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Biomedical subjects

D T Liu

Publications and source records attributed to D T Liu.

At least 19 recordsLinked to original sources

Primary structure of thymosin beta 12, a new member of the beta-thymosin family isolated from perch liver.

A new polypeptide termed thymosin beta 12 has been isolated from perch liver and its primary structure elucidated. This polypeptide contains 43 amino acid residues with a molecular weight of 4822 Da. The content of thymosin beta 12 from perch liver has been determined as 43 micrograms/g of tissue. The amino-terminal end of this polypeptide is blocked by an acetyl group as deciphered by fast-atom bombardment mass spectrometric analysis. Sequence analysis reveals that thymosin beta 12 is 79% homologous to thymosin beta 4, an immunomodulator which was originally isolated from calf thymus. Thymosin beta 12 also shows 84% sequence homology to thymosin beta 11, a beta 4 analog which replaces beta 4 in two species of bony fish, oscar and rainbow trout. The evolutionary implication of such results will be discussed. The isolation of a new beta 4-related peptide from perch liver which differs from beta 11 indicates that beta-thymosin peptides are widely distributed in lower vertebrate classes.

Amino Acid Sequence

Deamidation: a source of microheterogeneity in pharmaceutical proteins.

Most protein molecules undergo some degree of spontaneous deamidation in vivo. This process may also occur during the production, isolation, purification, formulation and storage of pharmaceutical proteins. Deamidation is a potential source of microheterogeneity for pharmaceutical proteins, and this is an important issue that needs to be addressed, not only by the manufacturers but also by the national control agencies. This article provides an overview of the scientific and regulatory issues pertinent to deamidation of pharmaceutical proteins.

Proteins

Chorionic villus sampling: evaluation of obstetric performance.

Chorionic villus sampling is frequently utilised in the Nottingham region as a means of early prenatal diagnosis of genetic problems. Its relative safety in the early antenatal period is well established but there has been some concern that perinatal mortality may be greater in the chorionic villus sampling group as compared to amniocentesis. We have in response studied our own data and report the obstetric outcome in 144 cases where the pregnancy has progressed beyond 28 weeks gestation. We have selected a procedure free control group matched for parity. We have found no significant difference in the perinatal outcome and obstetric performance and conclude that at this juncture we should continue to offer our services as chorionic villus sampling offers significant advantages in the first trimester over amniocentesis.

Adult

Inhibitory effect of circulating insulin on glucagon secretion during hypoglycemia in type I diabetic patients.

OBJECTIVE: To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. RESEARCH DESIGN AND METHODS: Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. RESULTS: Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. CONCLUSIONS: This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.

Adult

Intraplacental sonolucent spaces: incidences and relevance to chorionic villus sampling.

Detailed ultrasound examination of the placentae from 293 consecutive women requesting first-trimester chorionic villus sampling (CVS) showed evidence of intraplacental sonolucent spaces with varying density in 42.3 per cent of these placentae. Their presence, however, did not complicate the subsequent course of these women's pregnancies. Their prime significance relates to CVS, where inadvertent entry into these areas can lead to bleeding and contamination of the villus specimens with blood. A search for these spaces should be made before sampling, and when present, they should be avoided wherever possible.

Chorionic Villi Sampling

Bleeding as a consequence of chorion villus sampling.

A series of 4 separate studies were conducted to assess the incidence and short term consequence of bleeding associated with chorion villus sampling. Results support previous reports that risk of foetal-maternal transfusion as suggested by a rise in maternal serum alpha-fetoprotein (MSAFP) can occur. This occurrence is not consistent and need not be obvious even after therapeutic abortion. It is also transient and did not complicate mid-trimester neural tube screening or subsequent course of pregnancy. Eighty-seven percent of blood contaminating villus samples are of maternal origin. Following diagnosis 37% of patients reported some vaginal bleeding. This is mainly in the form of spotting which did not preclude normal pregnancy. Foetal loss occurred in 4 of the patients when bleeding considered heavier than spotting continued. In rhesus negative patients prophylactic anti-D gamma-globulin is advised, since neither Kleihauer counts nor MSAFP estimation reliably detect all foetal-maternal transfusions.

Chorionic Villi Sampling

Consideration of the production methods and safety evaluation of cytokines.

Cytokines are natural endogenous substances whose biological effects in humans are little known when given in therapeutic rather than physiologic doses. Yet, there is intense interest in seeking their possible clinical use. While E. coli are effective in making "simple proteins" with few disulfide bonds, mammalian cells are becoming more generally used for the production of "complex proteins" with multiple disulfide bonds and glycoproteins. There appears to be much less concern about the safety of possibly oncogenic residual DNA from transformed cell lines, but viral contamination of products continues to be an active concern. Both physicochemical and biological methods are necessary to establish the identity, purity and potency of biological drugs. For proteins to manifest their proper biological and therapeutic effects in humans, their correct conformation must be maintained throughout production, purification and formulation. Regulating novel biological drugs such as the cytokines might raise new scientific issues that are not currently apparent, but the basic principles involved will be consistent with those used to evaluate other biologics, e.g., sound scientific principles, flexibility, case-by-case approach, good common sense and risk vs benefit assessment.

Biological Factors

A prospective study of spontaneous miscarriage in ultrasonically normal pregnancies and relevance to chorion villus sampling.

A total of 1,068 patients were examined by ultrasound to ensure normality of pregnancy and followed prospectively from booking until 28 weeks. The spontaneous miscarriage rate was 2.7 per cent occurring within the first 16 weeks. Threatened miscarriage was associated with a 38 per cent fetal loss. Miscarriage was less likely as pregnancy advanced. The reduction in subsequent miscarriage rate before 11 weeks and from 11 weeks onwards is statistically significant (p less than 0.001). Gravidity, maternal age and a history of previous fetal loss did not contribute significantly to the miscarriage rate. Patients with a history of fetal loss were more likely to experience a threatened miscarriage. The relevance of these findings to chorion villus sampling is discussed.

Abortion, Spontaneous

Nefopam excretion in human milk.

Human milk and plasma samples were obtained from five healthy nursing mothers who were taking nefopam hydrochloride (60 mg four-hourly) for post-episiotomy pain. Concentrations of nefopam were quantified in milk and plasma paired samples, taken daily from birth for 5 days, by a specific paired-ion reverse phase h.p.l.c. method. Although nefopam was present in human milk in an equivalent concentration to plasma (milk: plasma ratio 1.2 +/- 0.7, mean +/- s.d.), the likely infant exposure was less than 0.05 mg kg-1 day-1 which, on a body weight basis, would be less than 3% of the maternal dose.

Adult

Endometriosis: its association with retrograde menstruation, dysmenorrhoea and tubal pathology.

Seventy-five women admitted for sterilization were laparoscoped during menstruation. Retrograde spillage of menstrual blood was observed in 76%. The occurrence of dysmenorrhoea was not associated with spillage of menstrual blood, observed endometriosis or tubal pathology. Mild or stage I endometriosis was detected in 43% of all the women but in only 54% of those who had retrograde spill. Retrograde spill was seen in 97% of those with endometriosis. A significant association (P less than 0.001) was found between endometriosis and tubal damage not due to endometriosis. The implication of these findings are discussed.

Adult

Nephrotoxic serum nephritis with hypertension: amelioration by antihypertensive therapy.

We have examined the effects of antihypertensive therapy on glomerular dynamics and on the clinical and morphologic features of a model of nephrotoxic serum nephritis (NSN) in which hypertension occurs. NSN was induced in uninephrectomized male Sprague Dawley rats, which drank 0.9% sodium chloride ad libitum. One-half were assigned randomly to a treated group whose blood pressure was normalized on a regimen of reserpine, hydralazine, and hydrochlorothiazide. Hypertension continued throughout the 6 weeks of study in untreated rats (blood pressure 148 +/- 5 vs. 103 +/- 3 mm Hg in treated rats, P less than 0.01). Urinary protein excretion was greater (437 +/- 110 vs. 254 +/- 81 mg/24 hr, P less than 0.005), and serum albumin lower (1.6 +/- 0.4 vs. 2.9 +/- 0.3 g/dl, P less than 0.01) in hypertensive animals. Diffuse glomerular endo- and extracapillary proliferation and arteriolar medial hypertrophy were observed frequently in nephritic rats with untreated hypertension. By contrast, structural abnormalities were limited primarily to focal segmental proliferation involving fewer than one-third of glomeruli in the absence of vascular changes in treated normotensive rats. Micropuncture studies performed 8 to 16 days after induction of nephritis showed a reduction in glomerular capillary pressure (46 +/- 1 vs. 55 +/- 1 mm Hg, P less than 0.001), glomerular plasma flow rate (115 +/- 20 vs. 160 +/- 20 nl/min, P less than 0.01), and single nephron filtration rate (42 +/- 4 vs. 56 +/- 5 nl/min, P less than 0.001) with antihypertensive treatment, suggesting that a hemodynamic mechanism may have been responsible for enhanced glomerular injury in the hypertensive nephritic animals.

Animals