Sarcoma-180 ascites tumour-bearing male mice were injected i.p. with single dose of 0.5, 2.5, 5 mg/kg body wt. of rifampicin. Cells were sampled for mitotic chromosome analysis 4, 16 or 24 h after treatment. The maximal yield of chromatid-type aberrations induced was found 24 h after treatment with 5 mg/kg of rifampicin. More than 60% of the cells carried at least one chromatid exchange. The majority of these were exchanges derived from breaks in the centromeric heterochromatin.

Animals↗

PubMedDate not supplied

Neuronal activity in primate visual cortex assessed by immunostaining for the transcription factor Zif268.

It is now well established that environmental signals mediated via neurotransmitters and hormones can induce responses in cells which involve a cascade of receptors, G proteins, and second messengers. These in turn can induce transcription factors which regulate long-term changes in gene expression. It has been proposed that the stimulus-transcription coupling properties of these DNA-binding proteins can be exploited to visualize activated neurons by way of immunostaining. We have used standard immunohistochemical techniques to detect the expression of one specific transcription factor, Zif268, in the visual cortex (area 17, V1) of vervet monkeys (Cercopithecus aethiops). Immunopositive neurons were present in large numbers throughout the visual cortex of the normal animal, being concentrated in layers 2/3 and 6 and at moderate levels in 4C beta and 5. To determine if Zif268 expression was affected by visual stimulation in the monkey, we restricted light input to one eye with the aim of revealing ocular-dominance columns in striate cortex. We found that short-term monocular deprivation induced either by enucleation, intravitreal TTX injection, or eyelid suturing resulted in dramatic changes in Zif268 levels, revealing vertically oriented columns of reduced Zif268 staining interdigitated with columns of normal expression. Furthermore, these columns were discernible after just 2 h of monocular blockade. A comparison of the ocular-dominance pattern obtained with Zif268 immunostaining and cytochrome oxidase histochemistry in long-term monocularly deprived animals showed a coincident reduction of both markers along columns that were precisely aligned in adjacent sections, indicating that Zif268 expression is restricted to cortical regions of high metabolic activity. Simultaneous immunostaining for Zif268 and the calcium-binding proteins calbindin and parvalbumin showed a negative correlation, suggesting that the Zif268 protein may be expressed selectively within excitatory neurons. A similar approach with immunostaining for neurofilament and microtubule-associated proteins (SMI-32 and MAP2) revealed pyramidal neurons which were regularly found to contain a Zif268-positive nucleus. Furthermore, confocal images of lucifer yellow filled neurons possessing Zif268-positive nuclei all showed pyramidal morphology. Taken together, these results point to activity-dependent expression of Zif268 within a subset of excitatory neurons.

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PubMedDate not supplied

Neuronal responses to edges defined by luminance vs. temporal texture in macaque area V1.

We examined the responsivity, orientation selectivity, and direction selectivity of a sample of neurons in cortical area V1 of the macaque using visual stimuli consisting of drifting oriented contours defined by each of two very different figural cues: luminance contrast and temporal texture. Comparisons of orientation and direction tuning elicited by the different cues were made in order to test the hypothesis that the neuronal representations of these parameters are form-cue invariant. The majority of the sampled cells responded to both stimulus types, although responses to temporal texture stimuli were generally weaker than those elicited by luminance-defined stimuli. Of those units exhibiting orientation selectivity when tested with the luminance-defined stimuli, more than half were also selective for the orientation of the temporal texture stimuli. There was close correspondence between the preferred orientations and tuning bandwidths revealed with the two stimulus types. Of those units exhibiting directional selectivity when tested with the luminance-defined stimuli, about two-thirds were also selective for the direction of the temporal texture stimuli. There was close correspondence between the preferred directions revealed with the two stimulus types, although bidirectional responses were somewhat more common when temporal texture stimuli were used. These results indicate that many V1 neurons encode orientation and direction of motion of retinal image features in a manner that is largely independent of whether the feature is defined by luminance or temporal texture contrast. These neurons may contribute to perceptual phenomena in which figural cue identity is disregarded.

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PubMedDate not supplied

The combination of insulin and metformin in treatment of non-insulin-dependent diabetes mellitus.

OBJECTIVE: To assess whether, in the treatment of non-insulin-dependent diabetes mellitus (NIDDM), (1) metformin in conjunction with insulin can safely cause a decrease in glycosylated hemoglobin (HbA1c) to 7% or less and (2) this combination therapy may result in weight loss and lower insulin dose in comparison with insulin treatment alone. METHODS: Forty patients with NIDDM being treated with insulin on their first visit to the Diabetes Center were identified by retrospective review of medical records of all patients encountered during a 1-year period. These patients were classified into groups who were receiving insulin only (group 1) or insulin + metformin (group 2) at the most recent visit. Group 2 was subdivided into those with a body mass index of either =30 kg/m 2 (group 2A) or >30 kg/m 2 (group 2B). Blood glucose, HbA1c, insulin dose, and weights were analyzed from their initial and most recent visits. RESULTS: HbA1c decreased from 10 +/- 2.7% to 7 +/- 1.1% (P<0.01) in group 1 and from 9.8 +/- 2.1% to 7.2 +/- 1.4% (P<0.01) in group 2. The magnitude of decrease in HbA1c, however, was not different between the two groups. Total insulin dose increased from 40 (33 to 50) U/day to 58 (41 to 67) U/day (P<0.05) in group 1 and from 63 (42 to 118) U/day to 67 (50 to 96) U/day in group 2 (not significantly different). The median increase in insulin dose was 8 U in group 1, whereas the median decrease was 3 U in group 2 (P<0.05). Similar decreases were noted in group 2A. The decrease in insulin dose was inversely related to the initial insulin dose per kilogram of body weight in group 2 (r = -0.5; P<0.01). Patients in group 1 had an increase in weight from 75.0 +/- 8.6 kg to 77.7 +/- 9.0 kg (P<0.01), whereas weight decreased from 100.4 +/- 24.2 kg to 98.5 +/- 22.3 kg in group 2 (P<0.05). A decrease in weight was seen even in group 2A. The increase in weight was 3 +/- 3.3 kg in group 1, whereas weight decreased by 1.9 +/- 3.9 kg in group 2 (P<0.01). CONCLUSION: Insulin + metformin is safe and is as effective as insulin alone in improving glycemic control in obese and nonobese patients with NIDDM. This combination therapy, however, lowers insulin dose and promotes weight loss, which may be of importance in decreasing the cardiovascular risk factors in these subjects.

Journal Article↗

PubMedDate not supplied

Study of respiratory failure in organophosphate and carbamate poisoning.

OBJECTIVE: To study the clinical profile and cholinesterase levels of subjects of organophosphate and carbamate poisoning and to identify those subjects who would require ventilatory support. DESIGN: Prospective, observational study. SETTING: Intensive care unit of a tertiary care urban hospital. SUBJECTS: Fifty-two patients admitted with a diagnosis of organophosphate or carbamate poisoning. OUTCOME MEASURES: Subject survival and ventilator requirement. INTERVENTION: Treatment with atropine and pralidoxime and mechanical ventilation for patients with respiratory failure. Clinical features were monitored at every stage, and blood for plasma and red blood cell cholinesterase levels was collected on admission. RESULTS: According to the ingested poison, subjects were divided into four groups: organophosphates (13 subjects), mixed organophosphate and carbamate (18), carbamates (13), and a fourth miscellaneous group (8). Dyspnea and vomiting were the most common symptom and miosis and cyanosis were the most frequently observed signs. Plasma and red cell cholinesterase levels were lowest in the mixed poison group and highest in the carbamate group. Twenty-seven subjects developed Type I respiratory failure and 7 had Type II respiratory failure. Mechanical ventilation was required in 31 subjects. Overall 33 subjects survived. A scoring system, on a point scale of 16, was developed using miosis, unconsciousness, fasciculations, and plasma cholinesterase levels to predict ventilator requirement. CONCLUSION: This study helps to identify at an early stage those patients with organophosphate or carbamate poisoning who would ultimately require ventilatory support. We found miosis, unconsciousness, fasciculations, and a low plasma cholinesterase level to be of greatest predictive value.

Adolescent↗