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Biomedical subjects

S E Read

Publications and source records attributed to S E Read.

At least 55 records · Page 3Linked to original sources

Assessment of lymph node size in hemophiliac children: observer agreement and association with serologic status to human immunodeficiency virus I.

Lymphadenopathy is an important component of a wide variety of different illnesses including the acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related conditions. In this study two pairs of observers independently examined the lymph nodes of hemophiliacs younger than 18 years of age to determine the level of agreement of assessments of lymph node mass (the product of the number and mean diameter of lymph nodes). Spearman correlation coefficients for the first and second pairs of observers were 0.75 (P less than 0.001) and 0.66 (P less than 0.005), respectively. The range of lymph node mass was quite different for controls (2.8 to 3.8), human immunodeficiency virus I (HIV)-seronegative hemophiliacs (4 to 5.7) and HIV-seropositive hemophiliacs (10.3 to 15.6). The HIV serologic status could be predicted by lymph node mass. In this group of hemophiliacs, if the lymph node mass was less than 5 cm, the probability of being HIV-seropositive was 0.14. The corresponding probabilities if the lymph node mass was in the range 5 to 9.99, 10 to 14.99, 15 to 19.99 and 20 or greater were 0.33, 0.8, 0.67 and 1.00, respectively. Thus there is adequate agreement between observers in assessing the lymph node mass and there is a direct relationship between lymph node mass and evidence of infection with HIV.

Acquired Immunodeficiency Syndrome↗

Serial studies on the cellular immune response to streptococcal antigens in acute and convalescent rheumatic fever patients in Trinidad.

Acute rheumatic fever (ARF) has the characteristics of an autoimmune disease, triggered by cross-reactive antigens shared by the group A streptococcus and a variety of tissues including the heart, endothelium, and basal ganglia. Using two parameters of cellular reactivity, migration inhibition and blastogenic transformation, ARF patients from Trinidad show significant lymphocyte reactivity to streptococcal antigens, particularly those from an ARF associated streptococcal strain. This reactivity, studied over a 2-year period, peaked at 1 to 6 months after the acute onset and remained significantly elevated for at least 2 years. The reactivity is directed mainly toward a nonionic detergent extractable material in the cell membrane. These studies suggest a possible streptococcal strain specificity in ARF and demonstrate persistent sensitization, which explains the increased susceptibility to recurrences in the 2 years following the acute episode.

Antigens, Bacterial↗

The relationship between 2-5A synthetase levels and persistent lymphadenopathy in homosexual men with antibodies to HTLV-III.

This study compared clinical and laboratory parameters in 37 individuals with serologic evidence of exposure to human T-cell lymphotropic virus type 3 (HTLV-III) and generalized lymphadenopathy. Basal levels of the interferon-induced enzyme, 2-5A synthetase were also measured and compared with the clinical parameters. A significant linear relationship (p less than .05) was demonstrated between the logarithm of the basal synthetase level and both the number and size of palpable nodes in the posterior cervical triangles of the men studied. No other lymph node chains demonstrated such a relationship. In addition, men with more than 3 palpable nodes (the median number) in the posterior triangles had lower mean levels of lymphocytes, reduced mean mitogen responses to PWM, PHA, and ConA, elevated mean levels of IgG, IgA, and IgM, and were more frequently anergic on skin testing. These findings suggest the need for further longitudinal study of the possibility that extent of lymphadenopathy and level of 2-5A synthetase might serve as useful parameters to monitor disease activity.

2',5'-Oligoadenylate Synthetase↗

Group G streptococci in healthy school-children and in patients with glomerulonephritis in Trinidad.

The group G streptococcus has generally not been considered a prominent pathogen. In a 1982 study of the colonization rate by beta-haemolytic streptococci in apparently healthy children, age 5-11 years, 25 of 69 isolates belonged to group G. This surprisingly high rate of group G colonization (14.3%) led to a retrospective study of school surveys in 1967 which showed that the colonization rate with this organism was 2.3% (range 1.3-3.5%). A review of bacitracin-sensitive streptococcal isolates from hospital admissions of patients with acute glomerulonephritis (AGN), rheumatic fever, and their siblings, between January 1967 and July 1980, was conducted. Of 1063 bacitracin-sensitive isolates, 63 were group G, and 52 of these were isolated from AGN patients and their siblings, i.e. 7 from skin lesions of AGN patients, 40 from the throats of siblings and only 5 from the skins of the siblings. The other 11 group G isolates were from rheumatic-fever patients and their siblings. Thus, the group G colonization rate fluctuates in the population. The isolation of only group G streptococci from skin lesions of patients with AGN suggests a possible association between group G streptococcal pyoderma and acute post-streptococcal glomerulonephritis.

Acute Disease↗

Elevated levels of interferon-induced 2'-5' oligoadenylate synthetase in generalized persistent lymphadenopathy and the acquired immunodeficiency syndrome.

The levels of the 2'-5' oligoadenylate enzyme synthetase in extracts of peripheral blood mononuclear cells from individuals with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) were measured and compared with synthetase levels in peripheral blood mononuclear cells (PBMs) from healthy heterosexual and homosexual controls. The mean basal synthetase level in heterosexual and homosexual controls was 14 +/- 13 and 12 +/- 9 pmol per hr/10(5) PBMs, respectively. Thirteen individuals with AIDS had a mean basal level of 129 +/- 75 pmol. Serial levels were persistently elevated in six of these individuals over a one- to 10-month period. Twelve of the 13 individuals had antibodies to human T cell lymphotrophic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV). Thirty-three individuals with ARC had a mean basal synthetase level of 68 +/- 84 pmol. Thirty-two of the 33 had antibodies to HTLV-III/LAV. Eleven (33%) have had consistently normal synthetase levels (less than 2 SD above the mean for the homosexual controls, i.e., 30 pmol) over a three- to nine-month follow-up period. Fourteen (42%) had persistently elevated levels over the same period; four (29%) of these developed AIDS during the follow-up period. Eight have had fluctuating levels but have remained clinically well. These studies suggest that persistently elevated synthetase levels in individuals with ARC and antibodies to HTLV-III/LAV indicate progressive virus-induced disease activity. Elevated synthetase levels may be an important prognostic indicator of increased risk of progression to AIDS.

2',5'-Oligoadenylate Synthetase↗

AIDS in a patient with hemophilia receiving mainly cryoprecipitate.

A 25-year-old man with hemophilia who had been treated primarily with cryoprecipitate presented with epigastric pain and loose, melenic stools. He had a long history of malaise and intermittent upper respiratory tract infection with fever. The patient was shown to have disseminated histoplasmosis and refractory herpes simplex. Immunologic studies demonstrated a markedly decreased ratio of helper to suppressor T cells, lymphopenia, cutaneous anergy and a slightly elevated serum IgA level. These findings met the criteria for the diagnosis of acquired immune deficiency syndrome. In addition, antibodies to human T-cell leukemia virus were detectable in the serum.

Acquired Immunodeficiency Syndrome↗

Suppression of cellular reactivity to group A streptococcal antigens in patients with acute poststreptococcal glomerulonephritis.

Lymphocyte reactivity to group A streptococcal antigens was studied in patients with acute poststreptococcal glomerulonephritis (AGN) in Trinidad. When compared with controls, patients with AGN had significantly lower responses. This finding was most prominent in the patients who were greater than 10 years of age at onset of disease. The total number of T lymphocytes was found to be decreased in patients with AGN, and in particular, the percentage of cells bearing Fc receptors for IgG (T gamma) was low. Removal of the T gamma-cell population abrogated the lymphocyte response to streptococcal antigens. However, removal of the adherent cells resulted in enhancement of the response to the level of the normal control population. The presence of suppressor activity in the adherent cell population of older patients with AGN may be an important factor in progression of AGN to chronic disease.

Adolescent↗

The host defense system in the human newborn: the role of interferon and the natural killer cell.

The human newborn is particularly susceptible to infections in the neonatal period, due in part to the immaturity and naive state of the immune system. The role of interferon and natural killer cells in host defense in this age group is poorly defined. We have studied natural killer cells and the activation of the interferon system in cord blood. Most newborns (75%) had low natural killer cell activity, and this was unrelated to levels of the intracellular interferon-associated enzyme, 2'-5' oligoadenylate synthetase (2-5A synthetase). Newborn cells responded to interferon in vitro with an increase in natural killer activity, suggesting that this low natural killer cell activity is the result of fewer numbers of effector cells rather than a functional immaturity. Circulating serum interferon was detected in greater than 50% of maternal samples tested; however, this did not correlate with 2-5A synthetase levels in maternal or the corresponding cord blood mononuclear cells. Natural killer cell activity was low in the newborn in spite of activation of the interferon system in 39% of these individuals. This may be an important factor in susceptibility to infections in this period.

2',5'-Oligoadenylate Synthetase↗

In vitro hyporeactivity to alpha-interferon in children with severe combined immunodeficiency disease.

Interferon (IFN) treatment of peripheral blood mononuclear cells from seven children with severe combined immunodeficiency (SCID) failed, with one exception, to induce the IFN-dependent enzyme, 2-5A synthetase or enhance natural killer cell activity. In one patient this hyporeactivity was demonstrated in both T cell enriched and T cell depleted lymphocyte preparations. These results may reflect the absence of an IFN reactive lymphocyte subpopulation or of the IFN receptor. This defect in SCID patients may be partly responsible for their increased susceptibility to viral infections and may contribute to the regulatory imbalances in T lymphocyte subpopulations.

2',5'-Oligoadenylate Synthetase↗

A case of neonatal herpes simplex with pneumonia.

A case of neonatal herpes simplex infection is discussed that presented as pneumonia, with subsequent development of skin lesions. The virus was isolated from skin scrapings. In spite of treatment with vidarabine, skin lesions continued to develop, and central nervous system involvement occurred. Acyclovir therapy led to prompt resolution of symptoms.

Acyclovir↗

Differential binding of human interferon-alpha subtypes to receptors on lymphoblastoid cells.

Highly purified human interferon-alpha subtype A (HuIFN alpha A) was iodinated for use in direct ligand binding studies on human lymphoblastoid (Daudi) cells. Unlabelled preparations of HuIFN alpha subtypes A, C, D, and hybrid molecules AD (Bgl II), AD (Pvu II), and DA (Bgl II) showed different responses in competition experiments with labelled alpha A probe. Specifically, IFNs alpha D and alpha DA were unable to displace the probe, whereas IFNS alpha A, alpha C, and the hybrid alpha ADs showed similar competition curves. These results support a two-idiotope model of IFN recognition by its receptor. IFN effects on [3H]-thymidine incorporation and cell growth (long term effects) did not reflect the apparent affinities of HuIFN alpha subtypes for cell surface receptor.

Binding, Competitive↗

Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpesvirus infections.

Natural killer cells capable of lysing herpes simplex virus type 1 (HSV-1)-infected fibroblasts were studied in three groups of patients unusually susceptible to severe herpes-virus infections. Cord blood was evaluated because of the known susceptibility of neonates to disseminated infections due to herpes simplex virus type 2 at birth. Only 30% of the cord blood specimens tested demonstrated normal lysis of HSV-1-infected fibroblasts and a normal increment in the lysis of infected over uninfected cells. Five out of six patients with Wiskott-Aldrich Syndrome (WAS) also were found to have abnormally low responses by these criteria. The one WAS patient with normal responses had had little difficulty with infections and had survived much longer than usual. Five patients with severe herpesvirus infections and no known primary cellular immunodeficiency had natural killer cell function significantly below normal (P less than 0.001). These data suggest that natural killer cells probably play an important role in human resistance to herpesvirus infection and that deficiencies of this system may result in unusual susceptibility to herpesvirus infections.

Adolescent↗

Group G streptococcal colonization and sepsis in neonates.

Group G streptococci were isolated from the blood of seven neonates over a five-year period at the New York Hospital. All but two were born near term. All presented clinically with signs and symptoms of neonatal sepsis. Only one case was associated with a major complication--epidermolysis bullosa; this patient died. Two presented as late-onset sepsis at 11 and 12 days of age. Six of the seven responded promptly to antibiotic therapy. A one-year survey was carried out of colonization with groups B and G streptococci at the time of discharge (day 3). Colonization with group G streptococci varied between 41 and 76% of babies each month. Group B streptococcal colonization ranged between 1 and 11%. Statistical analysis suggested that colonization with these organisms may be a mutually exclusive phenomenon.

Humans↗

Persistent clonotypes associated with group A streptococcal polysaccharide antibody response in man.

Elevated anti-streptococcal group A polysaccharide antibodies are present in the sera of acute rheumatic fever patients. Analytical isoelectric focusing of sera taken in the acute phase of the disease and sequentially for up to 2 years later reveals a stable clonotype pattern of anti-group A polysaccharide antibodies. In addition, with reinfection and recurrence of the rheumatic fever, the same clonotype pattern of antibodies is present. This finding indicates that naturally acquired immunity is associated with persistence of clonotype expression.

Antibodies, Bacterial↗