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Biomedical subjects

D Lonsdale

Publications and source records attributed to D Lonsdale.

At least 37 records · Page 2Linked to original sources

Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/2J mice.

Weanling mice of the DBA/2J strain are spontaneously audiogenically seizure prone between 19 and 24 days. Thereafter, susceptibility declines rapidly within the next 7-10 days. It was found that thiamine tetrahydrofurfuryl disulfide (TTFD) significantly delayed the natural disappearance of seizure proneness in male animals compared with controls treated with identical doses of saline. There was no significant difference between treated females and controls. Evidence is presented that suggests that TTFD is cholinergic in its action and has pharmacologic effects other than a simple vitamin replacement. The difference between males and females found in this strain of mouse in this experiment is consistent with previous information which indicates that sex-related differences exist in their response to stress.

Acoustic Stimulation↗

Brainstem dysfunction in the infant apnea syndrome.

Thirty-six infants identified as infant apnea syndrome (IAS) and 25 controls with a comparable age distribution were evaluated with Brainstem Auditory Evoked Potential (BAEP) testing. There was a significant predilection for leftsided BAEP abnormalities in IAS patients. Fifteen IAS patients had bilateral abnormalities, and of the 21 IAS patients with unilateral abnormalities, 17 had abnormalities on the left side (p less than 0.01 by McNemar's test). Significant differences (p less than 0.05 by analysis of covariance adjusting for age) between normal controls and IAS infants were found for peak latencies I, III, and V, and amplitude III. Linear regression analyses of the above parameters versus age in months for normal controls were constructed with 68% and 95% prediction interval bands to permit analysis of individual data points. Data points from the IAS infants with bilateral BAEP abnormalities have been plotted on these linear regression curves. No single measurement of latency or amplitude is abnormal in the majority of IAS infants, but many of the individual points fall outside of the 95% prediction curve.

Brain Stem↗

The syndrome of functional dysautonomia.

A perspective on disease is proposed which treats the brain and psyche as part of the soma. The brain, operating as a computer, coordinates energy metabolism in all organs, modulating the organisms's response to stress which results in a complex mixture of sympathetic, parasympathetic and endocrine drive governing behavior and host resistance. It is postulated that automatic activity in health maintains a balanced state of autonomic neurotransmission with behavioral responses varying according to the physiologic state of either sympathetic or parasympathetic dominance. The sympathetic system, irrespective of neurotransmitters involved, is defined as an action system which uses energy and the parasympathetic system is the opposing or balancing force. Genetic influences may create a greater state of sensitivity with one or other of these systems, thus governing behavior characteristics. The degree of dominance may be responsible for the unbalanced response to stress which will in turn have a major influence on the causation of organic disease. The state of reactivity within this system is influenced by the efficiency of the oxidative process which is in turn closely related to the quantity and quality of nutrition.

Animals↗

Hypermethioninemia associated with methionine adenosyltransferase deficiency: clinical, morphologic, and biochemical observations on four patients.

Four patients with hypermethioninemia were ascertained in neonatal mass metabolic screening programs. Hypermethioninemia has persisted in all cases. There were no other abnormalities in sulfur-amino acid concentrations, and routine serum chemical determinations, including the results of "liver function" tests, were normal. Hepatic methionine adenosyltransferase activity was found to be low, ranging from 7.8 to 17.5% (mean 11.4%) of the normal adult control value. Electron microscopy of liver showed increased smooth endoplasmic reticulum, decreased rough endoplasmic reticulum, and increased lysosomes; short breaks in the outer membranes of mitochondria were present to a variable extent. Despite the persistent hypermethioninemia, which argues for continued deficiency of hepatic MAT, all four children appear well. This ostensible well being may be a result of the normal activity of extrahepatic MATs, as shown for erythrocytes and for cultured fibroblasts and lymphoid cells.

Adult↗

Red cell transketolase as an indicator of nutritional deficiency.

Twenty patients who had symptoms that were apparently neurotically functional are reported because they proved to have abnormal red cell transketolase activity. Although in many of the cases the etiology appeared to be associated with heavy consumption of "junk" foods, carbonated or sweet beverages, and candy, this was not so in all of them and the etiology in these cases remains obscure. The symptoms in all 20 patients could be correlated with those well documented in early beriberi and all were clinically improved by the administration of thiamin. In only two cases were other vitamins administered. Such improvement was slow and there were no dramatic recoveries. In 10 patients improved transketolase activity was correlated with clinical well-being. The other 10 patients did not keep their return appointments. Telephone contract revealed that they were asymptomatic.

Adolescent↗

Recurrent febrile lymphadenopathy treated with large doses of vitamin B1: report of two cases.

The 2 children whose cases are reported here both had recurrent episodes of fever and cervical lymphadenopathy. The conventional approach had been unsuccessful in identifying the cause or therapy. In neither case was there an infectious agent demonstrated, and biopsy of a pathologically enlarged lymph gland revealed only reactive hyperplasia in each case. Abnormal metabolism was revealed in the first patient by detecting a substance in urine which is reported to be diagnostic for a form of subacute necrotizing encephalomyelopathy. In the second case, red cell transketolase indicated thiamine pyrophosphate deficiency. Both children had elevated concentrations of folate and B12 in serum. Neither of the 2 patients had further episodes when given a clinical trial with large doses of thiamine hydrochloride. Recurrent episodes of febrile lymphadenopathy are extemely frequent in children and spontaneous resolution occurs, while in others there is either proven or assumed infection. Although final proof of therapeutic efficacy is lacking, the rapid improvement and maintenance of health in both children was striking after conventional therapy had failed.

Child, Preschool↗

Hybrid plasmids containing an active thymidine kinase gene of Herpes simplex virus 1.

The gene for the thymidine kinase (TK) of Herpes simplex virus type 1 (HSV-1) is located in the KpnI m and BamHI p fragments of the genome (Wigler et al., Cell 11, 223-232 (1977)). These fragments have been inserted into the EcoRI and BamHI sites, respectively, of plasmid pBR322, and propagated in E.coli. The TK gene contained in the recombinant plasmids was shown to be biologically active when introduced into TK- mouse L cells. Detailed restriction site maps of the BamHI p fragment have been constructed and the approximate location of the TK gene has been determined. Mouse cells transformed with cloned HSV-1 tk+ DNA produced HSV-1-specific thymidine kinase; superinfection with HSV-1 tk- virus increased the level of TK activity tenfold, suggesting that the BamHI p sequences present in transformed cells respond to virus-encoded regulatory gene product(s).

Base Sequence↗

Transketolase activity in psychiatric patients.

The thiamine status of 42 physically healthy nonalcoholic psychiatric inpatients was evaluated by measuring transketolase activity in a hemolysate of their red blood cells, before and after addition of thiamine pyrophosphate to the hemolysate. Sixteen patients (38%) showed evidence of thiamine deficiency. Five of these patients had received thiamine-containing vitamins for a period of from 2 fo 47 days prior to testing, suggesting that poor nutrition may not fully account for the thiamine deficiency observed.

Adolescent↗

Determination of urinary thiamine by high-pressure liquid chromatography utilizing the thiochrome fluorscent method.

A sensitive, reproducible, and specific method for the determination of urinary thiamine has been established. Unique to the use of high-pressure liquid chromatography (HPLC) to separate the fluorescent thiamine derivative from interfering fluorescent compounds. Urine samples were passed through a Decalso catoin-exchange column, washed with 0.5 M KCl to remove some interfering compounds, and eluted with 3.4 M KCl. The eluted thiamine was converted to the fluorescent derivative, thiochrome, by reaction with alkaline potassium ferricyanide. The reaction mixture was extracted with isobutanol and subjected to HPLC monitored by a fluorescent detector. Within-day and day-to-day coefficients of variation proved to be 2.5% and 1.2% respectively. Recovery of added thiamine (range 0.04 to 2.0 microgram/ml) averaged 99.9 +/- 5.3%. The sensitivity of this method was 0.03 microgram/ml.

Animals↗

Urinary organic acid profiles of Reye's syndrome patients.

The status of mitochondrial functioning in Reye's syndrome was assessed by comparing organic acid profiles from nine pathological urines with those from normal urines. It was found that Reye's syndrome urines have a normal content of succinic, oxaloacetic, aconitic, and citric acids suggesting that the enzymes of the acid cycle are functional. Elevated pyruvate and depressed alpha-ketoglutarate levels were observed. Abnormal urinary constituents detected were salicylic and adipic acids. Presence of the latter indicates that the enzymes of fatty acid beta-oxidation are functional.

Aconitic Acid↗