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Biomedical subjects

L Kaplan

Publications and source records attributed to L Kaplan.

At least 91 records · Page 5Linked to original sources

Detection of IAP related transcripts in normal and transformed rat cells.

Intracisternal A-particles (IAP) genes in variable copy number exist in all rodent species studied. Expression is highly repressed in murine normal cells except in embryonic and transformed cells. We searched for IAP related sequences expression in another rodent species cells. Using the more conserved sequence of IAP gene between mouse, Syrian hamster, and rat species (0.4 kb HindIII-PstI fragment from PMIA14), we have been able to detect IAP related transcripts in rat cells. We found that, i) IAP related transcripts are poorly expressed in normal cells, since among 10 tissues tested, only the placenta shows IAP RNA. ii) IAPs are highly expressed in all the transformed cells tested. iii) the detected transcripts appear to have similar sizes in rat cells as in mouse cells (7.2 kb; 5.4 kb). None of the probes corresponding to other regions of the IAP gene nor the entire sequence of PMIA14 allowed us to detect such transcripts.

Animals↗

[Neuropathic pain unrelieved by morphine, alleviated by haloperidol].

Neuropathic pain, originating in damaged nerve and not peripheral nociceptors, is often resistant to treatment by opiates given by the oral, parenteral or spinal routes. This failure to obtain satisfactory pain relief is generally ascribed to psychological factors or to individual peculiarities in drug metabolism or kinetics. Currently, psychotropic and antidepressant drugs are among the first choices in treating painful conditions due to partial nerve lesions. We present a 56-year-old man who suffered intractable pain confined to his left knee following emergency L2-3 vertebral decompression, after collapse due to metastatic disease. 12 mg of morphine and 10 of diazepam given together intravenously did not lessen pain. Acute, solitary spinal nerve root injury was hypothesized. 2 mg of haloperidol injected IV gave complete relief of pain without hypotension or deep sedation. There is no definite explanation for the resistance of neuropathic pain to opiates.

Haloperidol↗

Airway complications in CHARGE association.

The association between catastrophic airway events and developmental delay was examined in patients with CHARGE (coloboma, heart disease, atresia choanae, retarded growth and/or development, genital hypoplasia, and ear anomalies and/or deafness) association. A retrospective chart analysis was performed from The Children's Hospital in Boston, Mass. Sixteen patients were identified with CHARGE association. Nine patients had at least one respiratory arrest, and 7 had no airway difficulties. Some degree of developmental delay was seen in 14 patients, but was most severe in those patients who suffered a respiratory arrest. We conclude that children with CHARGE association have a propensity for airway instability and that cerebral hypoxia contributed to the developmental delay in some of our patients. We recommend early tracheotomy rather than early choanal atresia repair in these patients to protect the central nervous system.

Abnormalities, Multiple↗

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma.

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

Adult↗

Food predictors of plasma beta-carotene and alpha-tocopherol: validation of a food frequency questionnaire.

Nutrient intakes from a food frequency questionnaire are usually calculated as the product of frequency of intake and nutrient composition of the food, summed over the food items. This involves assumptions about the accuracy of recording, food composition data, stability during storage and preparation, and bioavailability. This usual method of calculation was compared with one using empirical weights derived by multivariate linear regression. Food intakes reported on a food frequency questionnaire by Boston, Massachusetts, area subjects in 1982-1985 were used to predict plasma levels of beta-carotene among 370 male and female nonsmokers and plasma levels of alpha-tocopherol among 339 male and female nonusers of vitamin supplements. Nutrient intake computed using empirical weights yielded a significant correlation with plasma beta-carotene (r = 0.43, p = 0.0001), similar to the correlation using nutrient intake calculated from food composition tables (r = 0.38, p = 0.0001). However, the use of empirical weights significantly improved the correlation of vitamin E intake with plasma alpha-tocopherol levels (r = 0.32, p = 0.0001), compared with the weak correlation obtained using the food composition table method to calculate intake (r = 0.16). The results support the validity of published food composition data used to compute carotenoid intake and illustrate the potential utility of empirically derived weights for foods to predict plasma levels of some nutrients.

Adolescent↗

Pyomyoma associated with polymicrobial bacteremia and fatal septic shock: case report and review of the literature.

case of fatal septic shock due to pyomyoma (suppurative leiomyoma of the uterus) is reported. This unusual cause of sepsis and polymicrobial bacteremia should be rapidly identified because surgical therapy is essential for cure. Nine additional cases reported since 1945 are reviewed. Pyomyoma develops in association with either recent pregnancy or in postmenopausal patients who frequently have underlying vascular disease. The triad of: 1) bacteremia or sepsis; 2) leiomyoma uteri; and 3) no other apparent source of infection should suggest the diagnosis of pyomyoma.

Abscess↗

Secondary prevention of low-back pain. A clinical trial.

A clinical trial, aimed at secondary prevention of low-back pain, was performed in 142 hospital employees reporting at least three annual episodes of this condition. Participants were randomly assigned to one of three groups: a calisthenics program (CAL) for 3 months with biweekly sessions of flexion exercises, a back school program (5 sessions), and a control group. The effectiveness of the two intervention programs was evaluated over a 1-year period. Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected. A monthly surveillance for the whole year showed a mean of 4.5 "painful months" in the CAL group versus 7.3 and 7.4 months in the back school and control groups, respectively (P less than 0.0001). The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength. The increased trunk flexion was associated with the rate of participation in the CAL sessions. Further research is needed to answer the question of "intensity versus type of exercise" by comparing different intervention programs, with similar intensity.

Back Pain↗

Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) share a cytogenetic deletion of chromosome 15q11q13. To determine the extent of deletion in AS we analyzed the DNA of 19 AS patients, including two sib pairs, with the following chromosome 15q11q13--specific DNA markers: D15S9-D15S13, D15S17, D15S18, and D15S24. Three molecular classes were identified. Class I showed a deletion of D15S9-D15S13 and D15S18; class II showed a deletion of D15S9-D15S13; and in class III, including both sib pairs, no deletion was detected. These molecular classes appear to be identical to those observed in PWS. High-resolution cytogenetic data were available on 16 of the patients, and complete concordance between the presence of a cytogenetic deletion and a molecular deletion was observed. No submicroscopic deletions were detected. DNA samples from the parents of 10 patients with either a class I or a class II deletion were available for study. In seven of the 10 families, RFLPs were informative as to the parental origin of the deletion. In all informative families, the deleted chromosome 15 was observed to be of maternal origin. This finding is in contrast to the paternal origin of the deletions in PWS and is currently the only molecular difference observed between the two syndromes.

Abnormalities, Multiple↗

Immunoactive products of human placenta. I. An immunoregulatory factor obtained from explant cultures of human placenta inhibits CTL generation and cytotoxic effector activity.

Supernatants were prepared from short-duration explant cultures of term human placentas obtained after cesarean delivery. These supernatants inhibited murine and human mixed lymphocyte reactions, as well as CTL generation. The effects were reversed by an excess of IL-2-containing medium. Similarly, the material inhibited human natural killer cytotoxicity against K 562 targets. The material was subjected to gel-filtration chromatography on an ACA 44 or Bio-Gel A15m column. The apparent MW of the MLR-CML material was about 60-70 kDa, whereas the NK inhibiting activity was eluted in high-MW components (greater than 200 kDa) as well as in the 50-kDa range. The relevance of this material in local immunoregulation during human pregnancy is discussed.

Adjuvants, Immunologic↗

Quantitative calibration and use of DNA probes for investigating chromosome abnormalities in the Prader-Willi syndrome.

Ten genomic DNA probes, subcloned from inserts derived from a phage library constructed from the DNA of flow-sorted chromosomes, have now been mapped to locations within 15q11-15q13. By dosage blotting and densitometry, 5 of these probes map to the 15q11.2-15q12 segment missing in one 15 chromosome of a Prader-Willi syndrome (PWS) patient with a prominent cytological deletion. A sixth probe most likely maps to the same region. The other 4 probes map outside of this segment but within 15q11-15q13. Several of the 15q11.2-15q12 probes, and a cDNA probe homologous to one, have been used to test the DNA from 8 patients exhibiting a wide range of the clinical manifestations expected for PWS patients. DNA deletion was observed in all 3 patients with cytological 15q1 deletions as well as in a patient with an unbalanced (Y;15) translocation. DNA from 1 PWS patient with an unbalanced (5;15) translocation and an inverted duplication of the short arm and proximal long arm of 15 showed at least 1 and possibly 2 extra copies of each genomic probe tested. In the other 3 patients with no cytological deletions, no DNA deletions were found. Thus, the molecular probes described can be used in most PWS patients to analyze the region of proximal 15q implicated in this syndrome.

Adolescent↗

Isolation of a thymidine kinase negative mutant of Nocardia lactamdurans.

By selection for resistance to fluorodeoxyuridine in a fluorouracil/fluorouridine resistant background, we have isolated a thymidine kinase negative mutant of Nocardia lactamdurans. This strain is characterized by the inability to incorporate exogenous [2-14C]-thymidine into DNA. The incorporation of radioactive thymine is similarly reduced even in the presence of deoxyadenosine. This phenotype is readily explained by the inability to detect the enzyme thymidine kinase in crude extracts.

DNA, Bacterial↗

A resting cell system for efrotomycin biosynthesis.

Efrotomycin, a modified polyketide antibiotic with utility as a growth permittant in the animal industry, is produced by Nocardia lactamdurans. A resting cell system has been developed to facilitate biosynthetic studies. Washed cells harvested from oil-based medium at 64 hours and resuspended in buffer produce up to 700 mg/ml efrotomycin in 60 hours when supplemented with a carbon source, optimally glucose. No evidence of carbon or nitrogen repression was observed. Productivity declines progressively with cell age but becomes less dependent on ongoing protein synthesis. The protein synthesis dependent and independent systems were used to study carbon utilization, incorporation of labeled precursors and to examine inhibitors of efrotomycin biosynthesis. A system derived from an efrotomycin non-producer was used to examine the glycosylation of the aglycone, aurodox, to efrotomycin through a monosaccharide form, 6'-deoxyallosyl aurodox.

Anti-Bacterial Agents↗

Characterization of a lipid-rich fraction synthesized by Streptomyces avermitilis.

Isolation of the macrocyclic lactone parasiticide avermectin and other closely related natural products produced by Streptomyces avermitilis also yields a lipid-rich fraction. The latter has been characterized by techniques based on gas-liquid chromatography (GLC) and mass spectrometry (MS). Initial examination of the lipid-rich fraction by direct probe electron-impact (EI) MS and packed-column GLC showed that it consists primarily of a mixture of triglycerides possessing C14-C17 acyl groups. Further examination of this fraction by capillary column GLC-MS demonstrated that it contains low levels of C15-C17 free fatty acids, squalene and diglycerides and, as the major components, at least ten mixed acyl triglycerides (total number of acyl carbon atoms ranging from 43 to 50). Prominent among the triglycerides were a C15-C15-C16 species, a C15-C16-C16 species and a C15-C16-C17 species. Capillary-column GLC and GLC-MS of the fatty acid methyl esters resulting from transesterification demonstrated that the major triglyceride acyl groups are anteiso-C15 (12-methyltetradecanoyl), iso-C16 (14-methylpentadecanoyl), n-C16 (hexa-decanoyl) and anteiso-C17 (14-methylhexadecanoyl). Lower levels of the methyl esters of the following fatty acids were observed: iso-C14 (12-methyltridecanoic), n-C14 (tetradecanoic), iso-C15 (13-methyltetradecanoic), n-C15 (pentadecanoic), iso-C17 (15-methylhexadecanoic) and n-C17 (heptadecanoic). Little evidence was seen for either unsaturated acyl groups or acyl groups of less than 13 or more than 18 carbon atoms. Desorption chemical ionization MS (ammonia reagent gas) analysis confirmed the nature of the lipid-rich fraction, and is an attractive one-step approach for determining the molecular weights and distribution of triglycerides in a mixture.

Chemical Phenomena↗

Emergency aeromedical transport of patients with acute myocardial infarction.

Traditional medical treatment of acute myocardial infarction (AMI) calls for immediate admission and observation in a special care unit and prohibits early interhospital transfer of patients. If persons with AMI are to benefit from emergency thrombolytic therapy, angioplasty, and other interventions, they may require emergency transfer within hours to one of the 10% of hospitals that provide these services. We report our experience with the emergency aeromedical treatment and transfer for acute intervention of 104 consecutive patients with suspected AMI. Between May 1983 and December 1984, 104 patients with suspected acute myocardial infarction were transported by an aeromedical team, including a physician and nurse, for emergency cardiac evaluation. AMI was confirmed in 94 (90%), and emergency intervention was carried out in 75 of 104 (72%). Ninety patients (87%) survived to be discharged from the hospital. There were no deaths during transport. Complications requiring treatment occurred in 13 (12%) of the patients during transport; physician skill or judgment was exercised in 27 of 104 transports (26%) and did not correlate with the Killip classification of physical findings. We conclude that emergency transfer of patients with AMI, traditionally considered hazardous, can be carried out safely using an aeromedical team. Physicians appear to play an important role in safe transport.

Acute Disease↗

Histology and ultrastructure of the human flexor tendon sheath.

Twenty human flexor tendons and their sheaths were studied to determine the gross, microscopic, and ultrastructural morphology of their surfaces. Specimens were obtained at the time of autopsy or at the time of reconstructive and reparative surgery. The flexor tendon sheath consists of a noninterrupted layer of parietal synovium reinforced externally at intervals by dense bands of collagen, the annular and cruciform pulleys, and the palmar plates of the respective finger joints. The sheath contents are independently covered by a second similar layer of visceral synovium. These two layers are continuous at the proximal cul-de-sac, the vincula origins, and the tendon insertions. While the synovial cells lining the pulleys and tendons differ quantitatively from those of the membranous portion of the sheath, they are morphologically identical. The presence of a visceral synovial layer covering each tendon may indicate a key role of the synovial cell in tendon healing.

Cytoplasm↗

Meniscal tears: pathologic correlation with MR imaging.

Menisci from 12 autopsies and above-knee amputations were imaged with magnetic resonance (MR) at 1.5 T and then sectioned for gross and histologic examination. A histologic staging system was developed and showed a one-to-one correlation with corresponding grades of MR signal intensities. Histologic stages 1 and 2 represented a continuum of degeneration culminating in stage 3 fibrocartilaginous tears, seen most frequently in posterior-horn segments of the medial meniscus. Correlation of histologic stages with MR signal intensity allows for an improved diagnostic reading of MR images.

Aged↗