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Biomedical subjects

M S Roth

Publications and source records attributed to M S Roth.

At least 37 records · Page 2Linked to original sources
PubMed1990

Use of polymerase chain reaction-detected sequence polymorphisms to document engraftment following allogeneic bone marrow transplantation.

Distinguishing between host and donor origin of cells after bone marrow transplantation is important in understanding the engraftment process. Restriction fragment-length polymorphism (RFLP) analysis, the most generally applicable approach for this purpose, is limited by a requirement for at least 10(6) cells per assay. The small number of cells available at early time points post-BMT has thus precluded studies of early engraftment kinetics. This report describes the application of the polymerase chain reaction (PCR) to engraftment analysis following allogeneic BMT. We describe a series of PCR polymorphisms (PCRFLP/s) that allows the distinction of most patient-donor pairs (excluding identical twins). Thirteen patient-donor pairs were evaluated using this approach, and engraftment data obtained at time points when leukocyte counts were often too low for conventional analysis. This approach is quantitative and significantly more rapid than conventional techniques. (Analysis can be completed in less than a day). Serial evaluation at early time points post-BMT in five patients demonstrated residual host cells early (days 7-14) followed by their subsequent rapid disappearance. In one patient an apparent resurgence of host elements occurred around days 28-35, followed by a sharp decline by day 42.

Base Sequence↗
PubMed1990

Linkage relationship of X-linked juvenile retinoschisis with Xp22.1-p22.3 probes.

Linkage analysis was performed to evaluate the relationship between the locus for X-linked juvenile retinoschisis (RS) and five X-chromosomal markers-RC8 (DXS9), SE3.2L (DXS16), 99-6 (DXS41), D2 (DXS43), and 782 (DXS85)-all mapped to the interval Xp22.1-p22.3. Seven U.S. families with 56 affected males were studied. No recombinants were found between RS and DXS9 with a maximum lod score (Z) of 4.93 at a recombination fraction of zero. Obligate recombinants were found for RS with DXS16, DXS41, DXS43, and DXS85. Multipoint linkage analysis and consideration of recombination events within pedigrees suggest that DXS41 and DXS43, and also DXS41 and DXS16, flank RS and that DXS85 lies outside the interval DXS41-DXS43. Our pedigrees provide no evidence for genetic heterogeneity of RS, with five of our families individually showing evidence of linkage. (Z greater than 2.0) to the least one of these probes from Xp22.1-p22.3.

DNA Probes↗
PubMed1990

Detection of Philadelphia chromosome-positive cells from glass slide smears using the polymerase chain reaction.

Southern and Northern blot hybridization studies and the polymerase chain reaction (PCR) have been used to analyze the bcr-abl gene complex in chronic myelogenous leukemia (CML). Because fresh or cryopreserved cells may not always be available for molecular analyses, we investigated the possibility of using routinely prepared glass slide smears of blood or bone marrow as our source of cellular material. Cellular RNA was prepared directly from the blood or bone marrow smears using a modified RNA extraction procedure. cDNA was synthesized from RNA and amplified with PCR using bcr and abl-specific primers. Using this procedure, the bcr-abl fusion gene was detected by PCR in 21 of 21 patients with CML. Three patients who had undergone allogenic bone marrow transplantation (BMT) for CML were also studied by PCR. bcr-abl was identified transiently in one patient, persisted in one patient after BMT for 2 years until relapse occurred, and was absent in one patient to 18 months after BMT. We have shown that PCR can detect the bcr-abl gene of CML using material from glass-slide smears. This technique may be useful as a general approach in evaluating archival hematologic specimens for the expression of critical gene products.

Bone Marrow Transplantation↗
PubMed1989

Detection of Philadelphia chromosome-positive cells by the polymerase chain reaction following bone marrow transplant for chronic myelogenous leukemia.

Sixteen patients treated by allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr/abl-specific RNA transcripts at various time points after BMT. In reconstitution experiments, one CML cell per million normal mononuclear cells could be detected by direct agarose gel visualization of a bcr/abl-specific band following PCR. Bcr/abl message was found in ten out of 16 patients post-BMT. PCR-positive bcr/abl was present only transiently in three patients and correlated with relapse in three. One patient died in clinical remission, while two patients remain in remission despite persistence of bcr/abl-positive abl-positive cells at 180 days. Long-term follow-up of bcr/abl-positive patients in clinical remission may provide insight into the fate or residual Ph+ cells after BMT. This approach may aid in the identification of high-risk patients likely to relapse post-BMT.

Base Sequence↗
PubMed1988

Ki-1 lymphomas in children.

Three male children, ages 8, 11, and 14 at presentation, with the recently described Ki-1 lymphomas are reported. All three had lymph node involvement. The lymphoma was classified as immunoblastic in two children, and mixed small and large cell in the third child. In histologic terms, sinusoid, paracortical, and diffuse lymph node involvement by lymphoma was evident in each case. Both cases of immunoblastic lymphoma were T11+, T10+, T9+, HLA/Dr+, Tac+, Ki-1+, LCA+, and EMA+, while the lage neoplastic cells of the other case were T11+, Ki-1+, and LCA+. In all three cases DNA analysis of immunoglobulin heavy and light chain genes as well as T-cell receptor beta- and gamma-chain genes showed only germline patterns. The patients were treated with multi-agent chemotherapy. Two are in complete remission at 13 and 16 months, while the third failed to achieve remission and is alive with disease 12 months after a diagnosis had been established.

Adolescent↗
PubMed1988

Sizing of the human T cell receptor alpha locus and detection of a large deletion in the Molt-4 cell line.

The human T cell receptor alpha (TCR-alpha) chain gene consists of discontinuous DNA segments encoding multiple variable (V), multiple joining (J), and one constant (C) region. Unlike other immunoglobulin or TCR genes, however, the TCR-alpha locus exhibits an unusual dispersal of J segments that occupy a region of greater than 50 kilobases (kb) upstream of the C region, with the exact size still unknown. We report here the study of the TCR-alpha genetic locus by using pulsed-field gel electrophoresis (PFGE), which permits the separation of large DNA fragments. Analysis of DNA prepared from normal peripheral blood mononuclear cells, human endothelial cells, and a B cell line demonstrates that both V and C sequences are contained within a single 400-kb SfiI restriction fragment. PFGE analysis of the T cell line Molt 4 suggests a greater than 600-kb deletion involving the TCR-alpha gene.

Cell Line↗
PubMed1988

Rearrangement of immunoglobulin and T-cell receptor genes in Hodgkin's disease.

The precise cellular origin of the malignant cell population in Hodgkin's disease (HD) is unknown. Recent application of Southern blotting techniques to detect clonal rearrangements of immunoglobulin (Ig) and T-cell receptor (TCR) genes has yielded conflicting results. The authors report the detailed analysis of tumor tissue DNA obtained from 18 cases of HD using Ig and TCR gene probes. The distribution of HD subtypes was similar to that in other series. Samples were examined for rearrangement by means of multiple restriction enzymes with specific probes for the Ig heavy chain, Ig kappa, Ig lambda, TCR beta, and TCR gamma loci. Only germline bands were detected in all 18 cases with the Ig gene probes and in 15 of 18 cases with the TCR probes. In 2 cases blot analysis suggested a predominance of polyclonal (or oligoclonal) T cells. In 1 case monoclonal rearrangement of the TCR beta gene was detected. Based on the intensity of the rearrangement and the small percentage of Reed-Sternberg (R-S) cells in this case, the clonal population detected was most likely not the R-S cell itself. The data do not support the frequent occurrence of Ig or TCR monoclonal gene rearrangement in HD.

DNA, Neoplasm↗
PubMed1987

Light chain disease associated with the hyperviscosity syndrome.

The hyperviscosity syndrome refers to a group of symptoms and signs related to increased blood viscosity often produced by monoclonal immunoglobulins. It is most frequently associated with Waldenström's macroglobulinemia and, on occasion, with other immunoglobulins that are capable of forming highly polymerized molecules. This article is a report on the first case of pure light chain myeloma associated with the hyperviscosity syndrome. The hyperviscous plasma in this case is secondary to the unusual degree of aggregation of kappa light chain as demonstrated by high-resolution electrophoresis, serum immunofixation, and Sephadex g-200 (Pharmacia, Piscataway, NJ) column chromatography.

Bence Jones Protein↗
PubMed1987

Interferon therapy of non-Hodgkin's lymphoma.

In 1981, the National Cancer Institute undertook Phase II trials of interferon alfa-2a in patients with non-Hodgkin's lymphoma (including cutaneous T-cell lymphoma [CTCL]) and chronic lymphocytic leukemia (CLL). A dose of 50 X 10(6) U/m2, three times per week, was used initially, then adjusted downward as dictated by toxic effects. A 54% response rate was achieved among 24 patients with low-grade non-Hodgkin's lymphomas, and the median duration of response was 8 months. Less encouraging results emerged from studies in patients with intermediate- or high-grade disease. Responses were noted in only two of six patients in the former group, and only one of seven in the latter group. Results have likewise been disappointing in patients with CLL. Of 18 individuals treated, only two exhibited brief, partial responses. In CTCL, on the other hand, alpha interferon may be the most effective single agent. Among 20 patients with advanced disease who had failed previous therapies, 45% responded. The primary dose-limiting toxicity in all these trials has been flu-like symptoms, particularly fever and fatigue. Fever has generally resolved as treatment has been continued, but dosage reductions are usually necessary to alleviate fatigue. Future studies are likely to focus on the use of alpha interferon in combination with chemotherapeutic agents or other biologic response modifiers, such as monoclonal antibodies.

Drug Evaluation↗
PubMed1987

Regressing atypical histiocytosis: a review and critical appraisal.

Regressing atypical histiocytosis (RAH) has been defined as a primary cutaneous neoplasm composed of atypical histiocytes. In this study, ten cases of RAH were available for review including the two first reported cases. In addition, one new case was studied immunocytologically, for immunoglobulin and T cell receptor gene rearrangement, and for DNA ploidy analysis. Histologic study of ten cases permitted recognition of microscopic features both common and uncommon to RAH. Clinical follow-up of eight cases suggests an indolent course but with probable substantial long-term risk for development of systemic lymphoma. The histiocytic origin of RAH must now be considered questionable because the results of immunologic phenotyping and the discovery of rearrangement of T cell receptor beta- and gamma-chain genes found in the newly studied case indicate that this primary cutaneous neoplasm, previously considered histiocytic, is most probably of T cell lineage.

Histiocytic Sarcoma↗
PubMed1987

T-cell receptor gene rearrangement in regressing atypical histiocytosis.

A case of regressing atypical histiocytosis having characteristic clinical and light microscopic findings was studied immunologically for immunoglobulin and T-cell receptor gene rearrangement and for DNA ploidy analysis. Immunologic phenotyping and rearrangement of T-cell receptor Beta- and gamma-chain genes indicated that this primary cutaneous neoplasm, previously considered "histiocytic" in origin, is most probably of T-cell lineage.

Chromosome Mapping↗
PubMed1986

Alpha interferon in the treatment of hematologic malignancies.

The interferons are an important first member of a family of biologic response-modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Alpha interferon is the most extensively studied interferon species. Although antitumor activity has been seen both in vitro and in vivo in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. More than 90 percent of patients with hairy cell leukemia have a sustained recovery of their peripheral blood cell counts with alpha interferon therapy. Approximately 50 percent of patients with low-grade non-Hodgkin's lymphoma and cutaneous T cell lymphoma demonstrate a response to alpha interferon. More than 80 percent of patients with chronic myelogenous leukemia have a response to alpha interferon, and in one study, nearly half of the patients with response had complete suppression of the Philadelphia chromosome clone on at least one examination. Ongoing clinical trials are addressing such issues as optimal dosage, duration of alpha interferon therapy, and combinations of alpha interferon with other biologic agents, chemotherapy drugs, and radiation.

Humans↗
PubMed1986

Hemophilus influenzae type B cellulitis in adults.

Cellulitis due to Hemophilus influenzae type B is a rare but treatable event in adults. Herein is described a 67-year-old woman with anterior neck cellulitis caused by H. influenzae type B, documented by positive blood culture results. Six additional cases reported in the literature are reviewed. The following clinical syndrome emerges: the patient is usually older than 50 years of age, and pharyngitis develops first, followed by the onset of high fever and rapidly progressive anterior neck swelling, tenderness, and erythema associated with dysphagia. Because the causative organism may be resistant to ampicillin, the early use of chloramphenicol is recommended along with a beta-lactamase-resistant penicillin or cephalosporin (to cover other potential pathogens), or an appropriate third-generation cephalosporin that would also adequately cover all possible pathogens.

Aged↗
PubMed1986

Alpha interferon treatment of low-grade B-cell non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, and chronic lymphocytic leukemia.

The interferons represent an important first member of a family of biologic response modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Interferon alpha is the most extensively studied interferon species. Although antitumor activity has been seen both in vivo and in vitro in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. For the low-grade non-Hodgkin's lymphomas, response rates of 50%, with 10% to 15% complete responses, have been reported. A response rate of 15% has been reported for chronic lymphocytic leukemia in studies outside of the National Cancer Institute (NCI); in our phase II trials at the NCI, only two (11%) of 18 patients had brief partial responses to recombinant interferon alpha. For patients with cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome), a response rate of 45%, with 10% complete responses, was seen in patients treated with recombinant interferon alpha. Based on such findings, interferon appears to be one of the most effective single agents for cutaneous T-cell lymphomas. Further phase II trials are being conducted to determine whether lower doses of interferon alpha are as effective as the high doses used in the previously reported studies. Phase III trials will involve the use of interferons in combination with chemotherapeutic agents as well as in the adjuvant setting.

Humans↗
PubMed1979

Inhibition of human chorionic gonadotropin-induced progesterone synthesis by estradiol in isolated human luteal cells.

The purpose of this study was to determine whether estrogens exerted a direct inhibitory effect on progesterone synthesis in isolated human luteal cells in vitro. It was found that hCG stimulated progesterone synthesis by luteal cells, obtained from corpora lutea of the menstrual cycle, whereas cells isolated from corpora lutea of pregnancy were unresponsive to exogenous hCG. Estradiol markedly inhibited (P less than 0.001) this hCG effect in luteal cells of the menstrual cycle, and this inhibition was dose dependent. Estradiol did not block the stimulation of cAMP accumulated by hCG in the luteal cells of the cycle but did inhibit the stimulatory effect of dibutyryl cAMP on progesterone synthesis. These data suggest that estrogens may directly cause functional luteolysis in the human and that its site of action may be after the accumulation of cAMP.

Chorionic Gonadotropin↗
PubMed1978

Effects of steroids on serum lipids and serum cholesterol binding reserve.

Serum cholesterol binding reserve (SCBR) denotes the capacity of serum to solubilize additional cholesterol. It as been shown previously that a decrease of the SCBR in the presence of elevated cholesterol and/or triglyceride levels is associated with the development of coronary artery disease in man. This is a preliminary report of the effect on serum lipids and SCBR by alteration of the sex steroid environment in women. The hormonal changes associated with pregnancy appear to elevate cholesterol, triglycerides, and SCBR, SCBR being elevated to the greatest extent. No differences were observed in SCBR and serum lipids in a short-term study of premenopausal women when values prior to castration are compared with values after castration during administration of conjugated equine estrogens. In women observed over a period of over 20 weeks, who were using a combination oral contraceptive pill with 1 mg. of norethindrone and 50 or 80 mcg. of mestranol, there was a significant elevation of triglycerides, some decrease of cholesterol, and no change in the SCBR. The possible significance of these findings in relation to the risk of coronary heart disease deserves further investigation.

Adolescent↗