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Biomedical subjects

D L Cooper

Publications and source records attributed to D L Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1994

Thyroid lymphoma. The case for combined modality therapy.

BACKGROUND: Radiation therapy with or without surgery is generally considered standard treatment for lymphoma of the thyroid. Because of the small number of cases, the role of chemotherapy or combined modality treatment is difficult to determine. METHODS: The published literature was analyzed, supplemented by a series from Yale, for the incidence of local and distant relapse after radiation therapy, chemotherapy, or combined modality treatment for Stage I-II thyroid lymphoma. Patients with advanced disease or in whom radiation was probably inadequate were excluded. Only patients receiving an anthracyline-based regimen were considered in the group with chemotherapy. Patients receiving single agents or non-anthracycline-based regimens were excluded from analysis or, if they also received radiation, were included in the group that received radiation only. RESULTS: Including a series from Yale, a total of 211 patients with Stage IE and IIE thyroid lymphoma were identified. Distant and overall relapse rate were significantly lower in the group that received combined modality treatment. Local relapse was also less, but the difference was not statistically significant. In a small number of patients with disease confined to the neck, the results with radiation were similar to combined modality treatment if the mediastinum was included in the treatment port. CONCLUSION: Although mucosa-associated lymphoma tissue lymphomas are thought to have a low distant recurrence rate and are therefore often treated with local therapy alone, a review of the published literature suggests that 30% of thyroid lymphomas with clinically localized disease will have a distant relapse. The addition of chemotherapy to radiation significantly lowered distant and overall recurrence.

Aged↗
PubMed1994

Cardiogenic shock due to progression of cutaneous T-cell lymphoma.

We describe a patient with progressive cutaneous T-cell lymphoma (CTCL) and development of subacute cardiac failure. Symptomatic lymphomatous involvement of the heart may be more common in patients with CTCL than in other lymphomas because the former is more likely to be associated with circulating tumor cells and hematogenous spread to the myocardium. No single symptom or sign is highly predictive of cardiac involvement, but unexplained tachyarrhythmias, conduction disturbances, low voltage on ECG, and unexplained cardiac enlargement should arouse clinical suspicion. Although echocardiography may be helpful in suggesting cardiac involvement, endomyocardial biopsy should be considered in patients with a reasonable chance of responding to chemotherapy or radiation.

Electrocardiography↗
PubMed1994

A new diagnostic test for Gaucher disease suitable for population screening.

A new test for the diagnosis of Gaucher disease is described. The test is designed to screen large numbers of clinical specimens from high-risk populations. It consists of duplex PCR amplification of genomic DNA followed by hybridization to alkaline phosphatase-conjugated allele-specific oligonucleotide probes (ASOs). High melting temperature PCR primers were used to increase specificity and eliminate the need for a separate annealing step. All hybridization and washing steps were performed at one temperature. Chemiluminescent detection of signals is fast, and results are easily interpreted directly from x-ray films. Currently, the test is being used in our laboratories to screen Ashkenazi Jewish populations in whom Gaucher disease is common.

Gaucher Disease↗
PubMed1994

The variant mRNA isoform of human metastasis gene (CD44V) detected in the cell lines of human hepatocellular carcinoma.

The interaction of the cell surface receptor CD44 molecular with its ligands (addressin, extracellular matrix etc.,) plays an important role in fulfilling the lymphocyte homing and immune reaction. Recently alternatively spliced products of CD44 gene are found to be involved in tumor metastasis as well. Our report found that CD44 prototype RNA (CD44S) was present in all five tumor cell lines. Isoform CD44 RNA (CD44V) was recognized in three metastasized hepatocellular carcinoma cell lines, J5, HCC36, HEP3B. In addition, the J5 CD44 RNA isoform expressed two distinct transcripts which are of the same size as MDA-231 breast tumor cell line. The MDA-231 CD44 RNA variant (CD44V) has been confirmed to contain metastasis domain 4 and 5. It is implicated that the alternative RNA splicing may also play a major role in hepatocellular carcinoma metastasis.

Base Sequence↗
PubMed1993

Lymphoproliferative disorder of granular lymphocytes associated with severe neutropenia. Response to granulocyte colony-stimulating factor.

Lymphoproliferative disorder of granular lymphocytes (LPGL) is an indolent process that is often associated with neutropenia. Although splenectomy, corticosteroids and cytotoxic agents have all been used to treat patients with life-threatening neutropenia, there are few data supporting their effectiveness. We describe a patient with LPGL, severe neutropenia, and a life-threatening infection who had a dramatic response after treatment with granulocyte colony-stimulating factor (G-CSF). The neutrophil count increased from less than 10 cells/microliters to more than 10,000/microliters after seven doses of G-CSF. The infection promptly healed. A review of the literature indicates that 8 of 11 patients with LPGL and severe neutropenia responded to treatment with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF). In view of their relative lack of toxicity and rapid onset of action, the colony-stimulating factors should be considered for initial therapy in patients with LPGL and severe neutropenia. In addition, the high rate of response achieved with colony stimulating factors suggests that in many cases, a defect in myeloid maturation rather than accelerated granulocyte removal is the cause of neutropenia.

Aged↗
PubMed1993

Methyl-directed mismatch repair is bidirectional.

Methyl-directed mismatch repair is initiated by the mismatch-provoked, MutHLS-dependent cleavage of the unmodified strand at a hemimethylated d(GATC) sequence. This reaction is independent of the polarity of the unmodified strand and can occur either 3' or 5' to the mismatch on the unmethylated strand (Au, K. G., Welsh, K., and Modrich, P. (1992) J. Biol. Chem. 267, 12142-12148). The overall repair reaction also occurs without regard to polarity of the unmethylated strand. Both hemimethylated configurations of a linear heteroduplex containing a single d(GATC) sequence are subject to methyl-directed correction in Escherichia coli extracts and in a purified repair system. Repair of both heteroduplex orientations requires MutH, MutL, MutS, DNA helicase II, SSB, and DNA polymerase III holoenzyme, but the two substrates differ with respect to exonuclease requirements for correction. When the unmethylated d(GATC) sequence that directs repair is located 5' to the mismatch on the unmodified strand, mismatch correction requires the 5'--> 3' hydrolytic activity of exonuclease VII or RecJ exonuclease. Repair directed by an unmodified d(GATC) sequence situated 3' to the mismatch depends on the 3'--> 5' activity of exonuclease I. Specific requirements for these activities are evident with circular heteroduplexes containing a single asymmetrically placed d(GATC) sequence, with the requirement for a 5'--> 3' or 3'--> 5' hydrolytic activity being determined by the orientation of the unmethylated strand along the shorter path joining the two sites in the DNA circle. This observation suggests that the methyl-directed repair system utilizes the proximal d(GATC) sequence to direct correction. To our knowledge, these experiments represent the first instance in which exonuclease I, exonuclease VII, and RecJ have been implicated in a particular DNA metabolic pathway.

Adenosine Triphosphatases↗
PubMed1993

Cyclosporine treatment of refractory T-cell lymphomas.

BACKGROUND: Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas. METHODS: Patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity. RESULTS: A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant. CONCLUSIONS: Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug.

Adult↗
PubMed1993

Interleukin-5 mRNA in three T-cell lymphomas with eosinophilia.

The objective of this controlled pilot study was to determine if mRNA coding for interleukin-5 (IL-5), a cytokine that promotes eosinophil differentiation, growth, and migration, could be detected in three T-cell lymphomas that were infiltrated extensively by eosinophils. To detect mRNA coding for IL-5, we performed an RNA polymerase chain reaction on mRNA extracted from three T-cell lymphomas with eosinophilia and from 29 positive and negative validation controls. Using this procedure, we detected a 293-base pair, IL-5-specific amplification product in the three cases of T-cell lymphoma with eosinophilia and in 11 of 12 positive validation controls, including 10 cases of Hodgkin's disease with eosinophilia. IL-5 mRNA was not detectable in the 17 negative validation controls. This preliminary study suggests that IL-5 mRNA is detectable by polymerase chain reaction in three cases of T-cell lymphoma with eosinophilia.

Actins↗
PubMed1993

Members of the ALDH gene family are lens and corneal crystallins.

Many of the major lens proteins, known as crystallins, responsible for the structural integrity and functional utility of this visual tissue have been previously shown to be recruited proteins. This phenomena of a protein that is expressed and functions elsewhere acquiring a new function in another tissue has been termed 'gene sharing'. It is now becoming obvious that the cornea of vertebrates has similarly acquired proteins, and that at least one corneal protein, ALDH3 belongs to a gene family that has been previously identified as a lens crystallin. The recognition that both lens and corneal crystallins exist is a novel concept that has implications that involve the process by which multifunctional gene products have evolved. Members of the ALDH gene family function in both the cornea and lens as crystallins and the acquisition of multifunctionality by this gene family is unique. Based on our analysis we have deduced a supragene family relationship between the thiol protein esterases, aldehyde dehydrogenases, and the taxon-specific crystallins. Evolution of a complex organ such as the vertebrate eye is not a sequential and gradual process such as the Darwinian Giraffe's neck, since the eye can provide selective advantage only as a complete organ. Catastrophic theory proposes that the complex vertebrate eye with its lens, and focussing mechanism arose from the primitive eye spot which contained originally only the photoreceptor system by a one step event. In the evolution of the vertebrate eye it is evolutionarily plausible that several pre-existing proteins have been recruited to perform a structural role for this complex organ. It is also incumbent in evolutionary thought that any inherent enzymatic activity associated with this protein would be purely an incidental addition to the organ. However, the fact that most of these have pyridine nucleotide binding capacity, which is presumed important in giving protection from UV exposure, is noteworthy. Finally, to construct the vertebrate eye in one step from the existing visual pigment system such as the eyespot of unicellular organisms the following criteria would apparently be advantageous: (1) high water solubility; (2) transparency; and (3) common genetic regulatory elements (e.g. promoters/enhancers). Although it is an important observation that certain members of the aldehyde dehydrogenase gene family are present as structural proteins in the cornea and lens, it is not surprising that the phenomenon of gene sharing extends to another ocular tissue such as the cornea. In this context, it will be interesting to note if similar multifunctional gene products will be found as frequently in organs other than the eye.

Aldehyde Dehydrogenase↗
PubMed1993

Recognizing otolaryngologic symptoms in patients with temporomandibular disorders.

Temporomandibular disorders (TMD) afflict millions of men, women and children. Although the management of these disorders has traditionally been the pervue of dentistry, the most common symptoms are otolaryngologic. The involvement of an otolaryngologist was important and necessary in the role of primary diagnostician and as a secondary diagnostician to rule out primary otolaryngologic disease in many of the 2,760 patients evaluated over the past 13 years. In 996 patients referred to the Center for Myofacial Pain/TMJ Therapy from the Otolaryngology Clinic of the New York Eye and Ear Infirmary, 85% complained of ear symptoms, including otalgia (64%), dizziness (42%), and muffling (30%). Sixty percent complained of throat symptoms, while headaches were reported by 81%. In 1,764 private patients evaluated for TMD, 53% were seen and/or referred by an otolaryngologist. The dentist and otolaryngologist must act as a team in recognizing and diagnosing TMD. As many of the symptoms of TMD fall within the pervue of the otolaryngologist, he or she must be cognizant of the clinical presentation of TMD. Likewise, dental practitioners must utilize the services of their medical colleagues to rule out primary otolaryngologic disorders in all patients with suspected TMD.

Adolescent↗
PubMed1993

Hyperprolactinemic galactorrhea in a patient with Hodgkin's disease and intense pruritus.

We have described a patient with hyperprolactinemic galactorrhea associated with Hodgkin's disease and severe pruritus. Prolactin levels increased in parallel with the development of constitutional symptoms and returned to normal during successful treatment with chemotherapy. Explanations for the development of galactorrhea include chronic chest wall excoriation due to severe pruritus and cytokine-mediated pituitary prolactin release.

Adult↗
PubMed1993

Gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy.

PURPOSE: To determine the predictive value of gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality treatment. PATIENTS AND METHODS: A retrospective study was performed of 48 patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality therapy. Patients were monitored with whole-body planar scans (34 patients) or chest single-photon-emission computed tomography (SPECT) plus planar abdominal imaging studies (14 patients). Scans were performed at diagnosis, following three to eight cycles of chemotherapy, and after the end of treatment. The value of gallium scans in modifying treatment and predicting outcome was assessed. RESULTS: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum. After chemotherapy, four patients had residual mediastinal activity; two patients with persistent activity on planar scans failed to enter remission and died of disease; two other patients with abnormal activity only seen on SPECT had therapy modified and remain in remission. After chemotherapy, 44 patients had a normal gallium scan. Twelve patients with negative scans relapsed, including nine patients with recurrence above the diaphragm. CONCLUSION: The use of gallium scans after several courses of chemotherapy resulted in a modification of treatment in four patients, including two patients who are apparently cured. However, after negative scans, 20% of patients relapsed above the diaphragm. These results suggest that gallium imaging, including SPECT, is of limited value in predicting disease sterilization, although the number of patients studied with SPECT was small. At present, the major value of gallium scans is to identify patients who may benefit from a modification of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Disseminated intravascular coagulation and excessive fibrinolysis in a patient with metastatic prostate cancer. Response to epsilon-aminocaproic acid.

BACKGROUND: Disseminated intravascular coagulation (DIC) and primary fibrinolysis have both been reported in association with prostate carcinoma. The correct diagnosis of the coagulopathy can be difficult and the appropriate management controversial. METHODS: A case is presented of a man in whom DIC and soft tissue hemorrhage developed after prostatic biopsy. The results of therapy and a review of the literature are discussed. RESULTS: Fibrinogen levels continued to decrease despite high-dose estrogen therapy, but they rapidly returned to normal after therapy with epsilon-aminocaproic acid. Although routine coagulation tests were suggestive of primary fibrinolysis, the results of the D-dimer assay confirmed that the patient had DIC associated with excessive fibrinolysis. CONCLUSION: A review of the literature suggests that most cases of primary fibrinolysis are probably DIC with excessive secondary fibrinolysis. In cases in which bleeding is the primary manifestation of DIC and there is a significant reduction in alpha-2-plasmin inhibitor activity, a trial of epsilon-aminocaproic acid and low-dose heparin should be considered. The failure in this case of estrogen therapy to correct the coagulopathy, despite a later good tumor response, is consistent with the delay in which anorchid testosterone levels are obtained after initiating treatment.

Adenocarcinoma↗
PubMed1992

Brief chemotherapy, involved field radiation therapy, and central nervous system prophylaxis for paranasal sinus lymphoma.

Lymphoma of the paranasal sinus is a rare tumor characterized by bulky local disease, early systemic dissemination, and a propensity for central nervous system (CNS) spread. Treatment with radiation alone generally has been disappointing. Based on previous encouraging reports of initial brief chemotherapy followed by involved field radiation therapy (IFRT) for localized large cell lymphoma, four consecutive patients with paranasal sinus lymphoma were treated with 6 weeks of chemotherapy followed by IFRT and CNS prophylaxis. All patients had bulky localized disease and diffuse large cell lymphoma. Complete response was seen in all patients, and none have had a relapse (minimum follow-up, 25 months; range, 25 to 32 months). Chemotherapy and radiation therapy were well tolerated. One patient developed an osteogenic sarcoma in the radiation field 32 months after completion of therapy. Administration of early frequent chemotherapy followed by IFRT and CNS prophylaxis appears to be an effective treatment strategy for patients with localized large cell lymphoma of the paranasal sinuses.

Adolescent↗
PubMed1992

The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44.

We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms.

Amino Acid Sequence↗
PubMed1991

The multispecific cell adhesion molecule CD44 is represented in reticulocyte cDNA.

Identified originally as erythrocyte p80, whose expression is down regulated by the Lutheran inhibitor gene (In[Lu]), the In(Lu) related-p80 glycoprotein represents the red cell isoform of the human cell adhesion/recognition molecule CD44. The presence of a CD44 transcript within a reticulocyte cDNA library was indicated by the PCR amplification of an appropriately sized product generated by a pair of deoxyoligonucleotide primers derived from CD44 cDNA sequence. The amplified product was subsequently utilized to screen and isolate a positively hybridizing full-length reticulocyte cDNA clone (RETIC CD44) that contained an 1809 base pair insert that was DNA sequenced by the dideoxy chain termination method. This first isolate of a reticulocyte CD44 cDNA appears to be generated by a combination of RNA processing events that includes production of 3' mRNA heterogeneity by utilization of multiple poly(A) sites. Remarkably, the 3' untranslated (3'UT) region of this mRNA, encoding a prototypic hematopoietic CD44 isoform, has been previously reported present on only a transcript that encodes a CD44 epithelial isoform.

Amino Acid Sequence↗