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S Cohen

Publications and source records attributed to S Cohen.

At least 1,099 records · Page 61Linked to original sources
PubMed1976

Cytophilic activity of enzymatically derived fragments of guinea pig IgG2.

The hydrolysis products from short term exposure of guinea pig IgG2 to papain and pepsin have been characterized. Papain hydrolysis liberates 4 types of Fc fragment, only one of which retains both an interchain disulfide bond and an intact CH2 domain, cFc, mol.wt. 56 000. The other three fragments noncovalently linked Fc (nFc) (mol.wt. 56 000), incomplete Fc (iFc) (mol.wt. 39 000) and Fc' (23 000) represent further degradation products of covalently linked complete Fc (cFc). The cytophilic activities of these fragments as well as F(ab')2 and pFc' from pepsin hydrolysis, were studied to determine the domain(s) responsible for binding to homologous peritoneal macrophages. Only the native immunoglobulin and the intact cFc manifested cytophilic activity; in particular pepsin-derived pFc' and Fc' were inactive. Following mild reduction and alkylation, performed to affect only the interchain disulfide bonds, the cytophilic activity of cFc was markedly reduced. The low cytophilic activity in the pFc' fragment suggests that the CH2 domains play a major part in binding to the macrophage Fc receptor through a site(s) stabilized by the interchain disulfide bonds.

Amino Acid Sequence↗
PubMed1976

Human epidermal growth factor and the proliferation of human fibroblasts.

The effect of human epidermal growth factor (hEGF), a 5,400 molecular weight polypeptide isolated from human urine, on the growth of human foreskin fibroblasts (HF cells) was studied by measuring cell numbers and the incorporation of labeled thymidine. The addition of hEGF to HF cells growing in a medium containing 10% calf serum resulted in a 4-fold increase in the final density. The presence of hEGF also promoted the growth of HF cells in media containing either 1% calf serum or 10% gamma globulin-free serum. The addition of hEGF to quiescent confluent monolayers of HF cells, maintained in a medium with 1% calf serum for 48 hours, resulted in a 10- to 20-fold increase in the amount of 3H-thymidine incorporation after 20-24 hours. The stimulation of thymidine incorporation was maximal at an hEGF concentration of 2 ng/ml, was dependent on the presence of serum, and was enhanced by the addition of ascorbic acid. In confluent cultures of HF cells, subject to density dependent inhibition of growth, hEGF was able to stimulate DNA synthesis more effectively than fresh calf serum. Human EGF stimulated DNA synthesis in quiescent cultures, however, regardless of cell density. The addition of rabbit anti-hEGF inhibited all effects of this growth factor on HF cells.

Animals↗
PubMed1976

A new probe for heterogeneity in muscarinic receptors: 2-methyl-spiro-(1, 3-dioxolane-4, 3')-quinuclidine.

The title compound (MSDQ) is a new muscarinic agonist related to 3-acetoxyquinuclidine (3-AcQ) but also of a highly rigid structure. In view of this, it may constitute a probe for the detection of heterogeneity among muscarinic receptors. Indeed, equipotent molar ratios (EPMR) for ACh, 3-AcQ and MSDQ were as follows: guinea pig ileum, 1 : 14 : 240; vasodepressor effect in the cat, 1 : 6 : 188. But EPMR for 3-AcQ and MSDQ as stimulants of the superior cervical ganglion in the cat were 1 : 1 and for the induction of tremors in mice, 9 : 5. No such subtle differences in receptor specificity were detected when the probe used was the 2, 2-diphenyl analogue (DiPSDQ) of MSDQ which was a powerful competitive antagonist in all systems, more potent than atropine, but with a CNS/PNS activity of 1.1 compared to 26 for atropine. In view of this, the use of potent antagonists as probes for muscarinic receptor heterogeneity is questionable.

Animals↗
PubMed1976

A study of muscarinic receptor heterogeneity with weak antagonists.

A study of heterogeneity among muscarinic receptors was carried out with new rigid molecules, comprising structures in the fused quinuclidine-valerolactone, quinuclidine-cyclohexenone, quinuclidine-cyclohexanone and quinuclidine-cyclohexane derivatives. These are structurally related to the potent muscarinic agent, 3-acetoxyquinuclidine but substantially different from in it conformation. All proved to antagonize acetylcholine-like activity, but to a different extent in different systems. The equipotent molar ratio with respect to atropine (as 1) was: isolated guinea pig ileum, 10,000-1,000; salivary gland (mouse), 1,000-100; superior cervical ganglion (cat), 100-10; CNS (mouse), approximately 10. It is suggested that the rigid structure induces a three-point constrained fit in the receptor (onium group, hydrophobic moiety and carbonyl group), but that not all muscarinic receptors are capable of responding equally. In this case, receptor specificity of the drug is a direct consequence of its graded departure from the preferred conformation of acetycholine and, therefore, is necessarily associated with partial loss of potency.

Animals↗
PubMed1976

Cell mediated immunity and the inflammatory system.

In this review we have considered the evidence for the existence of lymphokines and have focused on the specific mechanisms by which lymphokines modify the behavior of the various inflammatory cells. These mechanisms are based for the most part on in vitro observations. We have therefore discussed in detail data that document an in vivo role for various lymphokines. This evidence is based on experiments falling into two broad categories: the identification of lymphokines in tissue extracts and serum, and the demonstration of various biologic activities of exogenous lymphokines administered locally or systemically. The details of these kinds of experiments have been presented throughout the preceding discussion. The demonstration of lymphokines in vivo adds a new dimension to our ability to study human disease. The detection of migration inhibition factor in serum, for example, is technically simpler than studies of lymphocyte reactivity in patients with altered cellular immunity. Migration inhibition factor has already been found in the serum in several clinical settings, as described. The capacity of exogenous lymphokines for suppressing manifestations of delayed hypersensitivity may provide an explanation for the altered immunoreactivity often observed in some of those diseases. A final comment is in order regarding the significance of lymphokine production in the overall biologic scheme of things. In previous sections we noted that although activation of lymphocytes for lymphokine production by specific antigen is a property of T cells, B cells may be so activated nonspecifically by certain mitogens. Moreover, it has been shown that migration inhibition factor, or substances with similar biologic and physicochemical properties, may be found in certain replicating cultures of nonlymphoid cells. Also, we have recently shown that migration inhibitory activity, as well as certain other lymphokine-like activities such as macrophage and lymphocyte chemotaxis, may appear following the in vitro or in vivo infection of nonlymphoid as well as lymphoid cells by certain viruses. All these results suggest that lymphokine production, rather than "merely" representing an effector mechanism for cell mediated immunity and for certain kinds of helper functions in antibody synthesis, represents a general biologic phenomenon that may play a role in various aspects of host defense. Thus, such mediator substances should be more properly called "cytokines." Lymphokines represent a restricted set of cytokines made by one class of cells (lymphocytes) activated in certain unique ways. In this view the lmyphocyte has acquired some specialized means for triggering such production, not available to other cells.

Animals↗
PubMed1976

The effect of human immune IgG on the in vitro development of Plasmodium falciparum.

Plasmodium falciparum parasites infecting Aotus trivirgatus erythrocytes were cultured in media (Harvard and TC199) augmented with human, foetal calf, or other sera. Conditions were established which supported growth of parasites and allowed cyclical multiplication when fresh erythrocytes (from Aotus or Homo) were added in sub-culture (mean multiplication rate: X3). Immunoglobulin G pools, prepared from plasma collected in endemic malarious areas in Africa and from unexposed Britons, were tested for effects on the in vitro growth (measured by incorporation of tritiated leucine) and multiplication of parasites. Whilst non-immune IgG was without effect, IgG from both East and West Africa inhibited the multiplication of East African (Uganda-Palo Alto strain) parasites.

Animals↗
PubMed1976

Synthesis and properties of 2-S-(N,N-dialkylamino)ethyl)thio-1,3,2-dioxaphosphorinane 2-oxide and of the corresponding quaternary derivatives as potential nontoxic antiglaucoma agents.

A new series of cyclic organophosphorus esters, 2-S-[2'-N,N-dialkylamino)ethyl]thio-1,3,2-dioxaphosphorinane 2-oxide and their quaternary derivatives, was synthesized and studied as potential antiglaucoma agents. Thes compounds inhibit acetylcholinesterase (E.C.3.1.1.7)at a bimoecular rate constant (ki) in the range of 10(3)-10(4) M-1 min-1. Values of the affinity (K) and phosphorylation (k') rate constants for this enzyme indicate that k' is responsible for the relatively low values of ki as compared with similar data for the open-chain analogues, O,O-diethyl phosphorothiolates (10(6) M-1 min-1). The mammalian toxicity of the new compounds in terms of acute LD50 values in mice is 1-3 x 10(3) less than that of phospholine, an open-chain analogue. In an initial clinical trial, one member of the new series (alkyl = C2H5) caused a significant decrease of intraocular pressure in aphakic glaucoma, while phospholine proved to be ineffective.

Animals↗
PubMed1976

125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts.

125I-labeled human epidermal growth factor (hEGF) binds in a specific and saturable manner to human fibroblasts. At 37 degrees C, the cell-bound 125I-hEGF initially may be recovered in a native form by acid extraction; upon subsequent incubation, the cell-bound 125I-hEGF is degraded very rapidly, with the appearance in the medium of 125I-monoiodotyrosine. At 0 degrees C, cell-bound 125I-hEGF is not degraded but slowly dissociates from the cell. The data are consistent with a mechanism in which 125I-hEGF initially is bound to the cell surface and subsequently is internlized before degradation. The degradation is blocked by inhibitors of metabolic energy production (azide, cyanide, dinitrophenol), some protease inhibitors (Tos-Lys-CH2Cl, benzyl guanidobenzoate), a lysosomotropic agent (chloroquine) various local anesthetics (cocaine, lidocaine, procaine), and ammonium chloride. After the binding and degradation of 125I-hEGF the fibroblasts are no longer able to rebind fresh hormone. The binding capacity of these cells is restored by incubation in a serum-containing medium; this restoration is inhibited by cycloheximide or actinomycin D.

Ammonium Chloride↗
PubMed1976

The 94-day cannabis study.

The UCLA cannabis project has provided several interesting observations that contribute to our knowledge about this plant and its constituents. Some of the findings (reduction in intraocular pressure, bronchodilation) may have therapeutic significance in the future. Certain results (testosterone lowering, airway narrowing after heavy use) indicate that side effects are also a possibility. Other data (unchanged immune response, lack of chromosomal alterations) seem to controvert the reports of other investigators. Still other information obtained (hemispheric lateralization, electroencephalographic changes) appears to represent new knowledge about the effects of cannabis on humans.

Adult↗
PubMed1976

In vitro comparison of netilmicin, a semisynthetic derivative of sisomicin, and four other aminoglycoside antibiotics.

One hundred isolates of Pseudomonas and Enterobacteriaceae, of which 85 were chosen because of their resistance to gentamicin or amikacin, were tested for susceptibility to netilmicin (SCH 20569), a new semisynthetic derivative of sisomicin, and to four other aminoglycosides. Tests were performed in Mueller-Hinton agar and, with 43 of these isolates, also in Mueller-Hinton broth. Most isolates of Escherichia coli, Klebsiella, Enterobacter, Citrobacter, and Serratia that were gentamicin resistant proved to be susceptible to netilmicin and amikacin. Tests of representative isolates of this group showed that they owed their resistance to the production of aminoglycoside-adenylylating enzymes. Four isolates of Serratia, detected by their resistance to amikacin, were also highly resistant to netilmicin but were susceptible to gentamicin. These isolates produced aminoglycoside-acetylating enzymes. Gentamicin-resistant Proteus and Providencia were, in general, highly resistant to netilmicin but were susceptible to amikacin. These isolates also produced aminoglycoside-acetylating enzymes. Most gentamicin-resistant strains of Pseudomonas were resistant to netilmicin, either by enzymatic aminoglycoside modification or by other undefined mechanisms. Thus, like amikacin, netilmicin extends the aminoglycoside susceptibility pattern of Enterobacteriaceae to include gentamicin-resistant isolates that produce aminoglycoside-adenylylating enzymes. It is ineffective against strains, some of them susceptible to amikacin, gentamicin, or tobramycin, that produce aminoglycoside-acetylating enzymes.

Amikacin↗
PubMed1976

Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle.

The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK.

Animals↗
PubMed1976

Gallbladder pressure-volume response to gastrointestinal hormones.

The pressure-volume (PV) response of the opossum gallbladder was studied under basal conditions and after the continuous intravenous infusion of gastrin I, secretin, and cholecystokinin (CCK). The hormone effects were examined individually and in combination. The unstimulated gallbladder was capable of accommodating increases in intraluminal volume with only slight changes in intraluminal pressure. Cholecystokinin significantly increased the pressure recorded from the gallbladder. The pressure generated depended on the concentration of CCK and the intraluminal volume. Gastrin I had no independent effect on the PV response of the gallbladder but reduced the stimulatory affect of CCK. Secretin, alone, decreased the PV response of the gallbladder. Secretin also antagonized the stimulatory response to CCK. These findings suggest that the regulation of gallbaldder motor function and pressure generation exclusive of neural input, may depend on the interaction of CCK with gastrin and secretin and the intraluminal volume of the organ at the time of stimulation.

Animals↗
PubMed1976

Intestinal myoelectric activity in response to live Vibrio cholerae and cholera enterotoxin.

The myoelectric response of the rabbit ileum was studied in response to live Vibrio cholerae culture, a whole cell lysate of cholera, and the purified enterotoxin. Each cholera preparation produced a series of highly organized migrating action potential complexes (MAPC). An MAPC was defined as action potential discharge with a duration of 2.5 s or longer, followed by similar activity on at least one other consecutive electrode site. The mean and modal onset time of MAPC activity occurred 4 h after the infection with live Vibrio cholerae culture, the freeze-dried whole cell lysate preparation, or the purified enterotoxin. After the onset of activity this pattern persisted for the duration of the recording period (up to 12 h). The MAPC had a mean propagation velocity of 0.85+/-0.07 cm/s (mean+/-SEM), which remained constant with time. Direct visual observation of the loop revealed that the MAPC's resulted in contractions that propelled intraluminal contents in an aborad direction. The mean fluid output from the 12-cm ileal loops was 6.4+/-1.1 ml/h (mean+/-SEM). Control experiments consisted of recordings from: (a) a ligated ileal loop into which nothing was placed; (b) a ligated ileal loop into which either uninfected culture broth or 0.9% NaCl solution was injected; (c) a ligated ileal loop infused with 0.9% NaCl solution at a rate of 11.2 ml/h, and (d) rapid injection of 1.0, 2.5, 5.0, or 10.0-ml boluses of 0.9% NaCl into the proximal catheter. MAPC activity was not observed in any of the control experiments. These studies indicate that in addition to a secretory component to cholera, there exists a highly organized MAPC that results in contractions that propel intraluminal contents in an aborad direction.

Action Potentials↗
PubMed1976

Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case.

Previous discussions center on early diagnosis, initial treatment, and follow-up therapy for the patient with vitamin D-resistant rickets. Both the medical and dental aspects of treatment for these patients has a long-range effect on the normal developmental patterns. Although treatment is begun at an early age, some rachitic skeletal effects such as minor bowing of the legs and bossing of the skull will invariably be noticed. In patients with controlled rickets the alveolar processes undergo normal development, with apparent normal dental eruption. The poor development and calcification of the alveolus seen in the untreated patient leads to loss of the lamina dura and periodontal ligament of the teeth. Patients with resistant rickets possess a functional dentition, although not without inherent defects. Various degrees of fracture and attrition of enamel can be seen, and hypoplasia of dentin is nearly a universal result. Defects extending to the dentinoenamel junction have been shown in repeated cases. Cementum, because of its close relationship with dentin calcification, also appears abnormal. Pulp tissue may undergo abberations of physiology in resistant rickets, although further work in this respect is needed. With respect to the possible dental pathoses seen in this disease, the dental history of the patient with resistant rickets discussed in this report showed that several of the deciduous teeth, possibly the mandibular left second premolar and right first molar, and definitely the maxillary right second premolar and canine and the mandibular left canine had all undergone pulpal degeneration of apparently unknown causation. In the maxillary right second premolar and the mandibular left canine, enamel fractures were clinically and radiographically apparent. However, the maxillary right canine originally had an acute abscess with no defects other than normal, minimal wear facets. No causative factor for its necrosis could be found. Overt enamel fractures in the maxillary right second premolar and the mandibular left canine may have led to microexposures of the pulp with subsequent bacterial pulpal contamination. Suppuration present in several of the pulps when first entered during endodontic treatment, as well as chronic fistulas in several areas, support the conclusion that contamination by some means does indeed occur.

Abscess↗