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J Patel

Publications and source records attributed to J Patel.

At least 253 records · Page 14Linked to original sources
PubMed1982

Characterization of adenosine receptors in brain using N6 cyclohexyl [3H]adenosine.

The presence of distinct binding sites for adenosine in both the CNS and PNS has been proposed in numerous studies. The recent availability of stable adenosine analogues such as cyclohexyladenosine, 2-chloroadenosine and diethylphenylxanthine has made the characterization of such a receptor feasible. In the present report the binding of N6 cyclohexyl [3H]adenosine ([3H]CHA) to rat brain synaptosomal membranes is characterized. [3H]CHA binding is saturable and exhibits a biphasic kinetic saturation profile characteristic of 2 binding sites. The high affinity site has a Kd of 0.7 nM and the low affinity site 2.4 nM. The respective Bmax values are 230 and 120 fmol/mg protein in fat forebrain. The highest density of binding sites is found in the hippocampus and subcellular distribution studies indicate that the [3H]CHA site is predominantly synaptosomal. [3H]CHA binding is highly dependent in the presence of adenosine deaminase since only 30% of the binding capacity is observed in synaptosomal membranes not treated with this enzyme. Of the many cations and anions tested only copper and zinc have effects on [3H]CHA binding. Both metals are potent inhibitors of binding with copper having an IC50 of 30 microM and zinc 150 microM. Sulfhydryl reducing and alkylating agents also inhibit binding indicating that the binding site is a sulfhydryl-dependent protein.

Adenosine↗
PubMed1982

Benzodiazepines are weak inhibitors of [3H]nitrobenzylthioinosine binding to adenosine uptake sites in brain.

Saturable, specific, high affinity binding of the potent adenosine uptake inhibitor [3H]nitrobenzylthioinosine ([3H]NBI) to brain membranes has been demonstrated. In an effort to test the hypothesis that benzodiazepine action may be due to the inhibition of adenosine uptake, the inhibition of [3H]NBI binding by diazepam, clonazepam and chlordiazepoxide was tested. The benzodiazepines are very weak inhibitors of [#H]NBI binding, having IC50 values several orders of magnitude above their therapeutic levels.

Adenosine↗
PubMed1982

[3H]nitrobenzylthioinosine binding as a probe for the study of adenosine uptake sites in brain.

The binding of the potent adenosine uptake inhibitor [3H]nitrobenzylthioinosine ([3H]NBI) to brain membrane fractions was investigated. Reversible, saturable, specific, high-affinity binding was demonstrated in both rat and human brain. The KD in both was 0.15 nM with Bmax values of 140-200 fmol/mg protein. Linear Scatchard plots were routinely obtained, indicating a homogeneous population of binding sites in brain. The highest density of binding sites was found in the caudate and hypothalamus in both species. The binding site was heat labile and trypsin sensitive. Binding was also decreased by incubation of the membranes in 0.05% Triton X-100 and by treatment with dithiothreitol and iodoacetamide. Of the numerous salt and metal ions tested, only copper and zinc had significant effects on [3H]NBI binding. The inhibitory potencies of copper and zinc were IC50 = 160 microM and 6 mM, respectively. Subcellular distribution studies revealed a high percentage of the [3H]NBI binding sites on synaptosomes, indicating that these sites were present in the synaptic region. A study of the tissue distribution of the [3H]NBI sites revealed very high densities of binding in erythrocyte, lung, and testis, with much lower binding densities in brain, kidney, liver, muscle, and heart. The binding affinity in the former group was approximately 1.5 nM, whereas that in the latter group was 0.15 nM, suggesting two types of binding sites. The pharmacologic profile of [3H]NBI binding was consistent with its function as the adenosine transport site, distinct from the adenosine receptor, since thiopurines were very potent inhibitors of binding whereas adenosine receptor ligands, such as cyclohexyladenosine and 2-chloroadenosine, were three to four orders of magnitude less potent. [3H]NBI binding in brain should provide a useful probe for the study of adenosine transport in the brain.

Adenosine↗
PubMed1982

Ontogeny of adenosine binding sites in rat forebrain and cerebellum.

The metabolically stable adenosine analogue N6-cyclohexyl [3H]adenosine ([3H]CHA) was used to label adenosine receptors in rat forebrain and cerebellum during development. [3H]CHA binding develops rather slowly, with adult binding levels obtained at 24 days in cerebellum and later in the forebrain. Ontogenic profiles in both areas are consistent with the onset of neuronal differentiation. High and low affinity sites appear to develop in parallel, since Scatchard analysis in forebrain tissue obtained from 5-day-old animals revealed both binding sites.

Adenosine↗
PubMed1982

Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial.

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement. Patients who responded were significantly older (p = 0.05) than nonresponders. Dose escalation in eight patients did not result in any clear evidence of additional responses. Major toxicities were fatigue, anorexia with weight loss, and reversible leukopenia (less than 3.5 x 10(9) leukocytes/L in 16 patients). Natural killer cell and antibody-dependent cell-mediated cytotoxicity were significantly (p less than 0.05) enhanced 48 hours after interferon administration began but subsequently declined despite continued therapy. Serum beta 2-microglobulin concentration increased on day 15 (p less than 0.05) and remained significantly elevated on day 22 (p less than 0.005). Peak interferon titers (mean, 62 U) occurred 6 hours after interferon was started, varied widely between patients, and were higher and more persistent with dose escalation. Once an optimal dose is defined, prospectively randomized trials will define what role interferons may have in systemic therapy of breast carcinoma.

Adult↗
PubMed1982

Characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864.

The binding of [3H]Ro 5-4864 to the peripheral-type benzodiazepine binding site in brain is characterized. The binding is saturable, high-affinity (KD = 1.6 nM), and reversible. The comparison of [3H]Ro 5-4864 and [3H]diazepam binding sites reveals major differences which include the following. There are about one-fourth as many peripheral-type binding sites than central sites in brain. Peripheral sites are present in many extranervous tissues and have a brain regional distribution distinct from that of the central-type receptor. The [3H]Ro 5-4864 binding site also is apparently highly localized in the nuclear membrane in contrast to the central-type receptor, which is synaptosomal. gamma-Aminobutyric acid has no effect on [3H]Ro 5-8464 binding, again in contrast to its marked effect on [3H]diazepam binding. Various putative benzodiazepine receptor ligands, such as purines, beta-carbolines, and kynurenamines, are also inactive as inhibitors of [3H]Ro 5-4864 binding. Blocking the benzodiazepine receptor by photoaffinity labeling decreases [3H]diazepam binding by more than 80% and has no effect on [3H]Ro 5-4864 binding. These results indicate that the peripheral-type benzodiazepine binding site in brain is a separate entity whose physiological function is probably distinct from that of the central-type benzodiazepine receptor.

Affinity Labels↗
PubMed1982

Effect of estrogen and progesterone on cellular replication of human breast tumors.

A total of 54 infiltrating carcinomas of the breast were studied for estrogen receptor concentration in the tumor cytosol and thymidine-labeling indexes. The results showed that there was no significant difference in the level of thymidine-labeling index between 22 primary and 32 metastatic breast cancers. No significant association between the levels of thymidine-labeling index and the presence or absence of estrogen receptors was observed. The effect of "physiological" doses of estrogen and progesterone on cell proliferative activity was studied by the level of thymidine-labeling indexes in the tumor cells in 10 patients with multiple skin and s.c. metastases. Tumor biopsies were performed for labeling indexes both before and after hormonal treatment. The results showed that physiological doses of estrogen and progesterone induced a significant rise in thymidine-labeling index within 3 days after hormonal treatment in seven of the 10 tumors. Of the seven tumors that showed a rise in thymidine-labeling index, three were estrogen receptor positive and four were estrogen receptor negative. Of the three nonresponsive tumors, one was estrogen receptor positive and two were estrogen receptor negative. The study suggests that estrogen and progesterone can induce cell replication in both estrogen receptor-positive and -negative tumors.

Adult↗
PubMed1982

Protection against pneumococcal sepsis in splenectomized rats by implantation of splenic tissue into an omental pouch.

Clinical and laboratory studies have documented high susceptibility to pneumococcal infection in asplenic humans and animals. Surgeons have stressed the need to preserve the spleen when possible to maintain host resistance. It has been suggested that autotransplantation of splenic tissue might be a method of providing host resistance when total splenectomy is necessary. However, previous studies of rats have failed to demonstrate any protective effect of autotransplanted spleen. This study evaluates the effect of splenic autotransplantation into the omental pouch on pneumococcal infections in rats. Healthy, young Sprague-Dawley rats were divided into three groups of 40 each. Group I served as anesthetized sham-operated controls. Group II had a splenectomy. Group III had a splenectomy with autotransplantation of two slices of spleen 3 mm thick into surgically created omental pouches. Sixteen weeks after surgery, all animals were inoculated with Streptococcus pneumoniae type 25 in a dose of 2 X 10(7) (LD50 for splenectomized rats). Fourteen days after inoculation, all group III survivors were killed and the transplants were removed for examination. Group I had 100% survival rate following bacterial inoculation. There was a significant difference in survival rate between group II (56%) and group III (89%) (P less than 0.001). Pathologic examination of group III demonstrated hyperplastic regeneration of splenic tissue within the omental pouch. Rats bearing reimplanted splenic tissue in an omental pouch were protected against pneumococcal peritonitis.

Animals↗
PubMed1981

Axillary lymph node metastasis from an occult breast cancer.

Twenty-nine cases were reviewed in which carcinoma manifested first as the enlargement of an axillary node from an occult breast carcinoma. A small hidden breast cancer was identified in 16 patients. In the remaining 13, the breast tumor was never discovered. Regardless of whether the primary tumors were discovered, the metastasis-free survival rates were comparable to those of patients with breast carcinoma with axillary nodal metastasis. The authors recommend that carcinoma found in an axillary node should be treated as a breast cancer, even in the absence of the breast tumor. Extensive investigative procedures in an attempt to uncover an extramammary primary site were largely unproductive and should either be omitted or performed selectively. Mammography, if positive or suspicious, can lead to the primary tumor in 75% of the patients, but, when negative, it does not necessarily exclude the breast as the source of the carcinoma. A carcinoma of the breast was found by pathologic examination in 44% of the patients with negative mammograms.

Adenocarcinoma↗
PubMed1981

The binding of [3H]adenosine to synaptosomal and other preparations from the mammalian brain.

1. A high-affinity adenosine-binding site with Kd(adenosine) 0.5-1.3 microM was demonstrated in particulate and synaptosomal fractions isolated from the cerebral cortex of guinea pig, rat and ox. 2. Binding of [3H]adenosine to this site was inhibited by theophylline and by 2-chloroadenosine, but not by four other adenosine analogues. 3. Endogenous adenosine, found to be present in some preparations at approx. 1 pmol/mg of protein, diminished the binding capacity of the preparations for [3H]adenosine. 4. Addition of the adenosine deaminase inhibitor erythro-9-[1-(1-hydroxyethyl)heptyl]-adenine revealed the presence of a second lower affinity binding site with Kd (adenosine) 5-9 microM and a higher maximal adenosine-binding capacity. The inhibitor partially blocked binding to the high-affinity site in preparations from which adenosine deaminase had been removed by washing. 5. To preparations of particulate fractions maintained under iso-osmotic conditions, adenosine attachment was non-saturable and temperature-dependent, indicating the existence of an active uptake process. 6. The location and binding constant of the high-affinity adenosine-binding site suggest that it corresponds to the receptor site for adenosine-activated adenylate cyclase.

Adenosine↗