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Biomedical subjects

L Weiner

Publications and source records attributed to L Weiner.

At least 73 records · Page 4Linked to original sources

Interferon gamma increases in vitro and in vivo expression of C1 inhibitor.

C1 inhibitor (C1 INH) is the major protease inhibitor of the first components of the classic complement system and of the proteases of the Hageman factor pathways. Since C1 INH may modulate inflammatory reactions associated with complement and contact system activation, we sought to determine if the cytokine gamma interferon (IFN-gamma) could modulate C1 INH production. Initial studies investigated the effect of IFN-gamma on the molecular and protein expression of C1 INH in human erythroleukemia (HEL) cells. HEL cells constitutively expressed the 2.1 kb mRNA for C1 INH. IFN-gamma (50 to 1,000 U/mL), but not interferon alpha or beta, increased twofold the amount of C1 INH mRNA expressed within HEL cells. Similarly, this cytokine increased HEL cell C1 INH synthesis of a 105 Kd protein 10-fold, from 1.9 +/- 0.5 microgram C1 INH antigen per 10(8) cells (mean +/- SEM) to 19 +/- 8 micrograms/10(8) cells in 8 days. C1 INH produced by HEL cells after IFN-gamma stimulation had fully intact kallikrein neutralizing activity. Moreover, conditioned media of IFN-gamma-treated HEL cells accumulated more secreted C1 INH in 8 days (6.7 micrograms/mL/10(8) cells) than untreated cells (0.6 microgram/mL/10(8) cells). Additional studies were done on plasma specimens from 22 patients with metastatic colorectal carcinoma who received IFN-gamma daily for 4 days by intravenous infusion. Before treatment, the mean +/- SEM C1 INH levels in these patients was 438 +/- 16 micrograms/mL. At day 10 from the start of the infusion, the plasma C1 INH in these patients increased to 586 +/- 32 micrograms/mL (P less than .0001). The extent of rise of plasma C1 INH after IFN-gamma treatment was independent of dose from 0.01 to 40 U/m2. After 30 days, the mean plasma C1 INH levels decreased to 502 +/- 27 micrograms/mL. These combined studies indicate that IFN-gamma can increase C1 INH protein expression in vitro and in vivo.

Blotting, Northern↗

Lead exposure among mothers and their newborns in Toronto.

Recent studies have suggested that a fetal blood lead level of 0.48 mumol/L (much lower than 1.21 mumol/L, which is the level previously believed to be toxic to the developing brain) may impair brain development permanently. We measured the maternal and umbilical cord blood levels of lead and free erythrocyte protoporphyrin (FEP) among 95 consecutive mother-infant pairs to determine whether neonates in Toronto are in the high-risk group. There was a significant correlation between the maternal and the cord blood lead levels (r = 0.59, p less than 0.0001). Most (99%) of the infants had cord blood lead levels below 0.34 mumol/L; in 11 cases the levels were below the detection limit of 0.01 mumol/L. The cord blood FEP levels were higher than the maternal levels. The US Centers for Disease Control, Atlanta, currently finds acceptable a blood FEP level of 0.62 mumol/L among children up to 10 years of age; however, this is not applicable to newborns since their higher FEP levels apparently reflect immature heme synthesis and increased erythrocyte volume rather than lead poisoning. Our data suggest that living in Toronto does not impose increased teratogenic risk from intrauterine exposure to lead; however, residents in high-risk areas should be followed up.

Adult↗

Phage shock protein, a stress protein of Escherichia coli.

Filamentous phage infection induces the synthesis of large amounts of an Escherichia coli protein, phage shock protein (Psp), the product of a previously undescribed gene. This induction is due to the phage gene IV protein, pIV, an integral membrane protein. The uninduced level of Psp is undetectable, but when induced by prolonged synthesis of pIV, it can become one of the most abundant proteins in the cell. Psp is also synthesized transiently in response to several stresses (heat, ethanol, and osmotic shock). High-level synthesis occurs only after extreme treatment. Unlike the members of the heat shock regulon, Psp induction does not require the heat shock sigma factor, sigma 32; some stimuli that elicit sigma 32-dependent heat shock proteins do not induce Psp synthesis. The level of Psp induction after extreme stress is even higher in sigma 32 mutant cells, which are unable to mount a normal heat shock response, suggesting that these parallel stress responses are interrelated.

Bacterial Proteins↗

Cadralazine challenge in patients with previous hydralazine-induced lupus: a 6-month study.

The objective of this study was to investigate the effect of cadralazine in patients who had previously had hydralazine-induced lupus. There were 11 patients included in the study, 10 of whom were treated for 6 months with 15 or 20 mg cadralazine given once daily in combination with beta-blockers and diuretics. All patients had a history of hydralazine-induced lupus and were slow acetylators. None of the patients included in this study showed any current signs or symptoms of drug-induced lupus. No evidence of lupus-like symptoms or of immunologic laboratory abnormalities were found during the study period. Side effects associated with vasodilator therapy were noted in some patients but were transient and mild. We concluded that a cross-reaction between cadralazine and hydralazine does not seem likely to occur and that cadralazine, because of its chemical properties, probably will not give rise to drug-induced lupus.

Acetylation↗

FAS/FAE: focusing prevention on women at risk.

Consumption of alcohol during pregnancy is well recognized as a risk factor associated with adverse fetal development. While precise safe or dangerous levels of maternal drinking have not been identified, it is clear that the women who drink most heavily are at the greatest risk. Prevention of alcohol-related birth defects requires development of programs directed to the special needs of addicted women and their families. The nature of addiction suggests that direct interventions focused on changing individual drinking behavior have the best chance of success.

Alcoholism↗

Extranodal non-T-cell lymphoblastic lymphoma in adults. A report of two cases.

Typical adult cases of malignant lymphoma, diffuse, lymphoblastic type (MLLB), are of the T-cell immunophenotype and occur as mediastinal masses. The authors report two unusual adult cases with initial extranodal sites of involvement and non-T-cell immunophenotype that were originally misclassified. One patient presented with a right submaxillary salivary gland mass and the other presented with a T7-8 spinal cord compression resulting from a vertebral body tumor. A lymphoblastic leukemic phase developed in both patients after 15 months and 5 months, respectively. The bone marrow blasts of both patients had positive results for cluster designation (CD) 10, CD19, HLA-DR, and terminal deoxynucleotidyl transferase. Because both extranodal sites of presentation and non-T-cell immunophenotype are unusual in adult MLLB, these features may have contributed to the original misclassification of these lesions.

Adult↗

Effects of bisoprolol on blood pressure, serum lipids and HDL-cholesterol in essential hypertension.

Fifty patients with essential hypertension WHO Grades I-II have been treated for 3 months with bisoprolol, a new selective beta blocker, in doses up to 40 mg once daily. Forty-three patients reached the preset target diastolic blood pressure of less than or equal to 90 mmHg on a mean daily dose of 16.8 mg bisoprolol. There was no effect on serum lipids and HDL-cholesterol during the study. The side-effects were mild and were those usually associated with beta-blocking therapy.

Adrenergic beta-Antagonists↗

Efficacy and safety of bisoprolol and atenolol in patients with mild to moderate hypertension: a double-blind, parallel group international multicentre study.

Three hundred and fifteen patients were randomly allocated to treatment for six months with bisoprolol 5 or 10 mg day-1 or atenolol, 50 mg day-1, in a double-blind, double-dummy parallel group, international multicentre study. Two hundred and ninety-two (175 men and 117 women) were eligible for statistical follow-up. Their mean age was 52.6 years (range 28-70). All patients had a supine diastolic blood pressure of 95-120 mmHg on two occasions during the four weeks of placebo treatment. Twenty-four patients ended the study prematurely and a further 19 had their regimes changed because of an insufficient effect. The reasons for drop-out were similar in the three treatment groups. Thus, 249 patients continued to receive the treatment they were allocated to, with 80, 83 and 86 patients in the three respective groups. The sex and age distributions and the number of previously treated hypertensives were similar in the three groups. At the end of placebo treatment the supine blood pressures in the three groups (bisoprolol 5 or 10 mg day-1 or atenolol 50 mg day-1, respectively) were 163.9/102.5, 157.4/101.8 and 160.0/102.2 mmHg, respectively. The systolic blood pressure was higher (P less than 0.05) in the group receiving bisoprolol 5 mg day-1 than in the 10 mg day-1 group. After 26 weeks of treatment the supine blood pressures in the three groups were 150.6/90.8, 142.0/89.1 and 148.6/91.7 mmHg, respectively. The largest estimated difference in blood pressure reduction was 4.6/2.3 mmHg between the group receiving bisoprolol 10 mg day-1 and the group receiving atenolol 50 mg day-1. A reduction in mean blood pressure of greater than or equal to 10 mmHg was noted in 66% of the patients in the bisoprolol group (10 mg day-1), in the other groups 66 and 59%, n.s. Bisoprolol is effective, well-tolerated and safe in the treatment of hypertension. A daily dose of 5 mg seems recommendable for the majority of hypertensive patients and seems equipotent with 50 mg day-1 of atenolol in the present study.

Adult↗

Antihypertensive effects of bisoprolol during once daily administration in patients with essential hypertension. A dose-ranging study with parallel groups.

Bisoprolol is a new beta 1-selective beta-blocking agent with a plasma half-time of 10-12 h and without partial agonist properties. Forty-eight patients with essential hypertension were randomly treated with 5, 10, or 20 mg bisoprolol given once daily for 8 weeks. All measurements were made 24 hours after the last dose. Bisoprolol had antihypertensive and beta-blocking properties both at rest and during exercise. The 20 mg dosage regimen was more effective than that of 5 mg and 10 mg. The drug was well tolerated and all the 48 patients completed the trial.

Adrenergic beta-Antagonists↗

Dose-effect relationship and long-term effects of bisoprolol in mild to moderate hypertension.

In an initial double-blind randomized study with three parallel groups, 48 patients, mean age 49.6 years (32-65 years), with hypertension WHO I-II, were given bisoprolol in doses of 5, 10, and 20 mg. Bisoprolol is a new beta 1-selective beta-blocking agent with a plasma half-life of 10-12 h and without intrinsic sympathomimetic activity (ISA). After the initial 8 weeks, systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) measured at rest and during exercise 24 h after last drug intake showed a significant decrease for all three parameters in all three treatment groups. There were no differences in efficacy between the 5 and 10 mg doses of bisoprolol, whereas 20 mg was significantly more effective than both 5 mg (p less than 0.01) and 10 mg (p less than 0.05). After 10 months of treatment with dose adjustments up or down, the reduction of SBP, DBP, and HR at rest and during exercise remained unchanged. One patient had an acute myocardial infarction (AMI) and died during the study; another patient had a car accident in which he got asphyxial cerebral lesions and could not complete the study. Twelve patients spontaneously expressed side effects of the kind normally seen in treatment with beta-blocking agents. Three of them complained of cold hands and feet, and one of them was unable to complete the study. The rest of the adverse effects were mild, and 45 patients completed the long-term study. Laboratory safety tests were normal, and there were no significant changes in the lipoprotein patterns (cholesterol, HDL cholesterol, and triglycerides).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

A comparison of the effects of bisoprolol and atenolol on lipoprotein concentrations and blood pressure.

Forty-two patients (28 men, 14 women, age range 27-65 years) with newly discovered mild to moderate hypertension were randomly allocated to treatment with either bisoprolol or atenolol for a double-blind comparison of these two beta 1-adrenoceptor blocking drugs. Two doses of each drug (10 and 20 mg/d for bisoprolol and 50 and 100 mg/d for atenolol) were given, each dose for a 3-month period, the dose to be given first being decided by random allocation of the patients. During the second 3-month period, the patient received the alternative dose. After treatment for 6 and 12 weeks with each dose, the blood pressure, heart rate, and lipoprotein concentrations were checked. Bisoprolol treatment (both 10 and 20 mg) resulted in a decrease in blood pressure in the supine position from 154/100 to 138/89 mm Hg; and atenolol treatment resulted in decreases from 161/102 to 145/90 mm Hg (50 mg/d) and 146/91 mm Hg (100 mg/d). The drugs and doses did not differ in their effect. The triglyceride content in very low density lipoproteins (VLDL) increased during treatment with bisoprolol (10 mg/d) from 1.04 to 1.31 mmol/l (p less than 0.05); during treatment with atenolol (100 mg/d) it increased from 0.90 to 1.14 mmol/l (p less than 0.05). The cholesterol content in low density lipoproteins did not change, but that in high density lipoproteins (HDL) decreased during treatment with both drugs (from 1.22 to 1.10 mmol/l with bisoprolol 20 mg/d, p less than 0.01: and from 1.21 to 1.13 mmol/l with atenolol 100 mg/d, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Long-term effects of bisoprolol on blood pressure, serum lipids, and HDL-cholesterol in patients with essential hypertension.

The objective of the study was to evaluate the effect of continuous therapy with bisoprolol on blood pressure, serum lipids, and HDL-cholesterol over a period of 10 months following an initial 3-month titration and short-term treatment period. The results of the short-term study have been presented in a separate report. Forty-two patients entered into this long-term study, and 41 of them completed the 10-month treatment period. The mean supine blood pressure was 134/85 mm Hg at the end of the short-term study and was maintained at 137/85 mm Hg after 10 months on bisoprolol. At the end of the study, all patients but one had a supine diastolic blood pressure of less than or equal to 90 mm Hg with a dose of 2.5-40 mg bisoprolol. Three of the patients required concomitant use of hydrochlorothiazide to keep this pressure level. A small but statistically significant increase in serum triglycerides was observed from the start of the titration period to the end of the long-term study. Within each study, the changes were not significant. No significant changes were observed for total cholesterol, or for low density lipoprotein (LDL)- or high density lipoprotein (HDL)-cholesterol. The side effects were rare and the usual for beta-blockers.

Adrenergic beta-Antagonists↗

Evaluation of a monoclonal antibody test to detect chlamydia in cervical and urethral specimens.

The MicroTrak Chlamydia trachomatis Direct Specimen Test (MT; Syva Co., Palo Alto, Calif.) was compared with cell culture in two patient populations. The sensitivity of the MT for a low-prevalence group was significantly lower (59.6%) than that for a high-prevalence group (84.4%). The results underscored the need to run the MT in parallel with culture initially if the prevalence of chlamydial infections is unknown and questioned the usefulness of the MT as a screening test for chlamydia in low-prevalence populations.

Antibodies, Bacterial↗