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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Phase I and pharmacokinetic study of the novel platinum analogue CI-973 on a 5-daily dose schedule.

CI-973, a platinum(II) derivative with a 2-methyl-1,4-butanediamine carrier ligand, has activity in cisplatin-resistant tumor models in vitro and in vivo. In a Phase I pharmacokinetic study, 31 patients were treated with CI-973 (24 to 50 mg/m2/day for 5 days; 28-day cycles) given i.v. over 30 min without routine antiemetic prophylaxis or hydration. Of the 29 patients evaluable for maximum tolerated dose determination, most had a performance status of 0 or 1, and most had received prior chemotherapy. Neutropenia was dose limiting at 40 and 50 mg/m2/day. Recovery from neutropenia was generally rapid with nadir counts and recovery usually occurring by Days 15 and 22, respectively. Drug-associated thrombocytopenia was uncommon and never severe, even in patients with Grade 4 neutropenia. Anemia was common, but did not appear dose related. Drug-related nausea and vomiting and changes in renal function were relatively infrequent and mild. No clinically evident ototoxicity was reported, although changes in audiograms were noted in several patients. CI-973 concentrations were measured in plasma ultrafiltrate and urine by high-pressure liquid chromatography. The harmonic mean terminal half-life was 2.0 h. The mean CI-973 renal and nonrenal clearance values were 42.3 and 37.4 ml/min/m2, respectively. The mean recovery of CI-973 in urine was 53% of the administered dose. The mean ratio of CI-973 renal clearance to creatinine clearance was 0.92. Total clearance correlated with creatinine clearance (r2 = 0.63). A relationship between toxicity, expressed as the percentage of reduction in absolute granulocyte count, and area under the CI-973 plasma concentration-time curve was found in a subgroup of "good-risk" patients. This relationship, described well by a sigmoidal Emax pharmacodynamic model, did not hold for patients with extensive prior therapy or poor performance status. A model for toxicity prediction based on dose and creatinine clearance has been derived and will be validated in future studies. The recommended Phase II dose of CI-973 is 30 mg/m2/day for 5 days.

Adolescent↗
PubMed1992

Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor.

We have determined the complete nucleotide and deduced amino acid sequence of the major protein core of the human heparan sulfate proteoglycan HSPG2/perlecan of basement membranes. Eighteen overlapping cDNA clones comprise 14.35 kilobase pairs (kb) of contiguous sequence with an open reading frame of 13.2 kb. The mature protein core, without the signal peptide of 21 amino acids, has a M(r) of 466,564. This large protein is composed of multiple modules homologous to the receptor of low density lipoprotein, laminin, neural cell adhesion molecules, and epidermal growth factor. Domain I, near the amino terminus, appears unique for the proteoglycan since it shares no significant homology with any other proteins. It contains three Ser-Gly-Asp sequences that could act as attachment sites for heparan sulfate glycosaminoglycans. Domain II is highly homologous to the LDL receptor and contains four repeats with perfect conservation of all 6 consecutive cysteines. Next is domain III which shares homology to the short arm of laminin A chain and contains four cysteine-rich regions intercalated among three globular domains. Domain IV, the largest module with greater than 2000 residues, contains 21 repeats of the immunoglobulin type as found in neural cell adhesion molecule. Near the beginning of this domain, there is a stretch of 29 hydrophobic amino acids which could allow the molecule to interact with the plasma membrane. Domain V, similar to the carboxyl-terminal globular G-domain of laminin A and to the related protein merosin, contains three globular regions and four EGF-like repeats. In situ hybridization and immunoenzymatic studies show a close association of this gene product with a variety of cells involved in the assembly of basement membranes, in addition to being localized within the stromal elements of various connective tissues. Our studies show that this proteoglycan is present in all vascularized tissues and suggest that this unique molecule has evolved from the utilization of modular structures with adhesive and growth regulatory properties.

Amino Acid Sequence↗
PubMed1992

T cell vaccination in multiple sclerosis: a preliminary report.

Multiple sclerosis (MS) is a presumed autoimmune disease of the central nervous system. Inoculation of attenuated T cell clones recognizing immunodominant regions of myelin autoantigens can protect animals from the induction of experimental autoimmune diseases. In this phase one trial, we investigated whether inoculations with attenuated T cell clones are feasible in humans for eventual trials with autoreactive clones and whether there are any associated immunologic effects. A total of seven inoculations with attenuated, autologous T cell clones isolated from the cerebrospinal fluid in four subjects with progressive MS was performed. No untoward side effects were observed. Immunologic studies suggested that the inoculation of autologous activated T cell clones followed by partial, short-term, immunosuppression as evidenced by a decrease of subsequent responses to stimulation via the CD2 pathway and increases in the autologous mixed lymphocyte response. We conclude that the use of attenuated autoreactive T cell clones appears feasible for further clinical trials in humans with autoimmune diseases.

Clone Cells↗
PubMed1992

Effects of platelets and plasma on fibrinolysis.

The effects of various concentrations of platelets and plasma on in vitro t-PA-induced fibrinolysis were investigated. At t-PA levels between 30 and 70 ng/ml, fibrinolysis proceeded faster in platelet-rich plasma (PRP) than in platelet-poor plasma (PPP). When PRP was serially diluted with PPP and the rate of fibrinolysis compared to PPP, higher platelet counts (up to 300 x 10(9)/l) were associated with increased enhancement of lysis. However, lysis was inhibited when platelets were added to plasma diluted with buffer. Thus, platelets enhance fibrinolysis in undiluted plasma but inhibit lysis in diluted plasma. This is probably because platelets provide a catalytic surface for fibrinolysis but also release inhibitors of fibrinolysis. In undiluted plasma, there would be sufficient fibrinogen and plasminogen to overcome the effect of the platelet inhibitors, but in diluted systems, the inhibitors would predominate, retarding fibrinolysis.

Blood Platelets↗
PubMed1992

Combined ovarian vein catheterization with ovarian stimulation in the diagnosis of androgen overproduction.

A 28-year-old woman was evaluated for late onset secondary amenorrhea, progressive hirsutism and an elevated serum testosterone concentration. Her serum cortisol, androstenedione, dehydroepiandrosterone sulfate and 17-hydroxyprogesterone levels were normal. Bilateral ovarian and adrenal vein catheterization demonstrated mild elevated testosterone and androstenedione levels in the right ovarian vein. Fifteen minutes after administering the intravenous injection of 5,000 IU human chorionic gonadotropin, there was a six and a half to sevenfold increase in the level of these two hormones in the right ovarian vein with no significant change in hormone levels from other sources. Based on the ovarian peripheral vein gradients obtained during venography following ovarian stimulation, the diagnosis of right ovarian hyperthecosis was made. This diagnosis could not have been reached without the combination of selective ovarian vein catheterization and ovarian stimulation. We recommend that this combined test, which may provide additional information on the source of the androgens in women with hyperandrogens, be performed in selected cases, when a virilizing tumor is suspected.

Adult↗
PubMed1992

Nontyphi Salmonella sepsis in an eight-year-old boy.

Nontyphi bacteremia is a rare event in older children, especially in those without predisposing conditions. We report a case occurring in a normal 8-year-old boy from south Louisiana whose prolonged illness may, in part, have been iatrogenic. Antibiotic treatment is also discussed.

Anti-Bacterial Agents↗
PubMed1991

The Xenopus YB3 protein binds the B box element of the class III promoter.

We have isolated a Xenopus cDNA encoding the YB3 protein which binds specifically to the B box promoter element of class III genes. Northern analysis shows YB3 is expressed in a variety of adult tissues. Fractionation of oocyte S150 extracts demonstrates YB3 is present in phosphocellulose fraction IIIC, as well as in the fraction isolated by B box DNA affinity chromatography. Silver staining indicates that YB3, or a protein of the same mobility in SDS gels, is the most abundant component in either fraction.

Adenoviridae↗
PubMed1991

Glial fibrillary acidic protein in the fish optic nerve.

The intermediate filament glial fibrillary acidic protein (GFAP) is the predominant cytoskeletal protein of mature glial cells in the mammalian nervous system. The nervous systems of lower vertebrates, such as fish, have been examined for the presence of GFAP and several investigators have shown that goldfish (Carassius auratus) brain contains GFAP-positive astrocytes. The same studies have demonstrated that, in contrast to the brain, the optic nerve of goldfish did not show any GFAP immunoreactivity, suggesting that this intermediate filament protein is not expressed in fish optic nerve astrocytes. The present study shows, however, that the monoclonal antibodies to porcine GFAP react with the optic nerve of carp (Cyprinus carpio), another member of the goldfish family. These antibodies to porcine GFAP cross react with rat brain and carp optic nerve, yielding a band of approximately 52 kDa in both species. Northern blot analysis using mouse GFAP DNA probe revealed that carp optic nerve RNA contains two transcripts of 2.3 and 2.1 kb, which hybridize with the mouse GFAP probe. Injury to the carp optic nerve was followed by a decrease of GFAP immunoreactivity from neural tissue and a strong expression around blood vessels and connective tissues. On the basis of these observations and within the limitation of the techniques it is reasonable to conclude that the carp optic nerve expresses GFAP immunoreactivity and that the pattern of expression of this intermediate filament protein is altered after injury. Such an alteration might be relevant to the process of regeneration.

Animals↗
PubMed1991

Isolation and sequence analysis of two intermediate filament cDNA clones from fish optic nerve.

The high post-traumatic regenerative ability of fish central nervous system has been partially attributed to the hospitable nature of the surrounding non-neuronal cells and their appropriate response to injury. Uncovering the correlation between fish non-neuronal cell structure and behavior might yield a better understanding of what makes them supportive to axonal growth. Towards this goal, structural proteins expressed by fish non-neuronal cells need to be characterized. In the present study we isolated cDNA clones encoding fish intermediate filaments which are prominent structural proteins in astrocytes. Among the isolated clones, one was identified as fish vimentin and another was found identical to the cloned fish keratin 8. Results are discussed with respect to the use of these cDNAs for further understanding of fish non-neuronal cell plasticity.

Amino Acid Sequence↗