Showing papers by "Johns Hopkins University School of Medicine published in 1969"
TL;DR: Spermine is synthesized by the preparation from the rat ventral prostate in the presence of S-adenosylmethionine and spermidine, but at a considerably slower rate than sperMidine synthesis from putrescine and S- adenosyl methionines.
381 citations
Journal Article•
TL;DR: It is suggested that the turnover of hepatic ornithine decarboxylase is extremely rapid, as shown in rats treated with puromycin or with cycloheximide after partial hepatectomy.
Abstract: Following partial hepatectomy, there is a dramatic enhancement in the residual liver in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17), an enzyme involved in polyamine synthesis. This increase in enzyme activity is completely prevented by treatment of the animals with puromycin at the time of hepatectomy, or by treatment with cycloheximide at the time of hepatectomy or up to 1 hr after hepatectomy. Actinomycin D administration at the time of operation prevents the subsequent rise in ornithine decarboxylase activity, but is only partially effective when given 30 min post-hepatectomy and ineffective 1 hr after operation. When cycloheximide is administered to unoperated rats or to animals 4 or 24 hr after hepatectomy, ornithine decarboxylase activity declines rapidly, with a half-life of about 11 min. After puromycin treatment, the decline of ornithine decarboxylase activity also shows a half-life of about 11 min. These findings suggest that the turnover of hepatic ornithine decarboxylase is extremely rapid.
358 citations
TL;DR: Inhibition of dopamine uptake may potentiate the synaptic actions of dopamine in the striatum and could explain the antiparkinsonian effects of these drugs.
Abstract: A variety of antiparkinsonian drugs are potent, noncompetitive inhibitors of dopamine uptake into synaptosomes in homogenates of rat corpus striatum. Inhibition of dopamine uptake may potentiate the synaptic actions of dopamine in the striatum and could explain the antiparkinsonian effects of these drugs. This hypothesis accounts for several clinical features of Parkinson's disease and predicts compounds which may be new therapeutic agents.
337 citations
TL;DR: The final (Na+-K+)-stimulated ATPase membrane is relatively free of brush border, mitochondria, nuclear and microsomal contamination and would appear to be plasma membrane, and is discussed in relation to active transport in the intestine.
290 citations
TL;DR: The syndrome has been compared to Fanconi's anemia, thalidomide embryopathy, limb-cardiovascular syndrome, and a syndrome of multiple congenital malformations, from which it can be distinguished.
259 citations
TL;DR: The elasticity of the pulmonary arterial tree appears to be as important as the state of the arterioles and capillaries in determining the energy required for pulsatile pulmonary blood flow.
Abstract: The differential pressure method of Womersley and McDonald was used to measure instantaneous blood flow in the main pulmonary artery in ten human subjects. Three subjects had normal pulmonary arterial pressures and flows, seven had mitral stenosis and pulmonary hypertension. The spectrum of input impedance versus frequency was similar to that previously reported for the dog and rabbit, with the modulus decreasing from relatively high values at zero frequency to a minimum between 2 and 5 cycles/sec. Characteristic impedance and phase velocity were lower in the normal subjects than in those with pulmonary hypertension (averages, 23 dyne sec cm -5 and 1.68 m/sec in the normals; 46 dyne sec cm -5 and 4.77 m/sec in the hypertensives). Hydraulic energy dissipated per unit time by pulsations in the pulmonary bed was usually higher in the hypertensive than in the normal cases, because of the greater stiffness of the pulmonary arteries in the subjects with pulmonary hypertension. The elasticity of the pulmonary arterial tree appears to be as important as the state of the arterioles and capillaries in determining the energy required for pulsatile pulmonary blood flow.
233 citations
Journal Article•
TL;DR: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma that lead to sensitization of the recipient and to graft rejection when appropriate vascularization is induced.
Abstract: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma. By appropriately inducing vascularization of the donor graft, the recipient becomes sensitized to and ultimately rejects the pure epithelial graft. The epithelium is rejected as a moving front of infiltrated and dying donor cells, with the rapidly regenerating recipient epithelium effecting immediate repair of the defect. The entire epithelial rejection process takes place in the absence of persisting stromal edema and cloudiness. Sensitization by, and rejection of, pure corneal stromal allografts were also studied. Rejection is characterized by a diffuse band of leukocytic infiltrate which sweeps across the donor tissue, leaving dead keratocytes in its wake. Endothelial allografts also lead to sensitization of the recipient and to graft rejection, again when appropriate vascularization is induced. Like epithelium, the rejection of corneal endothelium is associated with an advancing front of densely infiltrated and dying cells. In this instance, however, repair of the defect by recipient endothelium is so slow that edema and cloudiness of the overlying stroma develop and persist for long periods of time. Endothelial regeneration in the rabbit is associated with substantial recovery of corneal clarity.
190 citations
TL;DR: A soluble enzyme preparation catalysing the release of adenine from 5'-methylthioadenosine was purified some 30-fold from extracts of the rat ventral prostate, suggesting a phosphorolytic cleavage mechanism.
Abstract: A soluble enzyme preparation catalysing the release of adenine from 5′-methylthioadenosine was purified some 30-fold from extracts of the rat ventral prostate This reaction was completely dependent on addition of inorganic phosphate ions to the assay medium This absolute requirement for phosphate ions suggests a phosphorolytic cleavage mechanism After acid treatment, the other product of the reaction appeared to be 5-methylthioribose The actions of some other well-characterized enzymes of nucleoside metabolism of 5′-methylthioadenosine were also investigated; purified purine nucleoside phosphorylases from calf spleen and human erythrocytes did not attack 5′-methylthioadenosine The role of 5′-methylthioadenosine in mammalian tissues is discussed
176 citations
164 citations
TL;DR: The proposition that the sensitivity of humans to oscillatory mechanical stimuli at different frequencies, and the quality of the sensations evoked by them, are determined in the first instance by the properties of two distinct sets of peripheral afferent fibers is supported.
Abstract: We have studied the response properties of peripheral myelinated fibers ending in the hairy skin of the Rhesus monkey, activated by sinusoidal mechanical stimulation. In parallel experiments we measured thresholds of the sensations evoked in man by identical stimuli, delivered under similar conditions to corresponding areas of the hairy skin. We found that the sense of low frequency vibration (i. e., flutter) depends upon activity in rapidly adapting alpha fibers which end in or about the hair follicles. High frequency vibration is signalled by Pacinian afferents whose terminals lie deep to the skin itself. These two sets of fibers, by reason of their discharge patterns and differential sensitivities in different frequency ranges, are thought to provide the essential first order input for the human sense of vibration evoked by stimulation of the hairy skin. Rapidly adapting cutaneous afferents of the delta size and two classes of slowly adapting alpha fibers are also entrained by mechanical sinusoids, but are thought not to contribute to vibratory sensibility. Our findings support the proposition that the sensitivity of humans to oscillatory mechanical stimuli at different frequencies, and the quality of the sensations evoked by them, are determined in the first instance by the properties of two distinct sets of peripheral afferent fibers.
162 citations
TL;DR: The properties of the high affinity Ca++-binding sites suggest they may be contributed either by hypothetical high energy intermediates generated in electron transport or by a specific divalent cation carrier molecule in the membrane.
TL;DR: Experiments with C5-deficient mice revealed that C5 also plays a definite, but quantitatively less impressive, role in antipneumococcal defense, and its capsular localization was established by the use of monospecific anti-C3 antibody.
Abstract: When encapsulated type 25 pneumococci (Pn25) were opsonized with normal guinea pig serum, they consumed much more C3 than other complement (C) components. Fixation of C3 to the organisms was demonstrated by radio-labeling techniques, and its capsular localization was established by the use of monospecific anti-C3 antibody.
Treatment of the serum with an appropriate dose of a purified cobra venom factor (VF) destroyed C3 and all of the opsonic activity, without appreciably affecting the other C components. Addition of purified C3 completely restored the opsonic activity of the VF-treated serum, indicating a requirement for C3. Since purified C3 alone had no opsonic activity, it was concluded that the C3 molecules had to be cleaved (to C3b) to function as opsonins.
Experiments with C5-deficient mice revealed that C5 also plays a definite, but quantitatively less impressive, role in antipneumococcal defense.
01 Jan 1969
TL;DR: A large number of workers have reported the culture of amphibian cells, but most of the accounts are found in older literature and few of them report success in maintaining monolayer strains through serial subculture.
Abstract: A large number of workers have reported the culture of amphibian cells, but most of the accounts are found in older literature and few of them report success in maintaining monolayer strains through serial subculture. The first permanent amphibian line is that of Wolfe and Quimby (27), derived from bullfrog tongue. This line subsequently proved to be fibroblastic in morphology and subtetraploid in chromosome number. To date, it has passed through hundreds of cell generations in culture. Freed et al. (13, 14) and Seto (26) have also reported extended serial subculture of amphibian cell lines.
TL;DR: It is proposed that spermidine synthesis in the prostate gland may not involve free decarboxylated S-adenosylmethionine as an intermediate, and the role of polyamines in the androgen-dependent functional differentiation of the prostate is considered.
TL;DR: The investigated energized uptake of low levels of Ca2+ in the presence and absence of phosphate by isolated rat liver mitochondria, and the perturbation effected by this activity on ultrastructural and metabolic parameters of mitochondria have been investigated indicate that low levels, are accumulated in an osmotically active form into the water phase of the inner compartment.
Abstract: The energized uptake of low levels of Ca2+ in the presence and absence of phosphate by isolated rat liver mitochondria, and the perturbation effected by this activity on ultrastructural and metabolic parameters of mitochondria have been investigated. In the presence of phosphate, low levels of Ca2+ are taken up by mitochondria and result in various degrees of ultrastructural expansion of the inner mitochondrial compartment. This indicates that low levels of Ca2+ in the presence of phosphate, are accumulated in an osmotically active form into the water phase of the inner compartment. The first clearly observable quantitative increase in the volume of the inner compartment occurs after the accumulation of 100 nmoles Ca2+/mg protein. An accumulation of 150–200 nmoles Ca2+/mg protein, which is equivalent to the osmolar concentration of endogenous K+, is required to effect a doubling of the volume of the inner compartment. This degree of osmotic perturbation occurs as mitochondria transform from a condensed to an orthodox conformation. The osmotically induced orthodox conformation differs from the mechanochemically induced orthodox conformation previously described, in that its development is concomitant with a marked decrease in acceptor control and oxidative phosphorylation efficiency and it fails to transform to a condensed conformation in response to addition of ADP. In the absence of added phosphate, a maximum of 190 nmoles Ca2+/mg protein was found to be taken up by mitochondria (state 6). Ca2+ is apparently bound under state 6 conditions since the uptake does not effect an ultrastructural expansion of the inner compartment. Phosphate added after state 6 Ca2+ binding, however, results in an immediate ultrastructural expansion of the inner compartment. The addition of phosphate to mitochondria in the absence of exogenous Ca2- fails to effect an osmotic ultrastructural transformation. Under state 6 conditions, the binding of between 40 and 190 nmoles Ca2+/mg protein results in the formation of dense matrix inclusions which appear to be composed of tightly packed, concentrically oriented membranes. Under conditions in which the bound Ca2+ is subsequently released, there is a concomitant loss in the density of these matrix inclusions, leaving behind morphologically distinct membrane whorls in the mitochondrial matrix.
TL;DR: A time course study showed that hypophysectomy resulted in a delayed increase and an early decline of ORD activity after partial hepatectomy, and growth hormone treatment produced a greater enhancement, although enzyme levels were still lower than those of control rats.
Abstract: The effect of hypophysectomy and subsequent hormone therapy on ornithine decarboxylase (ORD) activity was examined in regenerating rat liver. Enzyme activity was determined by measuring the liberation of 14CO2 from carboxyl-labeled ornithine. In rats with intact pituitaries, ORD activity 4 hr after hepatectomy was 10 times that of sham-operated controls. Hypophysectomized rats failed to show an increase in ORD activity 4 hr after hepatectomy. A time course study showed that hypophysectomy resulted in a delayed increase and an early decline of ORD activity after partial hepatectomy. After the removal of thyroids, adrenals, ovaries, or testes, the increase in ORD activity 4 hr after hepatectomy was the same as in control animals. Treating hypophysectomized animals with triiodothyronine piior to hepatectomy produced a small but significant increase in enzyme activity. Growth hormone treatment produced a greater enhancement, although enzyme levels were still lower than those of control rats. Combined treatmen...
TL;DR: The ATP-dependent K influx responded linearly to [K]o from 1–20 mM and was independent of whether Na, Li, or choline was the principal cation of seawater and was determined to be about half that at physiological concentrations (2–3 mM).
Abstract: Measurements have been made of K influx in squid giant axons under internal solute control by dialysis. With [ATP](i) = 1 microM, [Na](i) = 0, K influx was 6 +/- 0.6 pmole/cm(2) sec; an increase to [ATP](i) = 4 mM gave an influx of 8 +/- 0.5 pmole/cm(2) sec, while [ATP](i) 4, [Na](i) 80 gave a K influx of 19 +/- 0.7 pmole/cm(2) sec (all measurements at approximately 16 degrees C). Strophanthidin (10 microM) in seawater quantitatively abolished the ATP-dependent increase in K influx. The concentration dependence of ATP-dependent K influx on [ATP](i), [Na](i), and [K](o) was measured; an [ATP](i) of 30 microM gave a K influx about half that at physiological concentrations (2-3 mM). About 7 mM [Na](i) yielded half the K influx found at 80 mM [Na](i). The ATP-dependent K influx responded linearly to [K](o) from 1-20 mM and was independent of whether Na, Li, or choline was the principal cation of seawater. Substances tested as possible energy sources for the K pump were acetyl phosphate, phosphoarginine, PEP, and d-ATP. None was effective except d-ATP and this substance gave 70% of the maximal flux only when phosphoarginine or PEP was also present.
TL;DR: Over the years much of the interest in bacterial endotoxins (lipopolysaccharides) has arisen because of the diversity of physiopathological and immunological effects these products have on the host.
Abstract: Bacterial endotoxins are derived from the outer membrane of the complex cell wall of gram negative bacteria (Mergenhagen et al., 1966; Bladen et al., 1967) and are macromolecular structures containing polysaccharide, phospholipid, and small quantities of protein. Over the years much of the interest in bacterial endotoxins (lipopolysaccharides) has arisen because of the diversity of physiopathological and immunological effects these products have on the host. The biochemist has largely been concerned with the chemical and molecular basis for endotoxin action while the immunobiologist has tried to relate biological activity to the well-established fact that endotoxins are potent antigens and may give rise to some as yet ill-defined forms of hypersensitivity phenomena. Several recent symposia and reviews pertaining to the historical, immunobiological, and chemical interests of bacterial endotoxins have been compiled (Landy and Braun, 1964; Zweifach and Janoff, 1965; Nowotny, 1966; Luderitz et al., 1968; Neter, 1969) and it is out of the scope of this discussion to reiterate what has already been well documented in the literature except where certain of these references have a direct bearing on the subject at hand.
TL;DR: Manometric studies of the pharynx and esophagus in 8 patients with evidence of diabetic neuropathy-gastroenteropathy revealed marked diminution in the amplitude of pharyngeal contractions, in the percentage of swallows followed by progressive peristalsis in the body of the Esophagus and in the effective lower esophageal intrasphincteric pressure.
TL;DR: Triton X-100 and EDTA were used as selective inhibitors of the enzymatic synthesis of mannan and the hypothesis that mannosyl-1-phosphoryl-undecaprenol was an obligatory intermediate in mannan biosynthesis was confirmed.
TL;DR: The present studies deal with the role of the direct antiphagocytic effect of influenza virus in the enhanced susceptibility to bacterial infection that is associated with influenza.
Abstract: Influenza complicated by bacterial pneumonia is probably the best known example of a viral infection that increases the susceptibility of the host to bacterial disease, an example for which there is both clinical [1] and experimental documentation [2-5]. Two mechanisms are recognized as important in the heightened susceptibility. First, viral lesions of the respiratory epithelium [1] may impair clearance of bacteria by the mucociliary apparatus and facilitate direct invasion by the bacteria; results of experiments in mice, however, led Harford and Hamlin [6] to question the nature and the significance of lesions of the bronchial epithelium. Second, edema of the lung may develop. Edema may promote bacterial multiplication and indirectly impair phagocytosis by diluting the exudate that forms as an antibacterial defense [2, 3, 7]. In vitro studies with guinea pig polymorphonuclear leukocytes (PMN) [8-10] suggest that a third factor may be important, namely, a direct antiphagocytic action of the virus on the leukocytes. The present studies deal with the role of the direct antiphagocytic effect of influenza virus in the enhanced susceptibility to bacterial infection that is associated with influenza. In addition, earlier investigations of PMN interaction with virus [11-14] and of the direct antiphagocytic action of influenza virus on PMN [8-10] have been extended to other types of leukocytes and to cells from other species.
TL;DR: Pretreatment of rabbits with cycloheximide (20 mg per kg, iv), a potent inhibitor of protein synthesis, prevented cholera exotoxininduced fluid production by in vivo jejunal loops and one interpretation of these data is that choleroexotoxin induces synthesis of a protein mediator of fluid secretion and that this secretion originates in the crypts of Lieberkuhn.
TL;DR: The carrier lipid involved in the enzymatic synthesis of mannosyl-1-phosphoryl-undecaprenol was isolated from the crude lipids of Micrococcus lysodeikticus and identified as undecapreyl phosphate.
TL;DR: Treatment groups were comparable when analyzed for the number of patients with fever at onset and the proportion shown to be taking the antibiotic by blood assay, but the groups with H. influenzae otitis treated with either penicillin plus sulfonamide or ampicillin had a better therapeutic response than those treated withPenicillin V alone.
Abstract: Three hundred and six children less than 3 years of age with acute otitis media were randomly distributed among three oral treatment regimens: penicillin V, penicillin V plus sulfonamide, and ampicillin. Treatment groups were comparable when analyzed for the number of patients with fever at onset and the proportion shown to be taking the antibiotic by blood assay. Response was determined in a double blind manner and correlated with the organism isolated from the middle ear aspirate. Results both for pneumococcal otitis and for all otitis regardless of culture were not significantly different with the three regimens. However, the groups with H. influenzae otitis treated with either penicillin plus sulfonamide or ampicillin had a better therapeutic response than those treated with penicillin V alone. Patients receiving ampicillin generally achieved a bacteriostatic serum level for strains of H. influenzae isolated by tympanocentesis while patients receiving penicillin V generally did not achieve such a level.
TL;DR: In vitro protein synthesis directed by bacteriophage MS2 RNA is inhibited by prior incubation of the RNA with MS2 coat protein, and coat protein inhibition results from the binding of a small number of protein molecules to the phage RNA at one or more sites outside the coat protein gene and prevents the translation of the other phage genes.
TL;DR: Amilorides hydrochloride labeled with C14 was given to 5 volunteers and there was no evidence of metabolic transformation of amiloride.
Abstract: Amiloride hydrochloride labeled with C14 was given to 5 volunteers. Serum level peaked at 3 hours, and the half‐life was 6 hours. There was no evidence of metabolic transformation of amiloride. Approximately half the oral dose was recovered in the urine. Amiloride is cleared by tubular transport and should be used with caution in patients with renal insufficiency.
Journal Article•
TL;DR: Evidence is presented that the epithelium on a donor corneal allograft is neither sloughed off rapidly in the immediate postoperative period, nor is it even slowly replaced by recipient epithelia in the technically successful corneals transplant.
Abstract: Evidence is presented that the epithelium on a donor corneal allograft is neither sloughed off rapidly in the immediate postoperative period, nor is it even slowly replaced by recipient epithelium in the technically successful corneal transplant. Specific immunologic rejection of the surviving epithelium of a graft may take place long after transplantation, and is characterized by a linear defect consisting of dying epithelial cells and inflammatory cells, stainable by topical methylene blue or fluorescein, which defect migrates slowly across the entire surface of the graft until all donor epithelium has been destroyed.