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Biomedical subjects

L Frenkel

Publications and source records attributed to L Frenkel.

At least 19 recordsLinked to original sources

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

Air↗

Report of a factor VIII inhibitor in a patient with autoimmune lymphoproliferative syndrome.

The occurrence of factor VIII inhibitors in non-hemophilic patients is a rare event with a potentially lethal outcome. Despite its infrequent occurrence, the association of this inhibitor with multiple autoimmune diseases is well recognized. We report the case of a patient with the recently described autoimmune lymphoproliferative syndrome (ALPS) who developed an inhibitor to factor VIII. ALPS is a disease characterized by defective lymphocyte apoptosis due to inherited mutations in genes that regulate apoptosis, with the resulting enlargement of lymphoid organs and a variety of autoimmune manifestations. Published 2000 Wiley-Liss, Inc.

Autoimmune Diseases↗

High environmental salinity induces memory enhancement and increases levels of brain angiotensin-like peptides in the crab Chasmagnathus granulatus.

Previous work on the brackish-water crab Chasmagnathus granulatus demonstrated that an endogenous peptide similar to angiotensin II plays a significant role in enhancing long-term memory that involves an association between context and an iterative danger stimulus (context-signal memory). The present results show that this memory enhancement could be produced by moving crabs from brackish water to sea water (33.0%) and keeping them there for at least 4 days. The possibility that such a facilitatory effect is due to osmotic stress is ruled out. Coincidentally, the level of angiotensin-II-like peptides in crab brain, measured by radioimmunoassay, increases with the length of exposure to sea water, reaching a significantly different level at the fourth day. The presence of angiotensin-II-like immunoreactive material in neural structures of the supraoesophageal and eyestalk ganglia was confirmed by immunohistochemical analysis. The results are interpreted as supporting the hypothesis that exposure to water of high salinity is an external cue triggering a process mediated by angiotensins that leads to enhanced memory in these crabs.

Angiotensin II↗

Effects of Lipochromin and Levosinum in the modulation of radiation-induced injury to pig skin.

Pig skin was used as a model to study the effectiveness of two topically applied creams, Lipochromin and Levosinum, in modifying the development of both early and late radiation damage to pig skin. Irradiated skin sites that received daily topical application of Levosinum or Lipochromin after exposure were compared with sites on the contralateral flank of the same animal that received irradiation only. Irradiation was with graded doses of 90Sr/90Y beta-rays. Incidence of moist desquamation (acute) and ischaemic dermal necrosis (late) were used as end-points. The latency period for the development of moist desquamation and its healing time was also assessed. The latency period for the development of moist desquamation in this model ranged from 4.00-6.75 weeks. There was no significant difference between the cream treatment and control sites. Application of Levosinum shortened the healing time of moist desquamation at each dose level by 5-10 days. In three out of four dose levels used, this shortening of the healing time was statistically significant (p < 0.03). Treatment with these topical applications also reduced the incidence of late dermal necrosis and increased the ED50 values for the incidence of dermal necrosis. This increase in ED50 values was equivalent to a dose modification factor of 1.11-1.13.

Administration, Cutaneous↗

Viremia in neonatal herpes simplex virus infections.

BACKGROUND: Polymerase chain reaction assays of the peripheral blood mononuclear cells (PBMC) and plasma may facilitate the diagnosis of neonatal herpes simplex virus (HSV). METHODS: Assays for HSV DNA were submitted from at least 1 specimen site (PBMC, plasma or cerebrospinal fluid) in 11 consecutive cases of neonatal HSV infection. RESULTS: HSV DNA was detected by PCR in the PBMC of 6 of 10 infants tested (60%), the plasma of 4 of 6 tested (67%) and the cerebrospinal fluid of 4 of 11 tested (36%). CONCLUSIONS: HSV viremia is more frequent than previously appreciated, and detection of HSV DNA in PBMC and plasma is a useful diagnostic tool, particularly in infants without skin lesions.

DNA, Viral↗

Vertical transmission of HIV in New York State: a basis for statewide testing of newborns.

Infants (n = 313) of HIV-infected mothers were enrolled (mean age 1.9 weeks, range 0-8 weeks) in a 3-year prospective study of vertical transmission. Fifty-six infants (17.9%) had laboratory and clinical evidence of HIV infection. Polymerase chain reaction (PCR) provided early and reliable identification of infected infants. Thirty-one of the 56 infected infants had specimens submitted when the infants were 4 weeks of age or less and 30 (97%) tested PCR positive. This percentage increased to 100% by 8 weeks of age when 51 of the 56 infected infants had specimens tested for that time period. Immune complex dissociation (ICD) antigen testing was a sensitive method for diagnosis of infection but only in infants older than 1 month. p24 antigen testing, although free of false positives, is less sensitive than either of the other methods. Among surrogate markers of HIV infection, elevation of soluble CD8 levels precedes an increase in immunoglobulin levels or a decline in CD4 T lymphocytes. Vertical transmission is significantly lower in Central and Western New York State than other regions. Transmission is significantly higher in low birthweight babies and in infants whose mothers have CD4 counts < 500. This study provided the basis for establishing a Pediatric HIV PCR Testing Service for the early diagnosis of HIV infection in neonates.

Blotting, Western↗

Activation of diacylglycerol in cultured endothelial cells exposed to cyclic strain.

Confluent bovine aortic endothelial cells (EC) were grown on flexible membranes and subjected to 10% average strain at 60 cycles/min for up to 500 s. A biphasic increase in diacylglycerol (DAG) occurred, with an initial transient peak at 10 s followed by sustained elevation to 500 s. The early peak corresponded to the transient formation of inositol 1,4,5-trisphosphate, demonstrating hydrolysis of L-alpha-phosphatidylinositol (PI) by PI-specific phospholipase C. To determine the origin of the sustained DAG phase, we incubated confluent bovine aortic EC with 1 microCi/ml [14C]myristate overnight and subjected them to cyclic strain. There was a decrease in phosphatidylcholine (PC) and a corresponding increase in DAG at 10 s and 250 s, suggesting PC hydrolysis with the generation of DAG at both an early (10 s) and a late (250 s) phase. [14C]phosphatidylethanol, a specific product of phospholipase D (PLD) in the presence of 1% ethanol, was measured in EC preincubated with [14C]myristate. Cyclic strain led to an immediate and sustained activation of PLD. Increased ethanol concentration led to a consistent decrease in DAG. Furthermore, when EC were pretreated with 1% ethanol, the strain-induced proliferative response was attenuated.

Animals↗

Noninvasive quantification of muscle oxygen in subjects with and without claudication.

The disabling pain of intermittent claudication (IC) arises from oxygen deprivation in the lower limbs during walking. Measurement of the oxygen deficiency within the limb tissue now appears possible with recently expanded understanding of the photon transport through tissue for photons in the visible and near infrared range. Noninvasive measurement consists of preferentially measuring photons that have traveled more deeply into limb tissues and that, therefore, may reach locations of ischemic tissue. Oxygen measurements appear to be possible up to a depth approaching 1.5 cm beneath the surface of the skin. The present study reports on data acquired from the limbs of 11 subjects with IC and 12 subjects without IC. The subjects with IC are patients with clinical findings of claudication based upon segmental Doppler pressure profiles and subjective reports by the patient of pain during exercise. The subjects without IC are individuals with no prior history of ischemic vascular disease. The results consist of photon reflectance measurements at red and infrared wavelengths (approximately 660 nm and 880 nm respectively) taken before, during, and after exercise. Infrared reflectance indices are plotted as well as oxygenation indices generated from combining red and infrared reflectances. A compilation of exercise data shows responses that are generally consistent with the expected physiological responses to mild exercise in subjects with and without IC. We anticipate that the findings of this study may lead to an objective noninvasive testing procedure for measuring the ischemic and exercise-induced changes in muscle oxygenation in the presence of claudication. If the testing of ischemic hypoxia continues to show consistency and accuracy in determining the disability of the subjects with IC, future studies can more effectively test modes of conservative management, such as cessation of smoking, alternative exercise regimens, weight loss, and alternative pharmacological agents.

Exercise↗

Bronchiectasis in children with lymphocytic interstitial pneumonia and acquired immune deficiency syndrome. Plain film and CT observations.

In a review of 77 HIV positive children seen between 1981 and 1990, 32 were diagnosed as having lymphocytic interstitial pneumonitis). Four of the LIP group developed bronchiectasis, a finding not previously reported. The precise factors leading to the bronchiectasis are unclear. All patients had chronically consolidated lung with volume loss. A history of recurrent bacterial superinfection was not noted in any of the cases. With more cases of HIV positive children living longer, bronchiectasis, long known to occur in primary immunologic disorders, will probably be more frequently noted.

Acquired Immunodeficiency Syndrome↗

Itraconazole treatment of phaeohyphomycosis.

Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents.

Adult↗

A prospective study of the effects of acyclovir treatment on the HSV-2 lymphoproliferative response of persons with frequently recurring HSV-2 genital infections.

In a randomized double-blinded fashion, herpes simplex virus type 2 specific lymphocyte proliferation (HSV-2-LP) was studied in patients with frequently recurring genital HSV-2 who were administered daily suppressive oral acyclovir (S-ACV) or placebo and acyclovir for 5 d (PLC/ACV) with recurrences. The pretreatment HSV-2-LP of subjects was low compared with that of controls with infrequently recurring genital HSV-2 (54,000 vs. 110,000 cpm). The HSV-2-LP increased with both S-ACV and PLC/ACV (101,000 and 94,000 cpm, respectively). After treatment was stopped, the HSV-2-LP decreased in both groups (59,000 cpm). Similar data were seen in a subpopulation given a second year of S-ACV. HSV recurrences were reduced in the S-ACV but not in the PLC/ACV group. These data suggest that a low HSV-2-LP in untreated patients is associated with frequent recurrences of genital HSV; a reduction of viral antigens by suppression with ACV or early treatment of HSV recurrences augments the HSV-2-LP response; and the recurrence pattern is not modulated by the HSV-2-LP response.

Acyclovir↗

Clonal B-cell proliferation in an infant with congenital HIV infection and immune thrombocytopenia.

An infant with congenital human immunodeficiency virus (HIV) infection had immune thrombocytopenic purpura (ITP) develop at four months of age. A bone marrow aspirate had normal results in morphologic characteristics and cellularity. Flow cytometry analysis of the marrow cells showed that the predominant cell in the "lymphocyte" cluster was of B-lineage and common acute lymphocytic leukemia antigen (CALLA) positive. Southern blot analysis of marrow DNA demonstrated gene rearrangements in both the immunoglobulin (Ig) heavy chain and kappa light chain loci, confirming the presence of a clonal B-cell lymphoid proliferation. At one year of age the patient is clinically well without evidence of malignant lympho-proliferative disease. This case exemplifies a limited clonal B-cell expansion in the bone marrow of a patient with HIV infection and a benign hematologic condition.

Acquired Immunodeficiency Syndrome↗

Increased amplification of plasmids pBR322 and pBR327 by low concentrations of chloramphenicol.

The replication and amplification of plasmids pBR322 and pBR327 is maximal during partial inhibition of protein synthesis by low concentrations (10-20 micrograms/ml) of chloramphenicol in rich medium (LB). In this manner, 5- to 10-fold greater yields of plasmid DNA at 2- to 5-fold greater initial purity (less protein and chromosomal DNA content) can be obtained than by using the standard high concentrations of chloramphenicol. These results have been obtained with an improved method of plasmid quantitation in unfractionated bacterial lysates.

Chloramphenicol↗

Teaching physicians to teach: a three-year report.

To meet the needs for an expanded preceptor faculty, the Department of Family Medicine at the College of Medicine and Dentistry of New Jersey-Rutgers Medical School has for three years conducted yearly training programs designed to prepare practicing family physicians for the teaching role. Thirty-six physicians have completed the program, which consists of four group seminars and three individual learning site visits spent in the office of an experienced preceptor while a fourth year student is present. Many lessons were learned in the course of these yearly programs which may be useful to others who plan to undertake similar faculty development activities. Therefore, detailed, practical, experiential information is presented regarding recruitment, orientation, the educational program of seminars and individual learning experiences, evaluation, and required resources. Some problems proved to be particularly difficult, such as the uneven quality of the individual learning visits and the attrition of some participants from the program. Feedback from participating physicians has been extremely positive.

Faculty, Medical↗