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Biomedical subjects

A L Cohen

Publications and source records attributed to A L Cohen.

At least 19 recordsLinked to original sources

Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice.

Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.

Animals

Diffractive bifocal lens designs.

Modifying the number, width, depth, and shape of the echelettes in a diffractive bifocal lens will influence the image intensity and quality within the zero, first, and higher order images. By appropriately varying these parameters optimal bifocal lens designs may be achieved.

Contact Lenses

A case-control study of late recurrence of malignant melanoma.

Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.

Case-Control Studies

Benign recurrent intrahepatic cholestasis (Summerskill and Walshe syndrome). Case report and revision of bibliography.

We describe the case of a 58-year old woman who had four episodes of choluric jaundice and severe pruritus, starting at age 48. Each episode lasted about four months and had a spontaneous remission. During icteric episodes, conjugated bilirubinemia, alkaline phosphatase, and to a lower degree transaminases, were increased; white cell count was higher and there was a marked rise in sedimentation rate. Between such episodes there was a complete clinical remission, and laboratory alterations returned to normal, although sometimes a high alkaline phosphatase persisted. There was no history of previous drug intake known to produce these disorders. During the last icteric episode, an exploratory laparatomy, with roentgenographic study was done, which demonstrated that the extrahepatic biliary tract was intact. Histology revealed that the liver showed a preserved, regular architecture, of which the salient feature was intrahepatic cholestasis. Corticoids and cholestyramine were of little benefit for pruritus.

Alkaline Phosphatase

Critical point drying: contamination in transitional fluid supply cylinders.

We call attention to the occurrence of an oily residue in the CPD bomb after critical point drying, as well as the presence of rust, dirt, and an oily residue in CO2 and Freon supply cylinders. Bottled gas is often tested for purity once after manufacturing and then is pumped and stored, perhaps several times, before the consumer's cylinders are filled. The cylinders may be in use for over 40 years, and may never be chemically cleaned, although they are hydrostatically pressure tested every five years, with the date of each test stamped on the cylinder. To the bottled gas industry we recommend regular inspection of tanks for bottom contamination, and vacuum and chemical cleaning when contamination is found. To users of bottled gas for critical point drying, we recommend becoming aware of the procedures of cylinder inspection, cleaning, and circulation among users. We suggest reporting to the gas supplier any contamination produced by inadvertently backfilling the supply cylinder. Although a common awareness of the problem of supply cylinder residues should lead to failures, the best assurance of clean, oil-free, dry liquid CO2 and other transitional fluids may be in the development of in-line filters which would remove particles, oil and moisture between the supply cylinder and the CPD bomb. We also suggest the use of gas grades higher than commercial, such as welding anhydrous (CO2) or specialty gases.

Gases

Introduction of metastatic heterogeneity by short-term in vivo passage of a cloned transformed cell line.

An experimental system for the study of metastasis has been developed using an epithelioid cell line of hepatic origin which had previously been chemically transformed in vitro. These metastatic cells were studied in the syngeneic rat strain. The cloned parent cell line metastasizes only to the lungs following intravenous, subcutaneous, or intraperitoneal injection. The metastatic phenotype is stable during in vitro passage, and subclones from the parent clone have a metastatic capacity statistically similar to that of the parent clone. Following ascites passage of the parent cell line, the cell population obtained exhibits the same metastatic ability as the parent clone. However, subclones obtained from the ascites-passaged population exhibit metastatic heterogeneity. This heterogeneity is introduced by the host passage and not by in vitro culture or subcloning. In the case of the two metastatic variants examined, the difference in the metastatic phenotype is found not to be due to differences in arrest or trapping of the cells but appears to be related to long-term survival and proliferation of the tumor cells following their arrest in the lungs. Morphologically the variants are very similar, and growth of the metastatic foci provokes a vigorous inflammatory response by the host.

Animals

Role of gravity in prism ballasting.

One of the techniques commonly used in stabilizing the rotation of a contact lens is prism ballasting. The idea is to gain stabilization by the action of gravity pulling on the base of the prism. The determination of just how much prism is necessary in any particular case is usually made empirically, gradually increasing prism amount when more stability is required. This paper will present the results of a mathematical investigation which demonstrates that gravity forces alone do not play the major role in the stabilization of prism ballasted lenses. It is hoped that this preliminary analysis will stimulate further theoretical work of a similar nature, in the growing field of contact lenses.

Contact Lenses

Purification, quaternary structure, composition, and properties of D-ribulose-1,5-bisphosphate carboxylase from Thiobacillus intermedius.

D-Ribulose-1,5-bisphosphate (RuBP) carboxylase has been purified from glutamate-CO2-S2O3(2)-grown Thiobacillus intermedius by pelleting the enzyme from the high-speed supernatant and by intermediary crystallization followed by sedimentation into a discontinuous 0.2 to 0.8 M sucrose gradient. The enzyme was homogeneous by the criteria of electrophoresis on polyacrylamide gels of several acrylamide concentrations, sedimentation velocity and equilibrium measurements, and electron microscopic observations of negatively stained preparations. The molecular weights of the enzyme determined by sedimentation equilibrium and light-scattering measurements averaged 462,500 +/- 13,000. The enzyme consisted of closely similar or identical polypeptide chains of a molecular weight of 54,500 +/- 5,450 determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The S(0)20,w of the enzyme was 18.07S +/- 0.22. Electron microscopic examination suggested that the octomeric enzyme (inferred from the molecular measurements mentioned) had a cubical structure. The specific activity of the enzyme was 2.76 mumol of RuBP-dependent CO2 fixed/min per mg of protein (at pH 8 and 30 C), and the turnover number in terms of moles of CO2 fixed per mole of catalytic site per second was 2.6. The enzyme was stable for 3 months at -20 C and at least 4 weeks at 0 C. The apparent Km for CO2 was 0.75 mM, and Km values for RuBP and Mg2+ were 0.076 and 3.6 mM, respectively. Dialyzed enzyme could be fully reactivated by the addition of 20 mM Mg2+ and partially reactivated by 20 mM Co2+, but Cd2+, Mn2+, Ca2+, and Zn2+ had no effect. The compound 6-phosphogluconate was a linear competitive inhibitor with respect to RuBP when it had been preincubated with enzyme, Mg2+, and HCO3-.

Amino Acids