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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 1,117 records · Page 62Linked to original sources
PubMed1988

Development of macroglial cells in rat cerebellum. I. Use of antibodies to follow early in vivo development and migration of oligodendrocytes.

The origin of oligodendrocytes and astrocytes in the CNS is still a focus of much experimentation and controversy. We have used antibodies against ganglioside GD3 and galactocerebroside (GC) to follow the origin and development of rat cerebellar oligodendrocytes both in vitro and in vivo. The immunofluorescent identification of GC+ cells in the rat neonatal cerebellum in vivo, revealed that cells initially GD3+/GC- appeared to make the transition via GD3+/GC+ cells to GD3-/GC+ oligodendrocytes. This sequence of events closely paralleled the maturation of cerebellar oligodendrocyte precursors found in serum-free dissociated culture. In contrast, whereas both GD3+ and glial fibrillary acidic protein-positive cells were seen in serum-containing dissociated culture and also in freshly dissociated suspensions of cerebellum at postnatal days 0 to 6, such cells could not be identified in situ. Putative GD3+/GC- oligodendrocyte precursor cells arose from the deeper regions of the cerebellum at birth, perhaps initially from the superior medullary velum adjacent to the fourth ventricle, and appeared to migrate into the developing folia just prior to myelination and the acquisition of GC.

Animals↗
PubMed1988

Neither laminin nor prior optic nerve section are essential for the regeneration of adult mammalian retinal ganglion cell axons in vitro.

Retinal explants obtained from normal adult rats and from operated animals in which the optic nerve had been sectioned 10 days previously were cultured in either serum-containing or serum-free medium on poly-L-lysine and laminin substrata. Regenerating ganglion cell axons growing from these explants have been identified using monoclonal antibodies against Thy-1.1 cell surface glycoprotein and the 200-kDa subunit neurofilament protein. Irrespective of substratum or medium composition, axons regenerated from 28-49% of normal rat retinal explants. This percentage increased to 60-84% of explants from operated rats. There were no significant differences in percentages of explants from normal or operated rats showing neurite outgrowth when substrata of either poly-L-lysine or laminin were compared in serum-free medium. In serum-containing medium the results were less easily interpreted due to the presence of an outgrowth of non-neuronal (glia and mesenchymal) 'flat cells', which served as a preferred axonal substratum in many cases. Thus we show that adult rat retinal ganglion cell axons will regrow in vitro, and that a 'priming' optic nerve section will increase this response. In neither case is the response laminin-dependent.

Animals↗
PubMed1988

Nonradioactive labeling of synthetic oligonucleotide probes with terminal deoxynucleotidyl transferase.

Synthetic oligonucleotides were tailed at the 3' end using terminal deoxynucleotidyl transferase. Nucleotide triphosphates with free primary amines at the end of side chains were compared for their tailing efficiency and/or detection sensitivity, using biotin-11-dUTP as a reference. Free primary amines were tagged with activated biotin or fluorescein isothiocyanate. The probes were then detected with either streptavidin-alkaline phosphatase complex or anti-fluorescein antibodies and alkaline phosphatase-conjugated secondary antibodies. Tailing conditions were optimized and the probes were tested for detection of Escherichia coli ST1a enterotoxin DNA and rotavirus RNA.

Affinity Labels↗
PubMed1988

Quantitative effects of short- and long-term vasectomy on mouse spermatogenesis and sperm transport.

To date, there are no comprehensive quantitative studies detailing the effect of vasectomy on the mouse testes. We examined the effects of vasectomy on testicular germ cell numbers using detailed light microscopy, and the effect of long-term vasectomy on sperm transport to the caput epididymis using radiolabelled germ cells. Short-term vasectomy has no significant effects on the number of germ cells within the testes; however, after long-term vasectomy, spermiogenesis was affected. Surprisingly, even after long-term vasectomy, the rate of spermatogenesis and sperm transport to the epididymis was unaffected.

Animals↗
PubMed1988

A prospective randomized controlled trial of perioperative antibiotic prophylaxis in renal transplantation.

We have carried out a prospective, randomized controlled trial of perioperative prophylaxis with cefuroxime and piperacillin in 53 recipients of renal allografts. Twenty-seven patients received antibiotic prophylaxis with three doses of cefuroxime 750 mg and piperacillin 4 g, and 26 patients received no prophylaxis. Risk factors for infection were well matched. Infection rates were analysed for the periods 0-5 days and 0-14 days post-transplant. In the first 5 days, patients receiving antibiotics had fewer infections (3 vs. 11, P = 0.04) but by 14 days this difference was no longer apparent (21 vs. 30, P = NS). There was a total of 15 wound infections, which were more common in the control group both at 5 days (1 vs. 5, P = NS) and at 14 days (4 vs. 11, P = 0.027). Urinary infections were unaffected by prophylaxis. We conclude that perioperative antibiotic prophylaxis results in a modest but worthwhile reduction in the incidence of wound infections after renal transplantation.

Adult↗
PubMed1988

Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities.

Fifty-nine patients with melanoma or soft tissue sarcoma of the extremities underwent hyperthermic isolated limb perfusion utilizing cisplatin and wide local excision. Doses of cisplatin ranged from 0.75 to 2 mg/kg. The mortality and morbidity rates were 0 and 6.8 percent, respectively. Pharmacokinetic studies indicate that cisplatin is rapidly bound to perfused tissues and remains bound for 1 month. Maximum tumor response in sarcomas occurs 1 to 2 weeks after perfusion, compared with 1 month after perfusions with l-phenylalanine mustard and actinomycin D. Local and regional recurrence rates were 0 and 3.4 percent, respectively, at 1 year. Further studies of hyperthermic limb perfusions with cisplatin are warranted.

Adult↗
PubMed1988

Endotoxemia in obstructive jaundice. Observations on cause and clinical significance.

Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl). Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors. Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05). Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05). There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization. Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05).

Cholestasis↗
PubMed1988

La3+-induced fusion of phosphatidylserine liposomes. Close approach, intermembrane intermediates, and the electrostatic surface potential.

The fusion of large unilamellar phosphatidylserine liposomes (PS LUV) induced by La3+ has been monitored using the 1-aminoapthalene-3,6,8-trisulfonic acid/p-xylenebis(pyridinium bromide) (ANTS/DPX) fluorescence assay for the mixing of aqueous contents. The fusion event is extensive and nonleaky, with up to 95% mixing of contents in the fused liposomes. However, addition of excess EDTA leads to disruption of the fusion products in a way that implies the existence of metastable intermembrane contact sites. The maximal fusion activity occurs between 10 and 100 microM La3+ and fusion can be terminated rapidly, without loss of contents, by the addition of excess La3+, e.g., 1 mM La3+ at pH 7.4. This observation is explained by the very large intrinsic binding constant (approximately 10(5) M-1) of La3+ to the PS headgroup, as measured by microelectrophoresis. Addition of 1 mM La3+ causes charge reversal of the membrane and a large positive surface potential. La3+ binding to PS causes the release of a proton. These data can be explained if La3+ can chelate to PS at two sites, with one of the sites being the primary amino group. This binding model successfully predicts that at pH 4.5 fusion occurs up to 2 mM La3+, due to reduced La3+ binding at low pH. We conclude that the general mechanism of membrane fusion includes three kinetic steps. In addition to (a) aggregation, there is (b) the close approach of the surfaces, or thinning of the hydration layer, and (c) the formation of intermembrane intermediates which determine the extent to which membrane destabilization leads to fusion (mixing of aqueous contents), as opposed to lysis. The lifetime of these intermembrane intermediates appears to depend upon La3+ binding to both PS sites.

Calcium↗
PubMed1988

Cryopreservation of zygotes and early cleaved human embryos.

Zygotes and 2- to 5-cell human embryos were frozen in 1,2-propanediol and sucrose; results of the first 50 cycles (45 patients) are presented. A total of 41 zygotes (17 attempts at thawing) were thawed, resulting in six singleton clinical pregnancies (15% per embryo; 35% per cycle), of which three delivered, one aborted, and two are ongoing. Fifty-seven cleaved embryos were thawed in 33 other cycles, resulting in four singleton and one twin pregnancy (11% per embryo; 15% per cycle), of which four delivered and one is ongoing. Depending on the cell stage, 61% to 81% of embryos survived cryostorage, but 2-cell embryos did not implant. One fifth of cryoinjury was due to the formation of cracks in the zona pellucida. The incidence of implantation was not enhanced when more than one freeze/thawed embryo was replaced, most pregnancies being obtained from single embryo replacements. At least 8% more births are expected in addition to conventional in vitro fertilization methods when the current policy of replacing three fresh embryos and freezing the remainder using this technique is applied. This method will result in two to four times more pregnancies per spare embryo, compared with other cryopreservation methods using older embryos.

Blastocyst↗
PubMed1988

Prognostic value of morphologic characteristics of cryopreserved embryos: a study using videocinematography.

Fifty embryos, previously frozen at the zygote or 2- to 4-cell stage, were studied. Observers, who were unaware of the occurrence of pregnancy, assessed the morphologic features of these embryos by retrospectively analyzing videocinematographic recordings that were made shortly before replacement. Seven of 26 zygotes and 4 of 24 cleaved embryos implanted, with the incidence of implantation being analyzed in relation to 12 morphologic characteristics. Smooth surface of the blastomere's membranes was a statistically significant predictor of implantation for frozen-cleaved embryos, and variable zona pellucida thickness was the only parameter with predictive value for frozen zygotes. A highly significant difference was found between the implanting capacity of previously frozen-cleaved embryos and the number of abnormal morphologic characteristics. Three quarters of the thawed embryos had at least two abnormal characteristics, indicating that cryodamage was high. Major advantages of videocinematography are the absence of time constraints associated with observing live embryos, the ability to observe new morphologic parameters by freeze-frame and slow motion, and the permanent storage of embryonic data for quality control evaluation.

Embryo Implantation↗
PubMed1988

Cryopreserved zygotes and embryos and endocrinologic factors in the replacement cycle.

Several parameters relating to features of replacement cycles in 88 patients were found to influence implantation of cryopreserved zygotes and early cleaved embryos. Cryopreserved embryos were replaced in 47 patients with a natural cycle, resulting in 12 (25%) clinical pregnancies. Patients who had anovulation or irregular cycles received either 50 mg clomiphene citrate on days 5 to 9 or 100 mg on days 2 to 6; the incidence of clinical pregnancy was 7 of 23 (30%) and 2 of 18 (11%), respectively. Neither a rise in follicular phase estradiol (E2) nor absolute levels of E2 predicted implantation. The length of the follicular phase during the replacement cycle correlated well with previous menstrual cycles in 43 (54%) of the patients, and 16 (37%) of these patients became pregnant. The follicular phase was either longer or shorter than anticipated in 39 patients, and only 5 (13%) became pregnant: a detrimental effect was especially apparent when the follicular phase was shortened.

Embryo Transfer↗
PubMed1988

A study of change in clinical service for general surgical patients.

The department of surgery at Long Island Jewish Medical Center in New York City conducted a study examining resource consumption and quality of care for patients referred to surgery from other hospital services, or "referred patients." Referred patients were compared with "nonreferred" surgery patients using several indicators of resource consumption. A quality assessment was also performed on a random sample from both groups using peer review organization guidelines. The study found that referred patients consumed more resources and may have received poorer quality care than nonreferred patients. Previous studies suggest that some resource utilization by referred patients may be avoidable. Thus, referral to the department of surgery may serve as an indicator for identifying patients in need of ongoing quality and/or utilization monitoring.

Health Resources↗
PubMed1988

New inhibitors of human renin that contain novel Leu-Val replacements. Examination of the P1 site.

Stereoselective syntheses of several nonpeptide sulfidoethanol fragments that function as Leu10-Val11 (P1-P1') scissile bond replacements in human angiotensinogen are presented. These fragments are prepared from a variety of amino acids with formal P1 side chains varying in size and lipophilicity by converting them to their corresponding N-protected aminoalkyl epoxide 5 followed by ring opening with isopropyl mercaptan. The coupling of these fragments to either Boc-Phe-Ala-OH or Boc-Phe-His-OH produces inhibitors of human renin, 6 and 7, respectively, which are compared to a series of dipeptide-aldehyde inhibitors, 4, by molecular modeling and biochemical methods. Qualitatively, histidine-containing (P2) inhibitors 7 possess greater inhibitory potency than their corresponding alanine (P2) analogues 6, which are more potent than the corresponding aldehydic inhibitors from series 4. Within a given series, inhibitors with the cyclohexylmethyl P1 side chain are more potent than the benzyl analogues, which in turn are more potent than cyclohexyl or isobutyl derivatives. Inhibitors with parger P1 side chains (e.g. adamantylmethyl and benzhydryl) are much less active. The inhibitory potency of these compounds against human renin is discussed in terms of specific interactions with the enzyme.

Amino Acid Sequence↗
PubMed1988

An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes.

Because cytotoxic T lymphocytes (CTL) may be important for preventing direct cell-to-cell transmission of human immunodeficiency virus (HIV), the agent responsible for acquired immunodeficiency syndrome, we have begun to investigate the epitope specificity and immune response (Ir) gene control of anti-HIV CTL responses in experimental animals. Mice were infected with a recombinant vaccinia virus expressing the HIV gp160 envelope gene, and the primed lymphocytes were restimulated in vitro with a transfected histocompatible cell line expressing the same gene. Our results show that H-2d mice are CTL high responders and H-2k mice are low responders to the HIV gp160 envelope protein under these conditions. Moreover, the H-2d mice respond predominantly to a single immunodominant site represented by a 15-residue synthetic peptide conforming to the amphipathic alpha-helix model of T-cell epitopes and seen by CD4- CD8+ CTL in association with the Dd class I major histocompatibility complex (MHC) molecules. The facts that CTL responses were detected in the context of only one of four class I MHC molecules tested and that the response was limited predominantly to a single epitope indicate that the CTL repertoire elicited by the HIV envelope protein in association with murine class I MHC molecules may be very limited. In addition, this epitope occurs in a highly variable segment of the envelope protein. This puts constraints on the use of a single peptide sequence from this region in a vaccine, as such a vaccine would have to be polyvalent. Nevertheless, this same variability suggests that this region may be under selective pressure from human CTL, and therefore that this site may be immunodominant in humans as well as mice and so of clinical importance in vaccine development.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cryopreservation of human embryos and oocytes.

The success rate of human embryo cryopreservation depends on technical and embryonic parameters. First of all, the cryoprotectant can affect embryo survival as we found by comparing two freeze-thaw procedures using propanediol (PROH) (1.5 mol) alone or with sucrose (0.1 mol). Embryo survival was significantly enhanced with sucrose (62 versus 32%). Embryo quality is another major parameter involved in the success of freezing; the rates of positive survival were found to be 67% for morphologically normal embryos versus 49% for embryos with fragments (P less than 0.001). The efficiency of embryo cryopreservation in an IVF programme could be estimated in 1986: a woman with extra embryos, stored after transfer of 3-4 fresh embryos (16% of all cycles), can expect a 22% pregnancy rate per transfer of fresh embryos and a 32% pregnancy rate per collection after transfer of the stored eggs. A comparative study of the cryopreservability of immature or mature oocytes was performed in humans. Human oocytes have a low survival rate (36%) whatever the cryopreservation protocol or the initial maturation stage. Immature human oocytes could survive freezing and thawing, mature and be fertilized in vitro, but with a very low efficiency.

Embryo Transfer↗