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Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 343 records · Page 19Linked to original sources
PubMed1986

Efficient constitutive production of human IFN-gamma in Chinese hamster ovary cells.

A human genomic DNA segment of 5.6 kb containing the entire gene for immune interferon-gamma was fused through its 5'-untranslated region to the corresponding region of the simian virus 40 (SV40) T-antigen gene. The SV40 early promoter used contained a modified transcriptional enhancer element with a 93-bp repeat. Supercoiled plasmid DNA was used to transfect Chinese hamster ovary (CHO) cells, the selectable marker being a SV40-dihydrofolate gene construct. Constitutive expression of the IFN-gamma gene in primary transformants was high, especially if a Harvey murine sarcoma virus long terminal repeat (LTR) was present in addition to the SV40 promoter. After gene amplification by methotrexate selection, CHO-gamma cell lines were obtained that produce 1.5-2 million units of IFN-gamma per million cells and per day (200,000 molecules per cell per minute). Metabolic labeling showed that over 90% of the protein secreted by such cells is human IFN-gamma. A one-step immuno-affinity chromatography on monoclonal antibodies yielded pure IFN-gamma with 1-2 X 10(8) units/mg protein. Like IFN-gamma from human white blood cells, the IFN-gamma from CHO-gamma cells is a mixture of two glycoproteins of 26,000 and 20,000 daltons with traces of the unglycosylated 17,000-dalton polypeptide. Large-scale cultures in 1% serum routinely yield over 600,000 units of human IFN-gamma/ml culture per day.

Animals↗
PubMed1986

A method for constructing multiple tandem repeats of specific DNA fragments.

We describe a new method for constructing tandem repeats of DNA fragments that allows one to control the number of tandem copies appearing in a final recombinant DNA clone. The principle of the method is to prepare DNA fragments with predetermined cohesive ends and to ligate them together in such a way that unique multimers are generated. First, the fragment of interest is inserted into a vector with a multisite cloning region. Clones are picked with the fragment in both orientations, and the fragments are excised using different pairs of restriction enzymes. The resulting fragments with preprogrammed cohesive ends are mixed, ligated, and digested with one enzyme whose site appears in the cloning region of the vector. From this material multimeric fragments containing specific ends can be isolated and recloned into appropriate vectors. As an example of the method, we show the construction of clones containing either three or six tandem copies of the origin of DNA replication of the mouse polyoma virus. The prospect of using this technique to construct inverted repeat structures is discussed. As part of this work we have constructed a modified M13mp8 vector which contains a unique Xho I cloning site.

DNA Replication↗
PubMed1986

Eurotransplant. Part II. The cyclosporine era 1981-1985.

1. The realization of the two main goals of the Eurotransplant Organization have been enhanced during the period between 1981 and 1985 by two factors: A reliable HLA-A, -B and -DR typing of kidney donors and recipients, reflected in this analysis by the Hardy-Weinberg analysis but also by the results of the regular tissue typing quality controls. The number of patients who received a kidney without HLA-DR mismatches was 53% (N = 2,904). A significant difference with the 390 of 5,535 (7%) patients who received a kidney with two HLA-DR mismatches. 2. Treatment with cyclosporine increases kidney graft survival significantly in recipients of a first cadaveric transplant which is in agreement with the results of many other groups. Also a significant improvement in kidney graft survival with cyclosporine treatment was observed in recipients of a cadaveric retransplant, an observation in contrast with those of UCLA. 3. Although no significant influence of HLA-A and -B matching was observed in patients treated with or without cyclosporine, the best matched patients had the best graft survival. As stated many times before, the beneficial effect of HLA-A and -B matching is best demonstrated four or five years posttransplantation. 4. The effect of HLA-DR matching on kidney graft survival is highly significant, regardless of whether cyclosporine has been used or not. This finding is also in accordance with those of other investigators. 5. Prolonged cold ischemia periods in cyclosporine-treated patients resulted in a significant decrease of kidney graft survival. This is in contrast with the observations in non-cyclosporine-treated recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporins↗
PubMed1986

Influence on psychological development of early treatment of congenital hypothyroidism detected by neonatal screening: a controlled study.

It has been shown that early diagnosis and treatment of congenital hypothyroidism based on neonatal screening will improve outcome. To test this hypothesis, we performed standard psychological tests (Gesell, Stanford-Binet, or Wechsler) in three groups of children with treated hypothyroidism: 14 were discovered by neonatal screening and 24 (15 with thyroid agenesis and 9 with ectopic thyroid) were diagnosed prior to institution of screening. Age (weeks) at initial treatment differed among the three groups (mean values +/- SE: screened 4.6 +/- 0.8, thyroid agenesis 19.3 +/- 4.0, ectopic thyroid 46.4 +/- 8.0). Age at testing averaged 3.3 years in all three groups. The global developmental quotient (DQ) or IQ score was lowest in the thyroid agenesis group (82 +/- 6, range 52 to 142), intermediate in the ectopic thyroid group (93 +/- 10, range 56 to 141) and highest in the screening group (104 +/- 4, range 75 to 127). Neonatal screening for congenital hypothyroidism results in earlier diagnosis than does use of the clinical criteria, and the consequent early treatment results in improved psychomental development.

Child Development↗
PubMed1986

Endometrial cyst of the liver.

A 21-yr-old woman with a history of epigastric pain and a right upper quadrant mass was found to have a large parenchymal hepatic cyst on CT scan. The cyst was removed at surgery and found to be lined by ectopic endometrial tissue. This is, to our knowledge, the first recorded instance of endometriosis of the liver. The clinicopathological features of this patient and the possible pathogenesis of her most unusual hepatic lesion are discussed.

Adult↗
PubMed1986

Dysphonia dissected.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1985

Priming affects the transcription rate of human interferon-beta 1 gene.

Priming human fibroblasts with low levels (100 units/ml) of homologous interferon (IFN) prior to induction of gene expression with poly(rI.rC) results in the accumulation of 5-10-fold higher levels of IFN-beta 1 mRNA when compared to induced but nonprimed cells. By run-on transcription assay we have determined that this increase results mainly from increased transcription rate of the IFN-beta 1 gene. We have also shown that priming leads to elevated cytoplasmic steady state levels of two additional RNA species which initiate at the major IFN-beta 1 mRNA initiation site and extend beyond the polyadenylation site for the IFN-beta 1 0.9-kilobase mRNA. Located next to the 3' end of the IFN-beta 1 gene we have also identified a novel poly(rI.rC)-induced gene which like the IFN-beta 1 gene is highly activated in cells primed with IFN prior to poly(rI.rC) induction. However, the expression of another poly(rI.rC)-induced gene located on a different chromosome is only slightly affected by the priming procedure used here. We postulate that IFN priming acts specifically on certain genes rather than by a general potentiation of poly(rI.rC) induction.

Cell Line↗
PubMed1985

Isolation and identification of delta 6-lithocholenic acid (3 alpha-hydroxy-5 beta-6-cholen-24-oic acid) as an intestinal bacterial metabolite of chenodeoxycholic acid in man.

Fecal bacterial biotransformation studies of chenodeoxycholic acid were performed. Incubations were carried out for 30-s to 12-h time intervals. delta 6-Lithocholenic acid was isolated by thin-layer chromatography. Its structure was confirmed by gas-liquid chromatography and mass spectrometry. The proportion of chenodeoxycholic acid biotransformed to delta 6-lithocholenic acid consistently ranged from 5.5 to 14.0%.

Aerobiosis↗
PubMed1985

Radical retroperitoneal tumor surgery with resection of the psoas major muscle.

Three patients with extensive retroperitoneal cancer are presented, in whom the psoas muscle was resected as part of a radical tumor excision. The resection of the psoas muscle, including the femoral nerve, which travels in its substance, and the genitofemoral and ilioinguinal nerves, caused little morbidity (denervation weakness of the quadriceps and anterior high numbness) and improved the quality of the excision. Ablation of the psoas muscle is technically possible; it may improve the patient's outlook both for palliation and for curative intent.

Adult↗
PubMed1985

Dynamic modification of the vestibulo-ocular reflex by the nodulus and uvula.

The time constant of the decay of slow-phase eye velocity of postrotatory nystagmus or optokinetic after-nystagmus is reduced during exposure to a stationary visual surround (visual suppression). It is also reduced after tilting the head (tilt suppression). A "dump" mechanism in the vestibulo-ocular reflex has been proposed to rapidly discharge activity from the central vestibular system during both types of suppression. Monkeys lost this mechanism after lesions of the nodulus and uvula. They also lost the ability to habituate the time constant of nystagmus on repeated exposure to optokinetic and vestibular stimuli. Periodic alternating nystagmus, which is believed to represent an instability in the vestibulo-ocular reflex, was observed in two of three monkeys. These data indicate that the nodulus and uvula play an important role in suppressing, habituating, and stabilizing the vestibulo-ocular reflex.

Animals↗
PubMed1985

Acquired immunodeficiency syndrome in the child of a haemophiliac.

Oral thrush developed during the second month of life in the 5-month-old son of a patient with haemophilia A. He did not feed well, and interstitial pneumonitis, lymphadenopathy, hepatosplenomegaly, and a cellular immune defect consistent with the acquired immunodeficiency syndrome (AIDS) followed. Both parents had signs of pre-AIDS during the year before their son's illness. Transmission presumably occurred in 3 steps: parenterally, via factor VIII concentrate in the haemophiliac; heterosexually, from the haemophiliac to his wife; and vertically, from mother to infant, or via close paternal-infant or maternal-infant contact. This first report of AIDS in the child of a haemophiliac supports the theory that AIDS is caused by an infectious agent. Concentrate-treated haemophiliacs may transmit this agent to their spouses or children, resulting in pre-AIDS or AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Horizontal saccades induced by stimulation of the central mesencephalic reticular formation.

The central mesencephalic reticular formation (cMRF) was electrically stimulated in the alert monkey. Saccadic eye movements were induced to the contralateral side in the horizontal plane at latencies of 18-35 ms. Smooth or slow eye deviations were not produced by cMRF stimulation. If the stimulus was given during slow phases of nystagmus, rapid eye movements were elicited, and the velocity of the slow phases was not affected. The function of cMRF neurons and/or of pathways that lie within it appear primarily related to generation of rapid eye movements in the horizontal plane. The amplitude of induced saccadic eye movements depended solely on the region of cMRF that was activated. When the stimulation frequency was lower, the latency was longer, but the size and characteristics of the induced movement were the same. The product of latency and stimulus frequency was approximately constant, suggesting that saccades had been triggered after a fixed number of pulses had been given. Stimulation of cMRF at frequencies that were too low to elicit rapid eye movements had a tonic effect on saccade generation. When the animal was having optokinetic nystagmus (OKN), stimulation modulated beat frequency according to the direction of the nystagmus: contralateral quick phases were facilitated and ipsilateral quick phases were suppressed. The frequencies of stimulation necessary to suppress ipsilateral quick phases increased as slow phase eye velocity increased. This demonstrates that both cMRF activity and slow phase velocity affect quick phase triggering. When the cMRF on both sides were simultaneously stimulated, the eyes were fixed in place, and no further rapid movements occurred until the stimulus had ended. Thus, activity in pathways and/or cells in cMRF is not only able to trigger saccades, but can also change the excitability of saccade generating mechanisms and promote fixation by suppressing eye movements. Two types of rapid eye movements were elicited from cMRF. From dorsal portions of cMRF saccades were induced whose size was relatively constant and not dependent on the initial position of the eyes in the orbit. The size of saccades increased from small to large as the stimulating electrode was advanced through cMRF from dorsal to ventral. This suggests that the tecto-bulbo-spinal efferents coursing through cMRF and/or cMRF neurons related to this input, are organized in a topographic fashion, with cells and fibers related to eye movements of increasing size being layered one beneath another.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Electrocardiographic finding simulating acute myocardial infarction in a compound metabolic aberration.

A patient with hypokalemic metabolic alkalosis, hypophosphatemia, and hypomagnesemia/hypocalcemia is described. Electrocardiography demonstrated the pattern of acute anterior myocardial infarction. Further evaluation revealed that the patient had not actually had the acute myocardial infarction and that the electrocardiographic change was a mere simulation. The possible role of hypomagnesemia in the pathogenesis of the electrocardiographic change and the interrelation between the metabolic disturbances noted are discussed.

Alkalosis↗
PubMed1985

Abnormalities in the expression of the leucocyte-common antigen in chronic lymphocytic leukaemia.

The surface glycoproteins of lymphocytes isolated from patients suffering from B cell chronic lymphocytic leukaemia (B-CLL) have been studied by radioactive labelling with impermeable probes and with MoAb. Several features not found in normal B cells have been observed. The abnormalities found in the expression of polypeptides of the leucocyte common (L-C) antigen, identified by appropriate MoAb, have been examined in detail. It has been shown by both biochemical analysis and MoAb binding that this group of polypeptides can, within a panel of B-CLL patients, range from a typical B cell pattern to the pattern resembling that normally found in T cells. The T lymphocyte profile is correlated with a poor prognosis (MVA C rating) and in the one patient where a change in the glycoprotein profile towards that of the T cell was observed, the change coincided with a clinical deterioration. The biological significance of the molecular diversity is discussed.

Antigen-Antibody Reactions↗