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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 397 records · Page 22Linked to original sources
PubMed1994

Neurotrophin-4/5 (NT-4/5) increases adult rat retinal ganglion cell survival and neurite outgrowth in vitro.

Retinal ganglion cell (RGC) survival and neurite outgrowth were investigated in retinal explants from adult rats. Neurotrophin-4/5 (NT-4/5) caused dose-dependent increases in neurite outgrowth with one-half maximal effects at approximately 0.5 ng/ml and maximal effects at 5 ng/ml. In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (BDNF); with either neurotrophin, nearly twice as many RGCs survived and there was a two- to threefold increase in the number of neurites formed by RGCs. Combinations of saturating concentrations of NT-4/5 and BDNF did not enhance these in vitro effects, implying that both neurotrophins share a common signaling pathway. In contrast, nerve growth factor (NGF), neurotrophin-3 (NT-3), or ciliary neurotrophic factor (CNTF) appeared to exert minimal influences on RGC survival or neurite outgrowth.

Animals↗
PubMed1994

Msx1 is close but not allelic to either Hm or Hx on mouse chromosome 5.

The Msx1 homeobox locus has been mapped in relation to the mutations hammer-toe (Hm) and hemimelic extra toes (Hx). Msx1 is expressed in the developing limb, while limb development is affected by the Hm and Hx mutations. Hm and Hx are very tightly linked loci. In interspecific crosses, the segregation of either mutation was followed in relation to polymorphic alleles of Msx1, Il6, and En2, to give a fine map around the mutant loci. Our results show that Msx1 is not allelic to either of the mutations, but is located about 3 cM from them. Il6 did not recombine with either Hm or Hx and, therefore, provides a point of access for the analysis of these mutations at the molecular level.

Alleles↗
PubMed1994

Identification of a T cell-specific transcriptional enhancer 3' of the human T cell receptor gamma locus.

Positive and negative transcriptional regulatory mechanisms are thought to play a major role in the expression of T cell antigen receptor (TCR) genes. Since the alpha beta and gamma delta T cell receptor heterodimers are expressed in a mutually exclusive fashion and since TCR genes are sequentially activated during T cell ontogeny, transcriptional activation and repression must at least in part determine T lineage-specific and developmental-specific expression of these genes. We have identified a transcriptional enhancer located 6.5 kb downstream from the human T cell receptor gamma (TRG) locus. The nucleotide sequence of the enhancer core element shows strong sequence homology to the recently identified murine C gamma 1 enhancer. The enhancer demonstrates T cell-specific activity, but not gamma delta sublineage-specificity in combination with either a heterologous or gene-specific promoter. Thus, additional regulatory elements may be required to repress the expression of rearranged TRG genes in non-gamma delta T cells.

Base Sequence↗
PubMed1994

Relationship between the parachute reactions and standing and walking in normal infants.

Assumption of the vertical position and independent walking are potentially hazardous motor milestones in the developing infant. It has been presumed that the parachute reactions evolved to protect infants from injury during this developmental stage. To determine the relationship between the appearance of the upper and lower parachute reactions and the developmental milestones of unsupported standing and independent walking, 190 normal infants were prospectively studied. The upper parachute reaction was found to precede the lower by less than a month (mean age of appearance: 8.9 and 9.2 months, respectively). More than one-half of the cohort achieved standing without either the upper (49%) or lower parachute reaction (57%); however, no independent walking occurred without the upper parachute reaction, and only 2 of 190 infants (1%) walked independently without the lower parachute reaction. Onset of walking occurred about 4 months after the appearance of the upper parachute reaction. The significance of these findings is discussed.

Accidental Falls↗
PubMed1994

The effect of breast-feeding frequency on serum bilirubin levels.

OBJECTIVE: Our purpose was to evaluate the effect of breast-feeding frequency on serum bilirubin levels in the first 3 days after birth. STUDY DESIGN: Two hundred seventy-five infants were randomly assigned to a frequent or demand breast-feeding schedule. RESULTS: Infants in the frequent group (n = 131) nursed nine (7.5 to 10.5) times per day (median and inner 80%), and the demand group (n = 143) fed 6.5 (5.5 to 8.0) times per day. The serum bilirubin level was measured in all infants between 48 and 80 hours (median 53 hours, inner 80% 48 to 68 hours) and was 7.4 (1.8 to 10.7) mg/dl in the frequent group and 8.0 (2.9 to 11.2) mg/dl in the demand group (p = 0.103). There was no correlation between the frequency of breast-feeding and the serum bilirubin level. CONCLUSION: Within the range of the frequency of nursing observed in this study, we could not demonstrate a significant effect on serum bilirubin levels in the first 3 days after birth.

Bilirubin↗
PubMed1994

Translation of the psbA mRNA of Chlamydomonas reinhardtii requires a structured RNA element contained within the 5' untranslated region.

Translational regulation is a key modulator of gene expression in chloroplasts of higher plants and algae. Genetic analysis has shown that translation of chloroplast mRNAs requires nuclear-encoded factors that interact with chloroplastic mRNAs in a message-specific manner. Using site-specific mutations of the chloroplastic psbA mRNA, we show that RNA elements contained within the 5' untranslated region of the mRNA are required for translation. One of these elements is a Shine-Dalgarno consensus sequence, which is necessary for ribosome association and psbA translation. A second element required for high levels of psbA translation is located adjacent to and upstream of the Shine-Dalgarno sequence, and maps to the location on the RNA previously identified as the site of message-specific protein binding. This second element appears to act as a translational attenuator that must be overcome to activate translation. Mutations that affect the secondary structure of these RNA elements greatly reduce the level of psbA translation, suggesting that secondary structure of these RNA elements plays a role in psbA translation. These data suggest a mechanism for translational activation of the chloroplast psbA mRNA in which an RNA element containing the ribosome-binding site is bound by message-specific RNA binding proteins allowing for increased ribosome association and translation initiation. These elements may be involved in the light-regulated translation of the psbA mRNA.

Animals↗
PubMed1994

Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe.

The mating-type genes of Schizosaccharomyces pombe are found at three locations in the same chromosomal region. These genes are in an active configuration at the mat1 locus and in an inactive configuration at the mat2 and mat3 loci. The mechanism that represses transcription of mat2 and mat3 also inactivates other promoters introduced nearby and is accompanied by a block to meiotic recombination in the mat2-mat3 interval, suggesting that this mechanism involves a particular chromatin structure. We present evidence that the transcription and recombination blocks require three newly defined trans-acting loci, clr2, clr3 and clr4, in addition to the previously identified clr1, rik1 and swi6 loci. We also investigated the role of mat2 cis-acting sequences in silencing. Four cis-acting elements that repress mat2 in a plasmid context were previously identified. Deletion of two of these elements proved to have little effect in a chromosomal context. However, when combined with mutations in trans-acting genes, deletion of the same two elements greatly enhanced mat2 expression. The observed cumulative effects suggest a redundancy in the silencing mechanism.

Gene Deletion↗
PubMed1994

Repeat hepatic resections for metastatic colorectal cancer.

OBJECTIVE: The authors weighed the risks and benefits of repeat liver resections for colorectal metastatic disease. METHOD: In the 6-year period between January 1985 and June 1991, 499 patients underwent liver resections for colorectal metastases at the Memorial Sloan-Kettering Cancer Center. Of these, 25 patients had repeat surgical resections for isolated recurrent disease to the liver. The clinical data for these patients were reviewed. RESULTS: The median interval between the two resections was 11 months. There were no perioperative deaths, and the complication rate was 28%. Median follow-up after the second liver resection is 19 months, with median survival of 17 months for nonsurvivors. Although the median survival after the second resection is 30 months, 20 of the 25 patients have had recurrences with a median disease-free interval of only 9 months. No characteristic of primary or metastatic disease predicted outcome, including time between presentation of the primary and development of liver metastases, disease-free interval after the first liver resection, and bilobar liver involvement. CONCLUSIONS: Although repeat liver resections can be performed safely and improves survival, the likelihood of cure from such resection therapy is low. This likelihood of further recurrences encourage studies of adjuvant or alternative treatments of this population.

Adult↗
PubMed1994

Expansion of CD3+CD4-CD8- T cell population expressing high levels of IL-5 in Omenn's syndrome.

Omenn's syndrome is a fatal, autosomal-recessive combined immune deficiency characterized by several erythematous exfoliative eruptions, lymphadenopathy, hepatosplenomegaly, and elevated eosinophil count. In some of these patients an expansion of CD3+CD4-CD8- double negative (DN) T cell population was observed. We show here that the DN population represents a clonal expansion of T cells which preferentially use V beta 14 in their T cell receptor complex. Using polymerase chain reaction, we show that patient's DN cells express spontaneously high levels of IL-5, thus possibly explaining the abundance of eosinophils in this disorder. The increase of IgE observed in patients with Omenn's syndrome is unlikely to be related to IL-4 production, as IL-4 levels in patient samples were low. However, patient's low expression of interferon-gamma (IFN-gamma), which has been reported to inhibit IgE production, may explain the elevated levels of IgE in this patient. The results thus highlight the importance of the inhibitory effect of IFN-gamma on regulation of IgE production.

Antigens, CD↗
PubMed1994

Two transthyretin mutations (glu42gly, his90asn) in an Italian family with amyloidosis.

A family with familial amyloidotic polyneuropathy (FAP) was previously found to have a substitution of asparagine for histidine at position 90 of transthyretin. Members with his90asn developed FAP. However, close examination of the transthyretin gene revealed that glu42gly is coinherited with his90asn in this family. Since glu42gly has already been seen in Japanese FAP patients, and his90asn has been found in Portuguese and German individuals without FAP, we conclude that his90asn is a nonpathogenic variant.

Adult↗
PubMed1994

Relationship of sweat electrolytes to apparent life-threatening events (ALTE): a case control study.

Twenty infants aged 25 days to 6 months who were consecutively investigated for apparent life-threatening events (ALTE) with negative results and 20 matched normal controls underwent an iontophoresis sweat test. A statistically significant elevated sweat potassium level (22.1 +/- 8.9 versus 12.4 +/- 6.5 mol/l) was noted in the ALTE patients compared with the control group (p < 0.001). No difference was found, however, between sweat sodium and chloride levels in the two groups. Na/K ratio in sweat was significantly different between the groups (p < 0.001). A between-groups discriminant analysis, using Na/K ratio as a discriminant variable, resulted in 80% accuracy in group assignment. A significant increase in sweat potassium concentration at night compared with day time was evident in ALTE patients. Elevated sweat potassium levels specifically characterized infants who experienced ALTE and may possibly indicate an underlying mechanism involving enhanced sympathetic activity.

Circadian Rhythm↗
PubMed1994

Papillary thyroid carcinoma after total body irradiation.

Two children developed papillary thyroid carcinoma after allogeneic bone marrow transplantation (BMT) probably due to radiotherapy during remission and pretransplantation conditioning. Establishing a relationship between the cellular thyroid stimulating hormone (TSH) effect and development of carcinoma in cases with high serum TSH concentrations is difficult. After BMT, patients should be regularly followed up with thyroid ultrasound and, when nodularity is found, fine needle aspiration and/or open biopsy are recommended.

Bone Marrow Transplantation↗
PubMed1994

Immunoradiometric assay of thyrotropin during the first six months of life.

The aim of this preliminary study was to assess variation in thyrotropin (thyroid-stimulating hormone; TSH) levels using an immunoradiometric assay during the first 6 months of life of normal infants. One hundred and five normal newborns (59 females, 46 males) were evaluated for TSH, triiodothyronine and thyroxine at 48 h of life, and TSH was additionally determined at 15 days (n = 42), 30 days (n = 38), 60 days (n = 24), 90 days (n = 28), and 180 days (n = 30). Complete determinations during the total period of the study were obtained in 17 infants. Samples corresponding to the 48-hour period did not exhibit a normal distribution. In this group, percentile 3 corresponded to 0.9 mU/l, the median to 4.2 mU/l and percentile 97 to 17.7 mU/l. Levels of TSH similar to those of the normal adult population were reached between 30 and 60 days of life. Nevertheless, TSH levels of some of the children remained at higher values for a longer period. In summary, our results suggest that high TSH levels might not always indicate an underlying pathology. A critical evaluation of the normality criteria could avoid unnecessary studies and treatments.

Female↗
PubMed1994

Causes and mechanisms of territorial and nonterritorial cerebellar infarcts in 115 consecutive patients.

BACKGROUND AND PURPOSE: Territorial cerebellar infarcts have mainly a thromboembolic mechanism. Cerebellar infarcts less than 2 cm in diameter have recently been reported as nonterritorial infarcts, but it is not clear whether they are low-flow or embolic infarcts. The aim of the present study was to compare the characteristics and causes of territorial and nonterritorial infarcts in a prospective series of 115 patients. METHODS: We collected data from 115 consecutive patients with cerebellar infarcts (79 territorial and 36 nonterritorial [ie, less than 2 cm]), using magnetic resonance imaging (88 patients) and computed tomography. RESULTS: Patients with territorial infarcts and those with nonterritorial infarcts had similar vascular risk factors and clinical presentations and an equal frequency of cardiac source of embolism (32% versus 42%; P = NS) and of large artery occlusive disease (23% versus 19%; P = NS). Occlusive lesions of large arteries at angiography occurred at the level of one cerebellar artery (5% versus 0%; P = NS) and proximal to the ostia of the cerebellar arteries (18% versus 19%; P = NS). Infarcts distal to occlusive lesions were subdivided into unilateral vertebral artery occlusive disease (presumed artery-to-artery embolic mechanism; 18% versus 5%; P = NS) and low-flow state distal to bilateral vertebral or basilar artery occlusion (presumed hemodynamic mechanism; 0% versus 14%; P = .004). Patients with nonterritorial infarcts had more frequent hypercoagulable state (17% versus 1.25%; odds ratio, 15.6 [95% confidence interval, 1.8 to 135]). For the remaining patients, the mechanism of the infarct was unknown (34% versus 22%; P = NS). CONCLUSIONS: Cerebellar infarcts less than 2 cm in diameter (ie, nonterritorial) have the same high rate of embolic mechanism as territorial infarcts (47% versus 49%; P = NS), have more frequent hypercoagulable state, and sometimes have a hemodynamic mechanism.

Arterial Occlusive Diseases↗
PubMed1994

Carotid artery dissection with renal infarcts. Two cases.

BACKGROUND: Clinical features of carotid artery dissection include ipsilateral local signs, contralateral ischemic stroke, or both. We observed two patients in whom these features were associated with renal infarcts. CASE DESCRIPTIONS: A 57-year-old woman had painful Horner's syndrome caused by a right internal carotid artery dissection. On days 3 and 4 she had acute abdominal pain, first on the right side and later on the left. The computed tomographic (CT) scan showed a left renal infarct. No aortic dissection or cardiac source of embolism was found. Transesophageal echocardiography showed a mild dystrophy of the ascending aorta and of the mitral valve. Cerebral angiography showed irregularities of the V3 segment of the left vertebral artery compatible with fibromuscular dysplasia. Erythrocyte sedimentation rate was 100 mm/h, and she complained of intense fatigue. She fully recovered within 3 months. A 53-year-old man had sudden severe abdominal pain followed by headache and difficulty in swallowing. He had 9th, 10th, 11th, and 12th cranial nerve involvement on both sides due to bilateral internal carotid artery dissections and pseudoaneurysms. CT scan showed a left renal infarct. Angiography showed extensive signs of fibromuscular dysplasia involving carotid, vertebral, renal, iliac, and mesenteric arteries as well as a dissection of the left renal artery. Erythrocyte sedimentation rate was 65 mm/h, and he complained of severe fatigue. His neurological signs returned to normal in 6 months. CONCLUSIONS: Renal infarct due to renal artery dissection may occur together with cerebral artery dissection. Acute abdominal pain, increased erythrocyte sedimentation rate, and intense fatigue are the warning symptoms.

Abdominal Pain↗
PubMed1994

Culture and schizophrenia: the DOSMD challenge.

The World Health Organization's International Pilot Study on Schizophrenia (IPSS) and subsequent Determinants of Outcomes of Severe Mental Disorder (DOSMD) studies have reported that the course of schizophrenia is more favourable in 'developing' than 'developed' societies. The 1992 DOSMD study attributes this difference to culture. We review studies concerning the course of schizophrenia and conclude that the evidence for a more favourable course in developing societies is not conclusive. Indeed, a favourable course has also been reported in various industrialised societies. We also raise questions about the findings reported in the recent DOSMD study, including the conclusion that the putatively more favourable course is a product of culture. Finally, we argue that longitudinal, direct observation of patients in their natural environments must be carried out before variations in the course of schizophrenia can be adequately understood.

Cross-Cultural Comparison↗
PubMed1994

Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma.

PURPOSE: To determine the toxicity, response rate, and survival of a regimen of hepatic arterial floxuridine (FUDR) with leucovorin (LV) and dexamethasone (Dec) for the treatment of unresectable hepatic metastases from colorectal carcinoma. PATIENTS AND METHODS: Sixty-two patients with hepatic metastases (33 previously untreated with chemotherapy) were treated with FUDR (0.30 mg/kg/d) and LV (15 mg/m2/d) and Dec (20 mg total dose) as a 14-day hepatic arterial infusion via an implantable pump alternating with 2 weeks of saline. RESULTS: The complete response (CR) plus partial response (PR) rate was 78% in previously untreated patients, with a median survival duration of 24.8 months; 1- and 2-year survival rates were 91% and 57%, respectively. In the previously treated group, the response rate was 52%, with a median survival duration of 13.5 months. Only 3% of patients (two of 62) developed biliary sclerosis; this was significantly lower than the 21% biliary sclerosis rate observed in our previous trial of hepatic arterial FUDR and LV without Dec (P = .002). CONCLUSION: The addition of Dec to hepatic arterial FUDR and LV reduces biliary toxicity while maintaining an excellent response rate and survival. We recommend that this treatment be studied further.

Adult↗