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J Hamilton

Publications and source records attributed to J Hamilton.

At least 109 records · Page 6Linked to original sources

Rotational resonance NMR determination of intra- and intermolecular distance constraints in dipalmitoylphosphatidylcholine bilayers.

Rotational resonance (RR) NMR methods are explored for determining intramolecular and intermolecular distances between 13C-labeled sites in membrane bilayers. Specific 13C labels have been incorporated into dipalmitoylphosphatidylcholine (DPPC) and a hydrophobic peptide corresponding to the transmembrane domain of human glycophorin A. The exchange of magnetization between these labels in the RR NMR experiment can be related to their internuclear separation. Intramolecular magnetization exchange rates have been measured between 13C labels incorporated at the 1-position of the sn-1 acyl chain (1-[1-13C]) and the 2-position of the sn-2 acyl chain (2-[2-13C]) of DPPC. These positions are 5.3-5.5 A apart in the crystal structure of dimyristoylphosphatidylcholine (DMPC), but are estimated to be 4.5-5.0 A apart in DPPC below the subphase transition temperature. These results are consistent with a smaller axial displacement between the sn-1 and sn-2 acyl chains than the approximately 3.6-A displacement observed in the DMPC crystal structure. Intermolecular magnetization transfer rates have been measured between 1,2-[2-13C]DPPC and 2-[1,13C]DPPC and between 1,2-[1-13C]DPPC and 2-[2-13C]DPPC. In addition, intermolecular magnetization exchange rates have been measured between 1,2-[2-13C]DPPC and the 13C-OH position of Y93 in the glycophorin transmembrane domain. These intermolecular distance measurements demonstrate that the relative orientation and location of membrane lipids and peptides can be established using RR NMR methods.

1,2-Dipalmitoylphosphatidylcholine↗

HPLC-purified bovine satietin suppresses food intake and weight without causing conditioned taste aversion.

Satietin (SAT) is a putative satiety agent found in a variety of species including man and the rat. In the present study, satietin was extracted from bovine plasma (b-SAT) and further high-pressure liquid chromatography (HPLC)-purified. Rats were given chronic third ventricle cannulas and patency was verified. In experiment 1, rats were divided into three groups and ICV infused with artificial cerebrospinal fluid (a-CSF) or b-SAT: group 1, a-CSF (n = 11); group 2, 20 micrograms/rat, b-SAT (n = 11); and group 3, 40 micrograms/rat, b-SAT (n = 9). Infusions were repeated thrice three days apart. Compared to a-CSF, the high b-SAT dose suppressed food intake for 24-h after each successive infusion. The low dose significantly decreased food intake only after the first infusion. Water intake was suppressed only after the first injection of the high dose. Body weight was decreased after the first and second infusions of both doses and following the third infusion of the high dose. In experiment 2, rats were trained to drink fluid for 1 h/day while food was ad lib. On day 1, both groups received no infusions and were given tap water. On day 2, the groups were ICV infused with a-CSF, but group 1 (n = 12) was given banana-flavored fluid (BFF) and group 2 (n = 12) almond-flavored fluid (AFF). On day 3, group 1 was again a-CSF-infused but given AFF, whereas group 2 received 40 micrograms/rat b-SAT and was given BFF.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Parathyroid hormone (PTH) secretion: stimulation of PTH secretion by a peptide derived from the adenosine diphosphate-ribosylation factor.

Using preparations of dispersed bovine parathyroid cells, we have investigated the effect of a 16-residue synthetic peptide, ARF-16, which corresponds to the N-terminus of the ADP-ribosylation factor, on the secretion of PTH. We find it to be a very effective secretagogue for PTH secretion, acting in a dose- and time-dependent manner. At concentrations in the range of 15-25 microM, the ARF peptide stimulated PTH secretion to a greater degree than low extracellular calcium, and at 25 microM was more effective than isoproterenol. The stimulatory effect of ARF was not dependent on the extracellular calcium concentration over the range of 0.5-3 mM. Upon testing other synthetic peptides of similar size we found no effect on PTH secretion, indicating that the ARF-16 effect is specific. In an attempt to define the structural elements of ARF that are required for activity, we tested several analogs of ARF with amino acids deleted from the N- and C-terminus. Deletion of the 2 N-terminal residues yielded a peptide with substantially reduced activity. Further deletions from the N-terminus yielded an inactive peptide. Similarly, a peptide with deletions of 3 residues from the C-terminus was inactive. Thus, the activity of ARF-16 requires both the N- and C-terminal sequence, suggesting that the 16-residue peptide is the minimal sequence required for full activity. Measurements of cAMP concentrations indicate that the stimulatory effect is not mediated via this second messenger. The ARF peptide does not alter intracellular calcium, suggesting that its effect is not mediated by calcium. Although cells incubated with ARF are vigorously stimulated to secrete PTH, this effect is reversible, as demonstrated by washing cells free of ARF, whereupon PTH secretion returns to basal levels. These results indicate that the peptide is not entering the cells, but is effecting secretion through a low affinity interaction at the cell surface. Other experiments, in which the capacity for ARF stimulation was abolished after a brief exposure of the cells to trypsin, support this conclusion. Characteristics of the ARF stimulatory effect, such as dose dependency and reversibility, lead us to conclude that the peptide is probably acting on the regulated secretory pathway. As the effect is not dependent on extracellular calcium levels and is not mediated via cAMP, we believe that this peptide will be a useful additional tool for future studies of the mechanisms of PTH secretion.

ADP-Ribosylation Factors↗

Abuse of children and older adults: uncanny parallels.

The violence around us seems to be growing. Daily we read or hear about children such as the 22-month-old girl who was found abandoned in a Chicago alley or a malnourished older adult living in squalor, while his or her adult child spends the parent's money. Can something be done?

Aged↗

Time brings change.

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History, 20th Century↗

Recurrent respiratory papillomatosis--the Manchester experience, 1974-1992.

A series of 59 patients of all ages with recurrent respiratory papillomatosis (RRP) treated over an 18-year period is presented. A number of these patients were initially diagnosed in childhood but required treatment throughout adult life. The frequency of laser treatment was not related to either disease duration or age at onset. In 28 patients, the HPV type was identified, showing that HPV type 11 was more common in children and ran a more protracted clinical course. The requirement for tracheostomy in this series was small, whereas the incidence of malignant change in adult patients was significant.

Adolescent↗

Pentoxifylline therapy for chronic claudication: are patients dependent on therapy?

BACKGROUND: The purpose of this study was to evaluate the efficacy of long-term pentoxifylline therapy. METHODS: Fifty consecutive patients on long-term pentoxifylline therapy entered a weaning program. The standard dose of 400 mg three times a day was reduced to 400 mg twice a day for 1 month, 400 mg daily for an additional month, and then withdrawn completely for 3 months. Subjective evaluation of each patient's symptoms and objective measurements (treadmill testing for initial claudication distance, maximum walking distance, and ankle/brachial indexes) were evaluated during treatment withdrawal. RESULTS: Twenty-seven patients tolerated withdrawal of therapy without symptomatic deterioration. Seven of nine patients who did not tolerate weaning had deterioration of treadmill ICD/MWD parameters; there was a significant absolute decrease (p = 0.016) in MWD from 430 +/- 78 to 221 +/- 23 feet. Patients with an initial low MWD were less likely to tolerate weaning. Sixty percent of the patients with successful weaning had clinically asymptomatic deterioration of treadmill ICD/MWD parameters. CONCLUSIONS: A substantial number of patients who have been on long-term successful pentoxifylline therapy for claudication can be weaned from the drug. Asymptomatic deterioration of treadmill test parameters is not an indication for resuming therapy.

Aged↗

Parathyroid hormone-like peptide and parathyroid hormone are secreted from bovine parathyroid via different pathways.

Parathyroid hormone-like peptide is a recently discovered protein which is thought to be responsible for the hypercalcemia of malignancy. Through the use of radioimmunoassay, Northern analysis and Western blot techniques this protein has been demonstrated to occur in a variety of tumor and normal cells. Its role in normal physiology is not established nor is there knowledge regarding its synthesis, secretion, and storage. We have investigated characteristics of the secretion of parathyroid hormone-like peptide in bovine parathyroid gland slices and cells to learn whether or not this protein is secreted in a manner similar to that of parathyroid hormone. We have used radioimmunoassays specific for PTH and PTH-rP to measure the secretion of each protein and have found that, unlike PTH, PTH-rP secretion was not influenced by the medium calcium concentration. Similarly, PTH-rP secretion was not influenced by other known PTH secretagogues such as c-AMP or isoproterenol. An examination of the subcellular distribution of PTH-rP revealed that 75-90% of it occurs in the soluble fraction of cell lysates. Analysis of isolated secretory granules demonstrated the presence of PTH while PTH-rP was undetectable in these organelles. We conclude that PTH-rP is not secreted from parathyroid cells via the regulated pathway utilizing PTH secretory granules.

Animals↗

Altered alpha 1-adrenoceptor binding in intact and adrenalectomized obese Zucker rats (fa/fa).

While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean (Fa/Fa) and obese (fa/fa) male Zucker rats were assayed for alpha 1-([3H]prazosin; [3H]PRZ) and alpha 2-adrenoceptor ([3H]paraminoclonidine; [3H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [3H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding (Bmax) in obese rats was associated with decreased affinity (increased Kd). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [3H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [3H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (Bmax) associated with Adx were accompanied by decreases in Kd. Unlike [3H]PRZ binding, there was no consistent genotype difference in [3H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher alpha 2- to alpha 1-adrenoceptor ratio than lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

A review of patients attending a preliminary cochlear implant assessment clinic.

The Cochlear Implant Programme at Manchester Royal Infirmary was established in 1988 and so far (January, 1992) 38 patients have been implanted with the Nucleus 22 channel intracochlear device and one with the Ineraid device. All patients who are referred for consideration for an implant are initially seen at a preliminary cochlear implant assessment clinic conducted by an ENT surgeon. One hundred and seventy three patients attended the initial outpatient screening clinic between 1987 and January 1992. Of these 112 patients (67.6 per cent) went on for further investigation regarding suitability for implantation. This paper details the aetiology and severity of deafness in these patients and explains how suitability for admission to the next stage of assessment was decided.

Adolescent↗

Merkel cell carcinoma of the eyelid.

The Merkel cell is part of the dendritic cell population of the epidermis, and studies suggest it has a role as a slowly adapting mechanoreceptor involved with mediating the sense of touch. Merkel cells can give rise to malignant neoplasms, one tenth of which occur in the eyelid and periocular area, and manifest as painless erythematous nodules, with overlying telangiectatic blood vessels. Merkel cell carcinoma can mimic other malignant lesions, and the diagnosis can be difficult. One third of the tumors recur, and there is a high rate of metastasis. The estimated 5-year survival rate is 38%. Initial treatment should be aggressive, including surgical resection, with consideration of postoperative radiation. Merkel cell carcinoma responds to chemotherapy, but routinely recurs on cessation of treatment. Two cases are presented to illustrate the typical presentation of Merkel cell carcinoma and the importance of electron microscopy and immunohistochemical studies.

Aged↗