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Biomedical subjects

M Blum

Publications and source records attributed to M Blum.

At least 217 records · Page 12Linked to original sources
PubMed1989

N-acetylation pharmacogenetics: a gene deletion causes absence of arylamine N-acetyltransferase in liver of slow acetylator rabbits.

The New Zealand White rabbit provides a widely used animal model for the human acetylation polymorphism, which confers marked interindividual variation in the effect and toxicity of numerous drugs, chemicals, and potential carcinogens. The relationship of a recently isolated cDNA clone, designated rnat, to genetically polymorphic arylamine N-acetyltransferase (NAT; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) of rabbit liver was established by its expression in monkey kidney COS-1 cells: (i) cytosols from transfected cultures contained high levels of an Ac-CoA-dependent NAT activity, which was kinetically indistinguishable from that observed in cytosols from livers of genetically rapid-acetylator rabbits; (ii) transfected cells also contained an immunoreactive protein, recognized by NAT-specific antibodies, with identical electrophoretic mobility to NAT from rabbit liver. The rnat clone and anti-NAT antibodies were then used to study the relationship between NAT activity, liver enzyme protein, and the level of mRNA in livers from in vivo phenotyped rapid- and slow-acetylator rabbits. Livers from slow acetylators were devoid of both immunodetectable NAT protein and its corresponding mRNA. Analysis of genomic DNA with a panel of restriction enzymes revealed the loss of specific hybridizing bands in the DNA of slow-acetylator rabbits. These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein.

Acetylation↗
PubMed1989

Androgen regulation of proopiomelanocortin gene expression and peptide content in the basal hypothalamus.

Previous studies have shown that the hypothalamic content of beta-endorphin (beta EP) and other POMC-derived peptides increases 4 weeks after orchiectomy and that this increase can be prevented by testosterone replacement. To determine if these changes in hypothalamic beta EP content are secondary to changes in the biosynthesis of beta EP we have measured POMC mRNA levels in intact and castrated adult male rats with and without testosterone replacement. After either 2 or 4 weeks of treatment the medial basal hypothalamus (MBH) was collected and homogenized. An aliquot was removed for beta EP RIA, RNA was isolated, and the amount of POMC mRNA was measured using a solution hybridization S1 nuclease protection assay. In agreement with previous results, the content of beta EP in the MBH from 4-week castrated animals (7930 +/- 568 pg/mg protein) was significantly increased compared to that in either castrated and testosterone-replaced rats (5792 +/- 568 pg/mg; P less than 0.02) or intact controls (6027 +/- 349 pg/mg; P less than 0.02). POMC mRNA in the MBH from the 4-week castrated group was significantly higher compared to that in the castrated and testosterone-replaced group (2.61 +/- 0.33 vs. 1.7 +/- 0.22 pg/microgram RNA; P less than 0.05), which is parallel to the changes we found in beta EP peptide levels. Two weeks after castration no significant change was detected in the beta EP content in the MBH from castrated rats (5401 +/- 318 pg/mg protein) compared to that in the castrated and testosterone-replaced group (4848 +/- 304 pg/mg protein). However, we were able to detect a significant difference in the amount of POMC mRNA in the 2-week castrated group (1.47 +/- 0.267 pg/microgram RNA) compared to that in the 2-week castrated and testosterone-replaced group (0.815 +/- 0.061 pg/microgram RNA; P less than 0.05). The finding that testosterone replacement for either 2 or 4 weeks to castrated rats significantly reduced POMC mRNA levels suggests that sex steroids have an inhibitory effect on the biosynthesis of POMC in the MBH.

Androgens↗
PubMed1989

Modulation of basal and corticotropin-releasing factor-stimulated proopiomelanocortin gene expression by vasopressin in rat anterior pituitary.

In several anterior pituitary hormone systems, factors that stimulate hormone release also stimulate hormone biosynthesis. In the corticotropes of the anterior pituitary, CRF stimulates ACTH release as well as cAMP accumulation and transcription of the POMC gene. Arginine vasopressin (AVP) is a well documented coregulator of ACTH release and potentiates CRF-stimulated cAMP accumulation. The present studies were undertaken to determine if AVP also potentiates the early effects of CRF on POMC gene expression in rat anterior pituitary primary cultures. We have measured the levels of the POMC primary transcript, processing intermediate, and mature mRNA in nuclear RNA samples and POMC mRNA in cytoplasmic RNA samples as well as ACTH release after treatment with CRF and/or AVP. After a 30-min treatment with 0.5 nM CRF, POMC primary transcript levels were increased by 200-400%. Thirty-minute or 1-h treatments with AVP alone (10 or 100 nM) did not affect primary transcript levels, but increased the amount of the processing intermediate, while a 2-h incubation with 100 nM AVP significantly decreased POMC primary transcript levels. The effects of CRF on the POMC primary transcript and nuclear processing intermediate were not potentiated by cotreatment with AVP, although a potentiation of CRF-stimulated ACTH release was observed. POMC nuclear and cytoplasmic mRNA levels were not affected by these 2-h or less treatments, while an 18-h incubation with 0.5 nM CRF alone or in combination with 100 nM AVP increased POMC cytoplasmic mRNA levels to about 140% of vehicle-treated control values. When a 1-h AVP treatment (100 nM) preceded presentation of CRF, we observed an attenuation of the stimulation of POMC primary transcript and processing intermediate levels by the 1-h CRF treatment. The effects of CRF on POMC primary transcript and processing intermediate levels in these experiments are consistent with a CRF-induced increase in POMC gene transcription. Our findings that AVP decreased primary transcript levels and attenuated the effects of CRF on this end point suggest that: 1) AVP clearly does not act in a synergistic manner with CRF to stimulate POMC gene expression; and 2) AVP possibly affects RNA stability and/or processing.

Adrenocorticotropic Hormone↗
PubMed1989

The use of preoperative localization of adenomas of the parathyroid glands by thallium-technetium subtraction scintigraphy, high-resolution ultrasonography and computed tomography.

Thirty-six patients with primary hyperparathyroidism were studied preoperatively by thallium-201 and technetium-99m pertechnetate subtraction (Tl-201/Tc-99m) scintigraphy, high-resolution real time ultrasonography and computed tomographic (CT) scanning. None of the patients had had previous surgical treatment of the parathyroid or thyroid glands. All of the patients underwent systematic bilateral exploration of the neck. All of the patients were successfully explored and 41 abnormal parathyroid glands were identified. Five patients had two adenomas. In six instances, adenomas were identified in ectopic anatomic sites. The sensitivity of correctly localizing the abnormal glands with these techniques was 49 per cent for the Tl-201/Tc-99m scintigraphy, 34 per cent for ultrasonography and 41 per cent for CT scanning. The Tl-201/Tc-99m scintigrams detected two of the six ectopically located adenomas, CT detected one, while ultrasound detected none. The five patients with multiple adenomas were not accurately identified as having multiple gland enlargement by any of these studies. Therefore, preoperative localization studies with these three techniques did not provide reliable information for initial bilateral exploration of the neck.

Adenoma↗
PubMed1989

Estrogen replacement therapy (ERT) by a special regimen in the years following menopause.

A group of 16 post-menopausal women, mean age 56.6 years, with typical and non typical climacteric symptoms, were treated by a combination of estrogen (Premarin 0.625) followed by clomiphene citrate. Beside an improvement in musculo-skeletal pain and a marked improvement of their sense of well-being there was an increase in Hdl cholesterol, the protecting factor against M.I., while weight and blood pressure remained stable. The link between mood, sleep and libido improvement and catecholamine raise, is discussed, and so are the effects on blood pressure, in long lasting ERT.

Blood Pressure↗
PubMed1989

[Serum fructosamine and oral contraception].

In 21 normal women on the combined oral contraceptive pill we examined the level of serum fructosamine before, and 3-5 months after starting the pill. The mean serum fructosamine concentration did not change significantly after administration of the pill (2.17 mmol/l before and 2.22 after). It increased in 14 (66.6%) and decreased in 7. Thus the screening of fructosamine levels is not a useful method of detecting glucose intolerance, a known side-effect of the combined oral contraceptive pill.

Adolescent↗
PubMed1989

Protein intake and kidney function in humans: its effect on 'normal aging'.

The effect of dietary protein on kidney function expressed by creatinine clearance was studied in healthy subjects following a "normal" unrestricted protein diet and compared with a group of vegetarians maintained on a long-term low-protein diet. Both groups had similar kidney function and displayed the same rate of progressive deterioration in renal function with age. These results suggest that, in contrast with the important therapeutic effect of low-protein intake on the progressive deterioration of kidney function in diseased kidneys, such a diet does not significantly affect kidney function with "normal aging" in healthy subjects.

Adult↗
PubMed1989

[Advantages of single-dose treatment of vaginal Candida albicans infection].

One-hundred forty women (60 pregnant and 80 non-pregnant women) with a history of Candida albicans infection were examined one month before treatment and were reexamined one month after treatment. Administration of a single agent consisting of 2,300 mg tablets of GynoTragoven (isoconazole nitrate, Schering, AG) resulted in immediate clinical improvement. One month after treatment, the success rate was 85-100 p. cent for non-pregnant women, and 83-100 p. cent for pregnant women. No side-effects were observed following therapy. According to studies published, a high percentage of infections develop during pregnancy, especially during the second (35 p. cent) and third (31.5 p. cent) trimesters. Because of the high rate of infections during pregnancy, preventive therapy should be considered during the final weeks of pregnancy, to prevent intrauterine infection during parturition.

Adult↗
PubMed1988

Effect of secondary substrate binding in penicillopepsin: contributions of subsites S3 and S2' to kcat.

The kinetic parameters kcat, KM, and kcat/KM were determined at 25 degrees C and pH 4.5, 5.5, and 6.0 for the series of penicillopepsin substrates Ac-Alam-Lys-(NO2)Phe-Alan-amide, where (NO2)Phe is p-nitrophenylalanine and m and n equal 0-3. KM values at pH 6.0 were the same for all 12 peptides and averaged 0.088 +/- 0.02 mM but increased to different degrees at lower pH. In contrast, kcat values increased with increasing chain length. At pH 6 and at the pH optimum of kcat, the largest increases (about 37-fold on average) were obtained when alanine residues were added in positions P2' and P3. Only 1-2-fold increases were observed for positions P2, P3', P4, and P4'. These results show that occupation of subsites S2' and S3 is largely responsible for the rate enhancements caused by secondary substrate interactions with this series of peptides. Additional support for an important role of subsite S3 comes from the observation that the two peptides where m = 1 and n = 1 or 2, respectively, are cleaved not only between lysine and p-nitrophenylalanine but also between the latter and alanine, suggesting that occupation of subsite S3 by the N-terminal alanine overcomes the unfavorable interaction of alanine in subsite P1'. Subsite S3 is also important in the binding of pepstatin analogues and in transpeptidation reactions. It is proposed that the roles of subsites S3 and S2' are to facilitate the conversion of the first enzyme-substrate complex into a productive complex and to assist in the distortion of the scissile bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid Endopeptidases↗
PubMed1988

Ataxia telangiectasia resists gene cloning: an account of parameters determining gene transfer into human recipient cells.

A subclone of an SV40-transformed fibroblast cell line from a patient with Ataxia telangiectasia (AT) with a relatively high rate of DNA uptake was isolated. However, more than 65000 independent genomic transfectants (using wild-type human DNA) did not contain the functional AT gene. This number represents the statistical distribution of an amount of DNA equivalent to more than three times the haploid human genome. The transfectants were screened by an X ray selection protocol that could rescue a single wild-type cell out of a population of 10(6) AT cells. This suggests a reversion frequency for AT of below 10(-8). The DNA uptake into human cells is compared with that into NIH3T3 cells and future possibilities for the isolation of human repair genes are discussed.

Ataxia Telangiectasia↗
PubMed1988

The link between contraceptive methods and Chlamydia trachomatis infection.

The effect of various contraceptive methods on Chlamydia trachomatis (CT) infection was examined in a group of 158 women, with a mean age of 26.9 years, patients of a family planning clinic. Their symptoms were mild abdominal pain or vaginal discharge. Antibodies to CT were examined by an indirect immunoperoxidase assay, with a commercial kit. From each patient a vaginal smear was collected for bacteriologic and mycologic study. In group I, consisting of 30 married women with a mean age of 31 years, 5 (16.7%) IUD users had a positive test for CT antibodies. In group II, comprising 57 women, with a mean age of 23.3 years, 22 (38.6%) oral contraceptive (OC) users, of whom 94.7% were unmarried, had positive tests for CT antibodies. The difference between these two groups was statistically significant (p less than 0.05). In group III, comprising 71 women with a mean age of 28.1 years, 62% unmarried and using other contraceptive methods, 15 (21.1%) had a positive test for CT antibodies. The incidence of CT infection was not different in the 3 groups under study, when the factors of age and marital status were taken into consideration (p greater than 0.30). Bacterial vaginal infection was found in 43.3% of the IUD users, compared with only 14% of the OC users (p less than 0.01). In contrast, in the OC users, candidiasis was predominant, the difference from the other groups being statistically significant (p less than 0.001). The women with positive antibodies also more frequently had colonies of bacterial and mycological vaginal infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Influence of oral contraceptive treatment on blood pressure and 24-hour urinary catecholamine excretion in smoking as compared with non-smoking women.

Microgynon-30 was administered to 15 smoking (group B) and 14 non-smoking young women (group A) for a period of 4 months. Prior to the institution of treatment supine blood pressure and daily urinary catecholamine excretion (DUCE) were measured in both groups of patients. Both values were elevated in group B in comparison with group A. Treatment with Microgynon-30 for 4 months induced a significant increase in DUCE in both groups, the increase being most marked in group B (p less than 0.0004). The increased catecholamine excretion accompanied small non-significant elevations in blood pressure. It is concluded that treatment with low-dosage estrogen oral contraceptives produces a significant increase in daily catecholamine excretion, especially in patients who smoke.

Adolescent↗
PubMed1988

Biologically active corticotropin-releasing hormone in maternal and fetal plasma during pregnancy.

Corticotropin-releasing hormone was measured in the plasma of 110 pregnant women and in the umbilical cord plasma of 25 premature infants and 43 infants born at term. Mean maternal plasma corticotropin-releasing hormone was undetectable (less than 41 pg/ml) until mid-second trimester, rose to a mean of 204 +/- 24 pg/ml by 30 weeks' gestation, to 326 +/- 41 by 35 weeks, and then rose sharply near term, with a mean of 2930 pg/ml at 38 to 40 weeks' gestation. Sequential measurements in seven pregnant women confirmed that plasma corticotropin-releasing hormone rose in a predictable pattern, with a dramatic increase in the final weeks of pregnancy. There was little hour-to-hour variability in maternal plasma concentrations. Corticotropin-releasing hormone was also detectable in umbilical cord plasma; mean corticotropin-releasing hormone was 194 +/- 44 in the preterm infants and 150 +/- 19 in the term infants. The corticotropin-releasing hormone extracted from both the maternal and fetal circulation was biologically active in vitro and caused the dose-dependent release of adrenocorticotropic hormone and beta-endorphin from cultured rat anterior pituitary cells. A significant correlation was found between maternal plasma corticotropin-releasing hormone and cortisol levels the morning after betamethasone administration, a finding that supports a physiologic role for maternal plasma corticotropin-releasing hormone. We conclude that the placenta secretes large amounts of biologically active corticotropin-releasing hormone into both the maternal and fetal circulation during pregnancy. We demonstrate that this corticotropin-releasing hormone is secreted into the maternal plasma in a reproducible pattern during normal term pregnancy and suggest that sequential corticotropin-releasing hormone measurements may prove to be of clinical utility. In addition, placental corticotropin-releasing hormone may be an important modulator of the hypothalamic-pituitary-adrenal axis during pregnancy.

Adolescent↗
PubMed1988

Sclerosing peritonitis. Possible early diagnosis by computerized tomography of the abdomen.

Sclerosing peritonitis (SP) has come to be recognized as a serious complication of peritoneal dialysis (PD). However, diagnosis is often established at a late stage of the disease and at laparotomy. The use of computerized tomography (CT) of the abdomen in 2 patients, clinically suspected of suffering from SP, revealed loculated ascites, adherent bowel loops, bowel lumenal narrowing, and thickening of the peritoneal membrane. Such radiological changes in patients on PD seem highly consistent with a diagnosis of SP. We feel that CT of the abdomen may help in attaining an early, correct, and noninvasive diagnosis of SP. We recommend that CT of the abdomen be performed in any patient on chronic PD who has clinical manifestations suggestive of SP. Early diagnosis of SP can lead to early cessation of PD and hopeful recovery of the peritoneal membranes and space.

Female↗
PubMed1988

Stimulation of pituitary luteinizing hormone secretion by gonadotropin-releasing hormone is not coupled to beta-luteinizing hormone gene transcription.

The physiological stimulation and inhibition of release of several peptide and protein hormones appears to be associated with transcription of the respective peptide- and protein hormone-encoding genes. In the current studies we investigated whether this was also true for the rat pituitary LH system. Using an anterior pituitary primary tissue culture system, we have analyzed the effects of 10(-9) M GnRH on beta LH gene transcription using a transcription run-on assay, and on nuclear beta LH RNA levels using a highly sensitive solution hybridization-S1-nuclease protection assay. GnRH-stimulated release of LH does not appear to be coupled to a significant change in the rate of beta LH gene transcription, but is associated with both a 2- to 3-fold increase in levels of the beta LH primary transcript and processing intermediates and a rapid decrease in the levels of fully processed beta LH mRNA in the nucleus. No significant change in beta LH cytoplasmic mRNA levels, however, was associated with GnRH-stimulated release of LH, in vitro. Our findings suggest that unlike several other peptide and protein hormone systems, stimulated release of beta LH by GnRH in vitro is not associated with an increase in beta LH gene transcription or cytoplasmic mRNA levels.

Animals↗