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T Hemachudha

Publications and source records attributed to T Hemachudha.

At least 19 recordsLinked to original sources

B-cell responses to myelin basic protein and its epitopes in autoimmune encephalomyelitis induced by Semple rabies vaccine.

Semple rabies vaccine is composed of rabies virus-infected sheep or goat brain inactivated with phenol and is administered daily after exposure for 14-21 days. Semple rabies vaccine-induced autoimmune encephalomyelitis (SAE) has clinico-pathological findings of demyelination similar to experimental autoimmune encephalomyelitis (EAE) caused by injection of central nervous system tissue or purified myelin proteins into experimental animals and frequently studied as a model for the human demyelinating disease, multiple sclerosis (MS). T-cell-mediated immune responses play a major role in induction of EAE, and antibody responses enhance disease severity. We studied the antibody responses to myelin basic protein (MBP) in 24 Thai patients with SAE and 77 control individuals to define the linear epitopes in human MBP that are encephalitogenic. Antibody levels were assessed by ELISA using native human MBP or synthetic MBP peptides of 20 amino acids. The major B-cell epitope was MBP61-80 and a minor epitope was MBP106-140 in SAE while in MS the major B-cell epitope is MBP84-96. MBP61-80-specific IgG1 and IgG3 levels were significantly higher in patients than controls while IgG2 and IgG4 were not. The data support the hypothesis that autoreactive Th1 cells induce SAE. The difference in B-cell epitope recognition may be due to differences in the genetic backgrounds of the populations studied or may reflect underlying differences in the pathogenesis of SAE and MS.

Adolescent↗

Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis.

Semple rabies vaccine is derived from brain tissue infected with rabies virus that is subsequently inactivated with phenol. Semple rabies vaccine-induced autoimmune encephalomyelitis (SAE) occurs in 1 in 220 immunized individuals. The immune response to myelin basic protein and pathological changes of demyelination in SAE suggest that this disease is the human homologue of experimental autoimmune encephalomyelitis (EAE). SAE and EAE are frequently studied as models for the human demyelinating disease multiple sclerosis. Major histocompatibility complex (MHC) class II and T-cell receptor (TCR) gene polymorphisms play important roles in rodent susceptibility to EAE and were analyzed to determine if the same was true in humans with SAE. HLA-DRB1, HLA-DQB1, and TCRBV gene polymorphisms were studied in Thai individuals with SAE (n = 18), with vaccination without neurological complications (n = 43), and without vaccination (n = 140). The allele frequencies of HLA-DR9 (DRB1*0901) and HLA-DR17 (DRB1*0301) were increased in SAE patients (DR9 = 22%, DR17 = 14%) compared with vaccinated controls (DR9 = 13%, DR17 = 6%) and with unvaccinated controls (DR9 = 9%, DR17 = 4%). The allele frequency of HLA-DQ7 (DQB1*0301) was decreased in SAE patients (8%) compared with vaccinated controls (15%) and with unvaccinated controls (25%). These susceptibilities are distinct from those associated with multiple sclerosis. The frequencies of TCRBV alleles and haplotypes were similar in SAE patients and vaccinated controls. These data suggest that genetic susceptibility associated with MHC class II alleles may have a role in the pathogenesis of SAE and its mechanism may be different from those involved in multiple sclerosis.

Alleles↗

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Journal Article↗

Idiopathic hypertrophic cranial pachymeningitis: an unusual cause of subacute and chronic headache.

Three cases of idiopathic hypertrophic cranial pachymeningitis are presented. The diagnosis was based on the CT scan or MRI findings (or both) of thickened enhancing dura. In all cases, meningeal biopsies were performed and microscopic findings were compatible with nonspecific inflammation. All cases presented with subacute and chronic localized headache. Two cases had associated chronic meningitis. One cases presented with a syndrome of multiple cranial nerve involvement (polyneuritis cranialis). Corticosteroids, in the form of prednisolone 60 mg/day, were effective in all cases. Two cases with less severe pachymeningitis received corticosteroids for 2 weeks, then were tapered off in 4 to 6 weeks. A case with extensive lesions needed a long-term low dosage of prednisolone, 5 to 10 mg/day for maintenance therapy. Idiopathic hypertrophic cranial pachymeningitis may be related to the Tolosa-Hunt syndrome, the syndrome of polyneuritis cranialis, and multifocal fibrosclerosis.

Adult↗

Rabies.

Rabies is a complex disease. We still do not understand the mechanisms of clinically diverse furious and dumb types and its fatal course. Moreover clinical symptomatology, once believed to be unique, may be variable, particularly in those patients who develop disease after exposure to virus of the insectivorous or frugivorous bat origin. This review summarizes classic and nonclassic clinical features associated with canine and bat rabies variants and also atypical presentations of rabies survivors. Difference in cellular tropism either at the inoculation site or in the central nervous system or differences in route of spread, or both, may account for these discrepancies. Furthermore, these may affect different sets of neurotransmitters that in turn modulate variable neurobehavioural patterns and neuroendocrine-immune cascades.

Animals↗

Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains.

Functions of the muscarinic acetylcholine receptor (mAChR) were studied in rabid dog brains using [3H]quinuclidinyl benzilate (QNB) as a radioligand. Of various brain regions, hippocampus and brainstem were the areas mostly affected in terms of impaired specific binding to [3H]QNB, as compared to other regions, as well as to those of controls. Saturation studies of the hippocampus revealed significantly elevated dissociation equilibrium constant (K(d)) values in both furious (n = 5) (9.80 + or - 2.77 nM) and dumb (n = 6) (6.01 + or - 1.08 nM) types of rabies as compared to 11 controls (2.15 + or - 0.31 nM), whereas the maximum number of receptor sites (B (max)) values were comparable among all subgroups of normal (1.38 + or - 0.10 pmol/mg protein), dumb (1.43 + or - 0.17 pmol/mg protein) and furious (1.28 + or - 0.12 pmol/mg protein) rabies types. Hippocampal K(d) values were comparable between high (fluorescent antibody test-FAT and polymerase chain reaction-PCR positive; n = 4) (7.47 + or - 3.27 nM), and low (FAT-negative and PCR-positive; n = 4) virus amount (8.34 + or - 3.93 nM) but these were significantly higher than controls (n = 4) (1.58 + or - 0.17 nM). Our data suggest a functional derangement of mAChR at specific sites of hippocampus and brainstem which is not dependent on the amount of virus.

Animals↗

Rabies and its prevention.

The increase in world-wide travel means that physicians everywhere require an understanding of rabies and its prevention, to advise intending travellers, or to follow-up on treatment begun overseas. In this article, we discuss measures to prevent rabies.

Animals↗

Diagnosis of rabies by polymerase chain reaction with nested primers.

A simple, sensitive, and specific polymerase chain reaction (PCR) protocol for detection of rabies virus is described. The process consists of sample preparation, reverse transcription, two-step DNA amplification, and detection of the amplified product. RNA was extracted from animal and human brain by phenol-chloroform using guanidinium thiocyanate. Viral RNA was then amplified in a two-step PCR that used two sets of nested primers designed to amplify rabies nucleocapsid (N) sequence. Rabies nucleocapsid sequence was amplified from all brain samples from 95 dogs and 3 humans with rabies confirmed by fluorescent antibody (FAT) and mouse inoculation tests (MIT). Rabies-negative brain samples (110 dogs, 2 humans) were PCR-negative. The process requires < 24 h. Detection of viral RNA was still possible in brain material that was left at room temperature for 72 h. As little as 8 pg of rabies virus RNA could be detected. This technique could have practical applications as a confirmatory test to FAT at busy rabies diagnostic centers.

Animals↗

Cells with natural killer activity in human rabies.

Cytotoxic lymphocyte function in 13 patients with rabies was studied by counting the number of CD56 cells and assessing natural killer (NK) cell activity. There was no significant difference in the number of killer cells between rabies patients and 31 normal controls (P greater than 0.05). Two of six non-fatal encephalitic patients due to causes other than rabies had reduced CD56 numbers. Base-line NK cell responses versus K562 cell targets did not differ among the normal control and rabies groups (P greater than 0.05). Study of the non-rabies encephalitis group showed heterogeneous results with wide variation. Significant enhancement of NK activity was seen in four rabies patients and in 10 normal control subjects tested after interferon-alpha (IFN-alpha) and IL-2. None of the four patients with encephalitis due to causes other than rabies showed such enhancement. Our results suggest that NK cells of rabies patients are not fully stimulated and that this might contribute to the virulence of rabies. The cause of this phenomenon remains unknown.

Adolescent↗

Immune response to rabies vaccine in Thai dogs: a preliminary report.

Serum neutralizing antibody to rabies virus was determined in previously unvaccinated Thai pet dogs after receiving one subcutaneous dose of inactivated tissue culture rabies vaccine (Rabdomun, Coopers Animal Health Company, Germany, 4.55 IU ml-1 potency). Geometric mean titres on days 14, 30, 60, 180 and 360 were 2.14, 2.30, 0.45, 0.14 and 0.05 IU ml-1, respectively, by the rapid immunofluorescent focus inhibition test. Titres of neutralizing antibody to rabies virus did not correlate with the age of the dog at the time of vaccination or with the presence or absence of anaemia or blood parasites. Six out of 50 (12%), 11 out of 43 (25.6%) and 13 out of 31 (42%) dogs had no detectable rabies antibody in serum 60, 180 and 360 days, respectively, after vaccination. Three of these antibody-negative dogs were given another dose of vaccine. Antibody reappeared on day 14 but rapidly declined within 60 days. These data suggest that one dose of tissue culture vaccine in dogs by the subcutaneous route of injection is not adequate to maintain rabies neutralizing antibody in serum for 1 year.

Animals↗

One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine.

The 2-1-1 rabies postexposure treatment schedule is an abbreviated regimen in which a tissue culture rabies vaccine is administered intramuscularly at two sites on day 0, and at one site on days 7 and 21. Compared to the standard five-dose intramuscular regimen, the 2-1-1 schedule reduces the number of clinic visits from five to three and the amount of vaccine used by 20%. One hundred Thai patients, who were severely exposed to rabies, were treated with rabies immune globulin and the 2-1-1 regimen using purified Vero cell rabies vaccine. They were followed for 1 year. Rabies antibody titres were measured in 10% of this group. All patients survived and adverse reactions were mild. A satisfactory antibody response (a titre greater than 0.5 IU ml-1) occurred in all ten patients studied at day 14, but persisted for 90 days in 80% and for 360 days in only 50%. The authors therefore do not recommend use of the 2-1-1 schedule in severely exposed patients who also need to receive rabies immune globulin.

Adolescent↗

Human immune response to rabies nucleocapsid and glycoprotein antigens.

Antibodies to two components of rabies virus, nucleocapsid (N) and glycoprotein (G), were compared in 11 rabies patients with those in nine recipients of Vero cell rabies vaccine. All rabies vaccinees had antibodies to N and G components by day 10 after the first vaccine injection. A similar but not identical response was observed in three out of 11 rabies patients. Serum antibodies appeared in rabies patients as early as 3 days after onset of the first symptoms of the disease. In these antibody-positive rabies patients, levels of both antibodies, but particularly of anti-N antibody, were lower than in the vaccinated group. Our results suggest that the process of immune recognition and of antibody development in human rabies is more likely to occur early in the pre-clinical phase, and that reactivity to N protein may be crucial for elicitation of neutralizing antibody.

Adult↗

Plasma C3c in immune-mediated neurological diseases: a preliminary report.

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase. Plasma C3c levels were elevated in the group with immune mediated diseases when compared with those of non-immune mediated diseases. The sensitivity and specificity of C3c as a diagnostic test for immune mediated neurological diseases were 61.4 and 100% respectively with a positive and negative predictive value of 100 and 41%. the C3c levels in plasma correlated well with disease severity in MG and GBS patients. Such a correlation was also evident in all CIDP patients except one that had persistent elevation in the presence of clinical improvement. Results suggest that the plasma C3c level may be useful for differentiating immune from non-immune mediated neurological diseases. Plasma C3c may also be used for monitoring disease severity, particularly in myasthenia gravis.

Autoimmune Diseases↗