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Biomedical subjects

X F Zhu

Publications and source records attributed to X F Zhu.

28 records · Page 2Linked to original sources

Cloning and functional expression of a novel geranylgeranyl pyrophosphate synthase gene from Arabidopsis thaliana in Escherichia coli.

A gene encoding a novel geranylgeranyl pyrophosphate (GGPP) synthase from Arabidopsis thaliana has been identified and termed GGPS5. The gene has been sequenced and expressed in Escherichia coli. The deduced amino acid sequence showed 64.5% and 57.5% identify with a putative GGPP synthase from Arabidopsis and Capsicum annuum, respectively. GGPP enzymatic activity was detected in E. coli cells expressing the GGPS5 gene in two different ways. One was the direct measurement of GGPP synthase activity in cell extracts and the other was the yellow color production of cells when the GGPS5 gene was co-expressed with crtB, crtI, crtY and crtZ genes derived from Erwinia uredovora.

Alkyl and Aryl Transferases↗

Organ loci of catabolism of short truncations of apoB.

Truncations of apolipoprotein (apo) B shorter than 3200 amino acids (3200/4536 = apoB-70) do not possess the LDL receptor-recognition domain and are not recognized by altered cells with normally functioning LDL receptors. To ascertain which organs remove such truncated apoB-containing particles, we isolated apoB-31-, apoB-38.9-, and apoB-43.7-containing particles from plasmas of familial hypobetalipoproteinemia heterozygous humans by a combination of sequential ultracentrifugation and preparative electrophoresis. Particles with labeled 125I- or 131I-dilactitol tyramine (I-DLT), were injected into New Zealand White rabbits, along with I-DLT-apoB-100-containing LDLs, and the decay of 125I- and 131I-TCA-precipitated counts was followed over 24 hours. At the end of 24 hours, rabbits were anesthetized and their bodies perfused. Organs were removed and homogenized, and TCA-precipitable counts determined. Fractional catabolic rates of apoB truncation particles were two to five times greater than those of apoB-100 LDLs. ApoB truncations accumulated in adrenals at one fifth the rates of apoB-100 LDL, compatible with the functional absences of LDL receptor-recognition domains in truncated apoBs. The major organ of uptake for apoB-100-LDLs was the liver, whereas truncation particles were readily removed by the kidney (kidney: liver uptake ratios were 0.10 to 0.30 for apoB-100 LDLs and 1.03 to 3.77 for truncations). Spleens accumulated little of either apoB-100 or truncation particles, suggesting particles were not "damaged" or aggregated. Thus, the absence of > 56% of the carboxyl end of apoB-100 increases the plasma clearance and redirects the organ uptake of the apoB truncation-containing lipoproteins from liver to kidney.

Adult↗

Effect of octreotide on dynamic excretion of bile in Chinese acromegalic patients assessed by [99mTc]EHIDA hepatobiliary scan.

We used [99mTc]EHIDA hepatobiliary scintigraphy to determine whether both hepatic bile secretion and gallbladder contractility are suppressed in acromegalic patients receiving long-term treatment with the somatostatin analogue octreotide. We studied three groups of patients: group 1, untreated patients; group 2, average dose of octreotide 500 +/- 100 micrograms/day for 33 +/- 4 months; and group 3, 1000 +/- 200 micrograms/day for 33 +/- 4 months. Images were taken at specified time intervals during the 120-min period following injection of EHIDA. After a single injection of octreotide, group 1 patients demonstrated delayed visualization of the radioisotope in the liver, gallbladder, and duodenum. At the end of long-term treatment, group 2 patients showed a delay in appearance of maximal radioactivity in the gallbladder. Two weeks following discontinuation of octreotide, this parameter had decreased significantly (P < 0.001). In group 3, visualization of the liver, gallbladder, and duodenum were prolonged, with delayed visualization of the gallbladder persisting two weeks after withdrawal (P < 0.005). These results indicate that gallbladder contractility is decreased after a single injection of octreotide and that during chronic octreotide therapy the rate of bile secretion is reduced. Impaired gallbladder contractility normalizes more rapidly after discontinuation of octreotide in patients receiving low doses of the analog.

Acromegaly↗

[An observation of the secretion of growth hormone and contraction of gall bladder after long-term use of growth-inhibition excitants].

We sought to examine the feasibility of intermittent dosing of octreotide in acromegalics to avoid the well-documented side effect of cholelithiasis. In fourteen acromegalic patients, we measured serum GH, five hour GH profile (mean GH, measured hourly 8:00 am to 12:00 pm) prior to the discontinuation of octreotide and weekly thereafter. In addition, gallbladder contractility was quantitated using the percent of relative gallbladder contractility (PRGC) obtained by ultrasound during a fat meal test. One week after withdrawal of octreotide, basal GH and five our GH profile (14.6 +/- 3.3 micrograms/L, 13.4 +/- 3.2 micrograms/L, respectively) were significantly less than (P < 0.01, P < 0.05), and represented 36% and 24% of their respective pretreatment values. At the end of two weeks, these parameters were 60% and 56% of their pretreatment levels. We also measured serum octreotide levels following withdrawal; the drug is completely eliminated from the serum within 3 day. In all of 6 patients who did not develop stones, PRGC normalized within one week. In 8 patients who developed stones, 3 of them had restoration of normal contractility in 2 weeks. Our results show that upon withdrawal of octreotide, gall bladder contractility normalizes while GH suppression persists for a longer period of time. Therefore, intermittent therapy may allow clearance of stagnated bile and hence decrease the incidence of cholelithiasis in acromegalic patients receiving long term octreotide therapy.

Acromegaly↗

Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.

This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.

Acromegaly↗

Restoration of gallbladder contractility after withdrawal of long-term octreotide therapy in acromegalic patients.

We sought to examine how the discontinuation of octreotide in long-term octreotide-treated acromegalic patients affects the well-documented side-effect of cholelithiasis. In 14 acromegalic patients, serum growth hormone levels, insulin-like growth factor I levels and percentage of relative gallbladder contractility were measured prior to and after the discontinuation of octreotide. Compared to pretreatment values, the basal growth hormone and 5-h growth hormone profiles were 36% and 24%, and 60% and 56% at the end of 1 and 2 weeks, respectively. Octreotide was found to be eliminated completely from the serum within 3 days after its withdrawal. In all of six patients who did not develop gallstones, the percentage relative gallbladder contractility normalized within 1 week. In eight patients who developed gallstones, four of them had restoration of normal contractility within 2 weeks. Our results show that upon withdrawal of octreotide, gallbladder contractility returns to normal while growth hormone suppression persists for a longer period of time. Therefore, discontinuation of octreotide therapy may allow for the clearance of stagnated bile and hence decrease the incidence of cholelithiasis in acromegalic patients receiving long-term therapy.

Acromegaly↗

Effect of small doses of somatostatin analog, octreotide, on gallbladder contractility in normal Chinese adults.

The acute effects of single different doses of the somatostatin analog octreotide on the contractility of the gallbladder stimulated by fatty meal were studied in six healthy Chinese volunteers. Gallbladder contraction after a fatty meal was significantly suppressed by octreotide at doses of 50, 25, 12.5, and 5 micrograms. Mean duration of suppression lasted for more than 10 hr at doses of 25 and 50 micrograms, after which the gallbladder contractility was restored at 24 hr in three and four, respectively, of the six subjects. The percentage of relative gallbladder contraction (PRGC) in all subjects receiving 12.5 and 5 micrograms octreotide returned to pretreatment values at 10 hr but had not returned to normal 6 hr after the injection of 5 micrograms octreotide. In summary, octreotide inhibits the contraction of the gallbladder even with a dose as low as 5 micrograms. It appears that it may not be possible to avoid gallbladder dysfunction during long-term octreotide therapy by decreasing the dose. Further studies including modalities to increase the contractility of the gallbladder are recommended.

Adult↗

[Prospective study of functional changes in the gallbladder and formation of gallstones induced by long-term treatment of somatostatin analogue SMS201-995 in patients of active acromegaly].

We reports the result about the changes of function of gallbladder in 17 acromegalic patients after treatment with long-acting somatostatin analogue SMS201-995 for 3-36 months by ultrasonogram. The number of cases developed bile sludges, gallstones, chronic and acute cholecystitis was 14, 8, 10 and 1 respectively during therapy. The contractibility of gallbladder after fatty meal was inhibited in all of the patients during the course of therapy. A bolus injection of SMS201-995 with a dosage of 100 micrograms for acromegalic patients resulted in marked suppression of the contractibility of the gallbladder. Our result indicates that the decreased contractibility of the gallbladder leads to the formation of gallstones during the long-term therapy of SMS201-995. Therefore, it is important to follow the gallbladder carefully in the course of the therapy of SMS201-995.

Acromegaly↗

Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients.

Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.

Acromegaly↗