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CHOH HAO LI

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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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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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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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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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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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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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ROLF LUFT, BJÖRN SJÖGREN and CHOH HAO LI

In a previous paper we have reported the metabolic effect of small doses of ACTH protein and an ACTH peptide mixture in a case of rheumatoid arthritis (Luft, Sjögren & Li, 1949). The hormone was administered for only 4—5 days and the following results were obtained:

(a) retention of sodium, chloride and fluid; (b) tendency to increased excretion of potassium, calcium, total nitrogen and uric acid; (c) increase of 17-ketosteroids in urine and (d) marked decrease of circulating eosinophils. The present investigation was a continuation of such studies using different dosages of ACTH protein in a longer period of administration.

1) These studies were aided by grants from the Medical Research Council of Sweden.

2) Read at the Annual Meeting of the Association for the Study of Internal Secretions in San Fransisco, June 23, 1950, at the International Congress of Internal Medicine in Paris, September 13, 1950, and at the

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ROLF LUFT, BJÖRN SJÖGREN and CHOH HAO LI

It has been demonstrated by one of us (Li, 1948) that a certain peptic digest of adrenocorticotrophic hormone (ACTH) retains the biological activity, and that the adrenocorticotrophic potency resides in the peptide residues. The present report concernes the effect of the adrenocorticotrophically active peptides (ACTH peptides) on a patient suffering from rheumatoid arthritis.

MATERIAL AND METHODS

Pure ACTH was isolated from sheep pituitary glands by a method previously described (Li et al., 1942—43). The ACTH peptide preparation was obtained by pepsin digestion as de

1) This study was aided by a grant from Statens Medicinska Forskningsråd (The Medical Research Council of Sweden).

2) On sabbatical leave from the University of California, Berkeley, California.

scribed by Li (1948). The protein hormone or the peptide mixture were dissolved in physiological saline. The daily dose was divided into six injections; each injection consisting of one ml. The patient was thus injected

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D. S. Flux and Choh Hao Li

ABSTRACT

Immunological cross reactions among the three gonadotrophins, ovine interstitial cell-stimulating hormone (ICSH), pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) have been investigated.

The earlier findings in this laboratory that rabbit antiserum to ICSH inhibited the biological activity of PMSG was confirmed. Antiserum to PMSG was found to inhibit ICSH. The biological activity of HCG in hypophysectomized female rats was not inhibited by antiserum to either ICSH or PMSG in these experiments, but other evidence shows that antiserum to ICSH is sufficiently high doses does inhibit the biological effects of HCG.

Both PMSG and HCG showed precipitin reactions with antiserum to ICSH, the amounts of protein precipitated being much less than when ICSH was used. No precipitate was formed when ICSH or HCG was added to antiserum to PMSG.

The antiserum to PMSG contained antibodies to the horse serum proteins that were present as contaminants of the PMSG. These were partly absorbed with horse serum without loss of the anti-PMSG activity.