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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1998

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103.

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.

Clinical Protocols↗
PubMed1998

Flexor tendon repair using a stainless steel internal anchor. Biomechanical study on human cadaver tendons.

We have developed a stainless steel internal tendon anchor that is used to strengthen a tendon repair. This study tested its use in vitro to produce a repair that can withstand the tensile strength demands of early active flexion. Fresh human cadaver flexor digitorum profundus tendons were harvested, divided, and then repaired using four different techniques: Kessler, Becker or Savage stitches, or the internal tendon anchor. The internal splint repairs demonstrated a 99-270% increase in mean maximal linear tensile strength and a 49-240% increase in mean ultimate tensile strength over the other repairs. It is hoped that this newly developed internal anchor will provide a repair that will be strong enough to allow immediate active range of motion.

Cadaver↗
PubMed1998

Effects of forearm pronation/supination on carpal tunnel pressure.

The effects of forearm rotation and metacarpophalangeal (MP) flexion on carpal tunnel pressure were investigated in 17 healthy adults who had no evidence of carpal tunnel syndrome (CTS). Pressure was continuously recorded with a saline-filled catheter inserted into the carpal tunnel and connected to a pressure transducer while test subjects slowly rotated the forearm from full pronation to full supination. Forearm rotation was repeated with MP flexion of 0 degrees, 45 degrees, and 90 degrees. Both forearm rotation and MP flexion, and their interaction term, significantly affected carpal tunnel pressure and accounted for most of the variability in the data. Highest mean pressures (55 mmHg) were recorded in full supination and 90 degrees MP flexion and lowest pressures (12 mmHg) were recorded at 45 degrees pronation and 45 degrees MP flexion. These data may be useful in the design of tasks and hand tools in the management and prevention of CTS.

Adult↗
PubMed1998

An implantable centrifugal blood pump with a recirculating purge system (Cool-Seal system).

A compact centrifugal blood pump has been developed as an implantable left ventricular assist system. The impeller diameter is 40 mm, and pump dimensions are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in a pump weight of 400 g including a brushless DC motor. The weight of a second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal system, the seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. Purge fluid is continuously purified and sterilized by an ultrafiltration unit which is incorporated in the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular (LV) apex descending aorta bypass was performed utilizing an expanded polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5-9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb levels were measured at less than 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (<0.5 ml/day). In both calves, the pumps demonstrated trouble free continuous function over 6 month (200 days and 222 days).

Alloys↗
PubMed1998

Total hip replacement rates are higher among Caucasians than Asians in Hawaii.

The etiology of hip osteoarthritis remains unknown but may involve genetic or lifestyle factors. Most cases of total hip replacement are performed because of osteoarthritis. To examine possible ethnic differences, hospital records in Hawaii from 1985 to 1989 were reviewed. Preoperative radiographs were reviewed for a subset of patients to ascertain the reason for total hip replacement. Osteoarthritis accounted for a greater percentage of total hip replacements among whites (59% for women and 66% for men) than among Japanese (36% of women and 30% of men). The incidence of total hip replacement for whites was three to 25 times greater than that of other ethnic groups (Japanese, Chinese, Filipino, and Hawaiians). For example, the risk of total hip replacement for white women 40 years to 84 years of age was 4.4%, compared with 1.1% for Japanese women and 1.7% for Chinese women of the same age group. Compared with published data, the incidence was similar for Chinese in Hawaii and San Francisco; however; whites in Hawaii had a total hip replacement incidence less than half that of whites in San Francisco. Lifestyle differences might account for the lower incidence of total hip replacement for whites in Hawaii, compared with those in San Francisco. The lower incidence among Asians suggests a possible genetic basis for osteoarthritis.

Adult↗
PubMed1997

A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation.

This study examines the intranasal instillation of lipopolysaccharide (LPS) into BALB/c mice causing acute pulmonary damage, due to neutrophil infiltration and sepsis. A dose response with LPS showed that an intranasal instillation of 167 microg/ml (10 microg/mouse) caused acute lung injury within 2-4 h and reached maximal damage at 24-48 h. We found the method of LPS administration for induction of acute pulmonary damage to be crucial. After 24 h post-LPS injection, a comparison showed a substantial increase in pulmonary damage with intranasal instillation of LPS. As for intravenous injection, it showed a baseline effect. This study indicates that LPS administered intranasally causes acute pulmonary damage, whereas with intravenous and intraperitoneal endotoxin administration a tissue-specific or similar degree of pulmonary injury may not develop.

Acute Disease↗
PubMed1997

Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.

Adult↗
PubMed1997

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Initial insensitivity to alcohol is a strong predictor of human alcoholism, a widespread and heritable health problem. The Long Sleep and Short Sleep lines of mice were developed by genetic selection for high or low alcohol sensitivity. We have identified seven quantitative trait loci (QTLs) specifying differences in alcohol sensitivity using intercross progeny from these selected strains. These QTLs (Lorel-Lore7) together account for approximately 60% of the total genetic variance for this trait. This represents the first report of linkages for genes influencing alcohol action in any mammalian system using stringent, genome-wide mapping criteria.

Alcoholic Intoxication↗
PubMed1997

Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation.

A 7 year old girl is described with congenital hypoplastic anaemia (Diamond-Blackfan anaemia, DBA) and an apparently balanced reciprocal translocation, 46,XX,t(X;19)(p21;q13). The girl has associated features including short stature, unilateral kidney hypoplasia, and a branchial cyst. Fluorescent in situ hybridisation (FISH) studies with 19q specific cosmids showed that the chromosome 19 breakpoint is located between the RYR1 and the XRCC11 loci spanning a physical region of 5 Mb. There is no family history of DBA and the parents and two healthy sibs have normal karyotypes. This is the first report of a balanced translocation associated with DBA and we suggest that the distinct phenotype has resulted from a de novo disruption of a functional gene. DBA can be inherited as an autosomal trait and our observation may indicate a candidate gene for the disorder in the 19q13 region.

Blood Transfusion↗
PubMed1997

Quick method for confirmation of quantitative trait loci.

Numerous algorithms for the identification and genetic mapping of quantitative trait loci (QTL) have been developed. Methods for confirming QTL maps involve either examination of independent segregating populations or the construction of congenic lines differing only in the QTL of interest. Because these projects require a minimum of several years or thousands of marker assessments in laboratory mice, an alternative, faster congenic method has been proposed. In a preliminary study, we tested this method for confirming QTLs identified in crosses between the ILS and ISS selected lines of mice for differential sensitivity to the hypnotic effects of ethanol. Herein, we report the construction of "segregating congenic" strains in which each QTL is made homozygous in a single generation, whereas the remainder of the genetic background is allowed to segregate. Sensitivity to ethanol among the progeny of such mice is consistent with predictions. Phenotypic variation is high, as expected, due to the background segregation, and statistical significance was attained in only 2 of 7 comparisons. Such segregating congenic populations may be a valuable research tool for confirming QTL map positions and for subsequent assessment of individual pathways and mechanisms of action of individual QTLs.

Alcoholism↗
PubMed1996

Strain distribution patterns for genetic markers in the LSXSS recombinant-inbred series.

We present the strain distribution patterns (SDPs) of 118 SSLP markers and three pigmentation genes that have been characterized in 27 strains from the LSXSS RI series. This coarse map provides a resource for linkage studies of phenotypes that are heritable in the LSXSS RI series. The LSXSS recombinant inbred (RI) strains were derived from the Long-Sleep (LS) and Short-Sleep (SS) selected lines of mice that were selected for differential sensitivity to ethanol but are also differentially sensitive to a variety of other alcohols, barbiturates, sedative hypnotics, and general anesthetics. Since the parents were not inbred, two atypical factors are present in these SDPs. First, more than two alleles are frequently found in these RIs, and second, some alleles can be uniquely associated with one or the other parent while other alleles may be found in both parental lines. To validate the markers found in the parental line, we genotyped all parental mice from one generation of both the LS and SS lines, thus leading to a set of marker SDPs that are useful for further phenotypic association and identification of provisional QTLs.

Alleles↗
PubMed1996

Recurrent lower gastrointestinal hemorrhage: ileal neoplasm diagnosed by scintigraphy with Tc 99m red blood cells and angiography.

A 71-year-old man with recurrent lower gastrointestinal bleeding had negative colonoscopic findings on three occasions. Preoperative diagnosis of a large stromal tumor in the right lower quadrant was based on scintigraphy with tagged red blood cells and mesenteric arteriographic features. The use of nuclear scintigraphy in the diagnosis and evaluation of stromal tumor of unknown malignant potential has not been previously described.

Aged↗