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Choh Hao Li

It has been known for a long time that when the same protein hormone is isolated from tissues of various species, the products are not necessarily identical; however, comparative studies of the anterior hypophyseal hormones did not begin to attract wide interest until 1956, when it was demonstrated that the growth hormone (somatotrophin) isolated from primate pituitary glands is chemically distinct from the bovine hormone, and that the primate hormones are metabolically active in human subjects whereas the bovine hormone is not. In this communication, we wish to report some comparative investigations which have been carried out in the author's laboratory on the biochemical endocrinology of pituitary growth hormone. Recent reviews on some aspects of the subject have been published (Li 1957, 1958, 1959; Russell & Wilhelmi 1958; Knobil & Greep 1959).

PHYSICOCHEMICAL CHARACTERIZATION

There are now growth hormone preparations from pituitary glands of six different species, namely, ox (Li,

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Choh Hao Li

Es cognoscite depost longe tempores que puando le mesme hormon proteinic es isolate ab le tissus de differente species, le productos non es necessarimente identic. Tamen, studios comparative del hormones antero-pituitari non gaudeva de multe interesse ante le anno 1956, quando il esseva demonstrate que le hormon de crescentia (somatotropina) isolate ab le pituitario de primates es chimicamente distincte ab le hormon de crescentia bovin e que le hormones ab primates sub-human es biologicamente active in le homine, durante que le hormon bovin non es active in ille. In le presente communication nos desira reportar certe investigationes comparative que esseva effectuate in le laboratorio del autor e que concerne le endocrinologia biochimic del hormon de crescentia del pituitario. Revistas de certe aspectos del thema ha recentemente essite publicate (1, 2, 3). (Li 1957, 1958, 1959; Russel & Wilhelmi 1958; Knobil & Greep 1959).

Characterisation physicochimic

Currentemente il existe preparatos de

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CHOH HAO LI

Page

I. Introduction 256

II. Discrepancies in Evaluation of ACTH Activity by Different Assay Methods 257

III. Homogeneity Studies of Li-Sayers ACTH Protein 265

IV. Purification of Peptic Digests of ACTH Protein Preparations 271

V. Preparation of Highly Active ACTH Fractions 275

VI. Properties of Preparation E 278

VII. Purification of Preparation E 282

VIII. Comments 287

Addendum 288

Acknowledgment 289

References 289

*) A portion of this paper was presented as a lecture before the Colston Research Society, University of Bristol, England, on April 1, 1952.

I. INTRODUCTION

In 1930, Smith demonstrated conclusively the pituitary control of adrenal cortical function, and provided evidence for the presence of adrenocorticotrophic activity in the pituitary gland. After that, numerous investigators, notably Collip, Anselmino, Morris, Bates and others, attempted to purify and isolate the hormone without success. In 1942—1943, two groups of workers (Li et al., 1942, 1943, Sayers et al., 1943)

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H Li-Fern and C Rajasoorya

A 39-year-old Chinese man with hypertension being evaluated for elevated serum alkaline phosphatase (SAP) levels was found to have an incidental right adrenal mass. The radiological features were characteristic of a large adrenal myelolipoma. This mass was resected and the diagnosis confirmed pathologically. His blood pressure normalised after removal of the myelolipoma, suggesting that the frequently observed association between myelolipomas and hypertension may not be entirely coincidental. Persistent elevation of the SAP levels and the discovery of hypercalcaemia after surgery led to further investigations which confirmed primary hyperparathyroidism due to a parathyroid adenoma. The patient's serum biochemistry normalised after removal of the adenoma. The association of adrenal myelolipoma with primary hyperparathyroidism has been reported in the literature only once previously. Although unconfirmed by genetic studies this association may possibly represent an unusual variation of the multiple endocrine neoplasia type 1 syndrome.

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Geneviève Bourdel and Choh Hao Li

ABSTRACT

Rabbit antiserum to sheep pituitary interstitial-cell stimulating hormone was shown to counteract the endogenous interstitial-cell stimulating hormone of adult female rats. The occurrence of oestrus was prevented when the antiserum was injected 36 hours before the expected time of ovulation. The treatment had also a striking effect on the ovary, uterus and vagina, as evidenced by histological examinations.

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Helen Thomopoulou and Choh Hao Li

Previous studies (Moon & Li, 1952) have already demonstrated the effect of pituitary follicle-stimulating hormone (FSH) on C57 Black mice. This paper represents a preliminary investigation on the histological changes which occur in the ovaries of another strain of immature mouse (Swiss White) following the injection of highly purified preparations of gonadotrophins (FSH and interstitial-cell stimulating hormone (ICSH)) isolated from sheep pituitary glands (Li, 1949).

Effect of FSH. Immature female mice, weighing 6–8 gm., were used. The hormone, in saline solution, was injected subcutaneously once daily for 5 days, with autopsy performed 24 hours after the last injection. The total dosages of FSH ranged from 0.1 to 2.0 mg. Paraffin sections of the uteri and the ovaries, stained with hematoxylin and eosin, were prepared.

The smallest doses of FSH affecting the weight and histology of the reproductive organs of the female mice used for the experiment was 0.3 mg. Larger

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Fu-Sheng Fang, Yan-Ping Gong, Chun-Lin Li, Jian Li, Hui Tian, Wei Huang, Liang-Chen Wang and Lin Li

Background

We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Patients and methods

In this 15-week, open-labelled, parallel-controlled, randomised study, 60 Chinese drug-naive patients with newly diagnosed T2DM were randomised (2:1) to receive repaglinide or metformin monotherapy. Primary endpoint was change in HbA1c from baseline to the end of the trial. Secondary endpoints included changes in glycaemic variability, insulin sensitivity and β-cell function.

Results

Patients in both repaglinide and metformin groups achieved significant reductions in HbA1c (−1.8±1.5 vs −1.6±1.5%), FPG (fasting blood glucose) (−1.7±1.7 vs −2.1±1.7 mmol/l) and 2-h PPG (post-prandial glucose) (−3.8±3.1 vs −3.8±3.6 mmol/l), with no statistical differences between the groups. Glycaemic variability, glucose infusion rate and β-cell function were all significantly improved from baseline in the two groups (all P<0.05), without any statistical differences in the improvement between the groups.

Conclusions

Repaglinide and metformin achieved comparable efficacy in improving glycaemic control, reducing glycaemic variability, enhancing insulin sensitivity and ameliorating β-cell function. Therefore, repaglinide is an optional agent for initial therapy in Chinese patients with newly diagnosed T2DM.

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Jameel Iqbal, Li Sun and Mone Zaidi

Bone loss due to menopause, natural or artificial, has been attributed solely to low estrogen. However, in a woman's life, the most precipitous bone loss begins 2 years prior to the last menstrual period, during which time estrogen levels are unperturbed whereas FSH is elevated. Our cell-based and mouse genetic studies have shown that FSH stimulates bone resorption by osteoclasts directly in a pituitary–bone axis, independently of the estrogen effect. On the basis of this and evolving clinical and scientific evidence, we propose that elevated FSH contributes to bone loss across the menopausal transition, particularly during late perimenopause. In the current issue of the European Journal of Endocrinology, Rendina et al. strengthen the view for a primary role of FSH signaling in the regulation of bone mass and bone remodeling in humans by demonstrating that an ‘activating’ polymorphism AA rs6166 causes low bone mass and high bone turnover.

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GN Shah, J Li and AD Mooradian

The technique of reverse transcriptase-polymerase chain reaction differential display was used to identify thyroid hormone (TH) responsive mRNAs in the adult rat cerebral tissue. A partial cDNA (0.76 kb) was cloned and sequenced. Comparison of the sequence to the GenBank data base showed almost 100% homology to mouse translational repressor (NAT-1) mRNA 3'-end. In a northern blot analysis this cDNA hybridized with a mRNA whose expression in hyperthyroid rat cerebral tissue was approximately 6-fold higher than in euthyroid rats. The time course studies showed a rapid induction of this mRNA within 3 h following thyroxine administration. This mRNA is widely expressed in various tissues, and in hepatic tissue it is also TH responsive. To determine if TH responsiveness of this mRNA persists during aging, 25-month-old aged rats were studied and the results were compared with those of 4-month-old rats. Unlike young mature rats, the TH responsiveness of NAT-1 mRNA in both the cerebral and hepatic tissue of aged rats was blunted. It is concluded that cerebral tissue in aging rats beyond the developmental stages, like the hepatic tissue, is associated with altered TH responsiveness.

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SN De Biasi, LI Apfelbaum and ME Apfelbaum

OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.