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Biomedical subjects

E Kass

Publications and source records attributed to E Kass.

At least 19 recordsLinked to original sources
PubMed2001

Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant.

Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants. Avipox-GM-CSF administered as a single s.c. injection significantly enhanced the percentage and absolute number of APCs in the regional lymph nodes that drain the injection site. Both the magnitude and duration of the cellular and phenotypic increases within the lymph nodes induced by the avipox-GM-CSF viruses were significantly (P < 0.05) greater than those measured in mice treated with four daily injections of recombinant GM-CSF protein. Temporal studies revealed that the APC enrichment of regional lymph nodes was sustained for 21-28 days after injection of the recombinant avipox virus expressing GM-CSF and, moreover, three injections of the recombinant virus could be given without any appreciable loss of in vivo bioactivity. Mice expressing human carcinoembryonic antigen (CEA) as a transgene (CEA.Tg) developed CEA-specific humoral and cell-mediated immunity after being immunized with avipox-CEA. The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice. The optimal use of avipox-GM-CSF, in terms of dose and dose schedule, especially when used with different immunogens, remains to be determined. Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM-CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen.

Adjuvants, Immunologic↗
PubMed2000

Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen- presenting cells in regional lymph nodes.

Repeated subcutaneous (s.c.) injections of recombinant granulocyte-macrophage colony-stimulating factor (recGM-CSF) for 4-5 days can enrich an immunization site with antigen-presenting cells (APC), which has been correlated with improved immune responses in experimental and clinical studies. A recombinant vaccinia virus encoding the GM-CSF gene (rV-GM-CSF) has been developed and can generate specific antitumour immunity in a whole tumour cell vaccine. In the present study, we examined whether rV-GM-CSF could produce and release GM-CSF locally which, in turn, might enrich a site of immunization for APC as previously shown for recGM-CSF. S.c. injection of rV-GM-CSF significantly (P<0.05) enhanced the percentage and overall number of APC, measured by class II expression levels, in the regional lymph nodes that drain the injection site. Dose- and temporal-dependent studies showed class II expression levels in the draining lymph nodes were maximally enhanced 5-7 days after a single injection of 10(7)plaque-forming units (pfu) of rV-GM-CSF. Flow cytometry revealed that the increase in class II expression resulted from (i) a higher class II expression level on CD19(+)B cells and (ii) an increase in the number of CD11c(+)/class II(+)professional APC within the draining lymph nodes. Moreover, isolation of lymph nodes from rV-GM-CSF-treated mice revealed their capacity to support higher levels of antigen-specific T cell proliferation and allospecific cytotoxic responses. A comparison between a single injection of rV-GM-CSF and a 4-day course of recGM-CSF revealed comparable changes in class II expression and functional T cell assays. GM-CSF can be delivered in a recombinant poxvirus, and the local production of the cytokine results in cellular and phenotypic changes that are similar to those of recGM-CSF. The ability to utilize rV-GM-CSF as a single inoculum may be more compatible with traditional immunization strategies.

Animals↗
PubMed1999

Induction of protective host immunity to carcinoembryonic antigen (CEA), a self-antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus.

Human carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human carcinomas has been a target for cancer immunotherapy. Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This study investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mice to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unresponsive to CEA, as shown by the lack of detectable CEA-specific serum antibodies and the inability to prime an in vitro splenic T-cell response to CEA. Furthermore, the administration of whole CEA protein in adjuvant to CEA.Tg mice failed to elicit either anti-CEA IgG titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers were found in those mice. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expressing CEA generated relatively strong anti-CEA IgG antibody titers and demonstrated evidence of immunoglobulin class switching. These mice also developed T(H)1-type CEA-specific CD4+ responses and CEA peptide-specific cytotoxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA.Tg mice against a challenge with CEA-expressing tumor cells. Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissue. The results demonstrate the ability to generate an effective antitumor immune response to a tumor self-antigen by immunization with a recombinant vaccinia virus. CEA.Tg mice should be an excellent experimental model to study the effects of more aggressive immunization schemes directed at established tumors with the possible development of accompanying autoimmune responses involving normal tissues.

Animals↗
PubMed1994

Outcome of nonspecific hydronephrosis in the infant: a report from the Registry of the Society for Fetal Urology.

Since 1988 the Society for Fetal Urology has worked to evaluate if there is consensus on management of infants with nonspecific hydronephrosis. Initially, multicenter agreement on the criteria to grade hydronephrosis and method of diuretic renography were developed to promote similarities in how infant kidneys with nonspecific hydronephrosis were profiled for grade (0 to 4), per cent differential function by diuretic renography and drainage response by diuretic renography (obstructed, not obstructed or indeterminate). Between 1989 and 1992 a total of 33 pediatric urologists from 21 cities registered 464 cases (582 kidneys) of hydronephrosis. Of the cases 275 (59%) were managed by observation and 189 (41%) were treated surgically. The operated kidneys showed profiles (hydronephrosis grade 3 or greater and diuretic renography obstructed) that were significantly different from the profiles of observed kidneys (hydronephrosis grade 2 or less and diuretic renography no obstruction) (p < 0.001 each). Six months postoperatively the mean grade of hydronephrosis (1.8) and diuretic renography diagnosis (no obstruction) were significantly better than they were preoperatively (p < 0.001 each). In addition, postoperatively the mean grade of hydronephrosis, diuretic renography diagnosis and per cent differential function were similar to age matched observed kidneys. We conclude that when radiographic tests are done similarly, there is consensus in the management of infant hydronephrosis by surgery or observation.

Databases, Factual↗
PubMed1991

Incubating syphilis in an adolescent female rape victim.

The risk of infection after rape is believed to be low. The use of presumptive treatment is, therefore, controversial. Some experts recommend treatment of all patients, and others suggest treatment if the doctor suspects infection, if the patient requests it, if follow-up examination of the victim cannot be ensured, or if the assailant has a known infection. No regimen will cover all possible pathogens. The Centers for Disease Control's empiric regimen for victims of sexual assault is effective against gonorrhea, chlamydia, and, most likely, syphilis. We present a case of incubating syphilis following rape, that did not respond to ceftriaxone.

Adolescent↗
PubMed1990

Is the Friday afternoon consult frequent? Timing of consultation requests on a psychiatric consultation service.

Two hundred psychiatric consultations were reviewed to determine if there was a pattern regarding the time of day and day of the week that consultations were requested. Consultations were found to be requested on a random basis although a survey of consultation psychiatrists perceived that consultations were more often requested late in the day. The implications of such misperceptions are discussed as they relate to negative attitudes towards consultative psychiatry by psychiatric physicians.

Child Psychiatry↗
PubMed1988

Alexithymia: relationship to severity of medical illness and depression.

The relationship of depression and the severity of medical illness to alexithymia was investigated in 75 medically ill patients seen in psychiatric consultation. Both depression and living alone predicted alexithymia but severity of medical illness was not related to an individual's alexithymic characteristics measured by the revised Schalling-Sifneos Scale. The implications of the findings are discussed in relationship to previous data regarding alexithymia in a psychiatric consultation population.

Adjustment Disorders↗
PubMed1986

Auranofin therapy in juvenile rheumatoid arthritis: a 48-week phase II study.

A 48-week phase II open, uncontrolled study of auranofin (AF) in patients juvenile rheumatoid arthritis (JRA) was conducted to assess efficacy, tolerance and serum gold levels, and to consider the feasibility of further controlled studies (phase III) in such patients. The study group included 25 patients (20 F, 5 M) with active pauciarticular (n = 4) or polyarticular (n = 21) JRA. Median age was 100 months (range 62-176); median disease duration was 55 months (range 13-155). AF was given at 0.1 mg/kg/day divided into 2 doses, and increases to maximum of 6 mg/day were permitted if clinical improvement was insufficient. Nonsteroidal anti-inflammatory drugs and physiotherapy also were allowed. Significant improvement (p less than or equal to 0.05) was observed in the various joint counts and articular indices, as well as in the physician's global assessment of health. Some subjective functional measurements also were improved, but the differences were not statistically significant. There were no clinically important trends in the laboratory measurements. No patient was withdrawn because of adverse reactions; 1 was withdrawn because of disease exacerbation and 3 for lack of response. Mild adverse reactions were seen in 9 patients: 6 had abdominal pain, 6 diarrhea/loose stools, 1 nausea, 3 rash, 2 pruritus. Two patients had dosage reduced because of loose stools. Serum gold levels varied greatly; increased dosage usually resulted in increased serum levels. Occurrence of adverse reactions or response to therapy was not related to increases in dose or to serum gold levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Isolated systolic hypertension in 14 communities.

In the Hypertension Detection and Follow-up Program, 158,906 individuals from 14 communities around the United States had their blood pressure measured in their homes in 1972-1973. Of the total population screened, 2.4% had isolated systolic hypertension (systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure less than 90 mmHg). Isolated systolic hypertension was present for 0.5% of those aged 30-39 years and 6.8% among those aged 60-69 years. The prevalence in blacks and women was greater than the prevalences in both whites and men. The prevalence among those taking antihypertensive medications at the time of screening was 6.1%, and 1.9% among those not on antihypertensive medications. From the individuals with "normal" diastolic blood pressure on the single home measurement (less than 90 mmHg), a random sample of 5,032 individuals were followed for mortality for eight years. Prevalence of isolated systolic hypertension was similar in this sample to that in the total. Among those not on antihypertensive medications, 8-year life table all-cause mortality rates adjusted for age, race, and sex were 17.6% for those with systolic blood pressure greater than or equal to 160 mmHg and 7.7% for those with systolic blood pressure greater than 160 mmHg. Among this population, all of whom had a diastolic blood pressure less than 90 mmHg, a multiple logistic analysis adjusting for baseline treatment status, age, race, sex, education, smoking, weight, pulse, physical activity, and systolic blood pressure revealed that each millimeter increase in systolic blood pressure was associated with approximately a 1% increase in mortality over the eight years of follow-up (p less than 0.05). Isolated systolic hypertension is both relatively common and a significant risk factor for subsequent mortality.

Actuarial Analysis↗
PubMed1985

Detection and treatment of hypertension in older individuals.

The Hypertension Detection and Follow-up Program screened 34,012 individuals aged 60-69 years old in their homes in 14 communities around the United States during 1972 and 1973. The prevalence of hypertension, defined as diastolic blood pressure greater than or equal to 90 mmHg or on antihypertensive medication, was 42.1%. After a second clinic screen, 2,376 hypertensives were identified and randomized into Stepped Care, a special intensive treatment group, or Referred Care, a group referred to their usual medical care sources. These individuals were followed for five years (until they reached the ages of 65-74 years). Over the five years, 79.4% of older individuals remained under active care and 81.4% of those were at their goal diastolic blood pressure. Side-effects tended to be less frequent in older individuals than in younger ones. Older Stepped Care participants with mild hypertension (diastolic blood pressure 90-104 mmHg) had a 17.2% reduction in all-cause mortality over five years compared to Referred Care, which was primarily due to a reduction in deaths attributed to cardiovascular causes. Thus, antihypertensive treatment can be safely and beneficially administered to individuals in this age range with diastolic hypertension, including those with mild hypertension.

Adult↗
PubMed1977

Visualization of the medullary rays on excretory urography in experimental ureteric obstruction.

Excretory urography occasionally delineates striations of alternating density in the renal parenchyma. Experimental observations on a dog model of ureteric obstruction show that the dense striations have the same dynamic alterations as the obstructive nephrogram. They become progressively more dense to a plateau and then fade with relief of obstruction. Previous obstruction is shown to facilitate visualization of the striations presumably by having dilated the tubules. Previous obstructive episode, previous symptoms, or chronic obstruction were present in each of the clinical cases collected which show a similar striation pattern. We conclude that the dense striations represent shadows produced by hyperconcentrated contrast material which has accumulated in dilated collecting ducts or groups of ducts within the medullary rays.

Acute Disease↗
PubMed1976

New approach to myelodysplasia.

Data from 60 patients with myelodysplasia are presented. Electromyography of the periurethral striated muscle in conjunction with simultaneous cystometry allows prediction of those patients at risk from urinary tract infection in 100 per cent of the cases. Intermittent self-catheterization is an effective form of therapy for bladder dysfunction in patients with myelodysplasia. An orderly approach to the evaluation and management of bladder dysfunction is outlined.

Adolescent↗