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Biomedical subjects

J Wolff

Publications and source records attributed to J Wolff.

At least 199 records · Page 11Linked to original sources
PubMed1982

Lactate dehydrogenase of Xenopus laevis laevis and Xenopus borealis depends on a multiple gene system.

Lactate dehydrogenase isozymes have been reinvestigated in Xenopus laevis laevis and Xenopus borealis. High resolution zymograms of various organs demonstrate that in both species the LDH isozymes are governed basically by a three-gene system: Ldh-a coding for positively charged polypeptide, and Ldh-b and Ldh-c for negatively charged polypeptides (at pH 8.9). These three LDH subunits when assembled in tetramers show differential sensitivity to heat inactivation; the C4 homotetramer is the most labile isozyme. Xenopus is thus similar to Osteichthyes, birds, and mammals that also have a three-gene system for LDH. With respect to tissue specific isozyme expression, Xenopus resembles the more primitive families of bony fish. Superimposed on this three-gene system is a probable gene duplication for both LDH-a and Ldh-b. Heterotetrameric isozymes are formed between the various subunits leading to multibanded zymograms with a total of at least 21 distinct zones of LDH activity. The expression of genes is tissue specific not only for the basic genes, but also for their presumed duplicates. Since both species of Xenopus are ancient tetraploids, duplication of Ldh genes is not surprising.

Animals↗
PubMed1982

Two opposing effects of calmodulin on microtubule assembly depend on the presence of microtubule-associated proteins.

The effect of bovine brain calmodulin on the assembly of pure bovine brain tubulin has been examined in the presence and absence of microtubule-associated proteins (MAPs). In the absence of MAPs, calmodulin enhances the rate and extent of polymerization of pure tubulin, probably by sequestering Ca2+ from tubulin since the effect is mimicked by ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid and parvalbumin. From stoichiometric considerations, all 4 Ca2+ binding sites of calmodulin appear to participate in this effect. In the presence of MAPs, calmodulin confers increased Ca2+ sensitivity on the tubulin polymerization process, enhancing the inhibitory effect of Ca2+ on the rate and extent of assembly. The effect of calmodulin on the assembly of tubulin is dependent on the presence of Ca2+. The data suggest that calmodulin of both low (Ca1-22+.calmodulin) and high (Ca3-42+.calmodulin) Ca2+-induced inhibition of polymerization. Thus, calmodulin has dual and opposing actions on Ca2+ sensitivity of tubulin polymerization depending on the presence or absence of MAPs.

Animals↗
PubMed1982

A freestanding ambulatory surgical unit: a success or failure?

The concept of a freestanding ambulatory surgical center was to provide the patient with a more cost-effective, safe, and convenient service. A study of 5,369 surgical patients treated at the Northeast Louisiana Surgical Center, Inc., in Monroe, Louisiana, was carried out to determine whether these objectives had been met. The finding was that a freestanding ambulatory surgical center was more cost effective than either a hospital ambulatory unit or an in-hospital service. The infection rate was 0.06%, and the hospital transfer rate was 0.04%. The concept of freestanding ambulatory surgical center has fulfilled the expectations of safety, convenience, and cost effectiveness for the patients.

Cost-Benefit Analysis↗
PubMed1982

Thyroid hypofunction after exposure to fallout from a hydrogen bomb explosion.

Thyroid function was evaluated in the Marshallese who were accidentally exposed to fallout-containing radioiodine isotopes in 1954. Measurements of thyrotrophin (TSH, thyroid-stimulating hormone) levels and free thyroxine (T4) index (FT4I) have revealed that, among 86 persons exposed on Rongelap and Ailingnae atolls, 14 have shown evidence of thyroid hypofunction. This was first noted in some individuals about ten years after exposure. Only two of these showed clinical evidence of hypothyroidism. The most marked TSH elevations were noted in nine persons exposed when younger than 6 years, with estimated doses to the thyroid from 390 to 2,100 rad. Most of this group subsequently had surgery for removal of thyroid nodules. The remaining five cases have been noted more recently among 36 surviving adults exposed at an older age who showed no other detectable thyroid abnormalities. This group had received estimated thyroid doses ranging from 135 to 335 rad and showed modest elevation of serum TSH levels (6 to 9 microU/mL) and a slightly subnormal FT4I. No abnormalities were found in persons on Utirik who received substantially less radiation, and hypothyroidism was present in less than 1% of the control, unexposed Marshallese. The high prevalence of a thyroid hypofunction in these persons indicates that this condition, as well as thyroid nodularity, can be a delayed complication of exposure to early fallout from a nuclear explosion. The fact that a significant fraction of the radiation to the thyroid was from short-lived radioiodine isotopes (132I, 133I, 135I), as opposed to 131I, may account for the severity of the thyroid damage.

Adolescent↗
PubMed1982

Interactions of fluoride and guanine nucleotides with thyroid adenylate cyclase.

The activation of bovine thyroid adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by Gpp(NH)p has been studied using steady-state kinetic methods. This activation is complex and may be characterized by two Gpp(NH)p binding sites of different affinities with measured constants: Ka1 = 0.1 micro M and Ka2 = 2.9 micro M. GDP beta S does not completely inhibit the Gpp(NH)p activation: analysis of the data is consistent with a single GDP beta S inhibitory site which is competitive with the weaker Gpp(NH)p site. Guanine nucleotide effects upon F- activation of adenylate cyclase have been studied. When App(NH)p is the substrate, 10 micro M GTP along with 10 mM NaF gives higher activity than NaF alone, while GDP together with NaF inhibits the activity by 50% relative to NaF. These features are not observed when the complex is assayed with ATP in the presence of a nucleotide regenerating system or when analogs Gpp)NH)p or GDP beta S are used along with NaF. These effects were studied in three other membrane systems using App(NH)p as substrate: rat liver, rat ovary and turkey erythrocyte. No consistent pattern of guanine nucleotide effects upon fluoride activation could be observed in the different membrane preparations. Previous experiments showed that the size of soluble thyroid adenylate cyclase changed whether membranes were preincubated with Gpp(NH)p or NaF. This size change roughly corresponded to the molecular weight of the nucleotide regulatory protein. This finding, coupled with the present data, suggests that two guanine nucleotide binding sites may be involved in regulating thyroid cyclase and that these sites may be on different protein chains.

Adenylate Kinase↗
PubMed1982

Adenosine receptor-mediated accumulation of adenosine 3',5'-monophosphate in guinea pig thyroid tissue.

The cAMP content of guinea pig thyroid fragments was increased 2- to 3-fold by adenosine analogs, 5'-N-ethylcarboxamide adenosine (NECA), the most potent, caused half-maximal stimulation of 0.7 microM, whereas N6-phenylisopropyl adenosine was much less potent (half-maximal stimulation at 20 microM). Exogenous adenosine by itself was slightly active, and its activity was increased in the presence of adenosine deaminase or transport inhibitors. Although adenosine analogs are partial agonists compared to TSH or the diterpene cyclase activator forskolin, the fractional rate of cAMP accumulation is greater for NECA than for TSH. The stimulatory effect of NECA was antagonized by theophylline. These effects of adenosine and its analogs on cAMP formation in intact thyroid tissue are characteristic of stimulatory adenosine receptors.

Adenosine↗
PubMed1982

Forskolin stimulation of thyroid adenylate cyclase and cyclic 3',5'-adenosine monophosphate accumulation.

The diterpene forskolin is a potent (100-fold) stimulator of guinea pig thyroid cAMP accumulation with half-maximal activation occurring at 40 microM. Forskolin stimulation is more rapid than that of TSH, attaining a 5-fold increase within 1 min of exposure. The stimulation is also rapidly reversible. The diterpene does not sensitize thyroid cAMP accumulation to TSH, and the concentration yielding half-maximal response is not altered by the presence of low levels of forskolin. At maximally stimulating concentrations, the effects of TSH and forskolin on cAMP accumulation are additive. Forskolin stimulates thyroid adenylate cyclase approximately 10-fold in membranes from several species with half-maximal effects occurring at 3--9 microM through an action on the maximum velocity and not the Km for ATP. The activation of thyroid membranes is readily reversible. Guanyl nucleotides are not required for stimulation by forskolin, and they do not sensitize to forskolin. Moreover, the drug did not sensitize the membrane adenylate cyclase to guanosine 5'-[beta, gamma-imido]triphosphate or to isoproterenol and was equally effective with either Mg++ or Mn++ as the divalent cation. Forskolin stimulation is additive with that of guanyl nucleotides and F-. The site of action of forskolin in the adenylate cyclase complex is uncertain. Data from Bordetella pertussis, testicular, and S-49 lymphoma mutant cyclases suggest that one of the guanyl nucleotide regulatory proteins may be required to promote the forskolin effect. We conclude that forskolin is a useful activator of thyroid adenylate cyclase both in vitro and in intact tissue, which will be useful in elucidating the coupling process of the adenylate cyclase system and in differentiating cAMP-mediated from other forms of activation of the thyroid.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1981

Intrinsic calcium sensitivity of tubulin polymerization. The contributions of temperature, tubulin concentration, and associated proteins.

The calcium concentration required to inhibit tubulin polymerization by 50% (Ca2+ sensitivity) extends from the micromolar to the millimolar range and is a function of a number of factors that include 1) a steep, inverse dependence on tubulin concentration: two-cycle tubulin has lower Ca2+ sensitivity than pure tubulin (prepared by a novel method described under "Appendix"); 2) temperature: Ca2+ sensitivity shows a steep increase below 24 degrees C; 3) microtubule seeds: these decrease sensitivity to Ca2+ inhibition; 4) the presence of 16 S oligomers or microtubule-associated proteins. Ca2+ increases the critical concentration for microtubule protein and decreases the initial rate of polymerization. All tubulin preparations examined contain small amounts of calmodulin. However, the molar ratio of calmodulin to tubulin is less than 0.01, hence this protein is not required for high Ca2+ sensitivity. Nevertheless, calmodulin at high molar ratios can increase the sensitivity of microtubule assembly toward Ca2+. We conclude that tubulin possesses high intrinsic as well as a calmodulin-mediated Ca2+ sensitivity, and propose that high Ca2+ sensitivity may be a property of the nucleation process.

Animals↗
PubMed1981

The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.

One-hundred-eighty-eight children up to 16 years of age were randomized in the second National Wilms' Tumor Study (NWTS) with tumors that were confined to the kidney and that had been totally excised (Group I). Most fared well whether treated for six or for 15 months with both actinomycin D (AMD) and vincristine (VCR). No postoperative radiation therapy (RT) was given. The two-year relapse-free survival (RFS) and two-year survival rates were 88 and 95%, respectively. Two-hundred-sixty-eight randomized patients with more advanced local lesions (Groups II and III) and 57 with distant metastases (Group IV) had postoperative RT and were scheduled for 15 months treatment with either AMD and VCR (Reg. C) or AMD plus VCR plus Adriamycin (Reg. D). The 77% two-year RFS rate for Reg. D was significantly different from the 63% with Reg. C. As in the first NWTS, patients with tumors of unfavorable histology (UH) had a significantly worse prognosis than those with favorable histology (FH), as did those with positive nodes. Survival rates at two years were 54% for UH vs. 90% for FH, and 54% vs. 82% for those with and without lymph node involvement.

Adolescent↗