24-hour ambulatory blood pressure and renal disease in young subjects with type I diabetes

OBJECTIVES: The clinical data on individuals who were diagnosed to have juvenile myoclonic epilepsy (JME) on the basis of myoclonic jerks alone has been analysed. The points in favour and against individuals with only myoclonic jerks being classified as "affected" for research on JME are discussed. MATERIALS AND METHODS: We studied 15 persons diagnosed with JME on the basis of only myoclonic jerks in a series of 161 patients with JME and their relatives. Detailed information on the seizure types in JME patients and their family members was collected. All affected individuals were examined by one person and had at least one conventional scalp EEG. CT/MRI of the brain was done as and when indicated. RESULTS: Nine of these were probands while 6 were the relatives of JME patients. The EEG was abnormal in 8 of 9 probands and 1 of 6 relatives with only myoclonic jerks. All the 9 probands and 2 relatives with only myoclonic jerks were treated with anti-epileptic drugs. Three of the 4 relatives had spontaneous remission of jerks after variable intervals. Four of 15 persons with only myoclonic jerks had a first degree relative with definite JME. CONCLUSIONS: It appears that persons with myoclonic jerks alone may represent a benign subgroup of JME that may be genetically distinct from classic JME and the jerks may even spontaneously remit in a few cases. It is suggested that those persons with only myoclonic jerks and a first degree relationship with a definite diagnosis of JME can be classified as "affected" for inclusion into molecular studies, till molecular tools are available to settle the issue of phenotypic variations in hereditary neurological disorders like JME.     

The influence of oral glucose intake on binding and degradation of 125I-insulin by receptors on erythrocytes as well as on insulin and C-peptide serum levels in patients after myocardial infarction and healthy individuals

In this study, we investigated the influence of glucose administration on binding and degradation of 125I-insulin by receptors on erythrocytes as well as on insulin and C-peptide serum levels in 15 patients after myocardial infarction and in 15 age-matched healthy persons. Venous blood samples were taken directly before and at 30, 60 and 120 minutes after oral administration of 75 g of glucose. In the collected blood samples serum glucose, insulin and C-peptide levels were determined. Binding and degradation of 125I-insulin by specific receptors on red blood cells were evaluated using the method described by Gambhir and modified by the authors. Serum insulin and C-peptide levels were significantly higher while binding of 125I-insulin to erythrocytes was decreased in patients after myocardial infarction. These results seem to support the hypothesis that insulin resistance and hyperinsulinism play a role in the pathogenesis of ischaemic heart disease. Impaired degradation of 125I-insulin during the oral glucose tolerance test in the patients after myocardial infarction indicates that insulin resistance is located at the receptor level.     

Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats

In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway.     

Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors

Truncated activin type II receptors have been reported to inhibit activin receptor signaling in Xenopus embryos, although the mechanism of action for this effect has not been fully understood. In the present study we demonstrate that in P19 embryonal carcinoma cells both the induction of the activin responsive 3TP-lux reporter construct and the inhibition of retinoic acid-induced neuronal differentiation by activin are blocked by expression of a truncated activin receptor. To reveal the mechanism of action of truncated activin receptors, the interaction between different activin receptors has been investigated upon coexpression in COS cells followed by cross-linking of 125I-activin A and subsequent immunoprecipitation. Complexes between a truncated activin type IIA receptor and activin type IA and type IB receptors can be formed, as demonstrated by coimmunoprecipitation of these type I receptors with the truncated activin type IIA receptor. Other type I receptors known as ALK-1 and ALK-6 also coimmunoprecipitate with the truncated type IIA receptor, whereas ALK-3 and ALK-5 do not. Furthermore, the activin type IIB2 receptor does not coimmunoprecipitate with the truncated type IIA receptor, but decreases activin binding to the truncated type IIA receptor. In double immunoprecipitation experiments with cell lysates from COS cells, in which full-length activin type IIA and type IIB2 receptors were cotransfected, no interaction between these receptors was found. In contrast, homomeric complexes of full-length activin type IIA receptors were detected. These results implicate that truncated activin receptors can interfere with activin signaling by interacting with activin type I receptors. Additionally, truncated activin type IIB2 receptors might also interfere with type IIA receptor signaling by decreasing activin binding to the type IIA receptor and therefore might be more potent in inhibiting activin signal transduction. Furthermore, our data indicate that truncated type IIA receptors can interact with other type I receptors and as such might inhibit signal transduction by type I receptors other than activin type IA and type IB receptors.     

Estimation of cholesterol sulphate in blood plasma and in erythrocyte membranes from individuals with Down's syndrome or diabetes mellitus type I

OBJECTIVES: Plasma and erythrocyte membrane cholesterol sulphate (CS) were measured in patients suffering from diabetes and Down's syndrome. DESIGN AND METHODS: The procedure for separation and determination of CS comprised HPTLC (high-performance thin-layer chromatography) and densitometry. RESULTS: The mean plasma and RBC membranes CS concentrations (+/- SD) of the control group (n = 16) was 188 +/- 47 micrograms/dL and 343 +/- 57 micrograms/10(12) RBC, respectively. In 15 patients with diabetes and 12 Down's syndrome patients substantially higher CS levels were found (diabetes: plasma-348 +/- 60 micrograms/dL; RBC membranes-646 +/- 113 micrograms/10(12) RBC; Down's syndrome: plasma-245 +/- 54 micrograms/dL; RBC membranes 427 +/- 74 micrograms/10(12) RBC). Analysis of variance and multiple comparison (Newman-Keuls test) show statistically significant differences between all samples both for erythrocytes, F(2.41) = 52.24, p < 0.05, and plasma, F(2.41) = 34.92, p < 0.05. CONCLUSIONS: It is postulated that differences in CS levels may contribute to changes of erythrocyte properties in these pathological states.     

Characterization of desamino-5-[125I]iodo-3-methoxy-zacopride ([125I]MIZAC) binding to 5-HT3 receptors in the rat brain

1. Antagonists at 5-HT3 receptors have shown activity in animal models of mental illness, however, few radiolabeled 5-HT3 ligands are available for preclinical studies. MIZAC, an analogue of the selective 5-HT3 antagonist, zacopride, binds with high affinity (1.3-1.5 nM) to CNS 5-HT3 sites. The authors report here the selectivity of MIZAC for these sites in rat brain homogenates. 2. Ninety-seven percent of total specific binding of [125I]MIZAC (0.1 nM) of was displaced by bemesetron (3 microM), a selective 5-HT3 antagonist. Competition studies using ligands with known affinities for 5-HT3 sites give a high correlation with reported pKi values (r2 0.98). Bemesetron displaceable binding has a regional distribution consistent with that of the 5-HT3 receptor, i.e. highest in cortex and hippocampus, and lowest in striatum and cerebellum. 3. Potent antagonists present at concentrations sufficient to occupy 95% of other 5-HT receptor populations (1A, 1B, 1D, 2A, 2B, 2C, 5A, 5B, 6, and 7) showed minimal ability to displace [125I]MIZAC binding (3 nM). Specificity studies using radioligand binding assays selective for 5-HT4, 5-HT6, and 5-HT7 receptors, and for binding sites of other neurotransmitters indicate a high degree of selectivity of [125I]MIZAC for the 5-HT3 receptor. 4. [125I]MIZAC binds to an apparent low affinity (benzac) site having a unique pharmacology. Low affinity binding was displaceable by benztropine, but not by other muscarinic agents nor inhibitors of dopamine uptake. The regional distribution of the low affinity site differed markedly from that of the high affinity site. The apparent affinity of [125I]MIZAC for the benzac site is two orders of magnitude lower than for the 5-HT3 receptor. Given its high selectivity for 5-HT3 binding sites, [125I]MIZAC appears to be a promising ligand for labeling 5-HT3 receptors in vitro and in vivo.     

Transforming growth factor-beta receptors on human endometrial cells: identification of the type I, II, and III receptors and glycosyl-phosphatidylinositol anchored TGF-beta binding proteins

BACKGROUND: Mutation of the p53 tumor suppressor gene is the most commonly found genetic alteration in human cancer. The E6 gene product of human papillomavirus (HPV) 16 and 18 can inactivate the p53 protein by promoting its degradation. Because most HPV-positive cervical carcinoma cell lines contain wild-type p53 whereas HPV-negative cell lines have point mutations in the p53 gene, a major role in the development of HPV-negative cervical cancer has been attributed to p53. Recent studies, however, have observed no consistent presence of p53 mutation in HPV-negative primary cervical carcinomas. The MDM2 oncogene, which forms an autoregulatory loop with the wild-type p53 protein, has been found amplified in a high percentage of human sarcomas, thus abolishing the antiproliferative function of p53. METHODS: Forty-three primary cervical carcinomas and 10 autopsy-derived distant metastases from one patient were examined for p53 mutation and MDM2 amplification. These tumors had been selected from 238 cervical cancers that had been HPV-typed by Southern blot hybridization and polymerase chain reaction as a representative sample for their HPV status and their clinicopathologic characteristics. Seventeen of the cases had a remarkably good or poor clinical outcome. Human papillomavirus DNA sequences had been detected in 30 of these 43 primary tumors and 13 were negative for HPV by both methods. p53 mutation in the highly conserved exons 5-8 was studied by single-strand conformation polymorphism analysis and direct sequencing. MDM2 amplification was analyzed by Southern blot hybridization. RESULTS: Only two missense point mutations and one nucleotide sequence polymorphism were detected: a TAC-->TGC transition in codon 234 in exon 7, resulting in a Tyr-->Lys substitution, a CGT-->TGT transition in codon 273 in exon 8, resulting in an Arg-->Cys substitution and a polymorphism (CGA-->CGG) in codon 213 in exon 6. Both tumors revealing the point mutations were HPV-negative carcinomas. Amplification of the MDM2 gene was observed in 1 of the 53 specimens tested. CONCLUSIONS: In contrast to data derived from cultured cervical carcinoma cell lines and primary sarcomas, these results indicate that p53 mutation and amplification of the MDM2 oncogene are rare even in HPV-negative primary cervical carcinomas. However, to the authors; knowledge, this is the first observation of MDM2 amplification in humans outside sarcomas and neuroepithelial tumors.     

Mitogen receptors in chick embryo fibroblasts. Kinetics, specificity, unmasking, and synthesis of 125I-insulin binding sites

Insulin, a mitogen for cultured chick embryo fibroblasts (Temin, H.M. (1968) Cancer 3, 771-787), has been employed to characterize the effects of mitogen/cell membrane interactions as it relates to growth. The specific binding of 125I-insulin to substratum-attached cells is time- and temperature dependent and is optimum at a pH of 7.0. Fetal calf and chicken sera, somatomedin "A/C mixed," and desalanine or native porcine insulin compete with 125I-insulin for membrane-binding sites. Proinsulin, although competing less effectively than native insulin for binding, is more effective than desoctapeptide insulin. Unrelated polypeptide hormones do not compete for 125I-insulin binding. The lowest concentration of insulin at which specific binding is detected is 0.1 nM. Scatchard plot analysis of the binding data indicates that there are two types of binding sites in confluent cultures of fibroblasts: one of high affinity (K1 = 2 to 6 X 10(8) M-1) and low capacity, the other of low affinity (K2 = 0.8 to 3.0 X 10(7) M-1) and high capacity. Approximately 1.9 and 7.1 X 10(3) molecules of insulin are bound at each site, respectively. A 10-min incubation at 24 degrees of the fibroblasts with 10 mug/ml of trypsin causes a 2-fold stimulation of specific 125I-insulin binding and a similar 2-fold increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation. Neuraminidase treatment also produces a 37% increase in specific 125I-insulin binding but treatment with alpha-chymotrypsin or phospholipase C are without significant effect. The results of this and additional experiments support the hypothesis that trypsin treatment of chick embryo fibroblasts leads to an unmasking of 125I-insulin binding sites. Serum starvation of fibroblasts for 12 or 24 h produces a 2.5- to 5-fold increase in specific 125I-insulin binding. This increase is the result of an increase in the number of hormone-binding sites from 9 X 10(3) to 6 X 10(4) per cell which are predominantly of the low affinity type. There is no change in the affinity constants. The presence of camptothecin, or cordycepin, or cycloheximide in the incubation medium completely blocks the increase in number of 125I-insulin-binding sites resulting from serum starvation. The addition of native insulin to the medium of serum-starved cultures also blocks this increase. The magnitude of insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation correlates with the levels of occupancy of the low affinity 125I-insulin-binding sites in untreated fibroblasts. In fibroblasts cultured in the absence of serum, the marked increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation parallels the increase in number of mitogen receptors. The concentration of insulin that produces a half-maximum stimulation of thymidine incorporation is calculated to be 5 X 10(-8) M. At this concentration of insulin, 42% of the receptor sites are occupied.     

Interferon-gamma and interleukin-4 responses in relation to serum IgE levels in persons infected with human T lymphotropic virus type I and Strongyloides stercoralis

Possible immunologic interaction between infection with human T lymphotropic virus type 1 (HTLV-1), a retrovirus, and the intestinal parasite Strongyloides stercoralis was investigated in persons infected with one or both agents. This was done by examining the cytokine responses of peripheral blood mononuclear cells (PBMC) to mitogens and Strongyloides antigen. PBMC of subjects infected with HTLV-1 spontaneously produced interferon (IFN)-gamma with levels that correlated inversely with serum IgE levels. HTLV-1-infected subjects also had poor interleukin (IL)-4 responses to mitogenic stimulation, unlike persons without HTLV-1 infection. It is postulated that the IFN-gamma produced by activated T cells in some HTLV-1-infected persons acts to down-regulate IL-4 with consequent reduction of serum IgE levels. The impaired IgE responses and other effects of IL-4 down-regulation may be contributing factors to more severe disease and impaired response to treatment of strongyloidiasis in some HTLV-1-infected persons.     

Demonstration of membrane estrogen binding proteins in rat brain by ligand blotting using a 17beta-estradiol-[125I]bovine serum albumin conjugate

Trasina is a herbal formulation of some Indian medicinal plants classified in Ayurveda, the classic Indian system of medicine, as Medhyarasayanas or drugs reputed to improve memory and intellect. Earlier experimental and clinical investigations have indicated that the formulation has a memory-facilitating action. In this investigation, the effect of Trasina, after subchronic administration for 21 days, was assessed on two rodent models simulating some biochemical features known to be associated with Alzheimer's disease (AD). The models, in rats, included intracerebroventricularly (i.c.v.) administered colchicine (15 micrograms/rat) and lesioning of nucleus basalis magnocellularis (nbm) by ibotenic acid (10 micrograms/rat). Retention of an active avoidance response was used as the memory parameter. In addition, the effect of Trasina was evaluated on i.c.v. colchicine-induced depletion of acetylcholine (ACh) concentrations, reduction in choline acetyltransferase (ChAT) activity, and decrease in muscarinic cholinergic receptor (MCR) binding in rat brain frontal cortex and hippocampus. The behavioral and biochemical investigations were done 7, 14, and 21 days after colchicine or ibotenic acid lesioning. Trasina (200 and 500 mg/kg) was administered orally (p.o.) once daily for 21 days, the first drug administration being given just prior to lesioning. Colchicine and ibotenic acid induced marked retention deficit of active avoidance learning that was attenuated in a dose-dependent manner by Trasina after 14 and 21 days of treatment. Frontal cortical and hippocampal ACh concentrations, ChAT activity and MCR binding was significantly reduced after colchicine treatment. Trasina (200 and 500 mg/kg) reversed these deficits after 14 and 21 days of treatment. The findings indicate that the herbal formulation exerts a significant nootropic effect after subchronic treatment that may be due to reversal of perturbed cholinergic function.     

Hemodynamic assessment at rest and during dynamic physical exercise in young subjects with and without hypertensive parents

The antifols, inhibitors of the dihydrofolate reductase (DHFR), such as pyrimethamine and proguanil, have been used against Plasmodium falciparum in the areas where chloroquine resistance is widespread. This use has selected resistant strains in Southeast Asia and South America. The resistance is correlated with point mutations in precise positions of the DHFR gene. A reliable semi-nested PCR diagnosis test was established and used to determine the genotypic features of 29 isolates of P. falciparum originating from Africa. The results obtained by the PCR technique were compared with those of the in vitro drug sensitivity test. Some isolates were found to be polyclonal. Among the mutations tested, only mutations on codon 108 which generate an asparagine induce a decrease in sensitivity to pyrimethamine and cycloguanil, whereas mutation on codon 59 strengthens resistance to both antifols. No mutation on codon 16 or codon 164 was found.     

Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation

Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [125I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [125I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [125I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [125I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [125I]insulin receptor binding was noted at all time points in the molecular layer of the dentate gyrus whereas binding in CA1-CA3 subfields and discrete layers of the Ammon's horn was found to be affected only after 12 h of treatment. These results, when analysed with reference to the observed histological changes and established neurotrophic/protective roles of insulin-like growth factors and insulin, suggest possible involvement of these growth factors in the cascade of neurotrophic events that is associated with the reorganization of the hippocampal formation observed following kainate-induced seizures.     

Binding of 2,4,6,-triiodobenzoic derivatives with blood cells. I. Binding of 125I-labeled uropolin with lymphocytes and erythrocytes during separation of blood in uropolin-dextran gradient

125I-labeled Uropolin (syn. Uropolinum, Uromiro, Urografin) is bound to lymphocytes and erythrocytes if used to isolate lymphocytes in uropolin-dextran gradient. After 24-hr storage of 4 degrees C lymphocytes retained 60% of their radioactivity, and erythrocytes 87% under the same conditions.     

Underutilization of lipid-lowering drugs in older persons with prior myocardial infarction and a serum low-density lipoprotein cholesterol > 125 mg/dl

OBJECTIVE: To investigate the prevalence of aspirin use in older patients with prior myocardial infarction at the time of admission to a nursing home. DESIGN: In a prospective study, the prevalence of aspirin use in 350 consecutive older patients with documented Q-wave myocardial infarction and no contraindications to aspirin use was investigated in patients aged 60 years or older at the time of admission to a nursing home. SETTING: A large, long-term, healthcare facility. PATIENTS: The patients included 231 women and 119 men, mean age 81 +/- 8 years (range 60 to 100). MEASUREMENTS AND MAIN RESULTS: Of the 350 patients with documented Q-wave myocardial infarction and no contraindications to aspirin therapy, 60 patients (17%) were receiving aspirin at the time of admission to the nursing home. CONCLUSION: There is a marked underutilization of aspirin in the treatment of older patients with documented prior myocardial infarction at the time of admission to a nursing home.     

TGF-beta receptor expression on human keratinocytes: a 150 kDa GPI-anchored TGF-beta1 binding protein forms a heteromeric complex with type I and type II receptors

Keratinocytes play a critical role in re-epithelialization during wound healing, and alterations in keratinocyte proliferation and function are associated with the development of various skin diseases. Although it is well documented that TGF-beta has profound effects on keratinocyte growth and function, there is a paucity of information on the types, isoform specificity and complex formation of TGF-beta receptors on keratinocytes. Here, we report that in addition to the types I, II, and III TGF-beta receptors, early passage adult and neonatal human keratinocytes display a cell surface glycosylphosphatidylinositol (GPI)-anchored 150 kDa TGF-beta1 binding protein. The identities of the four proteins were confirmed on the basis of their affinity for TGF-beta isoforms, immunoprecipitation with specific anti-receptor antibodies, sensitivity to phosphatidylinositol specific phospholipase C and dithiothreitol, and 2-dimensional electrophoresis. Interestingly, the antitype I TGF-beta receptor antibody immunoprecipitated not only the type I receptor, but also the type II receptor and the 150 kDa component, suggesting that the 150 kDa component form heteromeric complexes with the signalling receptors. In addition, two-dimensional (nonreducing/reducing) electrophoresis confirmed the occurrence of a heterotrimeric complex consisting of the 150 kDa TGF-beta1 binding protein, the type II receptor, and the type I receptor. This technique also demonstrated the occurrence of types I and II heterodimers and type I homodimers of TGF-beta receptors on keratinocytes, supporting the heterotetrameric model of TGF-beta signalling proposed using mutant cells and cells transfected to overexpress these receptors. The keratinocytes responded to TGF-beta by markedly downregulating all four TGF-beta binding proteins and by potently inhibiting DNA synthesis. The demonstration that the 150 kDa GPI-anchored TGF-beta1 binding protein forms a heteromeric complex with the TGF-beta signalling receptors suggests that this GPI-anchored protein may modify TGF-beta signalling in human keratinocytes.     

Variations in serum ferritin, serum iron, total iron binding capacity and saturation index in elderly hospitalized patients with iron deficiency anaemia after blood transfusion

Five xanthones from the bark of Garcinia cowa, namely 7-O-methylgarcinone E (1), cowanin (2), cowanol (3), cowaxanthone (4), and beta-mangostin (5), were found to possess in vitro antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to 3.00 micrograms/ml. Complete 1H- and 13C-NMR assignments of these compounds are also reported.     

Effect of bushenhuoxue tablet on serum lipid peroxide, blood lipid and blood sugar in type II diabetics

Sixty-eight patients suffering from diabetes mellitus (DM) type II with Kidney Deficiency and blood stasis were enrolled and divided randomly into treatment group (34 cases) and placebo group (34 healthy subjects). The amount of serum lipid peroxide (LPO), blood lipid and blood sugar was determined. The results showed that the serum LPO in treatment group was higher than that in placebo group. The serum LPO increased significantly in DM patients with vascular disease or with uncontrolled blood sugar. The serum LPO was positively correlated with triglyceride (TG). After using Bushenhuoxue Tablet (BSHX) serum LPO lowered, blood sugar decreased and high density lipoprotein-cholesterol (HDL-C)increased in treatment group, but in placebo group these three parameters were not changed significantly. These results indicated that LPO reaction in type II DM patients increased. The higher the blood sugar and TG or complicated with vascular disease, the LPO reaction enhanced markedly. BSHX tablets have the function of reducing the serum LPO and blood sugar, clearing cholesterol. Therefore, this tablet will have a good prospect in the prevention and treatment for DM patients complicated with vascular disease.     

Aging, limitation in physical strength and effects of exercise

HLA typing was performed on 384 individuals of an isolated population of 1,500 people with a familial aggregate of lymphoma and immunodeficiency cases. Eighty-five % of the total population were descendants of the founding couple. First cousin marriages were common. There was a three-fold or higher increase of the following haplotypes as compared to the frequencies in Sheffield: HLA-A28,Bw35, HLA-A28, B18, HLA-A10, B18, HLA-A2, B18,HLA-A11, Bw40 and HLA-A11, B7. The frequency of HLA-A1, B8 was low (5.4%). The most common genotype was HLA-A2, B12/A2, B12 followed by HLA-A2, B12/A28, Bw35. We found 20 HLA homozygous individuals, of these 15 were HLA-A2, b12/a2, b12. There were two possible HLA cross-overs which may be confirmed and three postulated cross-overs which can never be confirmed as one or both parents of the individuals in question are deceased. Some of the haplotypes could be traced back to the first, second and third generations, i.e. to the first half of the nineteenth century. No single haplotype or antigen was shared by the patients.     

2-[125I]Iodomelatonin binding sites in the quail heart: characteristics, distribution and modulation by guanine nucleotides and cations

To investigate whether melatonin has a direct action on the cardiovascular system, putative melatonin receptors were studied in quail heart membrane preparations using the specific melatonin agonist 2-[125I]iodomelatonin (125I]Mel, as the radioligand. The [125I]mel binding demonstrated in the mature quail heart was saturable, highly 5.2 pM; Bmax = 1.32 +/- 0.25 fmol/mg protein; n = 8). The linear Scatchard plots and the close to unity Hill coefficient indicated a single class of binding sites. The pharmacological profile was in the affinity order of 2-iodomelatonin = 2-phenylmelatonin > melatonin > 6-chloromelatonin > 6-hydroxymelatonin > 6-sulphatoxymelatonin > N-acetylserotonin>5-hydroxytryptamine. Guanosine 5'-triphosphate and guanosine 5'-O-(3-thiotriphosphate) (GTP gammaS) dose dependently inhibited the binding. Ten microM GTPgammaS lowered the binding affinity by 50% in saturation studies. The order of potency of inhibition by cations was: Ca2+ > Mg2+ > Li+ > Na+ > K+ > choline chloride. Contrary to most other melatonin binding sites, millimolar concentrations of Ca2+ and Mg2+ did not promote binding in the quail heart membranes. In vitro autoradiography indicated homogenous labeling in the heart. Our results demonstrated [125I]Mel binding sites in the quail heart. That guanine nucleotides and Na+ inhibited the binding indicated that these putative melatonin receptors are coupled to guanine nucleotide-binding proteins (G-proteins).