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Biomedical subjects

N Kaufman

Publications and source records attributed to N Kaufman.

At least 19 recordsLinked to original sources
PubMed1992

Activation of the contact system in lethal hypotensive bacteremia in a baboon model.

The hypotension in septicemia is believed to be mediated by the combined action of many mediators including cytokines, prostaglandins, and complement components. To evaluate the contribution of the contact/kinin-forming system to hypotension, the authors used an established experimental baboon model of bacteremia in which two concentrations of Escherichia Coli (E. coli) were used to produce lethal and nonlethal hypotension. The lethal group (n = 5) developed irreversible hypotension that significantly correlated with the decline in levels of high molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced reversible hypotension, a less striking decline in HK, and only slight elevation in alpha 2M-kal. No significant changes were found in levels of factor XII, prekallikrein, and factor XI in either group. A significant change in the contact system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system.

Animals↗
PubMed1991

Effect of heparin on the activation of factor XII and the contact system in plasma.

We examined in purified systems and in human plasma whether heparin serves as a contact system activating compound. Purified human factor XII zymogen was not activated by heparin through an autoactivation mechanism, but was activated in the presence of purified prekallikrein. Zn2+ (12 microM) did not support autoactivation by heparin. The activation of factor XII and the contact system by heparin in plasma anticoagulated with citrate or with hirudin (not chelating ions) was examined by the cleavage of 125I-labeled factor XII and high molecular weight kininogen (HK). Heparin at 1.6 and 16 USP U/ml was not able to produce activation, in contrast to dextran sulfate (20 micrograms/ml) which supported activation of both factor XII and HK. This study indicates that heparinized plasma does not support activation of the contact system mediated through activation of factor XII. It is not expected that heparin anticoagulant therapy will contribute to activation of the contact system.

Complement C1 Inactivator Proteins↗
PubMed1991

Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis.

Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.

Angioedema↗
PubMed1990

Brachytherapy in the treatment of solitary colorectal metastases to the liver.

It is well-established that 30-40% of patients with solitary liver metastases from primary colorectal tumors can be cured by resection. Conventional radiation therapy has had only a palliative role in treating liver metastases because the dose that the liver will tolerate is far below a tumoricidal dose. In contrast, brachytherapy allows one to deliver a tumoricidal dose to the tumor while limiting the dose to surrounding normal tissue to the tolerance dose. As a pilot study, 125I seeds were implanted into unresectable hepatic metastases, or positive margins of resection, at the time of surgery. This report concerns six patients whose liver lesions were the only known site of disease and in whom precipitous drops in carcinembryonic antigen (CEA) levels followed the implants. Recurrence was observed in only one of the 11 implanted site, with a median follow-up of 12 months.

Adenocarcinoma↗
PubMed1990

Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure.

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.

Acute Disease↗
PubMed1990

Thyroid function tests in patients undergoing bone marrow transplantation.

Thyroid function was studied prospectively in 27 patients receiving bone marrow transplants to determine the effect of this procedure and its sequelae on serum thyroid hormone levels and thyrotropin secretion. Serum triiodothyronine and free triiodothyronine concentrations declined to subnormal levels in nearly all of the patients; free thyroxine concentration became subnormal in 15 patients. At the time of the nadir of the serum T3 concentration, serum thyrotropin concentration, measured by a sensitive immunoradiometric assay, declined significantly and became subnormal in nine patients. The data suggest that the reduction of serum thyroxine levels after transplantation is attributable, at least in part, to inhibition of thyrotropin secretion.

Adult↗
PubMed1989

[Tuberculous meningitis].

2 cases of tuberculous meningitis are presented, 1 in a 54-year-old woman who had immigrated to Israel from Turkey 36 years before, and the other in a 10-year-old girl who recently immigrated from Ethiopia. Since diagnosis is difficult and prompt antituberculous treatment is life-saving, treatment may be instituted before the bacteriological diagnosis is established. A short term treatment of 9 months and a combination of rifampicin and isoniazid were successful in our patients.

Child↗
PubMed1989

Remote afterloading intraluminal brachytherapy in the treatment of rectal, rectosigmoid, and anal cancer: a feasibility study.

From 1981 to 1986, 28 patients (27 evaluable) were treated with intraluminal brachytherapy (ILBT) using a remote afterloading technique for persistent or recurrent anal, rectal and rectosigmoid cancers. Eighty-nine percent underwent previous surgery for colorectal cancer. Seventy-seven percent of the patients received external beam irradiation (ERT) as a part of the present treatment. Intraluminal brachytherapy was given with a 2 cm diameter cylinder and the dose per fraction ranged from 440 cGy to 840 cGy at 0.5 cm from the surface of the cylinder. Follow-up ranged from 1 to 74 months with a median of 12 months. Patients were divided into two groups. Group I consisted of 15 patients receiving elective ILBT; Group II: 13 patients with recurrent disease. Seventy-one percent of the patients in Group I and 39% of the patients in Group II achieved local control. The majority of patients tolerated treatment well with only transient reactions. However, three patients (11%) developed grade 3 (G3) complications requiring surgical intervention. Eight patients developed moderate complications--grade 2 (G2)--requiring only conservative treatment. This study has identified several factors which appear to influence the risk of developing complications with this combined treatment, using remote afterloading apparatus, among which are technique of previous external beam irradiation, treatment length, anatomical location, intraluminal brachytherapy fractionation, and total cumulative dose (ERT + ILBT). This experience suggests that intraluminal brachytherapy appears to be an acceptable form of treatment, as a boost to external beam radiation therapy, in the management of rectal and colorectal cancers.

Adult↗
PubMed1989

Human neutrophils contain and bind high molecular weight kininogen.

Because plasma kallikrein activates human neutrophils, and in plasma prekallikrein (PK) circulates complexed with high molecular weight kininogen (HMWK), we determined whether HMWK could mediate kallikrein's association with neutrophils. HMWK antigen (237 +/- 61 ng HMWK/10(8) neutrophils) was present in lysates of washed human neutrophils. Little if any plasma HMWK was tightly bound and nonexchangeable with the neutrophil surface. Human neutrophils were found to possess surface membrane-binding sites for HMWK but no internalization was detected at 37 degrees C. 125I-HMWK binding to neutrophils was dependent upon Zn2+. Binding of 125I-HMWK to neutrophils was specific and 90% reversible. 125I-HMWK binding to neutrophils was saturable with an apparent Kd of 9-18 nM and 40,000-70,000 sites per cell. Upon binding to neutrophils, 125I-HMWK was proteolyzed by human neutrophil elastase (HNE) into lower relative molecular mass derivatives. Furthermore, HMWK found in neutrophils also served as a cofactor for HNE secretion because neutrophils deficient in HMWK have reduced HNE secretion when stimulated in plasma deficient in HMWK or with purified kallikrein. These studies indicate that human neutrophils contain a binding site for HMWK that could serve to localize plasma or neutrophil HMWK on their surface to possibly serve as a receptor for kallikrein and to participate in HNE secretion by this enzyme.

Antigens↗
PubMed1985

A system of classifying leisure activities in terms of the psychological benefits of participation reported by older persons.

The psychological benefits of 18 commonly chosen leisure activities were investigated using the Paragraphs About Leisure-Form E (PAL-E), which measures the psychological benefits of participation in leisure activities. The data were cluster analyzed using Ward's heirarchical grouping procedure, and a conceptual framework was developed for understanding the psychological benefits derived from participation in leisure activities by persons in the 55 to 75 age range. The data support the conclusions that leisure activities may be grouped into meaningful families or clusters on the basis of their psychological benefits.

Aged↗
PubMed1978

Striatal nondopaminergic neurons: possible involvement in feeding and drinking behavior.

Intracaudate injections of kainic acid destroy striatal neurons containing acetylcholine and gamma-aminobutyric acid but leave dopaminergic nerve terminals in this brain region intact. Rats injected with the drug are aphagic and adipsic, and have other behavioral abnormalities strikingly similar to those seen in animals with lesions in the dopaminergic nigrostriatal bundle.

Animals↗
PubMed1977

Two microsomal-associated iron-binding proteins observed in rat small intestinal cells during iron absorption.

Acrylamide gel electrophoresis of microsomal protein obtained from rat small intestinal mucosal cells, after an injection of [3H]leucine, demonstrated increased quantities of two soluble iron-binding proteins during iron absorption, one with a high molecular weight (about 400 000) and the other of intermediate molecular weight (80 000). Both proteins were present in a ribosomal-enriched sub-fraction obtained during purification of the microsomal membrane but were not identified among the purified membrane proteins.

Animals↗