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Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 217 records · Page 12Linked to original sources
PubMed1989

Lack of involvement of the c-fms and N-myc genes by chromosomal translocation t(2;5)(p23;q35) common to malignancies with features of so-called malignant histiocytosis.

We report the molecular, cytogenetic, and immunologic characterization of three hematologic malignancies that contained characteristic t(2;5) chromosomal translocations. The clinicopathologic features in all three cases fit the disease spectrum of so-called malignant histiocytosis (MH). All cases expressed activation antigens including Ki-1 (CD 30), but no lineage-restricted pattern of cellular antigen expression was observed. Cell lines SUP-M2 and SU-DHL-1 established from two of the cases showed rearranged beta T-cell receptor (beta TCR) genes nonproductive of full-length beta TCR mRNA and therefore not helpful in unequivocal establishment of lineage derivation. The common cytogenetic feature was a reciprocal translocation between chromosomes 2 and 5, involving bands 2p23 and 5q35 near the reported chromosomal locations of the N-myc and c-fms genes, respectively. Normal-sized and truncated c-fms RNAs were observed in both cell lines, whereas no N-myc transcripts were detected. Sequence analysis of the truncated fms RNA showed that it consisted of the 3' half of the c-fms mRNA, but its derivation was not the result of a structural alteration of the c-fms gene. Our studies show that the t(2;5) does not involve the N-myc and c-fms protooncogenes and that this cytogenetic abnormality may be characteristic of a subset of primitive malignancies with an indeterminate lineage but with clinicopathologic features of so-called MH.

Adult↗
PubMed1989

A modified subtalar arthroereisis implant for the correction of flexible flatfoot in children. The STA Peg procedure.

The STA Peg procedure was developed to correct flexible flatfoot in young children prior to the age when secondary deformities are likely to develop. The procedure involves the implantation of a peg fashioned from ultra-high molecular weight polyethylene into the dorsal surface of the calcaneus, anterior to the posterior facet of the subtalar joint and fixed with polymethylmethacrylate. Smith has reported excellent overall results in the great majority of patients. The primary importance of the procedure is its rate of success, coupled with a relatively easy postoperative period, virtually no immobilization, its application for very young patients (beginning at 3 years of age), and its accommodation for the continued growth of the child.

Arthrodesis↗
PubMed1989

A circadian rhythm of aqueous flow underlies the circadian rhythm of IOP in NZW rabbits.

There is a daily rhythm of aqueous flow in New Zealand White rabbits entrained to 12 hr light:12 hr dark. The phase of the rhythm of flow is determined by the phase of the light:dark cycle, and the rhythm persists in constant dark. Therefore, in New Zealand White rabbits the rhythm of aqueous flow, like the rhythm of intraocular pressure, is circadian. The range of the circadian rhythm of flow suggests it plays a major role in producing the circadian rhythm of intraocular pressure. This animal model provides a powerful tool for studying endogenous mechanisms which regulate aqueous humor formation and intraocular pressure.

Animals↗
PubMed1989

Long-term growth of malignant thymocytes in vitro.

We report a new methodology for the long-term growth of malignant T-lymphoblasts from patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). When malignant cells were cultured in the presence of insulin-like growth factor I under hypoxic conditions, cellular proliferation occurred that resulted in the establishment of immortal cell lines from ten of 12 patient tumors. Authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and immunogenotype with the patient's tumor cells. This improved method of cell culture permits frequent establishment of cell lines from patients with T-ALL/T-LL, thereby aiding in analysis of thymocyte transformation and neoplasia.

Adolescent↗
PubMed1988

Philadelphia chromosome-positive acute lymphoblastic leukemia cell lines without classical breakpoint cluster region rearrangement.

The Philadelphia (Ph) chromosome translocation which is classically observed in chronic myeloid leukemia (CML) is sporadically found in acute lymphoblastic leukemia (ALL). In CML the translocation breakpoint on chromosome 22 is within the breakpoint cluster region, while in childhood ALL, no detectable change in breakpoint cluster region is routinely observed. In order to investigate the nature of this difference, we have established and characterized two cell lines from a child with Ph positive ALL. The cell lines have retained the cytochemical staining pattern, enzyme activity, monoclonal antibody profile, and immunoglobulin gene rearrangements of the child's malignant cells. The cell lines had the same Ph translocation t(9;22) (q34;q11) as the child's malignant cells along with additional chromosome changes. Southern blot analysis showed that the Ph translocation did not involve the 5.8-kilobase breakpoint cluster region segment characteristically seen in CML. The cell lines reported here will be a valuable resource in ascertaining the biological significance of the Ph translocation seen in ALL.

Adenosine Deaminase↗
PubMed1988

Doxorubicin and the alkylating anthracycline 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin: comparative in vitro potency against leukemia and bone marrow cells.

The new anthracycline analogue 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin (MRA-CN) is an intensely potent compound that has been shown to be 100-1,000 times more potent than doxorubicin (DOX) in vivo and in vitro. In addition, MRA-CN has been non-cross-resistant with DOX in DOX-selected models of multidrug resistance. We now report the effect of MRA-CN (and DOX) on leukemia cell lines established from patients with common, T-cell, and B-cell acute lymphoblastic leukemia, as well as with monoblastic leukemia. The effect of MRA-CN on the leukemia cells was compared to its toxicity on normal myeloid progenitors (therapeutic ratio) and to the effect of DOX on the leukemia and normal cells. MRA-CN was found to be 100 times more potent than DOX against normal myeloid progenitors--colony-forming units, granulocyte-macrophage (CFU-GM)--and 40-240 times more potent than DOX against leukemia cell lines. In addition, the therapeutic ratio was uniformly greater than 1, indicating that each leukemia cell line tested was more sensitive than CFU-GM to MRA-CN in vitro. There was a lack of correlation between MRA-CN and DOX at a drug concentration at which the colony formation is inhibited by 50% in the leukemia cell lines (correlation coefficient = 0.38), which supported the previous reports of non-cross-resistance between these two agents. The favorable therapeutic ratio, the non-cross-resistance with DOX, and the previously described lack of cardiac toxicity all make MRA-CN an attractive candidate for clinical trials in patients with acute leukemia.

Antibiotics, Antineoplastic↗
PubMed1988

Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL).

The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185ALL-ABL. Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210BCR-ABL but not P185ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph1-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph1-positive ALL cells. In Ph1-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5' of the CML junction. P185ALL-ABL represents the product of a BCR-ABL fusion gene in Ph1-positive ALL that is distinct from the BCR-ABL fusion gene of CML.

Amino Acid Sequence↗
PubMed1988

Chromosomal translocation involving the beta T cell receptor gene in acute leukemia.

DNA spanning a t(7;19) chromosomal translocation breakpoint was isolated from the human T cell line SUP-T7 established from an acute lymphoblastic leukemia. Nucleotide sequence analysis showed that the point of crossover on chromosome 7 occurred immediately adjacent to joining segment J beta 1.1 within the TCR-beta gene, suggesting that this translocation resulted from an error in TCR gene rearrangement. On chromosome 19, the translocation occurred within a previously uncharacterized transcriptional unit for which we propose the name lyl-1. An approximately 1.5-kb RNA is transcribed from this gene in a wide variety of hematolymphoid cell lines. The t(7;19) results in truncation of the lyl-1 gene and production of abnormal-sized RNAs, suggesting a role for lyl-1 in the pathogenesis of this leukemia.

Base Sequence↗
PubMed1988

Unilateral hindpaw amputation causes bilateral articular cartilage remodeling of the rat hip joint.

The purpose of this paper was to describe the remodeling of adult coxofemoral articular cartilage (AC) in response to altered weight bearing. Twelve adult male Sprague-Dawley rats underwent unilateral hindpaw transection at the distal tibiofibular junction (AmpCont group); another group of eight rats served as normal controls (Norm group). Subpopulations of both groups were injected with 35SO4 24 hr before harvest. All femora were harvested after 8 weeks. Safranin O stained longitudinal sections were used to determine AC thickness, cellularity, and proteoglycan (PG) staining. Regional grain counting was performed on autoradiographs. Analysis of the data revealed that the AC of Norm hips in the region near the fovea capitis femoris was significantly thicker, had a lower cell density, a greater PG density, and a lower 35SO4 incorporation rate per chondrocyte than the AC of the Norm lateral edge region. The intact limbs of the AmpCont animals demonstrated a relative thinning of the AC near the fovea capitis femoris, compared with the edge region, and reduced 35SO4 incorporation rate in the lateral edge region, compared with normal values. The operated limb of the AmpCont animals displayed a relative increase of PG density in the edge region compared with the foveal region and a reduced 35SO4 incorporation rate in the lateral edge region, compared with normal values. We concluded that rat coxofemoral AC responds bilaterally to unilateral hindpaw amputation through appropriate morphologic remodeling.

Amputation, Surgical↗
PubMed1988

Inappropriate fluid response in congenital diaphragmatic hernia: first report of a frequent occurrence.

Safe management of the newborn infant with congenital diaphragmatic hernia (CDH) requires precise fluid administration to avoid hypovolemia or fluid overload. Twenty-two CDH patients and 12 infants who underwent abdominal operations were studied for three postoperative days to determine whether the postoperative neonatal renal response to fluid administration was appropriate or inappropriate. Each response was categorized, on the basis of urine and blood measurements, as: (1) appropriate urine output and concentration, (2) inappropriate urine output and concentration with fluid retention or (3) renal failure. Fluid intake was similar in all groups. The CDH group had a significantly lower urine output, higher urine osmolarity, and lower serum osmolarity. All of the control group (100%) responded appropriately to intake. Sixty-four percent of the CDH group inappropriately retained water during the first 16 hours (appropriate, 27%; renal failure, 9%). By 24 hours, 34% still had inappropriate urine output and fluid retention. The majority of patients with CDH initially responded inappropriately to postoperative fluid intake. If this response is not recognized and fluid intake is not adjusted, serious fluid overload will result.

Cyclic AMP↗
PubMed1988

Neonatal abdominal calcification: is it always meconium peritonitis?

Intraluminal meconium calcifications are a rare cause of neonatal abdominal calcifications and can easily be misinterpreted as meconium peritonitis. We report three patients with anorectal anomalies, rectourethral fistula, and intraluminal calcified meconium. Intestinal stasis and mixing of urine and meconium may be predisposing factors for the calcification of meconium. Intraluminal calcifications appear as discrete punctate flecks within the distribution of the bowel, in contrast to meconium peritonitis, where the calcifications are linear and plaque-like, occurring anywhere in the abdominal cavity and scrotum. Careful differentiation of abdominal calcifications will allow more appropriate planning of the need and timing of surgery and can suggest the possibility of other anomalies that may not be suspected initially.

Abdomen↗
PubMed1988

Pancreatic injuries in childhood due to blunt trauma.

The records of 22 children who suffered pancreatic injury in whom laparotomy confirmed the diagnosis were reviewed. First, we wished to define diagnostic factors that would distinguish transections and injuries that resulted in pseudocysts (which we termed major injuries) from contusions and lacerations that required no specific operation (minor injuries). Second, we wanted to determine how the timing of diagnosis and treatment of major injuries influenced hospital course. There were 13 major injuries (ten transections, three pseudocysts) and nine minor injuries. Abdominal tenderness (present in 83%) failed to distinguish major from minor injuries. Major injuries appeared to be associated with rising values of serum amylase taken serially over 24 to 48 hours (P = .05). Computerized tomography and ultrasound obtained in the first days after injury gave nonspecific findings and failed to give a definitive diagnosis. Of 13 patients with major injuries, seven underwent laparotomy within 24 hours of injury; six, two days or more. The mean hospital stay in the early group (16.7 days) was significantly shorter than that in the late group (38.8 days). Our review suggests that timely diagnosis of major pancreatic injuries and prompt surgical treatment can shorten hospitalization without increasing morbidity. The diagnosis of surgically significant pancreatic injuries continues to be a primary clinical challenge.

Amylases↗
PubMed1988

Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines.

The loss of bands p21-22 from one chromosome 9 homologue as a consequence of a deletion of the short arm [del(9p)], unbalanced translocation, or monosomy 9 is frequently observed in the malignant cells of patients with lymphoid neoplasias, including acute lymphoblastic leukemia and non-Hodgkin lymphoma. The alpha- and beta 1-interferon genes have been assigned to this chromosome region (9p21-22). We now present evidence of the homozygous deletion of the interferon genes in neoplastic hematopoietic cell lines and primary leukemia cells in the presence or absence of chromosomal deletions that are detectable at the level of the light microscope. In these cell lines, the deletion of the interferon genes is accompanied by a deficiency of 5'-methylthioadenosine phosphorylase (EC 2.4.2.28), an enzyme of purine metabolism. These homozygous deletions may be associated with the loss of a tumor-suppressor gene that is involved in the development of these neoplasias. The relevant genes may be either the interferon genes themselves or a gene that has a tumor-suppressor function and is closely linked to them.

Chromosome Deletion↗
PubMed1988

Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro.

The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, we have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome.

Cell Line↗
PubMed1988

Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia occurs in two molecular forms, those with and those without rearrangement of the breakpoint cluster region on chromosome 22. The molecular abnormality in the former group is similar to that found in chronic myelogenous leukemia. To characterize the abnormality in the breakpoint cluster region-unrearranged form, we have mapped a 9;22 translocation from the Philadelphia chromosome-positive acute lymphoblastic leukemia cell line SUP-B13 by using pulsed-field gel electrophoresis and have cloned the DNA at the translocation junctions. We demonstrate a BCR-ABL fusion gene on the Philadelphia chromosome. The breakpoint on chromosome 9 is within ABL between exons Ia and II, and the breakpoint on chromosome 22 is approximately equal to 50 kilobases upstream of a breakpoint cluster region in an intron of the BCR gene. This upstream BCR breakpoint leads to inclusion of fewer BCR sequences in the fusion gene, compared with the BCR-ABL fusion gene of chronic myelogenous leukemia. Consequently, the associated mRNA and protein are smaller. The exons from ABL are the same. Analysis of leukemic cells from four other patients with breakpoint cluster region-unrearranged Philadelphia chromosome-positive acute lymphoblastic leukemia revealed a rearrangement on chromosome 22 close to the breakpoint in SUP-B13 in only one patient. These data indicate that breakpoints do not cluster tightly in this region but are scattered, possibly in a large intron. Given the large size of BCR and the heterogeneity in breakpoint location, detection of BCR rearrangement by standard Southern blot analysis is difficult. Pulsed-field gel electrophoresis should allow detection at the DNA level in every patient and thus will permit clinical correlation of the breakpoint location with prognosis.

Chromosome Mapping↗