90.5% of the normal and 100% of the autistic population. Using a stepwise procedure, the five elements with the greatest discriminatory power were calcium, copper, zinc, chromium and lithium. Analysis based on these five trace elements led to the correct classification of 85.7% of the normal and 91.7% of the autistic group. Results indicate that the concentrations of trace elements in hair from normal children differ from patterns observed in both autistic and autistic-like children. Furthermore, evidence suggests that hair analysis may have potential use as a diagnostic tool for autism.

Autistic Disorder↗

Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis.

The lymphocytes from eight patients with active visceral leishmaniasis (VL), a disease associated with marked immunologic dysfunction, were examined for ability to produce interleukin 2 (IL-2) and gamma interferon during in vitro cultivation. It was found that both IL-2 and gamma interferon production, in response to leishmania antigen, was absent during the active disease, but was restored after successful chemotherapy. Untreated VL patients produced IL-2 and gamma interferon when stimulated with phytohemagglutinin (PHA). Six patients with either active cutaneous or mucosal leishmaniasis, a disease not associated with immunosuppression, showed high levels of gamma interferon in response to leishmania antigen and PHA. Since IL-2 and gamma interferon have been shown to have important roles in the immune response and in the killing of leishmania, their absence may represent a key defect in the immune response in VL.

Antigens, Differentiation, T-Lymphocyte↗

Cardiac cholinergic muscarinic receptors: changes in multiple affinity forms with down-regulation.

The isolated working rat heart exhibits dynamic changes in the cholinergic muscarinic receptor in response to perfusion with the acetylcholine congener methacholine. For example, perfusion with 4 microM methacholine for 2.5 hr mediates a statistically significant and reversible 10 to 15% decrease in receptor content in right atrium and left atrium and ventricle. The muscarinic receptor exhibits a single affinity state for antagonists but multiple affinity states for receptor agonists. When agonist 3H-antagonist competition experiments are performed, the concentration dependence of displacement by agonists is flattened and extends over more than 2 log units. From such curves, it is difficult to extract values for the relative proportions of the multiple receptors or their KD values by inspection. We have developed a procedure for plotting the competition curves so that the KD values and proportion of multiple receptor forms can be estimated graphically. We determined these more accurately by computer using a nonlinear least-squares analysis. After perfusion of methacholine for 1 hr, there were increases in the KD of the low and high affinity forms of the receptor in the right and left atria. After 2.5 hr of perfusion, the KD of the high-affinity form increased further in the left atrium. In the right atrium, the two affinity states were converted into a single state of low affinity. Although there was a significant decrease in the amount of receptor in left ventricle, there were no changes in the KD values or proportions of the two states. All changes in receptor reversed during an additional 2.5 hr of perfusion without methacholine.

Animals↗

Cell mediated immunity in American cutaneous and mucosal leishmaniasis.

Cellular immune responses were studied in 35 Brazilian patients with either active cutaneous leishmaniasis (CL), active mucosal leishmaniasis (ML), or healed cutaneous leishmaniasis. The mean age and duration of illness in the two groups were as follows: 14 CL patients, age 28 +/- 13 yr, disease 5 +/- mo; and 16 ML patients, age 34 +/- 15 yr, disease 86 +/- 117 mo. Patients with CL and ML responded well to leishmania antigen in blastogenesis assays. However, the response of ML patients was over three times greater than the response of CL patients. There was a significant correlation between the magnitude of the lymphoproliferative response and the duration of disease activity. There were no significant differences between CL and ML patients in terms of the following parameters: lymphoproliferative responsiveness to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen) and peripheral blood lymphocyte subpopulations (T and B cells, oKT8+ and OKT4+ cells, OKT4:OKT8 ratio). Peripheral blood mononuclear cells from ML patients also generated interferon-gamma containing lymphokine in response to stimulation with leishmania antigen. This lymphokine was capable of inducing macrophages from ML patients to inhibit the intracellular multiplication of leishmania in vitro. These studies have determined that the parameters of lymphocyte and macrophage functions evaluated in ML and CL patients are comparable, except for an enhanced lymphoproliferative response, with leishmania antigen in ML patients. This later finding may be a function of the long duration of active disease in this population and unrelated to the pathogenesis of their mucosal lesions.

Adolescent↗

Coronary heart disease in young black and white males in New Orleans: Community Pathology Study.

The biracial population of New Orleans has a high overall mortality rate, high coronary heart disease (CHD) mortality rate, and high autopsy rate. In the New Orleans Community Pathology Study we investigated atherosclerosis and CHD in all deceased males aged 25 to 44 years, with major focus on the 52% of subjects from whom heart and arterial specimens were collected and evaluated according to standardized procedures. Morphologic correlates of CHD are the same in young black and white males. CHD mortality and mortality from cerebral hemorrhage, hypertensive heart disease, chronic renal disease, and diabetes are greater in young black males than young white males. Age, serum cholesterol, and hypertension were identified as important associated factors in the atherosclerotic process, as well as in CHD. The extent of coronary lesions seems to have decreased between 1960-1964 and 1969-1978 in young white males but not in blacks. Racial differences in coronary lesion involvement in non-CHD deaths are smaller than in our earlier studies.

Adipose Tissue↗