Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence.

The primary structure of a bone-specific sialoprotein was deduced from cloned cDNA. One of the cDNA clones isolated from a rat osteosarcoma (ROS 17/2.8) phage lambda gt11 library had a 1473-base-pair-long insert that encoded a protein with 317 amino acid residues. This cDNA clone appears to represent the complete coding region of sialoprotein mRNA, including a putative AUG initiation codon and a signal peptide sequence. The amino acid sequence deduced from the cDNA contains several Ser-Xaa-Glu sequences, possibly representing attachment points for O-glycosidically linked oligosaccharides and one Asn-Xaa-Ser sequence representing a likely site for the N-glycosidically linked oligosaccharide. An interesting observation is the Gly-Arg-Gly-Asp-Ser sequence, which is identical to the cell-binding sequence identified in fibronectin. The presence of this sequence prompted us to investigate the cell-binding properties of sialoprotein. The ROS 17/2.8 cells attached and attained a spread morphology on surfaces coated with sialoprotein. We could demonstrate that synthetic Arg-Gly-Asp-containing peptides efficiently inhibited the attachment of cells to sialoprotein-coated substrates. The results show that the Arg-Gly-Asp sequence also confers cell-binding properties on bone-specific sialoprotein. To better reflect the potential function of bone sialoprotein--we propose the name "osteopontin" for this protein.     

Follow-up study after colorectal polypectomy. The predictive value of a negative double-contrast barium enema

In this study the predictive value of a negative double-contrast barium enema for colonic polyps has been calculated as the ratio of the number of true negative radiologic examinations to the total number of negative radiologic examinations. The total number of negative double-contrast barium enemas for polyps of the colon was 357 in 228 consecutive patients with previous or suspected neoplastic colonic polyps examined in the period 1977-84. The predictive value of a negative double-contrast barium enema for all colonic polyps regardless of size was 87% (95% confidence interval, 84-91%). The corresponding predictive value of a negative result for polyps larger than 10 mm in diameter was 98% (95% confidence interval, 97-100%). Polyps that had not been detected by radiography were removed by colonoscopy, and 85% of them were available for histological examination. No cancers were found. The polyps were primarily neoplastic, but metaplastic and juvenile polyps were also ascertained.     

Small basic proteins of myelin from central and peripheral nervous systems are encoded by the same gene.

Peripheral nervous system (PNS) and central nervous system (CNS) rodent myelins, which are produced by different cell types, share common morphological and functional characteristics although their major integral membrane proteins are completely different. Both types of myelin however, contain sets of four myelin basic proteins (MBPs), which share similar immunochemical and electrophoretic properties. We have isolated and characterized cDNA clones corresponding to the rat mRNAs encoding the small MBPs (SMBPs) found in both CNS and PNS myelin. Sequence analysis of these clones indicate that SMBPs in both divisions of the nervous system are encoded by the same nucleotide sequences, which suggests that they are the products of the same gene expressed in both oligodendrocyte and Schwann cells. In dot-blot hybridization experiments with the CNS SMBP cDNA as a probe, it was shown that there is a 20-fold higher level of MBP mRNA in a CNS myelin fraction than in total brainstem mRNA. It also was found that in optic and sciatic nerves, which contain oligodendrocytes and Schwann cells respectively, there are higher levels (4-fold and 2-fold, respectively) of MBP mRNA than in brainstem. Blot-hybridization experiments showed that a probe derived from the coding region of the rat SMBP cDNA hybridizes to an homologous mRNA (approximately equal to 2.6 kilobases) present in human optic nerve, which is not detectable with a probe derived from the 3' untranslated region. This conservation of coding-region sequences is in accord with the highly homologous amino acid sequences reported for the MBPs in the two species.     

多普勒组织成像技术对高血压患者左室舒张功能的评价

目的：探讨多普勒组织成像(DTI)技术评价高血压病(EH)患者左室舒张功能的价值，以寻求一种可靠、客观的评价高血压左室舒张功能的新方法。方法：采用放免法测定19例正常人和41例EH患者(伴心肌肥厚者19例和不伴心肌肥厚者22例)的血清I型前胶原(PC I)和Ⅱ型前胶原(PC Ⅱ)的浓度。用DTI法检测正常人及EH患者二尖瓣环舒张早期运动速度(Ea)、舒张晚期运动速度(Aa)及Ea／Aa，并用二尖瓣血流多普勒法检测舒张期血流速度E、A及E／A，比较两种方法测值与血清I、Ⅱ型前胶原的相关性。结果：1．EH患者非左室肥厚(non—LVH)组及左室肥厚(LVH)组二尖瓣口血流参数、二尖瓣环DTI参数均明显低于正常对照组(P＜0．01)；2．EH患者non—LVH组与LVH组间E、E／A无明显差别(P＞0．05)，但LVH组Ea、Ea／Aa明显低于non—LVH组(P＜0．05)；3．EH患者non—LVH组血清PC I、PC Ⅱ与E／A及Ea／Aa均呈负相关(r＝—0．58P＜0．01、r＝—0．61P＜0．01及r＝—0．62P＜0．01、r＝—0．49P＜0．05)；而LVH组血清PC I、PCⅡ与Ea／Aa亦呈负相关(r＝—0．50P＜0．05、r＝—0．55P＜0．05)，与E／A无明显相关(r＝—0．41P＞0．05、r＝0．02P＞0．05)。结论：DTI能更准确定量高血压患者二尖瓣环舒张期运动速度的改变，DTI法检测二尖瓣环运动速度之比与反应心肌纤维化程度的血清PC I、PC Ⅱ浓度相关良好，有利于舒张功能受损程度的判断，优于传统的二尖瓣口血流法。     

Posture-induced airflow limitation in asthma: relationship to plasma catecholamines and an inhaled anticholinergic agent

Postural influence on ventilatory function was investigated in thirteen asthmatic subjects on three consecutive days starting at 10.00 am. Lung function was measured in the seated position before and after four hours lying supine. Peak expiratory flow (PEF) was measured every 0.5 h in the supine position. Blood samples for determination of plasma catecholamines were collected before, during and after lying supine. After the initial lung function testing, placebo or ipratropium bromide (0.125 mg) was inhaled. On the third day the whole trial was performed seated, without any drug, as a control experiment. On the placebo day lying supine induced an initial, rapid fall of PEF followed by a progressive decrease during the four hours. The progressive decrease in PEF was apparently caused by bronchoconstriction. Ipratropium bromide prevented this posture-induced bronchoconstriction. On the day seated there was also a tendency towards a decline of PEF though less pronounced than in the supine position on the placebo day. No significant alterations in plasma levels of catecholamines were observed. We conclude that the supine posture is a stimulus to bronchoconstriction in asthma, likely to be involved in nocturnal wheezing. Postural bronchoconstriction is not explained by lowered plasma levels of adrenaline, as has been suggested for nocturnal asthma. The results raise the question of whether cholinergic mechanisms are involved.     

One-year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo

In a double-blind, placebo-controlled study, 273 patients with suspected acute myocardial infarction (AMI) were randomized to receive either 48-h magnesium (Mg) or placebo therapy intravenously, initiated immediately on admission to hospital. We describe the results from a 1-year survey in 270 of the patients, who were available for follow-up. Patients were equally divided: 135 received Mg and 135 received placebo. Mg treatment was associated with a marked reduction in 1-year death rate from 32% in the placebo group to 20% in the Mg group (p = 0.018). If only death from ischemic heart disease is considered, the figures were 28% in the placebo group as opposed to 15% in the Mg group (p = 0.006). This reduction was mainly due to a reduction in mortality during the initial 30 days after inclusion in the study (17% vs. 7%), after which the difference in mortality between the two groups did not reach statistical significance (18% vs. 15%, p = 0.56). The beneficial effect of Mg on mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%), and partly to a reduced incidence of infarction (63% vs. 48%) during the initial hospitalization. However, factors unknown to us were also involved, as revealed by a remaining statistically significant partial regression coefficient, when sex, age, cardiovascular history, development of AMI, and development of arrhythmias were considered. It is concluded that intravenous Mg treatment is beneficial to patients with acute ischemic heart disease and should be adopted as part of the routine treatment of these patients.     

Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: evidence from dichotic listening

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonant-vowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interfere with correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reports with the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scores with the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlations were close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere.     

Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia

Background

Current models of levodopa (L -dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L -dopa. However, patients with LID receive combination therapies that often include dopamine agonists.

Objective

Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.

Methods

Different regimens of L -dopa monotreatment and L -dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L -dopa monotreatment or L -dopa combined with ropinirole.

Results

We defined chronic regimens of L -dopa monotreatment and L -dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L -dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood–brain barrier hyperpermeability was markedly reduced after L -dopa-ropinirole cotreatment compared with L -dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L -dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L -dopa-ropinirole cotreated animals.

Conclusions

Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis.

The bacteriological and clinical efficacies of cefuroxime axetil suspension (20 mg/kg of body weight per day in two divided doses) were compared with those of penicillin V suspension (50 mg/kg/day in three divided doses) in a multicenter, randomized, evaluator-blinded study. Children aged 2 to 13 years with clinical signs and symptoms of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. Patients were assessed and samples from the throat for culture were obtained at the time of diagnosis, 3 to 7 days after the initiation of treatment, and 4 to 8 days and 19 to 25 days after the completion of 10 days of therapy. Of the 385 evaluable patients, GABHS were eradicated from 244 of 259 (94.2%) cefuroxime-treated patients and 106 of 126 (84.1%) penicillin-treated patients (P = 0.001). Complete resolution of the signs and symptoms present at the time of diagnosis was achieved in 238 of 259 (91.9%) cefuroxime-treated patients and 102 of 126 (81.0%) penicillin-treated patients (P = 0.001). Potential drug-related adverse events were reported in 7.0 and 3.2% of the cefuroxime- and penicillin-treated patients, respectively (P = 0.078). In the present study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriological and clinical efficacies than those of penicillin V suspension given three times daily to pediatric patients with acute pharyngitis and a positive throat culture for GABHS.     

Comparison of ciprofloxacin and ceftriaxone as single-dose therapy for uncomplicated gonorrhea in women.

Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.