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Biomedical subjects

S L Allen

Publications and source records attributed to S L Allen.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effect of somatostatin analog (SMS 201-995) on in vivo intestinal fluid transport in rats. A limited systemic effect.

Somatostatin analog, SMS 201-995, effectively inhibits the release of hormones from gastrointestinal endocrine tumors and reduces hormonally mediated diarrheas. Its clinical efficacy in nonhormonally mediated diarrhea is limited, despite a potent antisecretory and proabsorptive effect in vitro. The effect of serosal addition of SMS 201-995 on in vitro short-circuit current responses in rat intestine is dependent upon chloride and more marked in colon and ileum than jejunum. In contrast, in vivo loop studies demonstrated that systemic administration of SMS 201-995 for five consecutive days produced a paradoxical decrease in basal colonic fluid absorption with no effect in jejunum or ileum. Furthermore, systemically administered SMS 201-995 did not alter cholera toxin-stimulated intestinal secretion. We conclude that despite a previously identified intestinal antisecretory and proabsorptive effect of SMS 201-995 in vitro, this effect is not seen in vivo and may explain the limited use of SMS 201-995 as an antidiarrhoeal agent in nonhormonally mediated diarrhoea.

Animals↗
PubMed1988

The karyotype of Philadelphia chromosome-negative, bcr rearrangement-positive chronic myeloid leukemia.

Philadelphia (Ph) chromosome negative chronic myeloid leukemia (CML) can be distinguished from clinically similar disorders on the basis of the presence of rearrangement of the breakpoint cluster region (bcr) of chromosome 22. We have identified six patients with Ph-negative CML, each with bcr rearrangement. Apparently normal karyotypes were observed in two cases, and a third contained a rearrangement that did not appear to involve chromosomes 9 or 22. The other three cases had translocations involving chromosome band 9q34 but no case contained the common derivative chromosome 9pter----9q34::22q11----22qter. One case appeared to contain either a deletion of an unrearranged bcr locus in approximately 50% of cells or duplication of rearranged bcr, both 5' and 3' of the chromosome 22 breakpoint. Considerable complexity exists in the types of genetic changes that can juxtapose bcr and the c-abl oncogene in CML. Based on the molecular and cytogenetic analyses of these and other cases described in the literature, we conclude that most cases of true Ph-negative CML arise from submicroscopic genetic exchanges rather than masking of simple t(9;22)(q34;q11) translocations by secondary rearrangements.

Adult↗
PubMed1988

Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia.

Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.

Doxorubicin↗
PubMed1988

Monosomy 5 in acute megakaryoblastic leukemia. Report of two cases.

Two cases of acute megakaryoblastic leukemia are reported. The diagnoses were confirmed by clinical, morphologic, and cytochemical analysis. Karyotypic analysis demonstrated monosomy 5 in both patients, providing further evidence that acute megakaryoblastic leukemia is a subset of the acute nonlymphocytic leukemias and may be etiologically related to the myelodysplastic syndromes.

Adult↗
PubMed1988

Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog.

A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.

Animals↗
PubMed1988

Scintigraphic and magnetic resonance studies in a patient with Gaucher's disease.

In-111 chloride imaging was used in the evaluation of a patient with Type I Gaucher's disease before splenectomy for pancytopenia. This case is the first report of its use in this clinical setting. The image demonstrated the presence of adequate marrow reserve, thereby suggesting that the pancytopenia was due to hypersplenism rather than marrow replacement. Normalization of blood counts after splenectomy confirmed this interpretation. Eight months later, the patient had acute pain in the left knee. Bone imaging suggested a left lateral tibial plateau fracture that was not seen on plain radiographs or magnetic resonance imaging, but was confirmed by x-ray tomography. The significance and implications of these findings are discussed.

Bone and Bones↗
PubMed1988

Atrophie blanche in chronic myelogenous leukemia.

Atrophie blanche is a syndrome of painful vasculitic infarctive lesions of the lower extremities that heal leaving characteristic atrophic, porcelain white scars. The syndrome may occur as an idiopathic entity or associated with various hematologic and collagen vascular disorders. We present the first recognized case of atrophie blanche in a patient with chronic myelogenous leukemia. This presentation may be part of the expanding spectrum of nonspecific cutaneous manifestations of leukemia (leukemids).

Aged↗
PubMed1988

Marker discrepancy as a diagnostic criterion for lymphoid neoplasms.

Multimarker studies were conducted on 195 lymph node, 59 bone marrow, 44 peripheral blood, eight body fluid, and eight internal organ specimens. The markers were identified by fluorochrome-labeled antibodies quantified with flow cytometry. T-cell receptor gene rearrangements were used for the determination of T-cell clonality. These studies confirmed that CD 19 (B4, Leu 12) is highly sensitive for B-lymphoblastic leukemia, CD 7 (Leu 9) is highly sensitive for T-lymphoblastic leukemia, and CD 5 (Leu 1) is highly sensitive for chronic lymphocytic leukemia. When these markers were compared to antigens of the same cell lineage (e.g., CD 19 to CD 20 [Leu 16] or to surface immunoglobulin, CD 7 to CD 3 [Leu 4], and CD 5 to CD 3), a marked discrepancy between them was diagnostic of the corresponding tumor. T-cell marker discrepancy (CD3 vs. CD 7) was demonstrated in T-cell lymphomas, but it was also shown occasionally in polyclonal T-cell populations. On the other hand, a marked discrepancy between the percentages of a B-lineage (CD 19 or CD 20)-positive and a surface-immunoglobulin-positive population is a reliable phenotype for the diagnosis of a surface-immunoglobulin-negative B-cell lymphoma.

Antigens, Surface↗
PubMed1987

Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors.

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposi's sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposi's sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposi's sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Genomic organization and developmental fate of adjacent repeated sequences in a foldback DNA clone of Tetrahymena thermophila.

DNA sequence elimination and rearrangement occurs during the development of somatic cell lineages of eukaryotes and was first discovered over a century ago. However, the significance and mechanism of chromatin elimination are not understood. DNA elimination also occurs during the development of the somatic macronucleus from the germinal micronucleus in unicellular ciliated protozoa such as Tetrahymena thermophila. In this study foldback DNA from the micronucleus was used as a probe to isolate ten clones. All of those tested (4/4) contained sequences that were repetitive in the micronucleus and rearranged in the macronucleus. The presence of inverted repeated sequences was clearly demonstrated in one of them by electron microscopy. DNA sequence analysis showed that the left portion of this clone contains three tandem, directly repeated copies of a 340-bp sequence, a 120-bp portion of which appears in inverted orientation at a 1.6-kb distance. This clone, pTtFB1, was subjected to a detailed analysis of its developmental fate. Subregions were subcloned and used as probes against Southern blots of micronuclear and macronuclear DNA. We found that all subregions defined repeated sequence families in the micronuclear genome. A minimum of four different families was defined, two of which are retained in the macronucleus and two of which are completely eliminated. The inverted repeat family is retained with little rearrangement. Two of the families, defined by subregions that do not contain parts of the inverted repeat, one in the "loop" and one in the "right flanking region," are totally eliminated during macronuclear development--and contain open reading frames. A fourth family occurs in the "loop" region and is rearranged extensively during development. The two gene families that are eliminated are stable in the micronuclear genome but are not clustered together as evidenced by experiments in which DNAs from nullisomic strains are used to map family members to specific micronuclear chromosomes. The inverted repeat family is also stable in the micronuclear genome and is dispersed among several chromosomes. The significance of retained inverted repeats to the process of elimination is discussed.

Animals↗
PubMed1986

The relaxant action of nicorandil in guinea-pig isolated trachealis.

Nicorandil (1-1000 mumol l-1) caused concentration-dependent relaxation of guinea-pig isolated trachealis. Propranolol (1 mumol l-1) did not modify the relaxant action of nicorandil but antagonized isoprenaline. Among K+-channel inhibitors tested, apamin (0.1 mumol l-1) and procaine (5 mmol l-1) did not modify the relaxant action of nicorandil. In contrast, tetraethylammonium (TEA, 8 mmol l-1) caused five fold antagonism. Trachealis exposed to K+-rich (120 mmol l-1) Krebs solution developed near-maximal tension. Nicorandil relaxed the K+-depolarized tissue though its concentration-effect curve was shifted markedly to the right. In tissues in which tone was induced by histamine, methylene blue (100 mumol l-1) antagonized nicorandil and sodium nitroprusside but did not modify the relaxant action of aminophylline. Intracellular electrophysiological recording showed that nicorandil (1 mumol l-1) could evoke some relaxation in the absence of electrical changes. Higher concentrations (10-1000 mumol l-1) reduced the amplitude and frequency of spontaneous electrical slow waves. Nicorandil also caused concentration-dependent hyperpolarization and relaxation. When the hyperpolarization was sufficiently pronounced slow wave activity was abolished. TEA (8 mmol l-1) induced slow waves which were surmounted by a spike potential. TEA slightly reduced the maximal hyperpolarization induced by nicorandil and increased the time required for nicorandil to abolish slow wave discharge. Procaine (5 mmol l-1) induced slow waves of relatively low frequency. Sometimes these were surmounted by a spike potential Procaine markedly reduced the hyperpolarization induced by nicorandil and increased the time required for abolition of slow waves. In studies of the efflux of 86Rb+ from muscle-rich strips of trachea, nicorandil (1000 mumol l-1) increased the efflux rate constant, whereas isoprenaline (1 mumol l-1) was without effect. It is concluded that nicorandil-induced relaxation does not involve the activation of beta-adrenoceptors but is partly attributable to the formation of nitric oxide from the nitrate moiety in its molecular structure. Nicorandil can evoke relaxation in the absence of membrane potential change but towards the upper end of its effective concentration range, nicorandil increases membrane K+ conductance and thereby evokes hyperpolarization of trachealis cells. The K+ channels opened by nicorandil are permeable to 86Rb, insensitive to apamin and TEA but may be inhibited by procaine.

Aminophylline↗
PubMed1986

Mechanical and electrical aspects of the relaxant action of aminophylline in guinea-pig isolated trachealis.

Aminophylline (1-1000 mumol l-1) suppressed the spontaneous tone of guinea-pig isolated trachealis in a concentration-dependent manner. In Krebs solution containing acetylcholine (1 mmol l-1), histamine (200 mumol l-1) or K+ (120 mmol l-1) isolated trachealis muscle developed near-maximal tension. The log concentration-effect curve for aminophylline was shifted 20 fold, 3 fold and 4 fold to the right, respectively, in the presence of these spasmogens. Three K+-channel inhibitors were tested: tetraethylammonium (TEA, 8 mmol l-1) did not modify the action of aminophylline, procaine (5 mmol l-1) shifted the log concentration-effect curve for aminophylline 2 fold to the left and 4-aminopyridine (5 mmol l-1) shifted the curve 2.5 fold to the right. Intracellular electrophysiological recording showed that aminophylline 10 mumol l-1 could cause relaxation in the absence of electrical changes. Higher concentrations of aminophylline (100-1000 mumol l-1) suppressed spontaneous slow waves and hyperpolarized the trachealis cells. In the presence of procaine (5 mmol l-1) or TEA (8 mmol l-1), the hyperpolarization induced by aminophylline (1000 mumol l-1) was significantly reduced but its relaxant effect was unchanged. In trachealis skinned of its plasma membranes, tension development induced by Ca2+ (20 mumol l-1) was unaffected either by aminophylline (1000 mumol l-1) or by isoprenaline (1 mumol l-1). In studies of the efflux of 86Rb+ from muscle-rich strips of trachea, aminophylline (100-1000 mumol l-1) was without effect whereas nicorandil (100 and 1000 mumol l-1) increased the efflux rate constant. It is concluded that aminophylline does not directly reduce the sensitivity of the contractile proteins to cytosolic Ca2+. In low concentration (1-10 mumol l-1) its relaxant action is not accompanied by membrane potential change but towards the upper end of its effective concentration range, aminophylline evokes hyperpolarization. This hyperpolarization may involve the opening of K+-channels which are inhibited by procaine and (to a lesser extent) by TEA. These K+-channels may be impermeable to 86Rb+.

Acetylcholine↗
PubMed1986

Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis.

BRL34915 (0.1-10 microM) suppressed the spontaneous tone of guinea-pig isolated trachealis in a concentration-dependent manner. BRL34915 was not antagonized by propranolol (1 microM). In trachea where spontaneous tone was suppressed by indomethacin (2.8 microM) but subsequently restored to the same level with acetylcholine or histamine, the relaxant potency of BRL34915 was reduced. In Krebs solution containing K+ (120 mM), isolated trachealis muscle developed near-maximal tension. The relaxant effects of BRL34915 were virtually abolished in this medium. Concentration-effect curves for KCl, acetylcholine and histamine were constructed in tissues treated with indomethacin (2.8 microM). BRL34915 (10 microM) depressed the foot of the concentration-effect curve for KCl and caused minor rightward shifts in the concentration-effect curves of acetylcholine and histamine. Four K+-channel inhibitors were tested. Apamin (0.1 microM) did not modify the action of BRL34915. Tetraethylammonium (8 mM) had little effect but procaine (5 mM) and 4-aminopyridine (5 mM) each significantly inhibited the relaxant action of BRL34915. Intracellular electrophysiological recording showed that BRL34915 (0.1 microM) caused very minor relaxation and little, if any, electrical change. Higher concentrations (1-10 microM) evoked relaxation, suppression of spontaneous electrical slow waves and marked hyperpolarization of the trachealis cells. In the presence of TEA (8 mM) or procaine (5 mM) the hyperpolarization induced by BRL34915 was significantly reduced. In trachealis skinned of its plasma membranes, tension development induced by Ca2+ (20 microM) was unaffected either by BRL34915 (10 microM) or by nicorandil (1 mM). In studies of the efflux of 86Rb+ from muscle-rich strips of trachea, BRL34915 (1 and 10 microM) increased the efflux rate constant. It is concluded that BRL34915 evokes relaxation of the trachealis by a mechanism that involves neither beta-adrenoceptor activation nor direct reduction of the sensitivity of the intracellular contractile machinery to cytosolic free Ca2+. The action of BRL34915 may depend on the opening of K+ channels in the plasma membrane which are permeable to 86Rb+. The opening of these channels, or the effects of their opening, may be reduced by K+-channel inhibitors such as 4-aminopyridine, procaine and TEA but not by apamin.

Acetylcholine↗
PubMed1986

Alternative processing of sequences during macronuclear development in Tetrahymena thermophila.

DNA is eliminated during development of the somatic MACronucleus from the germinal MICronucleus in the ciliated protozoan, Tetrahymena thermophila. Facultatively persistent sequences are a class of sequences that persist in the MAC DNA of some cell lines but are eliminated from the MAC DNA of other cell lines. One cloned MAC fragment contains a persistent sequence as well as sequences normally retained in the MAC. When this cloned fragment was used to construct MAC restriction maps of this region in cell lines whose MAC DNAs do, or do not, contain the persistent sequence, extensive variation in the map flanking this region was observed. The different DNA rearrangements of this MIC segment are epigenetically determined during or soon after MAC development. Moreover, different rearrangements may occur among the 45 copies of this MIC segment as a MAC is formed, resulting in polymorphisms that are later resolved by phenotypic assortment.

Animals↗
PubMed1985

Eliminated sequences with different copy numbers clustered in the micronuclear genome of Tetrahymena thermophila.

As the ciliated protozoan Tetrahymena thermophila develops a new macronucleus (MAC) from products of its micronucleus (MIC), several repetitive sequences are eliminated from the MAC genome. Four MIC DNA clones containing repetitive sequences that are eliminated from the MAC were obtained. One clone contains a representative from each of three families of eliminated sequences. One, present in 200-300 copies in the MIC, is almost completely eliminated from the MAC. A second, present in approximately 50 copies in the MIC, is scattered throughout the genome, although up to half of the family members examined could be localized to chromosome 2. Approximately one tenth of the members of this less repetitive family persist in the MAC while the rest are eliminated. The third type of eliminated sequence has three to four members, all of which are eliminated from the MAC. Three of the members are located on three of the five MIC chromosomes, and one could not be mapped. This sequence is clustered with the other two families of sequences in at least three of the four sites. All three types of eliminated sequences are found in similar arrangements in the MIC of several different inbred strains of T. thermophila.

Animals↗
PubMed1985

Immature teratoma of the ovary with predominant malignant retinal anlage component. A parthenogenically derived tumor.

An immature teratoma with predominant malignant retinal anlage component occurred in the ovary of a 17-year-old woman. Karyotype analysis from Q-banded preparations revealed that the tumor was parthenogenically derived and exhibited chromosome instability and aneuploidy. On light-microscopical examination, the malignant elements resembled retinal anlage. Ultrastructurally, large, polygonal, pigmented cells had features of ependymal epithelium: a continuous, well-developed basal lamina; microvilli; parallel arrays of rough endoplasmic reticulum; and very large, densely pigmented melanosomes. Adjacent cells identified by light microscopy as immature neuroglia contained glial fibrillary acidic protein by immunohistochemical staining. The presence of neuroglia, not a feature of tumors of neural crest origin, and the ependymal characteristics of the pigmented cells indicate that the neoplasm was most likely of neural groove derivation.

Adolescent↗
PubMed1985

The effects of the dihydropyridine Bay K 8644 in guinea-pig isolated trachealis.

In trachea bathed by Krebs solution containing indomethacin 0.8 mumol l-1, Bay K 8644 (0.01-1 mumol l-1) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol l-1 potassium chloride (KCl) to the Krebs solution. Bay K 8644 (1 mumol l-1) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine. Bay K 8644 (1 mumol l-1) caused a small potentiation of the effect of calcium chloride (CaCl2) tested in trachea bathed by a K+-rich, Ca2+-free, MOPS-buffered physiological salt solution. Organic inhibitors of calcium influx such as nifedipine (0.1 mumol l-1), verapamil (1 mumol l-1) or diltiazem (10 mumol l-1) each caused marked depression of concentration-effect curves to KCl. Bay K 8644 (0.01-1 mumol l-1) provided concentration-dependent protection against this effect in all three cases. Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 mumol l-1) was able to promote the cellular influx of Ca2+. Intracellular electrophysiological recording showed that Bay K 8644 (1 mumol l-1) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 mumol l-1 nifedipine. The ability of Bay K 8644 to promote Ca2+ influx and its ability to protect against the effects of several structurally-unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage-operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗