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Biomedical subjects

J B Green

Publications and source records attributed to J B Green.

At least 55 records · Page 3Linked to original sources

Liver vitamin A levels in rats are predicted by a modified isotope dilution technique.

We tested the hypothesis that the fraction of an injected dose (FDp) of [3H]retinol remaining in plasma could be used to predict liver vitamin A mass. Rats (n = 36) with liver vitamin A ranging from 1.4 to 23,000 nmol received an intravenous dose of [3H]retinol-labeled plasma. Plasma samples obtained at 4, 4.4, 5, 5.4, 6, 7 and 8 d were analyzed for radioactivity; liver vitamin A levels were determined at 8 d. Using a regression equation developed previously [liver vitamin A (nmol) = 7493.exp(-148.FDp)], there was a log linear relationship between FDp and liver vitamin A mass from 1.4 to 5200 nmol retinol; the equation did not predict levels > or = 7500 nmol. By expanding the regression equation [liver vitamin A (nmol) = 88,928.exp(-1347.FDp) + 5606.exp(-120.FDp)] and using the FDp at 4.4 d, liver vitamin A levels ranging from < 4 to 23,000 nmol were well predicted. Satisfactory equations were also developed for data obtained at 4, 5 and 5.4 d. We conclude that this modified isotope dilution technique is a sensitive and reliable method for assessing vitamin A status in rats over a wide range of vitamin A nutriture. It is likely that this method could be modified for use in humans.

Animals↗

Angiotropic lymphoma manifested by fever and painful swollen legs.

In summary, angiotropic lymphoma is generally of B-cell origin and can be manifested by isolated cutaneous lesions. More commonly, however, the disease involves the CNS. Angiotropic lymphoma should be included in the differential diagnosis of patients with clinical features of panniculitis or diffuse multisystem vasculitis.

Edema↗

Vitamin A metabolism in rat liver: a kinetic model.

Vitamin A metabolism in the liver involves both hepatocytes and the nonparenchymal perisinusoidal stellate cells. To describe and quantitate the dynamic relationships between retinol in these cells and in plasma, we administered either chylomicrons labeled with [3H]retinyl esters or plasma containing [3H]retinol-retinol-binding protein-transthyretin to rats. Radioactivity and retinol masses were measured in plasma, liver, and isolated hepatocytes for 15 days; data were analyzed by model-based compartmental analysis. The resulting model predicts that: 1) approximately 20% of the total plasma turnover of retinol goes to the liver (vs. nonhepatic tissues) and approximately 20% of plasma retinol input is from liver (vs. nonhepatic tissues), 2) about one-half of the retinol recycling from plasma to liver is taken up by hepatocytes and about one-half by nonparenchymal cells, 3) retinyl esters in both cell types are derived preferentially from newly taken up retinol rather than from the main intracellular retinol pools, and 4) at least one-half of the retinol secreted by hepatocytes of rats consuming low levels of vitamin A is directly transferred to nonparenchymal cells. In addition, the data are compatible with the hypothesis that retinol-binding protein is the vehicle for transfer of retinol from hepatocytes to nonparenchymal stellate cells and between plasma and liver cells.

Animals↗

Endoscopic resection of primary rectal teratoma.

A 76-year-old female was noted to have a rectal mass on evaluation for postmenopausal bleeding. There was no history of abdominal pain, constipation, or rectal bleeding. Flexible sigmoidoscopy revealed a 3-cm pedunculated rectal mass at 10 cm. Hair fibers were visible through the smooth glistening surface. At colonoscopy, the polyp was removed by snare polypectomy. Histology showed epidermal, mesodermal, and endodermal components diagnostic of benign cystic teratoma. Subsequent total abdominal hysterectomy and bilateral salpingo-oophorectomy revealed endometrial carcinoma and postmenopausal ovaries. Primary rectal teratoma is a very rare rectal mass that may present endoscopically. Since 1865, only 33 cases have been reported in the literature. Endoscopic photographs, histology, and a review of the literature are presented.

Aged↗

Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.

The potent mesoderm-inducing factors activin and FGF are present as maternally synthesized proteins in embryos of X. laevis. We show that activin can act on explanted blastomeres to induce at least five different cell states ranging from posterolateral mesoderm to dorsoanterior organizer mesoderm. Each state is induced in a narrow dose range bounded by sharp thresholds. By contrast, FGF induces only posterolateral markers and does so over relatively broad dose ranges. FGF can modulate the actions of activin, potentiating them and broadening the threshold-bounded dose windows. Our results indicate that orthogonal gradients of activin and FGF would be sufficient to specify the main elements of the body plan.

Activins↗

The middle latency auditory evoked potential may be abnormal in dementia.

The P1 potential (50 msec) of the middle latency auditory evoked potential was lacking in 12 of 31 (39%) patients with probable Alzheimer's disease and seven of 12 (58%) demented patients with Parkinson's disease. Component P1 was not present in one normal control subject and one nondemented Parkinson's disease patient. Clinical and experimental evidence suggests that abnormalities of P1 in dementia may be due to cholinergic dysfunction.

Adult↗

Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction.

The Brachyury (T) gene is required for mesoderm formation in the mouse. In this paper we describe the cloning and expression of a Xenopus homolog of Brachyury, Xbra. As with Brachyury in the mouse, Xbra is expressed in presumptive mesodermal cells around the blastopore, and then in the notochord. We show that expression of Xbra occurs as a result of mesoderm induction in Xenopus, both in response to the natural signal and in response to the mesoderm-inducing factors activin A and basic FGF. Expression of Xbra in response to these factors is rapid, and will occur in dispersed cells and in the presence of a protein synthesis inhibitor, indicating that this is an "immediate-early" response to mesoderm induction.

Activins↗

A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer.

A total of 211 patients with epithelial ovarian cancer (168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33 different Southwest Oncology Group institutions had their tumors sampled and specimens shipped to two central laboratories for drug-sensitivity testing in a human tumor cloning assay. The 168 patients with a prior history of chemotherapy failure (median of four prior chemotherapeutic agents) were treated with the most effective agent(s) found in the cloning assay (23 patients), and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent(s) were treated with a clinician's choice of agent(s) (101 patients). The remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death. The complete and partial response rate in patients treated according to assay results was 28% versus 11% for the patients treated according to clinician's choice (P = 0.03). There was no statistically significant difference in survival between the two options (6.25 versus 7 months, respectively). The 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy, and their clinical response was compared with their in vitro sensitivity to the same agents. Overall there was a 100% true-positive rate and 100% true-negative rate for the seven evaluable patients. From these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy-refractory ovarian cancer. The study is weakened, however, by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients (because of early death or a rapid decline in performance status). The assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy. Finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting.

Antineoplastic Combined Chemotherapy Protocols↗

Esorubicin in advanced endometrial cancer: an ineffective and potentially toxic therapy. A Southwest Oncology Group study.

The Southwest Oncology Group conducted a phase II study of esorubicin treatment in patients with advanced endometrial cancer who had received no prior chemotherapy. Twenty of 31 patients were fully evaluable for response and toxicity. There were no clinical responses to treatment and 60% (12/20) of the patients developed severe or life threatening leukopenia on therapy. One evaluable patient was removed from study after a cumulative dose of 150 mg/M2 due to a reduction in left ventricular ejection fraction on MUGA scan and another developed congestive heart failure several months after discontinuation of treatment. Esorubicin has significant toxicity and limited clinical activity in patients with advanced endometrial cancer.

Antibiotics, Antineoplastic↗

Growth factors as morphogens: do gradients and thresholds establish body plan?

Theories of morphogenesis have centred around gradients of morphogens interpreted by cells according to preset concentration thresholds. Growth factor proteins have been candidates for such morphogens, and experiments in the frog Xenopus, among other organisms, now show that embryonic cells are capable of interpreting growth factor concentrations according to the models. This opens up questions of whether such mechanisms are sufficient, and-if there are growth factor gradients-which factors are actually used and how.

Animals↗

Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate.

The protein XTC-MIF, a Xenopus homologue of activin A and a potent mesoderm-inducing factor, can induce responding animal pole explants to form several different cell types in a dose-dependent manner, higher doses eliciting more dorso-anterior tissues. This graded response, characteristic of classically postulated morphogens, may underlie pattern formation, but the response of intact animal caps to XTC-MIF provides only a crude indication of trends. Here we report the effects of XTC-MIF on dispersed blastomeres rather than intact animal caps. Under these conditions, responding cells distinguish sharply between doses of pure XTC-MIF differing by less than 1.5-fold. Two different response thresholds have been found, defining three cell states. This suggests that XTC-MIF has an instructive effect. Notochord and muscle are both induced in the same narrow dose-range. Mixing treated with untreated cells does not seem to shift the dose thresholds, showing that at least some cells can stably record the received dose of inducing factor.

Actins↗