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Biomedical subjects

R Desai

Publications and source records attributed to R Desai.

At least 19 recordsLinked to original sources
PubMed2005

Quantitative measurement of serotonin synthesis and sequestration in individual live neuronal cells.

Synthesis and subsequent sequestration into vesicles are essential steps that precede neurotransmitter exocytosis, but neither the total neurotransmitter content nor the fraction sequestered into vesicles have been measured in individual live neurons. We use multiphoton microscopy to directly observe intracellular and intravesicular serotonin in the serotonergic neuronal cell line RN46A. We focus on how the relationship between synthesis and sequestration changes as synthesis is up-regulated by differentiation or down-regulated by chemical inhibition. Temperature-induced differentiation causes an increase of about 60% in the total serotonin content of individual cells, which goes up to about 10 fmol. However, the number of vesicles per cell increases by a factor of four and the proportion of serotonin sequestered inside the vesicles increases by a factor of five. When serotonin synthesis is inhibited in differentiated cells and the serotonin content goes down to the level present in undifferentiated cells, the sequestered proportion still remains at this high level. The total neurotransmitter content of a cell is, thus, an unreliable indicator of the sequestered amount.

Alanine↗
PubMed2005

Some neurophysiological constraints on models of word naming.

The pronunciation of irregular words in deep orthographies like English cannot be specified by simple rules. On the other hand, the fact that novel letter strings can be pronounced seems to imply the existence of such rules. These facts motivate dual-route models of word naming, which postulate separate lexical (whole-word) and non-lexical (rule-based) mechanisms for accessing phonology. We used fMRI during oral naming of irregular words, regular words, and nonwords, to test this theory against a competing single-mechanism account known as the triangle model, which proposes that all words are handled by a single system containing distributed orthographic, phonological, and semantic codes rather than word codes. Two versions of the dual-route model were distinguished: an 'exclusive' version in which activation of one processing route predominates over the other, and a 'parallel' version in which both routes are equally activated by all words. The fMRI results provide no support for the exclusive dual-route model. Several frontal, insular, anterior cingulate, and parietal regions showed responses that increased with naming difficulty (nonword > irregular word > regular word) and were correlated with response time, but there was no activation consistent with the predicted response of a non-lexical, rule-based mechanism (i.e., nonword > regular word > irregular word). Several regions, including the angular gyrus and dorsal prefrontal cortex bilaterally, left ventromedial temporal lobe, and posterior cingulate gyrus, were activated more by words than nonwords, but these 'lexical route' regions were equally active for irregular and regular words. The results are compatible with both the parallel dual-route model and the triangle model. 'Lexical route' regions also showed effects of word imageability. Together with previous imaging studies using semantic task contrasts, the imageability effects are consistent with semantic processing in these brain regions, suggesting that word naming is partly semantically-mediated.

Adolescent↗
PubMed2004

Live cell ultraviolet microscopy: a comparison between two- and three-photon excitation.

We compare conventional infrared laser based three-photon excitation with a visible laser based two-photon excitation scheme for imaging the ultraviolet fluorophore serotonin in solution and in live cells. To obtain a signal level of 1000 photons per second per mM serotonin solution, we need a back aperture power of 5 mW at 550 nm (for two-photon excitation) and 33 mW at 740 nm (for three-photon excitation). The detectivity of serotonin (defined as the concentration of serotonin that yields a signal equivalent to three times the standard deviation of the signal obtained from the buffer alone) is 12 microM for two-photon, and 220 microM for three-photon excitation. Surprisingly, for live cell imaging of vesicular serotonin in serotonergic cells, three-photon excitation appears to provide better image contrast than two-photon excitation. The origin of this is traced to the concentration-dependent shift of the serotonin emission spectrum.

Animals↗
PubMed2004

Spontaneous coronary artery dissection in the postpartum period: association with antiphospholipid antibody.

Spontaneous coronary artery dissection (SCAD) is an extremely uncommon cause of myocardial infarction, occurring predominantly in women during or after pregnancy. The exact aetiology is unknown. This report describes a 33 year postpartum woman with diagnosed SCAD who tested positive for anticardiolipin antibody. This is the first case of SCAD in a patient with antiphospholipid antibody. The authors hypothesised that there should be a strong association between them.

Adult↗
PubMed2003

Eosinophilic granuloma with oral manifestations: a case report.

Eosinophilic granuloma is the most benign disorder of the triad commonly known as histocytosis X. In this article a case of a 6 year old female child with multiple eosinophilic granuloma with additional liver dysfunction and its oral manifestation is presented. This case demonstrated that oral findings, may be an early manifestation of the disease, definitive diagnosis needs to be determined by correlation of the clinical findings with histologic features. For the duration of 8 years the case has been followed up, there has been a progressive healing of the lesion, the clinical manifestations of the disease resolved with only chemotherapy and provided a very good prognosis.

Child↗
PubMed2001

Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation.

BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant syndrome characterized by febrile seizures (FS) and a variety of afebrile generalized seizure types. GEFS+ has previously been linked to mutations in two genes encoding the voltage-gated sodium channel alpha-subunit (SCN1A) and beta1-subunit (SCN1B). We studied a large family with FS and partial as well as generalized seizure types. METHODS: All but two living affected family members were interviewed and examined. Information on deceased affected family members was sought. EEG for 11 affected family members and one unaffected family member were obtained. Genetic linkage analysis and mutation screening of SCN1A were performed on blood samples from 16 affected individuals and their first-degree relatives. RESULTS: There were 27 affected family members; 18 were alive at the time of the study. All affected family members had FS; seven had FS only, and 19 also had afebrile seizures. Eleven individuals continued to have FS beyond 6 years of age. FS were complex in 12 family members, usually with prolonged duration. The index patient had right temporal lobe epilepsy and hippocampal sclerosis. Four other patients had strong historical evidence of temporal lobe epilepsy, and three others had nonlocalizing evidence of partial epilepsy. Pedigree analysis indicated autosomal dominant transmission. All affected individuals who were tested and one asymptomatic individual had a sodium channel mutation of SCN1A, an A-->C transversion at nucleotide 3809 resulting in the substitution of lysine 1270 by threonine in the D3/S2 segment (designated as K1270T). CONCLUSIONS: Our findings indicate that partial epilepsy preceded by FS can be associated with sodium channel mutations and may represent a variant of GEFS+.

Adolescent↗
PubMed2001

synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo.

Synaptotagmin has been proposed to function as a Ca(2+) sensor that regulates synaptic vesicle exocytosis, whereas the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is thought to form the core of a conserved membrane fusion machine. Little is known concerning the functional relationships between synaptotagmin and SNAREs. Here we report that synaptotagmin can facilitate SNARE complex formation in vitro and that synaptotagmin mutations disrupt SNARE complex formation in vivo. Synaptotagmin oligomers efficiently bind SNARE complexes, whereas Ca(2+) acting via synaptotagmin triggers cross-linking of SNARE complexes into dimers. Mutations in Drosophila that delete the C2B domain of synaptotagmin disrupt clathrin AP-2 binding and endocytosis. In contrast, a mutation that blocks Ca(2+)-triggered conformational changes in C2B and diminishes Ca(2+)-triggered synaptotagmin oligomerization results in a postdocking defect in neurotransmitter release and a decrease in SNARE assembly in vivo. These data suggest that Ca(2+)-driven oligomerization via the C2B domain of synaptotagmin may trigger synaptic vesicle fusion via the assembly and clustering of SNARE complexes.

Adaptor Protein Complex alpha Subunits↗
PubMed2001

Perceived needs and service use of Spanish speaking monolingual patients followed at a Hispanic clinic.

This study compared Spanish speaking monolingual patients at a Hispanic Clinic, with Hispanics and non-Hispanics at a conventional mental health center. A questionnaire in English and Spanish surveyed sociodemographic characteristics and subjectively reported health needs. The monolingual Hispanic Clinic patients perceived a significantly greater need for help with health and benefits, and better access to physical health care providers. Hispanics seen at the Hispanic Clinic report more difficulties managing medications than the other groups suggesting that this problem is not adequately addressed by receiving services in a culturally sensitive clinic, possibly due to the persistent effect of language barriers and low level of education. Additional interventions may be needed to address this problem.

Adult↗
PubMed2001

Consumer experience with payeeship provided by a community mental health center.

We surveyed 28 participants in a program in which the clinical therapist and money manager were different staff members. Patients reported strong therapeutic alliances with both the money manager and treating therapist as assessed by the Working Alliance Inventory. Alliance scores for the two providers were highly correlated (p = .68) and not significantly different from each other. Most patients endorsed overall satisfaction with the money management service, and report program-related benefits in housing, achieving abstinence, avoiding financial predators and budgeting arrangements. A significant minority endorsed some feeling of coercion, and coercion was associated with a weaker therapeutic alliance.

Adult↗
PubMed2001

Impact of clozapine prescription on inpatient resource utilization.

Although clozapine has been demonstrated to be clinically superior to typical neuroleptics in refractory schizophrenia, it is also more expensive. It had been hoped that the increased costs associated with its use would be offset by decreases in the utilization of other expensive resources, especially inpatient care. All patients who had clozapine initiated during an inpatient hospitalization within the VA for schizophrenia over a 4-year period (N = 1415) were matched with a comparison group (N = 2,830) on key service utilization variables and other possible confounding demographic and clinical variables using propensity scoring-an accepted statistical method, although still relatively little used in psychiatry. By using centralized VA databases, subsequent inpatient resource utilization for the 3 years after index discharge was examined. Veterans exposed to clozapine while inpatients recorded 33 (36%) more inpatient days in the subsequent 3 years after discharge than the comparison group (124 +/- 190 days vs. 91 +/- 181 days, p = .0002). When all patients exposed to clozapine were divided according to whether they had received 1 year of clozapine treatment after discharge, those that received less than 1 year's treatment recorded significantly more inpatient days than either those maintained on clozapine or controls. These results suggest that in actual practice clozapine treatment may cost substantially more than treatment with conventional neuroleptics.

Adult↗
PubMed2001

Impact of clozapine on completed suicide.

OBJECTIVE: Clozapine has been found to be superior to typical neuroleptics in ameliorating the symptoms of refractory schizophrenia. This study evaluated clozapine's effect on the rate of death due to suicide. METHOD: All patients over a 4-year period who initiated treatment with clozapine while hospitalized within the Department of Veterans Affairs (VA) system (N=1,415) were matched with a schizophrenic control group (N=2,830) by propensity scoring-a widely accepted statistical method that has been used relatively little in psychiatric research. Centralized VA databases and a national death registry were used to identify all deaths within the two groups, along with listed causes, for the 3 years after discharge. RESULTS: Veterans exposed to clozapine while inpatients were significantly less likely to die during the follow-up period than those in the control group, but this was entirely attributable to the much lower rate of death due to respiratory disorders in the clozapine group. There were no significant differences in rates of suicide or accidental death. CONCLUSIONS: These results fail to support the hypothesis that clozapine treatment is associated with significantly fewer deaths due to suicide.

Adult↗
PubMed2000

Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization.

Previous studies have demonstrated the presence of apamin-sensitive, small-conductance Ca(2+)-activated K(+) currents in human leukemic Jurkat T cells. Using a combined cDNA and reverse transcriptase-polymerase chain reaction cloning strategy, we have isolated from Jurkat T cells a 2.5-kilobase cDNA, hSK2, encoding the human isoform of SK2 channels. Northern blot analysis reveals the presence of a 2.5-kilobase hSK2 transcript in Jurkat T cells. While present in various human tissues, including brain, heart, skeletal muscle, kidney, and liver, no hSK2 mRNA could be detected in resting and activated normal human T cells. The hSK2 gene is encoded by 8 exons and could be assigned to chromosome 5 (q21.2-q22.1). The protein encoded by hSK2 is 579 amino acids long and exhibits 97% identity with its rat counterpart rSK2. When expressed in Chinese hamster ovary cells, hSK2 produces Ca(2+)-activated K(+) currents with a unitary conductance of 9.5 pS and a K(0.5) for calcium of 0.7 microm; hSK2 currents are inhibited by apamin, scyllatoxin, and d-tubocurarine. Overexpression of the Src family tyrosine kinase p56(lck) in Jurkat cells, up-regulates SK2 currents by 3-fold. While IKCa channels are transcriptionally induced upon activation of normal human T cells, our results show that in Jurkat cells SK2 channels are constitutively expressed and down-regulated following mitogenic stimulation.

Amino Acid Sequence↗
PubMed2000

Extracellular K(+) and opening of voltage-gated potassium channels activate T cell integrin function: physical and functional association between Kv1.3 channels and beta1 integrins.

Elevated extracellular K(+) ([K(+)](o)), in the absence of "classical" immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell beta1 integrin moieties, and to induce integrin-mediated adhesion and migration. Gating of T cell voltage-gated K(+) channels (Kv1.3) appears to be the crucial "decision-making" step, through which various physiological factors, including elevated [K(+)](o) levels, affect the T cell beta1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1beta, the neuropeptide calcitonin gene-related peptide (CGRP), as well as elevated [K(+)](o) levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the beta1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K(+)](o)). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.

Cell Adhesion↗
PubMed2000

Benchmarking treatment of schizophrenia: a comparison of service delivery by the national government and by state and local providers.

This study compared treatment of schizophrenia in two types of organization: a national, government-operated health care system, the Department of Veterans Affairs (VA), and in hospitals and clinics operated by state and local providers. Between 1994 and 1996, 746 male patients with a clinical diagnosis of schizophrenia residing in two states in the Southeast and Midwest were surveyed: 192 VA inpatients were compared with 96 non-VA inpatients, and 274 VA outpatients were compared with 184 non-VA outpatients. VA patients were older and had higher incomes than non-VA patients but did not differ significantly on measures of clinical status, satisfaction with providers, or community adjustment. VA outpatients were more likely to have been hospitalized during the previous year than non-VA outpatients and were less likely to have received services from a day hospital, from a case manager or social worker, or to have received crisis intervention services. On 5 of 26 Schizophrenic Patient Outcomes Research Team treatment recommendations, a smaller proportion of VA than non-VA patients adhered to standards. Four of these reflected reduced access among VA patients to psychosocial services such as work therapy, job training, or case management services. Cross-sectional surveys can be used to compare quality of care across service systems. VA care was associated with similar satisfaction and clinical outcomes but greater reliance on hospital treatment and less use of community-based psychosocial services.

Adult↗
PubMed2000

Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group.

We report here the second 2-yr extension of a clinical trial among postmenopausal women; 235 women continued blinded treatment with 5 or 10 mg alendronate daily, and 115 women who had been treated with alendronate for 5 yr were switched to blinded placebo. Continuous treatment with alendronate (10 mg daily) for 7 yr increased lumbar spine bone mineral density (BMD) by 11.4% compared to baseline. After the initial 18 months, each additional year of treatment through yr 7 increased spine BMD by 0.8% for the 10-mg dose and 0.6% for the 5-mg dose, with significant increases during yr 6-7. Previously reported increases in BMD at other skeletal sites and decreases in biochemical markers of bone turnover remained stable during yr 6-7. Among women previously taking alendronate for 5 yr who were switched to placebo, there was no significant decline in BMD at the spine or hip, whereas small, but significant, decreases in BMD at the forearm and total body and small increases in biochemical markers were observed. The safety and tolerability profiles were similar to those of placebo. This is the largest published long-term study of antiresorptive therapy. Our findings indicate that long-term alendronate treatment is well tolerated and effective for 7 yr. Increases in spinal BMD continue for at least 7 yr, and other skeletal benefits are maintained. Discontinuation does not lead to accelerated bone loss, but continuous treatment yields better skeletal benefits than shorter treatment.

Absorptiometry, Photon↗
PubMed2000

Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions.

BACKGROUND: Lobular capillary hemangiomas (pyogenic granulomas) occur on both mucosal and cutaneous surfaces. There are conflicting data regarding the increased prevalence of lobular capillary hemangiomas in female versus male subjects. Some studies have noted a female predominance of lobular capillary hemangiomas, but other studies do not reveal such a disparity. Because of an increased prevalence during pregnancy, oral tumors are also known as "granuloma gravidarum" or "pregnancy tumors." A hormonal influence for these mucosal lesions has been postulated. There are, however, no studies that address a possible relationship between hormones and cutaneous lesions. OBJECTIVE: This study presents the epidemiology of lobular capillary hemangiomas, with an emphasis on cutaneous lesions. METHODS: We reviewed 63,759 dermatopathology reports from a regional, private dermatopathology laboratory and found 325 cases of lobular capillary hemangiomas over a 1-year period. RESULTS: In our study of lobular capillary hemangiomas, cutaneous lesions accounted for 86%, with mucosal lesions representing only 12% of cases. Seven cases were excluded (one was intravascular, two were subcutaneous, and in 4 the location was not specified). Overall, male patients outnumbered female patients. The peak incidence for cutaneous lobular capillary hemangiomas was found in the second decade of life. The most common cutaneous sites were the trunk, upper extremities, and head. Mucosal lesions were primarily seen on the lips, gingiva, and tongue, and these affected females more than males by a ratio of 2:1, most commonly in the fourth decade of life. CONCLUSION: Cutaneous lobular capillary hemangiomas were equally prevalent in male and female patients. This would refute a female hormonal influence in the induction of cutaneous lobular capillary hemangiomas. Our data may suggest a hormonal influence on mucosal lesions because mucosal lobular capillary hemangiomas were twice as common in female patients. However, the small number of lesions in our study precludes us from making such a conclusion.

Adolescent↗