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L Kaplan

Publications and source records attributed to L Kaplan.

At least 73 records · Page 4Linked to original sources
PubMed1993

A non-lymphoma idiotype is indicative and predictive for B cell malignancies in AIDS.

The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol 22:1749;1992) is expressed on antibodies reactive to different proteins of HIV (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly higher in patients with HIV lymphoma as opposed to HIV-infected individuals, normal controls and non-HIV lymphoma patients, we hypothesized the B-cell neoplasms were the source of the idiotype. However, immunohistochemistry on cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited significant 1F7 reactivity. The reactivity appeared in paracortical and perifollicular lymphoid regions, predominantly regions of B, T and antigen presenting cells in lymph nodes or tonsils. A survey of electrophoretically defined paraproteins with anti-HIV specificities derived from HIV-infected patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody. Therefore, the idiotype does not appear to be a direct product of B-cell neoplasia or abnormal B-cell proliferation, but is produced by B cell clones responding to HIV infection. This high level of serum 1F7 reactivity could be an important clue in the pathogenesis of HIV lymphomas and confers a highly predictive serological test for HIV lymphoma.

Animals↗
PubMed1993

Clinical aspects of HIV-related lymphoma.

The number of cases HIV-associated non-Hodgkin's lymphoma continues to increase as the AIDS epidemic grows. Approximately 3% of AIDS-defining illnesses are non-Hodgkin's lymphoma. The number of non-Hodgkin's lymphoma cases may actually be higher because many cases go unreported. There is also evidence that increasing numbers of patients who are surviving longer on antiretroviral therapy are developing non-Hodgkin's lymphoma. A majority of HIV-related lymphomas are large cell, either high-grade immunoblastic or aggressive intermediate grade, diffuse cleaved, or small noncleaved (Burkitt's-like). HIV-related non-Hodgkin's lymphomas behave aggressively. They are predominantly extranodal and often show unusual patterns of organ involvement. They are typically stage III or IV at the time of diagnosis. Current treatment strategies involve the use of combination chemotherapy regimens with or without antiretroviral therapy. Current studies are evaluating the efficacy of low-dose chemotherapy regimens versus standard-dose regimens with granulocyte-macrophage colony-stimulating factor support. New strategies for treating AIDS-associated non-Hodgkin's lymphoma will incorporate our current knowledge of AIDS-related lymphoma pathogenesis. Factors that reflect a patient's state of immunodeficiency seem to be the most important prognostic features determining clinical outcome after treatment. Patients with good prognostic features may benefit the most from aggressive treatment regimens. AIDS-related primary central nervous system lymphomas continue to comprise approximately 15% of AIDS-related non-Hodgkin's lymphoma cases. Treatment is limited. Although whole-brain radiation therapy can result in an improved neurologic status, the median survival remains 3 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1993

Marriage, spousal caregiving, and a husband's move to a nursing home. A changing role for the wife?

1. Gerontological nurses, when working with elderly couples experiencing role transitions upon nursing home placement, must attend to the needs of the healthier spouse, as well as the institutionalized patient. 2. Letting the community-dwelling wife set the tone for what her continued role will be allows her to define her marriage in a way that serves her needs at this transitory time. 3. If a woman defines herself as a wife, the nurse or nurse clinician's task may be to aid her in redefining the role's tasks, responsibilities, and limitations imposed by the nursing home setting. 4. If a woman does not perceive herself as a wife, nurses must help her accept these feelings as natural, and support her need to establish an identity as an individual and not as part of a couple.

Aged↗
PubMed1993

Enzymatic synthesis and immunosuppressive activity of novel desmethylated immunomycins (ascomycins).

31-O-Desmethylimmunomycin O: methyltransferase (DIMT), an enzyme involved in the biosynthesis of immunomycin (ascomycin/FR-900520), was used to synthesize three analogs of this immunosuppressant compound. These compounds were assigned the following structures: 13-O-desmethyl-, 15-O-desmethyl- and 13,15-O-bisdesmethyl-immunomycins. Two of these compounds, namely, 15-O-desmethyl- and 13,15-O-bismethyl-immunomycins have novel structures and were examined for possible immunosuppressive activity by in vitro T-cell proliferation assay. The results showed that methylation of the C-15 hydroxyl is critical for full biological activity of the immunomycin.

Animals↗
PubMed1993

Anterior vascularized rib strut graft in the treatment of Pott's disease in the young child.

Two young children suffering from acute thoracic kyphosis due to vertebral tuberculosis (Pott's disease) are described. One patient presented with recent onset spastic paraplegia due to cord compression. Anterior decompression and stabilization with a vascularized rib strut graft was performed in both patients. The neurological recovery in the compromised patient was remarkable; spinal stability was achieved in both patients, thus avoiding the necessity for a posterior spinal fusion.

Child, Preschool↗
PubMed1992

Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation.

To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF-responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk results in marked changes in NGF-induced differentiation. Whereas PC12 cells elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells overexpressing gp140trk by 20-fold(trk-PC12) began this process within hours. Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity was sustained for many hours following ligand binding. The tyrosine phosphorylation or activity of several cellular proteins, such as PLC-gamma 1, PI-3 kinase, and Erk1 and the expression of the mRNA for the late response gene transin were also sustained as a consequence of gp140trk overexpression. The data indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF-induced differentiation pathways, possibly through the elevation of gp140trk tyrosine kinase activity.

Animals↗
PubMed1992

Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma.

PURPOSE: A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS: DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS: The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS: EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.

Blotting, Southern↗
PubMed1992

Pneumocandins from Zalerion arboricola. II. Modification of product spectrum by mutation and medium manipulation.

Zalerion arboricola ATCC 20868 produces pneumocandin A0 (L-671,329), a cyclic hexapeptide with a dimethylmyristic acid side chain. This compound has anti-candida and anti-pneumocystis activities. We were interested in looking for other related compounds produced by this organism. To facilitate this search, a simple medium (S2) composed of D-mannitol, peptonized milk, lactic acid, glycine, KH2PO4 and trace elements, which supported the production of a number of such compounds, was designed. For the isolation of mutants, either spores or growing mycelia were treated with N-nitroso-N-methylurethane or N-methyl-N'-nitro-N-nitrosoguanidine and survivors were screened for changes in the product spectrum. From approximately 1,500 survivors tested, 5 mutants were isolated. Mutants ATCC 20957, 74030, 20958 and 20988 exclusively produce various pneumocandins other than A0. These compounds were active against Candida and Pneumocystis carinii. The yield of A0 was found to be increased 2.5-fold over that of the parent in the fifth mutant, MF5415. Further medium studies indicated that the addition of soybean oil to S2 medium improved the yields. Subsequent development of another series of media containing Pharmamedia as a nitrogen source resulted in increase in production by 10- approximately 20-fold. Overall, these studies resulted in substantial improvement in the production of A0 as well as discovery and/or facile production of 7 other related compounds.

Anti-Bacterial Agents↗
PubMed1991

Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma. A prospective multi-institutional trial.

OBJECTIVE: --To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS). DESIGN: --A phase II prospective clinical trial, with median follow-up of 33 months. SETTING: --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases. PATIENTS: --Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response. INTERVENTION: --A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m2 intravenously (IV); doxorubicin, 25 mg/m2 IV; vincristine sulfate, 1.4 mg/m2 IV; bleomycin, 4 mg/m2 IV; dexamethasone, 3 mg/m2 orally on days 1 through 5; methotrexate, 500 mg/m2 IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy. MAIN OUTCOME MEASURES: --Response rate and number of opportunistic infections. RESULTS: --Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival. CONCLUSIONS: --Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Biosynthesis of the immunosuppressant immunomycin: the enzymology of pipecolate incorporation.

Immunomycin, an immunosuppressant closely related to FK 506, contains a pipecolate residue in amide linkage with an acyl group in its polyketide backbone. An enzyme activating L-pipecolic acid has been isolated from Streptomyces hygroscopicus var. ascomyceticus, which produces immunomycin. Purification results in a monomer of 170 kDa exhibiting N-terminal heterogeneity, apparently arising from proteolysis of a single species. It is a dimer under native conditions. The reaction appears to use an aminoacyl adenylate as an intermediate in the activating reaction, as do most activating enzymes involved in nonribosomal peptide synthesis. A range of pipecolate and proline analogues act as substrates in the pyrophosphate-ATP exchange resulting from the adenylation reaction. Several analogues are inhibitors of the subsequent thioesterification of the enzyme. Antibody raised to the purified enzyme was used to follow antigen during the course of fermentation. Maximal levels of antigen are found when synthesis of immunomycin is maximal. Ten of twelve immunomycin nonproducing mutants lack detectable pipecolate-activating enzyme in Western blots. From the enzymatic characteristics, substrate specificity, and immunological properties, we propose that we have isolated the enzyme responsible for activating pipecolic acid for immunomycin biosynthesis.

Adenosine Triphosphate↗
PubMed1991

The biosynthetic origin of the pyridone ring of efrotomycin.

Nocardia lactamdurans has been shown to catabolyse uracil via the reductive pathway. The end product of this pathway, beta-alanine, is incorporated into the pyridone ring of efrotomycin. Support for this proposal includes: (1) reversal of thymine inhibition of efrotomycin biosynthesis by dihydrouracil and N-carbamoyl-beta-aline, two intermediates of the catabolic pathway; (2) incorporation of [5,6-3H]-uracil into efrotomycin with a relative molar specific activity of approximately 0.5, close to the theoretical maximum; and (3) 13C coupling at C4 and C5 of efrotomycin after feeding resting cells with [4,5-13C]-uracil. Our results do not rule out the possibility of an alternative source of beta-alanine or the coexistence of uracil catabolism via oxidative reactions.

Anti-Bacterial Agents↗
PubMed1991

Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis.

In order to determine the utility of amniocentesis for detecting subclinical chorioamnionitis in asymptomatic afebrile women in preterm labor with intact membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective study. After enrollment, 38 women fulfilled all clinical and laboratory criteria for the study; nine women were excluded because they had a leukocyte count exceeding 15,000/microL. None of the 38 asymptomatic afebrile women had a positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses. Sepsis was not proved in any of the 38 infants delivered to these patients. There was a clear relationship between histologic evidence of chorioamnionitis and failure of tocolytic therapy. Fetal lung profiles were mature in 29% of the amnionic fluid samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples before 30 weeks. Amniocentesis does not seem useful to detect chorioamnionitis in asymptomatic afebrile women with preterm labor and intact membranes at 27-32 weeks' gestation, and should be reserved for those cases in which information about fetal lung maturity would be helpful.

Adolescent↗
PubMed1991

Transverse ligament rupture and atlanto-axial subluxation in children.

We report four children aged two to nine years with traumatic tears of the transverse ligament of the atlas and atlanto-axial subluxation. This is extremely rare in this age group since trauma usually causes a skeletal rather than a ligamentous injury. The injuries resulted from falls or motor vehicle accidents, with considerable delay in diagnosis. Flexion radiographs showed atlas-dens intervals (ADI) of 6, 7, 8 and 13 mm; all four patients were treated by posterior fusion at C1-C2 after the failure of conservative treatment. In one child with quadriparesis and a fixed ADI of 13 mm, transoral anterior resection of the odontoid was performed before the fusion. Diagnosis of this traumatic lesion requires a high level of suspicion. Conservative treatment is likely to fail; surgical stabilisation is indicated.

Atlanto-Axial Joint↗
PubMed1991

The Sexual Desire Conflict Scale for Women: construction, internal consistency, and two initial validity tests.

The development of a 33-item Sexual Desire Conflict Scale for Women is described. The scale was designed to measure women's experiences of subjective discomfort and conflict in relation to sexual desire. 54 women participated: 18 survivors of childhood sexual abuse, 18 survivors of nonsexual trauma, 18 controls with no histories of trauma. Three factors accounted for 25.6, 12.9 and 7.6% of the variance. While no social desirability confounding was detected, the three groups had very different scores. Suggestions for research and clinical application are made.

Adult↗
PubMed1991

Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma.

The pathogenesis of the HIV-associated lymphomas is not well understood. In order to begin characterizing this class of lymphoma, we initiated a molecular genetic study of DNA extracted from 31 diagnostic biopsy specimens from patients diagnosed with AIDS-associated non-Hodgkin's lymphoma. Analysis of 25 peripheral lymphomas showed that 14 were monoclonal B-cell processes, while 11 appeared to be of polyclonal origin. Five of the 14 monoclonal lymphomas were found to have rearrangements of the c-myc gene. Epstein-Barr virus (EBV) genomes were found in seven out of 14 monoclonal samples, but only two out of nine polyclonal samples. The six primary central nervous system (CNS) lymphoma samples were more homogeneous than the peripheral samples and all were monoclonal, positive for EBV and lacked detectable c-myc gene rearrangements. This study allows us to subdivide the HIV-associated lymphomas into three major molecular subtypes: (1) monoclonal B-cell process frequently associated with c-myc rearrangement or detectable EBV genomes, (2) polyclonal B-cell process typically without evidence of EBV, and (3) monoclonal primary CNS process associated with EBV genomes and lacking detectable c-myc rearrangement.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Silicone injection management of diabetic foot ulcers: a possible model for prevention of pressure ulcers.

Long-term clinical and histologic findings with injectable fluid silicone to reduce mechanical forces over plantar skin are described. The fluid induces a relatively stable soft tissue prosthesis between skin and bone, reducing the frequency of insensitive ulcer recurrence in the foot. On the basis of these favorable findings, studies are warranted to determine the fluid's efficacy in prevention of pressure ulcers.

Adult↗
PubMed1991

T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis.

T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death.

Adult↗