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Y Khan

Publications and source records attributed to Y Khan.

32 records · Page 2Linked to original sources

Increased interaction of dopamine-immunoreactive varicosities with GABA neurons of rat medial prefrontal cortex occurs during the postweanling period.

A double immunofluorescence technique has been used to assess postnatal maturational changes in the extent to which dopamine-immunoreactive (DA-IR) varicose fibers form contacts with gamma-aminobutyric acid (GABA)-immunoreactive (IR) neuronal cell bodies in rat medial prefrontal cortex (mPFCx). Two separate measures of interaction, the percentage of GABA-IR cell bodies having DA-IR varicosities in apposition and the number of such profiles in contact with any given GABA-IR cell, were assessed. Between birth and adulthood, there was a progressive linear increase (r = 0.75, P < or = 0.0005) in the percentage of GABA-IR cell bodies having at least one DA-IR varicosity in apposition. While the number of varicosities in contact with any given GABA cell body showed very little change during the preweanling period, later during the postweanling interval, this parameter increased in a curvilinear fashion toward adult levels (r = 0.81, P < or = 0.0005). Taking together these latter two measures, an index of interaction was found to be 1.8 times higher when adult animals were compared to postweanling rats, and 2.5 times higher when compared to preweanling rats. Overall, these results are consistent with the view that there are late postnatal changes in the extent to which midbrain DA afferents interact specifically with GABAergic interneurons in rat mPFCx.

Animals↗

Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects.

Recent investigations have reported a reduced density of interneurons and an increase of GABAA receptor binding occurring preferentially in layer II of the anterior cingulate cortex of schizophrenic subjects [Benes F.M. et al. (1992) J. Neurosci. 12, 924-929]. Since a reduction in the density of interneurons has also been found in layer II of the prefrontal cortex, this study has sought to determine whether an un-regulation of the GABAA receptor binding activity might also be found in this region of schizophrenics. A high-resolution autoradiographic analysis of bicuculline-sensitive [3H]muscimol (GABAA) receptor binding on individual neuron cell bodies in layers II, III, IV and VI has been applied to Brodmann area 10 from normal controls (n = 16) and schizophrenic (n = 7) subjects. A computer-assisted technique has been used under strictly blind conditions to determine whether differences in binding occur in the schizophrenic group. A significant increase of GABAA receptor binding activity has been observed in layers II, III, V and VI in the schizophrenic group. When the binding is expressed as a density with respect to neuronal cell size, there is a gradient of binding across layers II, III, V and VI, with neuronal cell bodies in layer II having the greatest density of grains. When different subpopulations of neurons distinguished according to size criteria are examined separately, large (pyramidal) neurons show significantly higher binding, particularly in layer II, where it was increased by 90% in schizophrenics. Small (non-pyramidal) cells do not show significant differences in binding in schizophrenics, except in layer VI, where there was a 135% increase. Potential confounding effects from age and post mortem interval do not explain the differences between the two groups, because both young and old schizophrenics, as well as schizophrenics with long and short post mortem intervals, showed increased GABAA receptor binding activity when compared to control cases distinguished in a corresponding fashion. These data suggest that there may be a preferential reduction of inhibitory GABAergic inputs to pyramidal neurons, particularly in layer II of the preferential cortex, in schizophrenia. This change could potentially result in an increased excitatory outflow from the prefrontal area to other cortical regions of the schizophrenic brain. Overall, these results are consistent with the idea that reduced amounts of GABAergic activity in the prefrontal cortex could be related to a perinatal disturbance and could be a potentially important component of the pathophysiology of psychosis.

Adult↗

Eating attitudes in young females with diabetes: insulin omission identifies a vulnerable subgroup.

Eating attitudes were investigated in young females with diabetes (YFDs) and healthy age-matched female controls. Results from the Eating Disorder Inventory confirmed that YFDs had higher scores for drive for thinness, body dissatisfaction and bulimia. In addition, YFDs who omitted insulin injections had high scores for ineffectiveness and interoceptive awareness and had increased sensitivity to external eating cues (as measured by the Dutch Eating Behaviour Questionnaire). It is suggested that dieting and weight gain associated with diabetes treatment precipitate a deterioration in eating attitudes. Furthermore, omission of insulin and increased sensitivity to external eating cues serve as markers for a group of YFDs who are at increased risk of developing an eating disorder. The present results provide support for the spiral model of eating disorders (Heatherton & Polivy, 1992) and its emphasis on the importance of self-esteem and self-awareness.

Adolescent↗

Sleep studies and supportive ventilatory treatment in patients with congenital muscle disorders.

Eight ambulant children aged 6-13 years, four with congenital myopathy, two with congenital muscular dystrophy and two with the rigid spine syndrome, presented with recurrent chest infections, morning headaches, shallow breathing at night, or respiratory failure. Polysomnography confirmed the presence of nocturnal hypoxaemia with oxygen saturation on average less than 90% for 49% of sleep and less than 80% for 19% of sleep accompanied with severe hypoventilation. Additionally there was sleep disturbance characterised by an increased number of wake epochs from deep sleep (in comparison to 10 non-hypoxaemic subjects). The severity of sleep hypoxaemia did not correlate with symptoms. Treatment with night time nasal ventilation was started and repeat polysomnography showed normal overnight oxygen saturation and a reduced number of wake epochs during deep sleep. It is important to be vigilant for sleep hypoventilation in these patients and sleep studies should be part of the routine respiratory evaluation. Treatment with nasal ventilation is effective in reversing the nocturnal respiratory failure without significant disturbance to life style.

Adolescent↗

Cellular colocalization of dopamine D1 and D2 receptors in rat medial prefrontal cortex.

In a recent study in rat medial prefrontal cortex (mPFC), a fluorescently coupled, high-affinity ligand for the D1 receptor subtype was localized to nonpyramidal neurons, while a ligand selective for the D2 subtype was found on neurons with a size distribution overlapping with both small pyramidal and large nonpyramidal cells. These observations raised the possibility that a subpopulation of cortical neurons with an intermediate size range may coexpress both the D1 and D2 receptor subtypes. In the present study, the D1 and D2 receptor subtypes have been simultaneously localized in layer VI of rat mPFC using 20 nM SCH 23390-Bodipy and 20 nM N-(p-aminophenethyl) spiperone-Texas red, respectively, in the presence of 100 nM mianserin (5-HT2 receptor antagonist). The localization of receptor binding fluorescence was assessed in paired images using fluoroscein isothiocyanate (FITC) and rhodamine dichroic filters for the D1 and D2 subtypes, respectively. Under the conditions employed here, most cell bodies showed either D1-like or D2-like receptor binding fluorescence, while a colocalization of both fluoroprobes was observed on only 25% of the labeled cells. When the size of each single-labeled cell body was measured using the respective FITC (D1-probe) and rhodamine (D2-probe) epifluorescence filters, the distribution of cells showing only D1-like receptor binding fluorescence was similar to nonpyramidal neurons (68.6 +/- 1.8 microns 2), while that for cells showing only D2-like receptor binding fluorescence was similar to that of both large interneurons and small pyramidal cells (106.9 +/- 2.4 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chorionic villi sampling: laboratory experience with 4,000 consecutive cases.

Experience with 4,000 consecutive CVS cases shows that 1) the combination of both the direct and culture methods greatly reduces false diagnoses and maternal cell contamination; 2) the time interval between the sampling procedure and processing of villus specimens influences the quality of direct preparations; 3) maternal cell contamination (MCC) can be minimized with dissection of CVS specimens. We have compiled a large volume of confined placental mosaicism (CPM) cases to serve as a resource in interpreting mosaic cytogenetic findings. It was noted that, in up to 92% of the mosaic cases, the abnormal cell line was confined to the placenta. The frequency of true chromosomal mosaicism was 0.2%, and is not different from that for amniocentesis.

Cells, Cultured↗

Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood.

BACKGROUND: A previous study demonstrated that myelination of the superior medullary lamina along the surface of the parahippocampal gyrus is occurring in human brain during adolescence. To further investigate whether postnatal increases of myelination may continue during the second decade and possibly even longer, the extent of myelination in this region has been analyzed in 164 psychiatrically normal individuals aged newborn to 76 years. METHODS: Cross sections of the hippocampal formation with adjoining hippocampal gyrus were analyzed on a blinded basis using either a global rating scale or measurements of the area of myelin staining. RESULTS: A curvilinear increase in the extent of myelination between the first and sixth decades of life (r = .71 and r = .67, respectively) was observed. When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades and an additional increase of 60% between the fourth and sixth decades. Female subjects showed a significantly greater degree of myelin staining than did male subjects during the interval of ages 6 to 29 years; however, after the third decade, there were no gender differences in the area of myelin staining. CONCLUSIONS: The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. During the fourth through sixth decades, however, it extended to progressively more lateral locations along the surface of the presubiculum. The precise origin(s) of the axons showing progressive myelination is unknown; however, the axons in the subiculum may include some perforant path fibers, while those found in the presubiculum may include cingulum bundle projections. Overall, our data are consistent with the idea that both early and late postnatal increases of myelination occur in a key corticolimbic relay area of the human brain and underscore the importance of applying a neurodevelopmental perspective to the study of psychopathology during childhood, adolescence, and even adulthood.

Adolescent↗

Obstructive apnoeas in Duchenne muscular dystrophy.

BACKGROUND: In order to clarify the treatment of sleep hypoxaemias in Duchenne muscular dystrophy polysomnographic studies were performed on patients at home with the purpose of recruiting them into two clinical therapeutic trials. Observations concerning the nature of sleep hypoxaemia in these patients are presented. METHODS: Twenty one non-ambulant patients with Duchenne muscular dystrophy aged 13-23 years with no symptoms of sleep hypoventilation or apnoea were studied for two consecutive nights with eight channel polysomnography. A comparative study was performed in 12 age matched normal male subjects. The evolution of sleep hypoxaemia with age was studied in 14 patients with Duchenne muscular dystrophy. RESULTS: Thirteen of the 21 patients had hypoxaemia below 90% during sleep, and 12 of the 13 had discrete hypoxaemic dips in association with apnoeas; 60% of all apnoeas were obstructive in nature. The hypoxaemic periods became more frequent with increasing age and, in two patients at three year follow up, were more frequently associated with central or possibly "pseudocentral" apnoeas. Although the normal subjects had a few apnoeic episodes, none had sleep hypoxaemia below 90% saturation. CONCLUSION: The sleep related breathing abnormality in Duchenne muscular dystrophy is initially obstructive and this has implications for management.

Adolescent↗

Cellular distribution of dopamine D1 and D2 receptors in rat medial prefrontal cortex.

The relative distribution and cellular localization of the dopamine D1 and D2 receptor subtypes were assessed in frozen sections of rat medial prefrontal cortex (mPFC). The D1 and D2 receptor binding sites were labeled with the selective high-affinity antagonists SCH 23390 and N-(p-aminophenethyl)-spiperone (NAPS), respectively, coupled to either Bodipy or Texas red fluorophores. Under the incubation conditions employed, kinetic, competition, and selectivity studies showed that these modified ligands retained pharmacological selectivity. Optimal binding fluorescence was at 100 nM of each ligand, and fluorescence increased linearly from 1 to 15 min of incubation at 2 degrees C. NAPS-Texas red binding fluorescence was inhibited with 10 nM quinpirole (D2 agonist), but not 10 nM SKF 38393 (D1 agonist), while SCH 23390-Texas red binding was inhibited with SKF 38393, but not quinpirole. The localization of dopamine receptor binding was assessed in montages constructed from low-magnification photomicrographs through the depth of the cortex, or in corresponding high-magnification photomicrographs. Cells showing D1- or D2-like receptor binding fluorescence were present in layers II-VI, with the highest density observed in layers V and VI. The addition of mianserin (100 nM, 5-HT2 antagonist) to incubated sections slightly reduced the numbers of labeled cells in each cortical layer, but retained the preferential localization to the deeper layers. Two separate observations supported the idea that the fluorescently coupled ligands were localized to neuronal cell bodies. First, receptor labeling with the fluorescently coupled ligands co-localized almost exclusively to cells in the cortical mantle showing neuron-specific enolase immunoreactivity. Second, a comparison of the cell size distribution taken from adjacent Nissl-stained sections with the size of cells showing D1- or D2-like receptor binding fluorescence revealed complete overlapping of fluorescence with neuronal cell bodies. In mPFC layer VI, the size of cells showing D1-like receptor binding fluorescence was 77.8 +/- 5.1 microns2, similar to non-pyramidal neurons, while that for D2-like receptor binding fluorescence was 108.2 +/- 4.5 microns2, consistent with both large interneurons and small pyramidal cells. Only a small percentage of cells showing D1- or D2-like receptor binding overlapped in size with glia, but this occurred almost exclusively within the white matter region below the cortical mantle. These findings are consistent with the hypothesis that the D1 and D2 receptor subtypes are found on different populations of neurons, although some overlap probably occurs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pustular acneiform secondary syphilis.

A patient with a generalized acne-like skin eruption on the trunk, extremities, and face is described. Examination of a skin biopsy specimen revealed syphilis as did positive results of serologic tests. Physicians should be aware of this type of secondary syphilis.

Acne Vulgaris↗

A multitrait-multimethod analysis of the Preschool Behavior Questionnaire.

The Preschool Behavior Questionnaire is a teacher rating instrument yielding a total score reflecting overall level of adjustment and three subscale scores labeled Hostile/Aggressive, Anxious/Fearful, and Hyperactive/Distractible. This study assessed the convergent and discriminant validity of this teacher rating measure against two alternative measures within a multitrait-multimethod analysis. The results supported the construct validity of the Hostile/Aggressive and Anxious/Fearful scores as well as the overall score. There was, however, no support for the validity of the Hyperactive/Distractible score.

Aggression↗

Relation of platelets to catecholamine induced myocardial injury.

To test the thesis that myocardial injury, induced by catecholamines, is ischaemic in origin due to platelet accumulation in the coronary microvasculature, sustained left intracoronary and systemic infusion of catecholamines in toxic dosage was given to dogs previously infused with autologous 51Cr-labelled platelets. Subsequent determination of tissue radioactivity and electrolytes, as well as electronmicrography, indicated that the induced myocardial injury was not related to microvascular occlusion by platelets.

Animals↗

Primary fallopian tube carcinoma presenting with a sinus in the posterior portion of cervix.

Primary fallopian tube carcinoma is an aggressive but rare tumor. This is an unusual presentation of papilliferous tubal carcinoma presenting with vaginal discharge through a large sinus approximately 2-3 cm in size, located posterior to the neck of cervix. Surgery was undertaken with the initial diagnosis of primary ovarian carcinoma and the fistula was left to heal spontaneously. Surgical resection was followed by adjuvant chemotherapy. The patient is doing well after the therapy.

Adenocarcinoma, Papillary↗