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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 91 records · Page 5Linked to original sources

Biotinylation: a simple method for labelling complement component C8 with preservation of functional activity.

Biotinylation of human C8 with the water-soluble biotin derivative biotinylamidohexanoic acid, N-hydroxysulfosuccinimide ester is an excellent method for labelling this terminal complement component with preservation of its functional activity. The biotinylated product can be detected both in native form and also following its incorporation into the terminal complement complexes. Detection assays include Western blotting, crossed immunoblotting, ELISA, and immunocytochemistry. Biotinylation is an attractive alternative method for labelling C8 and may be used for detecting and quantifying C8 and C5b-9 complexes in their soluble and membrane-bound forms.

Biotin

Penetrating injuries involving the anterior cranial fossa.

Penetrating injuries of the anterior cranial fossa may result in permanent neurologic changes or even death if injuries are unrecognized and remain untreated. The diverse etiologies of such injuries are reviewed, as well as their diagnosis, treatment and prognosis.

Cerebrospinal Fluid Rhinorrhea

Recombinant human interleukin-1 beta decreases serum carboxypeptidase N and modifies serum amino acid concentrations in rats.

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on various serum constituents were studied following subcutaneous injection (12.5 or 125 micrograms/kg) in female Wistar rats. Protein electrophoresis and the determination of the serum concentrations of carboxypeptidase N (CPN), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, aldolase, total proteins, iron, urea, creatinine, and several amino acids were performed 12, 24, and 72 hr after injection. With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration. Iron and CPN were still low after 24 hr but returned to normal levels after 72 hr. With the higher dose of rhIL-1 beta, only alanine and phenylalanine levels were increased after 12 and 72 hr, taurine after 12 hr, and methionine after 24 hr. There were no biochemical or histological signs of hepatotoxicity. The findings indicate that rhIL-1 beta produces a reversible alteration of various biochemical plasma constituents without any apparent signs of cytotoxicity. Moreover, the decrease in CPN observed may influence the degradation of inflammatory peptides.

Amino Acids

Age-related decrease in an early step of DNA-repair of normal human lymphocytes exposed to ultraviolet-irradiation.

A monoclonal antibody-based immunoassay has been used to detect age-related changes in the rate of loss of photoproduct antigenicity from the DNA of peripheral blood lymphocytes irradiated with 10 J m-2 uv-C. Lymphocytes were obtained from 75 healthy volunteers whose ages ranged from 14 months to 82 years. The samples were divided by age decades into groups of 10 individuals, except the first decade which contained only 5 individuals. The mean loss of antigenicity +/- 1 standard deviation was determined for each group at 10, 30, and 60 min after irradiation. The data were analyzed by Mann-Whitney U test and by the Kruskal-Wallis test. After a recovery period of 10 min the loss of antigenicity was most rapid in group I (0-9 years), less rapid in group II (10-19 years), and least rapid in all other groups. The differences between groups became less at 30 min and were not significant at 60 min incubation. These data obtained from normal cells concur with our previous conclusions, that reductions in the rate of loss of antigenicity in nondiseased cells isolated from patients with melanoma and dysplastic naevus syndrome reflect genetic abnormalities in these patients.

Adolescent

An insertion mutation in the pol gene of Moloney murine leukemia virus results in temperature-sensitive pol maturation and viral replication.

An insertion mutation in the pol gene of Moloney murine leukemia virus (M-MuLV) was found to render the virus temperature-sensitive for replication. A provirus containing a 12-bp insertion at the boundary between the reverse transcriptase (RT) and integrase (IN) domains induced the formation of mutant virions containing a partially processed RT-IN fusion protein. Some proteolytic processing to form mature RT and IN was observed at 32 degrees, but only aberrantly processed proteins were detected at 39 degrees. The uncleaved precursor was found to exhibit DNA polymerase activity, even though it could not support replication of the virus in vivo at 39 degrees.

Animals

Quantitative whole-body autoradiographic determination of tacrine tissue distribution in rats following intravenous or oral dose.

Tacrine (1,2,3,4-tetrahydro-9-acridinamine) has been employed in diverse clinical situations but has recently been of considerable interest for the treatment of cognitive deficits associated with senile dementia (Alzheimer's disease). The present studies examined tissue distribution of radiolabeled tacrine by quantitative whole-body autoradiography. Tacrine radioequivalents were widely distributed to tissue following iv or peroral dose, with an apparently prolonged absorption phase following po dose. The presence of high levels of activity in kidneys and ureters indicates a major role for urinary excretion, but there is also evidence for biliary excretion and direct secretion of compound or metabolites into the intestinal lumen. Tacrine was rapidly taken up into the brain and demonstrated regional localization to cortex, hippocampus, thalamus, and striatum. Although the inhibition of acetylcholinesterase by tacrine is well documented, regional uptake in brain did not correlate consistently with distribution of the enzyme, supporting suggestions by others that the alleged action of tacrine in treatment of senile dementia may be by mechanisms other than cholinesterase inhibition.

Administration, Oral

Zero-order release formulation of oxprenolol hydrochloride with swelling and erosion control.

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower Cmax, higher values of tmax, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.

Animals

The prevalence of dementia as measured by the Cambridge Mental Disorders of the Elderly Examination.

General practice patients aged 75 years and over were screened for cognitive impairment using the Mini-Mental State Examination. Those scoring 23 or below and a sample of those scoring 24 or 25 were assessed using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), a structured interview schedule specifically designed to detect mild dementia. The CAMDEX includes a mental state examination, a psychiatric history, detailed cognitive testing and an information interview. The prevalence of dementia in 2311 patients was found to be 10.5%, about half that found in most earlier studies. Possible reasons for this low rate are discussed.

Aged

The pharmacokinetics and pharmacodynamics of a human relaxin in the mouse pubic symphysis bioassay.

The effects of dose, route, regimen, and the presence or absence of a repository vehicle [benzopurpurine (BPP)] were determined for a human relaxin (hRlx) in the mouse pubic symphysis bioassay. Administration of 88 micrograms/kg hRlx sc in 1% BPP resulted in delayed, prolonged absorption. Although peak hRlx concentrations were lower, serum concentrations remained elevated longer in the presence of BPP compared to a single sc administration of hRlx in saline at the same dose. The bioavailabilities with and without BPP were similar (109 and 96%, respectively). While the pharmacodynamic effect (i.e. lengthening of the pubic ligament in estrogen-primed mice) was approximately maximum at 88 micrograms/kg hRlx sc with BPP, single sc administration of hRlx without BPP up to 264 micrograms/kg had no effect on pubic ligament length. In the absence of the BPP vehicle, manipulation of the regimen (e.g. multiple sc doses) showed that emulation of the serum concentration-time profile observed for hRlx in the presence of BPP resulted in similar pharmacodynamic effects. It appears that BPP delays the absorption of hRlx after sc administration, resulting in prolonged, elevated hRlx serum concentrations. hRlx has been shown to be effective in this model without BPP if it is administered by a multidose sc schedule. As has been observed with other protein therapeutics, the dosage regimen employed for hRlx delivery appears to be an important determinant of the expression of its pharmacodynamic effects.

Animals

Avoidance behaviour and major depression in panic disorder: a report from the Cross-National Collaborative Panic Study.

Avoidance behaviour and secondary major depression are both frequent in clinical samples of patients with panic disorder. Their status is unclear: indicators of severity of panic disorder or indicators of separate psychiatric disorders. Among the data of the Cross-National Collaborative Panic Study (n = 1,168) we found that especially avoidance behaviour defines more severe states of panic disorder (earlier age at onset, higher frequency of panic attacks and higher level of psychopathology); co-occurrence of major depression is less clearly associated with more severe panic disorder. The results are compatible with the DSM-III-R concepts of comorbidity of panic disorder and major depression and of subtyping panic disorder by avoidance behaviour.

Adult

The definition of panic attacks, Part I.

Phenomenological data are presented for panic attacks and non-panic anxiety in 159 patients. Anxiety episodes of sudden onset tend to have greater severity, more symptoms, and shorter duration and some distinctive cognitive features. This cluster of features emerged from the analysis as characteristic of the panic attack. There were no differences between situational and spontaneous attacks nor are attacks occurring in depressed patients different from those in-patients who suffered from anxiety disorders. The ideas characteristic of normal anxiety are directed towards ordeals in the future. It is the immediacy of the anxious cognitions of imminent death, collapse or becoming insane that are characteristic of panic attacks. A definition of panic attacks is suggested.

Adolescent

The phenomenological study of 90 patients with panic disorder, Part II.

This paper examines the nosological and aetiological relationships of panic disorder to the anxiety states and depression. The phenomenology is detailed from an unbiased sample of 90 cases selected, on the basis of meeting positive criteria for panic disorder, from 3 series of consecutive cases. Panic attacks were found to be only quantitatively distinct from non-panic anxiety. Truly spontaneous attacks, not preceded by anxiety-provoking cognitions, were uncommon. No unique association with agoraphobia was seen, other anxiety states and depression being common. Social phobia and generalized anxiety often preceded the development of panic disorder, as did some cases of agoraphobia. Depression was usually non-specific and secondary when only DSM-III MDE criteria were used. Significant neurotic traits were found, particularly anxiety, dependency and poor sexual adjustment. Panic disorder has multiple causal factors only one of which is a genetic tendency for panic attacks. While important therapeutically, panic attacks should not be given the primary place in diagnosis.

Adult

[The "envelope" versus the biomechanical function of the spine].

As a continuation of argumentation presented in a number of previous communications, the author advocates the view according to which the developing spine and its neural content ["spinal cord-nerve roots complex"] are linked by an equally intimate morphogenetic relation like that existing between the brain and its skeletogenic envelope. A specific feature of the neurovertebral developmental relation consists in the fact that the elongated spinal cord-nerve roots complex is enveloped by its skeletogenic case both in the transversal and in the longitudinal direction. The matter is further complicated by lagging of the spinal neural growth behind that of the vertebral column. The development of the basic anatomical features of the individual vertebrae such as their length and width, the girth of the vertebral body as well as the shape of the intervertebral foramina cannot be understood without taking into account the gross developmental dynamics of the two main components of the axial organ, viz., of the spinal cord-nerve roots complex and of the vertebral column.

Animals

Do general practitioners miss dementia in elderly patients?

General practitioners and community nurses were asked to rate the likelihood of dementia for each of their elderly patients. Cases of dementia were identified by research psychiatrists using the Cambridge mental disorders of the elderly examination (CAMDEX), a new structured diagnostic interview. General practitioners correctly identified dementia as at least a possibility in 121 of the 208 cases found. Nevertheless, they mistakenly rated as demented several patients suffering from functional psychiatric disorders, in particular depression. Community nurses correctly identified dementia as at least a possibility in 64 of the 74 demented patients known to them, but they incorrectly suspected dementia in a greater proportion of instances. Both general practitioners and families appeared to have low expectations of what general practice has to offer demented elderly people. General practitioners should take the initiative in diagnosing dementia in very elderly patients who show signs of the condition. In some cases it may be secondary to treatable disorders, and in others all that may be required are understanding, support, and advice to families.

Aged