Retroviruses and schizophrenia in Jamaica.

Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called "an epidemic of schizophrenia," with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Island, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/HTLV-I associated myelopathy. We therefore examined inpatients as the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating the HTLV-1 and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.

Dopamine D4 receptor variant in Africans, D4valine194glycine, is insensitive to dopamine and clozapine: report of a homozygous individual.

The D4Valine194Glycine receptor is a variant of the dopamine D4 receptor and is found in 12.5% of the Afro-Caribbean population. Glycine replaces valine at a position one amino acid away from a serine which is critical for the attachment of dopamine. To determine whether this mutation had an effect on the properties of the dopamine D4 receptor, we constructed this variant and tested the sensitivity of the expressed protein with various drugs. We found that the variant receptor was two orders of magnitude less sensitive to dopamine, clozapine and olanzapine. The variant receptor was insensitive to guanine nucleotide, indicating the absence of a high-affinity state or functional state. The one 15-year-old individual found homozygous for this variant also had sickle cell disease. The patient revealed an overall pattern of low weight and no axillary or pubic hair.

Identification of human T cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis.

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I-positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining in the adjacent myocytes. Two other specimens were weakly positive for gp46 in rare mononuclear cells. All control specimens were negative for the presence of HTLV-I DNA and protein. CONCLUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.

Tropical spastic paraparesis/HTLV-I associated myelopathy. Etiology and clinical spectrum.

In 1985 we had the first indication that human T-cell lymphotropic virus (HTLV-I) was the possible etiological agent of a chronic myelopathy that seemed to be peculiar to the tropics and that is now known as endemic tropical spastic paraparesis (TSP). IgG antibodies to HTLV-I were found in serum and cerebrospinal fluid of patients from Jamaica, Colombia, Martinique, and shortly after in southern Japan, where the disease is called HTLV-I-associated myelopathy (HAM). The HTLV-I seropositivity was first determined by enzyme-linked immunoassay and confirmed by western immunoblot and in the cerebrospinal fluid specific IgG oligoclonal bands to HTLV-I were found in cerebrospinal fluid and not in serum. These laboratory findings indicated that HTLV-I could be neuropathogenic and for the first time a single etiological agent was identified in patients from different countries. Thus, in less than a decade a century of research and speculation was seemingly resolved when this disease, which was thought to occur only in blacks of poor socioeconomic status in tropical countries, was shown to occur in all ethnic groups of varying socioeconomic status in temperate, subtropical, and tropical climates.

HTLV-I DNA sequences in CNS tissue of a patient with tropical spastic paraparesis and HTLV-I-associated myelopathy.

Human T cell lymphotrophic virus type I (HTLV-I) is the etiologic agent of adult T cell lymphoma/leukemia (ATLL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We studied an HTLV-I-seropositive, white man diagnosed in 1977 with ATLL and 10 years later, 6 months prior to his death, with TSP/HAM. Sections of brain, spinal cord, and visceral tissues were examined histologically, immunohistochemically, by in situ hybridization, and by the polymerase chain reaction (PCR). PCR amplification of a region of the polymerase (pol) gene of HTLV-I from visceral tissue demonstrated the presence of proviral HTLV-I DNA in paraffin-embedded sections from the liver and in DNA extracted from frozen sections of kidney and spleen, but failed to demonstrate viral sequences in paraffin sections of the lung and a lymph node. PCR analysis of CNS tissue demonstrated viral sequences in regions of the brain including frozen samples from cerebellum and cerebral cortex and paraffin sections of the thoracic spinal cord, but failed to detect proviral DNA in sections from a region in the lumbar cord. These results map the distribution of HTLV-I DNA sequences in the CNS of a patient with TSP/HAM for 3 months.

In situ hybridization detection of HTLV-I RNA in peripheral blood mononuclear cells of TSP/HAM patients and their spouses.

This is the first report of the direct detection of HTLV-I RNA in uncultured peripheral blood mononuclear cells (PBMNC's) of patients with tropical spastic paraparesis and HTLV-I-associated myelopathy (TSP/HAM) and their spouses, using the technique of in situ hybridization. Twenty-one Colombian patients were tested, all of whom had antibodies to HTLV-I; the presence of HTLV-I proviral DNA in their PBMNC's was confirmed by the polymerase chain reaction technique. Of the 21 patients 15 had a clinical diagnosis of tropical spastic paraparesis (TSP/HAM), 5 were asymptomatic relatives, and 1 patient had leukemia. In situ hybridization was positive in samples from 5 patients; 2 of these were TSP/HAM patients and the other 3 were healthy wives of TSP/HAM patients. This study demonstrates for the first time that viral RNA is expressed in uncultured PBMNC's of some patients with TSP/HAM in whom proviral DNA is also present; furthermore, the detection of HTLV-I RNA in the blood of female partners of TSP/HAM patients clearly illustrates the high likelihood of HTLV-I transmission through sexual contact.

Human T-lymphotropic virus type I: A retrovirus causing chronic myeloneuropathies in tropical and temperate climates.

Human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus to be isolated, is the cause of endemic tropical spastic paraparesis (TSP). Originally, this chronic neurological disorder was described as a disease seen among blacks of low socioeconomic status living in tropical countries, and thus for many decades TSP remained a little known curiosity outside the endemic regions. The link between HTLV-I infection and TSP was made fortuitously, when antibodies to HTLV-I were found in serum and cerebrospinal fluid of TSP patients in Jamaica, Colombia, and Martinique. Soon thereafter a similar disorder, designated HTLV-I associated myelopathy (HAM), was reported from southern Japan. This broadened the geographic and ethnic boundaries of this chronic myelopathy and the disease has now been reported in multiple ethnic groups from more than 40 countries, in both tropical and temperate regions. The name TSP/HAM is now used to include all patients (regardless of race or country of origin) who have HTLV-I-positive endemic TSP or HAM.

Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy).

Human T lymphotropic virus type I (HTLV-I) was isolated from peripheral blood- and cerebrospinal fluid-derived mononuclear cells of a 13-y-old boy and from the peripheral blood lymphocytes of both his parents. All three had IgG antibodies to HTLV-I and varying degrees of the clinical features of tropical spastic paraparesis (TSP). The son also had IgM antibodies specific for HTLV-I in his serum. Isolations were successfully made from peripheral blood lymphocytes and cerebrospinal fluid lymphocytes stimulated with interleukin-2 or cocultivated with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen by immunfluorescence and cell-associated virus by electron microscopy; cells became transformed in vitro as determined by their continuous growth in the absence of exogenous interleukin-2. This boy is the youngest TSP patient known to be reported, and the isolation of HTLV-I from all three family members suggests the causative role of this virus in TSP.