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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 919 records · Page 51Linked to original sources
PubMed1992

Serious physical illness as a stressor: effects on family use of medical services.

The purpose of this study was to investigate the effect of stress on the family due to the hospitalization of a family member for a serious chronic illness. The data were the health insurance claims of 3,591 families obtained from the largest U.S.A. insurer of federal employees. It was hypothesized that the nonhospitalized family members would have a stress-related increase in medical expenses for some period of time after the chronically ill person was hospitalized. Multiple regression analysis with adjustments for a number of covariates found increases in mean medical charges of $326 per person (p less than 0.01) (excluding the hospitalized person) in the 3 years following the hospitalization. This finding lends support to the theory that stress--in this case, hospitalization of one family member--affects the entire family system. No significant differences were found in medical charges between families who did and did not receive mental health treatment following the hospitalization.

Adaptation, Psychological↗
PubMed1992

In-vitro stimulation of TNF-alpha from human whole blood by cell-free supernatants of gram-positive bacteria.

Gram-positive bacteria are being recognized increasingly as the cause of shock-like syndromes, clinically indistinguishable from those seen in association with Gram-negative endotoxic shock. Much clinical and experimental data link tumour necrosis factor-alpha (TNF-alpha) with the pathogenesis of endotoxic shock, and a number of studies of individual Gram-positive species have also implicated TNF-alpha. We report here the first systematic study of the ability of cell-free supernatants of common Gram-positive bacteria to induce TNF-alpha from human peripheral blood monocytes in vitro. Almost all the 63 strains were able to induce TNF-alpha, although the levels were substantially lower than those obtained from supernatants of Gram-negative bacteria, used as controls. Streptococcus pneumoniae, S. pyogenes, viridans streptococci and coagulase-negative staphylococci were consistently more active than group B and D streptococci. TNF-alpha induction did not correlate with conventional markers of pathogenicity; amongst strains of Staphylococcus aureus, commensal and blood culture isolates did not induce significantly different amounts of TNF. We conclude that cell-free supernatants of most Gram-positive bacteria are capable of inducing TNF-alpha from human peripheral blood monocytes in vitro, but the significance of this finding remains to be determined.

Bacterial Toxins↗
PubMed1992

Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor.

Chemotherapy can serve as a stimulus for mobilizing hematopoietic progenitor cells to the peripheral blood for harvest via leukapheresis. Mobilized peripheral blood stem cells (PBSC) support rapid hematologic reconstitution after bone marrow aplasia induced by intensive myelosuppressive treatments. Our purpose was to develop effective mobilization regimens allowing collection of large quantities of PBSC. We administered high-dose cyclophosphamide (HDC, 4 gm/m2) or cyclophosphamide (4 gm/m2) plus etoposide (600 mg/m2) (HDCE) in a nonrandomized, sequential fashion to 94 patients with breast cancer, lymphoma, and other malignancies with collection of PBSC via leukapheresis during white blood cell (WBC) recovery from nadir counts. Each apheresis product was analyzed for total nucleated cell number, granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Twenty-four additional patients with comparable pretreatment characteristics received HDCE plus recombinant human granulocyte colony-stimulating factor (HDCE+G) after chemotherapy through the end of apheresis. Patients receiving HDC were matched for age, sex, and disease but were more heavily pretreated. HDCE was superior to HDC in mean daily CFU-GM and CD34+ yield (p < 0.05), even when groups were adjusted for performance status and amount of prior therapy. HDCE+G led to 3.7 times more CFU-GM and 4.7 times more CD34+ cells than HDCE. Target PBSC yield, defined as > 20 x 10(4) CFU-GM/kg and >4 x 10(8) cells/kg, was achieved by 92% of HDCE+G patients after a median of three aphereses, 56% of HDCE patients after five aphereses, and 16% of HDC patients after six apheresis (p < 0.0001). Prior chemotherapy inversely correlated with the quantity of PBSC harvested regardless of regimen utilized. Our results demonstrate effective chemotherapy regimens for harvesting hematopoietic progenitors in a diverse patient population. HDCE+G produced the highest number of progenitors, suggesting that increasing dose intensity and adding rhG-CSF enhances mobilization. Correlation between cumulative CD34+ and CFU-GM allows real-time flow cytometric analysis of the number of aphereses required to harvest target numbers of PBSC.

Adolescent↗
PubMed1992

Interactions between genes involved in exocytotic membrane fusion in paramecium.

Crosses between members of two independent collections of Paramecium tetraurelia mutants blocked in the final membrane fusion step of trichocyst release (nd mutants) allowed us to define 13 complementation groups comprising 23 alleles. The mutant nd9a was then used as a target in a mutagenesis experiment designed to screen both revertants and new mutants in order to identify interacting genes. This mutant was chosen because it is the best known of its class to date and seems to be altered in assembly of the material connecting the trichocyst membrane to the plasma membrane and in assembly of the "rosette," a complex array of intramembranous particles in the plasma membrane at the trichocyst insertion sites. No revertants were obtained but two new mutants deficient for rosette assembly were identified, nd16b and nd18, whose gene products appear to interact with that of nd9. Indeed, the double mutants grown at 18 degrees, a permissive temperature for each of the single mutants, are characterized by a deficiency in exocytosis and in rosette assembly, as are also double mutants combining other allelic forms of the same genes. Moreover, aberrant dominance relationships among alleles of nd9 and of nd16 indicate the existence of interactions between identical subunits, which most likely assemble into multimeric structures. The nd16 gene product was shown by microinjection experiments to be a cytosolic factor, as is the nd9 gene product. It is therefore tempting to propose that the nd16 gene product also belongs to the connecting material and is involved in rosette assembly, in cooperation with nd9 and nd18.

Animals↗
PubMed1992

Role of interferon-gamma in experimental gram-negative sepsis.

To study the role of interferon-gamma (IFN-gamma) in gram-negative shock, mortality was compared in mice receiving either a monoclonal antibody to IFN-gamma (H22) or an irrelevant monoclonal antibody (L2-3D9) before or after an LD90 dose of Escherichia coli O111:B4. H22 given either 1 h before or 0.5 h after bacterial challenge protected mice from death (mortality at 48 h, 28% vs. 83%, P less than .001). Serum tumor necrosis factor-alpha (TNF alpha) levels and bacterial counts in blood and organs (liver, spleen, heart, and brain) were similar in H22-treated animals and controls. The peak serum TNF alpha levels were 95.7 +/- 16.4 ng/mL and 80.7 +/- 14.9 ng/mL in the H22 and control groups, respectively. These results indicate that IFN-gamma plays a significant role in the pathogenesis of gram-negative sepsis.

Animals↗
PubMed1992

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

Adolescent↗
PubMed1992

Evaluation of Vero cell co-culture system for mouse embryos in various media.

Our objective was to evaluate and compare the efficacy and mechanisms of co-culturing mouse embryos with Vero cells in both Dulbecco's modified Eagle's medium/Ham's F12 (DMEM/F12) and human tubal fluid (HTF) culture medium. Two-cell CB6F1 mouse embryos were cultured either in the presence of Vero cells (group A) or in culture medium alone (group B). In DMEM/F12 significantly more morulae developed in group A than in group B on day 3 (91 versus 23%; P less than 0.01). In contrast, the mouse embryos grew rapidly in HTF and significant differences were noted only in later embryonic stages (on day 5; 86% and 50%, P less than 0.01 of group A and B respectively, hatching or hatched). Similar experiments using DF1 and ICR mouse strains also revealed enhanced embryo development in the presence of Vero cells. To determine whether the embryo-enhancing effects of Vero cells were due to the removal of toxins or to the secretion of embryotrophic factors, ICR mouse embryos were cultured in fresh media with cells (group A), without cells (group B) and in cell-free conditions using cell-conditioned media which were obtained in the presence (group C) or absence (group D) of embryos. These results demonstrated that completion of hatching was highest (52%; P less than 0.01) in group A after 6 days in culture. There were no significant differences between groups B, C and D (rates of total hatching 18, 17 and 17%, respectively). It is concluded that Vero cells improve the development of mouse embryos and this is likely to be due to removal of substances inhibitory to development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis.

Assisted hatching by zona drilling using acidic Tyrode's solution was performed during three randomized trials in 330 in-vitro fertilization patients. The trials were designed in order to study the overall effect of the procedure and whether characteristic patient [i.e. maternal age and basal levels of follicle stimulating hormone (FSH)] and embryonic features (i.e. zona pellucida thickness) are important for the decision to perform assisted hatching routinely. Couples (n = 137; Trial 1) in whom the female partner had normal basal FSH levels were randomized in a control group (without micromanipulation) and a zona drilling group (all embryos micromanipulated). The incidence of implantation (67/239; 28%) of zona-drilled embryos compared favourably with that of control embryos (49/229; 21%), but the difference was not significant. Retrospective analysis revealed that those embryos whose zonae were thicker than 15 microns were rescued. In order to test the validity of this finding, selective assisted hatching was performed on embryos with a poor prognosis in 163 other patients (Trial 2). The couples were randomized into a control group and a group in which embryos were selectively zona-drilled, based on zona thickness and other embryonic features. The rate of embryonic implantation in the selectively zona-drilled group was 25% (70/278), significantly (P less than 0.05) higher than that of control embryos (51/285; 18%). Although it was demonstrated retrospectively and prospectively that assisted hatching by zona drilling is effective in embryos with thick zonae (greater than or equal to 15 microns), patients whose embryos have thin (less than 13 microns) zonae may be jeopardized by the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryo Implantation↗
PubMed1992

Is the human oocyte plasma membrane polarized?

Using scanning electron microscopy, we have shown that the plasma membrane of the human metaphase II oocyte is organized in evenly spaced, short microvilli of 1-3 microns in length. In contrast to other mammals studied to date, there is no microvillus-free area overlying the metaphase spindle and there were no other indications of polarization at this level of organization. Functional polarity of the plasma membrane, studied using localized microsurgery of the zona pellucida followed by insemination, suggests that sperm fusion and entry in the human may occur anywhere over the oocyte surface. Aged oocytes and those exposed to acidic Tyrode's solution had surfaces which were not homogeneously covered by microvilli. Oocytes exposed to a sucrose solution and subzonally injected with spermatozoa showed evidence of partial cortical granule exocytosis.

Cell Membrane↗
PubMed1992

The Cornell Interview of Peers and Friends: development and validation.

The Cornell Interview of Peers and Friends (CIPF), a 30-minute semistructured interview, evaluated 7- to 11-year-old children's perceptions of their social relationships. Significant differences on the CIPF were found between clinical and nonclinical groups and between boys and girls. Three CIPF subscales, Developmental Appropriateness, Social Skills, and Self-esteem, were assessed and significantly differentiated between clinical and nonclinical populations. Satisfactory interrater reliability is reported for the interview's total score and the three subscale scores. The CIPF offers potential for screening children at risk for emotional disturbance and for assessing outcomes of therapeutic interventions.

Child↗
PubMed1992

Localization of group-specific epitopes on the major capsid protein of group A rotavirus.

Chemical cleavage of the VP6 protein of bovine rotavirus showed that VP6-specific monoclonal antibodies (MAbs) reacted with the amino acid sequence between glycine 48 and asparagine 107. Furthermore, three synthetic peptides (amino acids 48 to 64, 60 to 75 and 91 to 108) containing part of this sequence and 22 consecutive overlapping heptapeptides corresponding to the region between amino acids 48 and 75 were analysed for their immunoreactivity using group-specific MAbs. The MAbs recognized peptides 48-64 and/or 60-75, and a set of overlapping heptapeptides located between residues 53 (asparagine) and 67 (glycine), which have two short sequences in common: IRNW (residues 56 to 59), recognized by MAb RV-133, and (NW)NFD (residues 58/60 to 62), recognized by MAbs RV-50, -1026 and -443. These results indicate that the sequence between amino acid residues 48 and 75 is present in one of the immunodominant sites of VP6.

Amino Acid Sequence↗
PubMed1992

Bovine rotavirus segment 5 protein expressed in the baculovirus system interacts with zinc and RNA.

The cDNA sequence of genomic segment 5 of bovine rotavirus (RF strain) has been inserted into baculovirus transfer vectors, downstream of the polyhedrin promotor. Recombinant baculoviruses containing gene 5 were selected and the protein was expressed to high yields in Spodoptera frugiperda cells. The recombinant protein was inoculated into rabbits and mice to produce specific hyperimmune antisera. The polyclonal antiserum reacted with a protein in rotavirus-infected MA104 cells and with a protein translated in vitro. This serum was also used to confirm that the gene 5 protein is not a structural protein. Recently, the gene 5 product has been predicted to be a zinc finger protein and reported to contain a highly conserved arrangement of cysteine residues; here, we demonstrate that the recombinant gene 5 protein binds zinc and is an RNA-binding protein as are several other zinc finger proteins.

Amino Acid Sequence↗
PubMed1992

An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity.

Invasive pulmonary aspergillosis, usually caused by Aspergillus fumigatus, is a life-threatening condition of immunosuppressed patients. We have created a mutant strain of this fungus that lacks an extracellular alkaline protease (AFAlp). This was accomplished by transformation of A. fumigatus with a plasmid containing a selectable marker for hygromycin B resistance, and a 504 bp segment of the AFAlp gene, obtained by polymerase-chain-reaction-based amplification of A. fumigatus genomic DNA. Approximately 25% of transformants resulted from disruption of the AFAlp gene. SDS-polyacrylamide gel electrophoresis of proteins from the culture filtrate of a strain carrying the AFAlp gene disruption showed that it lacked a major protein of 33 kDa. Furthermore, in contrast to the culture filtrate from wild-type cells, the mutant had undetectable activity on azocollagen and elastin-Congo red, over a broad pH range. This shows that AFAlp accounts for most, if not all, of the extracellular elastinolytic activity of A. fumigatus, and that the mutant strain will be useful in assessing the role of AFAlp in pathogenicity.

Aspergillus fumigatus↗