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Biomedical subjects

D Kaplan

Publications and source records attributed to D Kaplan.

At least 19 recordsLinked to original sources
PubMed1992

Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities.

The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins.

Animals↗
PubMed1992

Arthritis and hypertension in patients with systemic lupus erythematosus.

OBJECTIVE: The purpose of this study was to test the hypothesis that patients with systemic lupus erythematosus (SLE) who have, as part of their disease, persistent rheumatoid-like arthritis are less likely to be hypertensive than are other patients with SLE. METHODS: A retrospective chart analysis of 662 patients with SLE seen in a university clinic was performed. RESULTS: Data analysis revealed that hypertension and persistent arthritis were inversely correlated, particularly in those patients without nephritis and particularly in black patients. CONCLUSION: We conclude that rheumatoid-like arthritis in patients with SLE is protective against hypertension, and speculate that this protection is conferred by a higher frequency of the DR4 allele.

Arthritis↗
PubMed1992

Cryptococcal osteomyelitis and cellular immunodeficiency associated with interleukin-2 deficiency.

We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age. His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age. He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies. Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters. Immunoglobulin levels and specific antibodies were normal. The patient has been in good health since treatment of his osteomyelitis. However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid. Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes. The generation of messenger ribonucleic acid for interleukin-4 was not affected. Interferon-gamma was produced at subnormal levels. The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors. The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency. Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine.

Adolescent↗
PubMed1992

Gene transfer in human lymphocytes using a vector based on adeno-associated virus.

Adeno-associated virus is a nonpathogenic, dependent parvovirus that integrates at a specific site in human chromosome 19. We have used the inverted terminal repeats of the virus, which mediate integration, to establish a vector for gene transfer in human lymphocytes. A neomycin resistance gene has been stably introduced into nontransformed human T-cell clones and a subsequent analysis of the functional properties of the infected clone revealed no detectable alterations. Rescue and replication of the wild-type virus was accomplished with adenovirus superinfection; however, the vector was not rescued and did not replicate by this procedure, indicating the stability of the integrated vector and demonstrating an additional level of safety incorporated in its construction. An adeno-associated virus-based vector represents an alternative to retroviruses for gene therapy in lymphocytes.

Base Sequence↗
PubMed1992

Predictors of adolescent female decision making regarding contraceptive usage.

The relationship of cognitive capacity, cognitive egocentrism, and experience factors to decision making in a contraceptive usage problem was examined. Fifty sexually active, unmarried females, ages 14-19, served as subjects. Using correlational, regression, and canonical correlational analyses, cognitive capacity and cognitive egocentrism variables, not experience with contraceptives, were found to be significantly related to, and predictive of, five of seven decision-making variables. Forty-one percent of the variance was accounted for in predicting the canonical decision-making variable. The implications of these results for future research are discussed.

Adolescent↗
PubMed1991

Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate.

177Lutetium (177Lu) is a member of the family of elements known as lanthanides or rare earths. Monoclonal antibody (MAb) CC49, a murine IgG1, which is reactive with the tumor-associated antigen, TAG-72, has been shown previously to react with a wide range of human carcinomas; CC49 reacts to a different epitope on the TAG-72 molecule than MAb B72.3 and has a higher binding affinity. We report here the first use of a 177Lu-labeled immunoconjugate, 177Lu-CC49, in an experimental therapy model for human carcinoma. 177Lu-CC49 was shown to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50 microCi. Overt toxicity was observed with the administration of approximately 500 microCi of 177Lu-CC49 in which 5 of 9 mice died of apparent marrow toxicity. A single administration of 200 or 350 microCi of 177Lu-CC49, however, was shown to eliminate established tumors through the 77-day observation period after MAb administration. Dose fractionation experiments revealed that at least 750 microCi of 177Lu-CC49 (250 microCi/week for 3 consecutive weeks) was well tolerated in that 9 of 10 mice survived. Moreover, this dose schedule was able to eliminate the growth of relatively large (300 mm3) human colon tumor xenografts in 90% of the animals treated. Single-dose and dose fractionation studies were also carried out with an isotype-matched control MAb, 177Lu-MOPC-21. In all dose schedules, a large differential was seen between the therapeutic effects of the 177Lu-CC49 versus that of the 177Lu-control MAb. The merits and limitations of the use of 177Lu-labeled immunoconjugates (in particular, 177Lu-CC49) are discussed in terms of potential novel therapeutics for human carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1991

A preliminary study of excess risk of cardiovascular disease in the mothers of patients with rheumatoid arthritis.

Family histories were obtained from 123 patients with rheumatoid arthritis and 152 patients with other musculoskeletal complaints. The subjects were female patients aged 40 years or more seen at the Arthritis Clinic of the State University of New York Health Science Center at Brooklyn between October 1985 and February 1986. It was found that death due to heart disease or stroke was more common (adjusted p less than 0.02) in the mothers of patients with rheumatoid arthritis than in the mothers of control patients, and that heart disease was also reported to be more common in these mothers (adjusted p less than 0.005). Thus, it is possible that cardiovascular disease at least partially accounts for the previously noted (J Rheumatol 1986; 13:903-6) shorter life expectancy of the mothers of patients with rheumatoid arthritis.

Adult↗
PubMed1991

Single cell fusion events induced by influenza hemagglutinin: studies with rapid-flow, quantitative fluorescence microscopy.

Fusion of individual human erythrocytes to fibroblasts expressing the influenza virus hemagglutinin Cells were attached to coverslips fitted in a specially designed flow chamber mounted on a microscope stage, and fusion was triggered by rapid acidification to pH less than 5.2. Fusion between single cell pairs was monitored by a fluorescence increase due to redistribution of fluorescent dyes between either membrane or cytoplasmic compartments of fusing cells. The single cell fusion events were broadly heterogenous in lag times, rise times, and overall shape of the curves. Lag times obtained with a water-soluble dye were within the range obtained with a water-soluble dye were within the range obtained with the membrane-bound fluorophores, (10-160 s). Fusion was both all-or-nothing and irreversible, in that once dye redistribution in any cell commenced, it completed, regardless of pH. Short pulses of pH 4.9 for 6-10 s led to about half of the cell pairs fusing, but pulses greater than 14 s were as effective as constant low pH. Pulses that were too short to trigger fusion did not partially activate nor deactivate the fusion process, as shown by the ability of a second acidification to cause fusion of the same cells, with similar lag times. These results indicate that the overall hemagglutinin-mediated fusion process is composed of at least two stages, one required for commitment of the hemagglutinin to a fusogenic state that is pH-dependent and a maturation stage that is pH-independent.

Animals↗
PubMed1991

Arthritis and nephritis in patients with systemic lupus erythematosus.

Previous publications suggest that in patients with systemic lupus erythematosus (SLE), rheumatoid factor (RF) may be "protective" against nephritis. In our study of 662 patients with SLE, we found that persistent, rheumatoid-like arthritis showed a much stronger inverse correlation with nephritis than RF. Of 186 such patients, 59 developed clinically evident nephritis (32%) compared to 263 of the other 476 patients (55%) (p less than 10(-7). RF showed only a weak inverse relationship to nephritis (p = 0.064). We conclude that the presence of persistent rheumatoid-like arthritis in patients with SLE identifies a clinical subset of patients who are less likely to develop nephritis than those with no arthralgia, no objective arthritis or only episodic arthritis. We hypothesize that such patients represent a genetically determined subset among patients with SLE and that perhaps they are more likely to bear the HLA-DR4 allele.

Adolescent↗
PubMed1990

Presence of peripheral benzodiazepine binding sites on primary rat skeletal fibroblasts.

Employing [3H]Ro5-4864 as a radioligand, the existence of peripheral benzodiazepine binding sites in rat hind limb skeletal fibroblasts was explored. Saturable, high affinity binding of this ligand is described for fibroblasts and cell membrane preparations, demonstrating a pharmacological profile characteristic for such receptors. The binding of [3H]Ro5-4864 exhibited higher affinity and density in fibroblasts compared to membrane preparations. A quaternaryamine derivative of PK 11195 showed a similar potency as a displacer of [3H]Ro5-4864 in both preparations. The data suggest that peripheral benzodiazepine receptors are present in the plasma membrane of primary mammalian fibroblasts.

Animals↗
PubMed1990

Total deficiency of plasma cholesteryl ester transfer protein in subjects homozygous and heterozygous for the intron 14 splicing defect.

The molecular basis of cholesteryl ester transfer protein (CETP) deficiency was investigated in 4 unrelated CETP-deficient families. The high density lipoprotein-cholesterol levels of the probands exceeded 150 mg/dl. The plasma of the probands was totally deficient in CETP activity and mass. The genomic DNA of the patients was amplified by polymerase chain reaction, using two oligonucleotide primers located in the intron 12 and 14 of the CETP gene, and the amplified products were directly sequenced. Two patients were homozygous for a G-to-A change at the 5'-splice donor site of the intron 14. The G-to-A change would cause impaired splicing of pre-messenger RNA. The other two probands were heterozygous for the mutation, but totally lacked CETP. Their lipoprotein patterns were also similar to those of the two homozygotes. Thus, other genetic defects or metabolic factors influencing CETP expression are implicated. The data suggest that the G-to-A mutation may be common in human plasma CETP deficiency. Furthermore, there could be compound heterozygotes who totally lack plasma CETP and have lipoprotein profiles similar to those of homozygotes.

Adult↗
PubMed1990

Diaphragmatic plication for unilateral diaphragmatic paralysis: a 10-year experience.

Unilateral paralysis of the diaphragm due to nonmalignant disease is an uncommon disorder previously thought to have benign implications. Some patients, however, experience dyspnea and orthopnea with impairment of pulmonary function. Unilateral diaphragmatic plication was performed on 17 patients (16 men and 1 woman with a mean age of 53.7 years [range, 28 to 74 years]) during the last 10 years. Preoperatively each patient was shown to have paradoxical movement of the paralyzed diaphragm on sniffing and to have a reduction in forced vital capacity and lung volumes. These reductions were greater when the patient was in the supine position. All patients had moderate hypoxemia (mean arterial oxygen tension, 73.1 +/- 10.9 mm Hg). Plication was performed by imbricating the diaphragm in layers through a thoracotomy incision. After plication, all patients showed both subjective and objective improvement. Six patients were reassessed 5 or more years after plication (range, 5 to 7 years), and the improvement was maintained. Diaphragmatic plication is a safe and effective procedure for adult patients with dyspnea due to unilateral diaphragmatic paralysis; furthermore, the initial improvement is maintained.

Adult↗
PubMed1989

Prenatal cocaine exposure is associated with respiratory pattern abnormalities.

As retrospectively determined, the rate of sudden infant death syndrome in 66 infants prenatally exposed to cocaine was 15%, compared with only 4% among infants exposed to opiates. This prospective evaluation of cardiorespiratory pattern in 32 cocaine-exposed and 18 methadone-exposed infants was therefore performed to further evaluate the effects of intrauterine exposure. The two groups were similar in maternal age, race, and cigarette, alcohol, and marijuana use and in gestational age, sex, and birth weight. Apnea density and episodes of periodic breathing exceeded the 95th percentile for normal infants in 12 (38%) of 32 of cocaine-exposed infants vs only 1 (6%) of 18 opiate-exposed infants. Five cocaine-exposed but no opiate-exposed infants had apnea of infancy, and all 5 of these infants had an abnormal cardiorespiratory pattern. In all 13 infants with an abnormal cardiorespiratory pattern, theophylline treatment resulted in normalization of the respiratory pattern and was associated with absence of any (further) clinical events. In summary, infants prenatally exposed to cocaine have a higher incidence of cardiorespiratory pattern abnormalities than do infants with methadone or no prenatal drug exposure.

Apnea↗
PubMed1989

Unna's boot.

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Bandages↗
PubMed1989

Kaposi's sarcoma.

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History, 19th Century↗