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Biomedical subjects

J W Clark

Publications and source records attributed to J W Clark.

At least 145 records · Page 8Linked to original sources

Transmission of HTLV-I and HIV among homosexual men in Trinidad.

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.

Acquired Immunodeficiency Syndrome↗

Extracellular currents and potentials of the active myelinated nerve fiber.

This paper is concerned with the accurate and rapid calculation of extracellular potentials and currents from an active myelinated nerve fiber in a volume conductor, under conditions of normal and abnormal conduction. The neuroelectric source for the problem is characterized mathematically by using a modified version of the distributed parameter model of L. Goldman and J. S. Albus (1968, Biophys. J., 8:596-607) for the myelinated nerve fiber. Solution of the partial differential equation associated with the model provides a waveform for the spatial distribution of the transmembrane potential V(z). This model-generated waveform is then used as input to a second model that is based on the principles of electromagnetic field theory, and allows one to calculate easily the spatial distribution for the potential everywhere in the surrounding volume conductor for the nerve fiber. In addition, the field theoretic model may be used to calculate the total longitudinal current in the extracellular medium (I0L(z)) and the transmembrane current per unit length (im(z)); both of these quantities are defined in connection with the well-known core conductor model and associated cable equations in electrophysiology. These potential and current quantities may also be calculated as functions of time and as such, are useful in interpreting measured I0L(t) and im(t) data waveforms. An analysis of the accuracy of conventionally used measurement techniques to determine I0L(t) and im(t) is performed, particularly with regard to the effect of electrode separation distance and size of the volume conductor on these measurements. Also, a simulation of paranodal demyelination at a single node of Ranvier is made and its effects on potential and current waveforms as well as on the conduction process are determined. In particular, our field theoretic model is used to predict the temporal waveshape of the field potentials from the active, non-uniformly conducting nerve fiber in a finite volume conductor.

Mathematics↗

Intra-oral effects on acid-softened enamel of NaF lozenges administered in divided daily doses.

The purpose of this investigation was to study the intra-oral effects of multiple daily applications of NaF lozenges upon acid-softened enamel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and subsequently mounted in a mandibular removable Hawley appliance. Control slabs were worn for seven days by eight adult male subjects who brushed their natural dentition daily with a fluoride-free dentifrice. Test slabs were exposed to one 0.55-mg NaF lozenge (0.25 mg F) 4x/day for seven days and the natural dentition brushed with a fluoride-free dentifrice. The efficacy of 0.25-mg F lozenges used 4x/day over that of a 1-mg F lozenge administered 1x/day was established by a pilot study with two subjects. Microhardness testing was performed after intra-oral exposure (IOE) and following immersion in 0.01 mol/L lactate buffer containing Ca and PO4 for 24 hrs at a pH of 4.0. Fluoride uptake was measured on separate control and test slabs after KOH wash and after acid-resistance-testing (ART). Recovery of microhardness following IOE was 40.9% for controls and 53.9% for treated slabs, while control slabs retained 1.3% resistance to ART, compared with 25.6% for test slabs. The F content of the control slabs was significantly less than that of lozenge-treated and lozenge-treated-ART slabs throughout the depth of the lesion. The F content of the lozenge-treated-ART slabs was significantly less than that of the lozenge-treated slabs only at the 0-5-microns depth.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Regression of melanoma nodules in a patient treated with ranitidine.

Human malignant melanoma may regress spontaneously or with immunotherapy, such as Calmette-Guerin bacillus, interferon alfa, interleukin-2, and interleukin-2 plus lymphokine-activated killer cells. Histamine type 2 receptor antagonists can modulate immune function by inhibiting suppressor T-cell induction and activity, and melanoma regressions have been reported after the use of cimetidine with coumarin or interferon alfa. This article describes the complete regression of melanoma nodules in a patient treated with ranitidine hydrochloride, another histamine type 2-receptor antagonist. Ranitidine and cimetidine should be considered to be possibly active immunotherapeutic agents in the design and evaluation of clinical trials.

Female↗

Modes of transmission and evidence for viral latency from studies of human T-cell lymphotrophic virus type I in Japanese migrant populations in Hawaii.

Human T-cell lymphotrophic virus type I (HTLV-I) seroprevalence was 20% among Hawaiian Japanese migrants (issei) and their offspring (nisei) from Okinawa compared to 35% in similarly aged men who were lifetime residents of Okinawa. A control group of migrants from a nonendemic area of Japan, Niigata, had low rates of HTLV-I antibodies, suggesting that Hawaii per se is not an endemic area for HTLV-I. Factors that were significantly associated with seropositivity in the Okinawa migrant groups were years of residence in Japan before migration (issei) and age for offspring of Okinawa migrants (nisei). Antibody titer was highest in Okinawa lifetime residents, intermediate in migrants (issei), and significantly lower in offspring of Okinawa migrants (nisei), with increasing titer observed with advancing age in the offspring of the migrant group. Based on these data, infection within the household occurring early in life appears to be a major route of HTLV-I transmission and may help to explain the curious geographic clustering of this virus in certain locales. As yet to be defined cofactors, including sexual transmission and/or environmental exposures (e.g., particularly before age 20), also may contribute to HTLV-I seropositivity. The pattern of rising seroprevalence and titer with age in the offspring of migrants who resided all of their lives in Hawaii raises the possibility that HTLV-I infection acquired early in life may become dormant and reexpressed with reactivation of latently infected T cells. The importance of this model in the process of viral leukemogenesis is supported by recent reports of adult T-cell leukemia in offspring (nisei) of Okinawa migrants.

Age Factors↗

A family with craniofrontonasal dysplasia, and fragile site 12q13 segregating independently.

Coronal craniosynostosis, hypertelorism, telecanthus, broad grooved nasal tip, dental anomalies, mild syndactyly and broad thumbs, consistent with craniofrontonasal dysplasia are described in a family of four affected females over three generations. Documentation of the family is of interest because of variable clinical features and an excess of affected females. The excess of females observed in this condition is as yet unexplained, but cannot be referred simply to X-linked dominance with lethality in the male. Autosomal dominance with less frequent and less severe expression in the male is more tenable. Chromosome analysis on two affected family members revealed a fragile site at 12q13, which was also found in a phenotypically normal family member. A third affected individual did not exhibit this fragile site. Thus it appears that there is a heritable fragile 12q13 site segregating in this family separately from the gene for craniofrontonasal dysplasia.

Abnormalities, Multiple↗

In vivo effects of a SnF2 gel on acid-softened enamel.

The purpose of this investigation was to study the intra-oral rehardening of acid-softened enamel and fluoride uptake from SnF2 gel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and then mounted in a mandibular removable Hawley appliance. Control slabs were worn for 96 hrs by seven adult males whose teeth were brushed daily with a fluoride-free dentifrice. Test slabs were exposed once/day to 0.4% SnF2 gel. The gel was swabbed onto the slabs for one minute before being replaced in the mouth unrinsed. The natural dentition was brushed 4 X /day with a fluoride-free dentifrice. Microhardness testing was performed after intra-oral exposure (IOE) and after acid-resistance-testing (ART) following immersion in 0.01 mol/L lactate buffer for 24 hrs at pH of 4.0. Fluoride uptake was measured on separate controls, test slabs, and test slabs after ART, with 0.5 mol/L HClO4 etches of from 15 to 60 sec. The F content was measured with a F-ion-specific electrode and the phosphate content by spectrophotometry. Following IOE, microhardness recovery was 35.6% for control and 37.9% for test slabs, and control slabs retained 1.4% resistance to acid, as compared with 18.6% for the test slabs. The F content of control slabs was significantly less than that of SnF2-treated slabs from 5 to 60 micron in depth, and the F content of SnF2-treated slabs after ART was significantly less at depths of from 5 to 35 micron than that of SnF2-treated slabs not exposed to ART. Both control and SnF2 enamel slabs demonstrated rehardening after IOE, but only SnF2-treated enamel retained a significant fraction of that rehardening after ART.

Adult↗

Intraoral effects of a fluoride-releasing device on acid-softened enamel.

Among the anticaries benefits of fluorides is the remineralization of incipient carious lesions. There is increasingly convincing evidence that low-potency fluoride agents applied frequently are effective in remineralizing early carious lesions. This study of in vivo remineralization used an intraoral appliance with demineralized enamel slabs mounted in the appliance and an innovative method of fluoride delivery, the fluoride-releasing device, which releases a controlled amount of fluoride (0.3 mg fluoride every 24 hours) on exposure to saliva. After control and treatment periods of 7 and 30 days, the enamel specimens were removed from the appliance and evaluated for microhardness, acid resistance, and fluoride uptake. The treated specimens significantly exceeded the values of their corresponding controls in all parameters measured, indicating that considerable remineralization of the treated enamel had occurred at both 7 and 30 days. Although the longer period of treatment produced greater results, considerable effects were observed after 7 days. This model system provided for an in vivo environment to study the effects of treatment of the FRD and allowed for subsequent recovery of the enamel specimens for evaluation. The results of this study are encouraging with respect to the efficacy of a fluoride-releasing device but indicate that subsequent clinical testing of the effects of FRDs on incipient carious lesions in the natural dentition of human subjects is necessary.

Adult↗

Molecular and immunologic analysis of a chronic lymphocytic leukemia case with antibodies against human T-cell leukemia virus.

The human T-cell leukemia virus type-I (HTLV-I) is a unique, exogenous, horizontally transmitted retrovirus which is T-cell tropic, and has been associated with a specific type of aggressive leukemia/lymphoma of mature T-cell origin. In a survey of lymphoid malignancies in Jamaica, antibodies to HTLV-I were also found in 6 of 17 patients with chronic lymphocytic leukemia (CLL), raising the possibility of an etiologic relationship. Further studies were undertaken on one of these patients to clarify the nature of the disease and possible virus relationship. Cell surface marker analysis of her peripheral blood cells documented that the majority of circulating lymphocytes were B-cells. DNA-cloned probe analysis with a complete HTLV-I proviral genome of these peripheral malignant B-cells, was negative for integrated virus. A T-cell line was established in culture from her peripheral blood. The presence of HTLV-I in the cultured T-cell line was established by the detection of expressed viral specific gag protein p-19 and proviral DNA. Thus, a B-cell lymphoid malignancy can occur in the presence of HTLV-I infected T-cells, suggesting the possibility of an indirect leukemogenic mechanism.

Aged↗

Acute injury of the ligaments of the knee: magnetic resonance evaluation.

Eleven acutely injured knees and 13 normal knees were examined by magnetic resonance imaging (MRI) to assess the value of this modality in detecting acute ligamentous injury of the knee. The presence of torn ligaments in the injured knees was determined by arthroscopy and/or arthrotomy in ten cases and clinical follow-up in one case. The anterior and posterior cruciate ligaments (ACL and PCL) were demonstrated by sagittal spin echo (SE) images through the intercondylar notch (TE = 30 ms; TR = 2,000 ms). The tibial and fibular collateral ligaments (TCL and FCL) were evaluated on coronal SE images (TE = 30 ms, TR = 200 or 530 ms; TE = 120 ms, TR = 2,000 or 2,120 ms). The ACL and PCL were considered torn on MR if they appeared disrupted or were not seen in their normal anatomical positions. The collateral ligaments were considered torn if abnormal high-intensity signal was noted in adjacent soft tissues on TE = 120 ms images or if disruption of a ligament was apparent. Eleven of 15 torn ligaments and 80 of 81 normal ligaments were correctly identified by these criteria. It is concluded that MR imaging may be useful in detecting acute injury of ligaments of the knee.

Acute Disease↗

Gingival and bacterial plaque response to instrumentation, oral hygiene instruction and nutritional therapy.

Thirty-three male subjects participated in a study to examine the effect of supplements of multiple vitamins and minerals, local therapy (periodontal instrumentation and oral hygiene instruction) and a combination of both on gingival inflammation and bacterial plaque formation. Subjects were given either multivitamin and mineral supplements or placebos on a double-blind basis for 21 days. On Day 7, the mandibular incisors were instrumented, and each subject was instructed in brushing and flossing. Observations were taken at Days 0, 7 and 21. There was a significant (P = 0.004) effect from micronutrient supplementation at Day 7 on the gingival index but no significant effect on the plaque index. On Day 21 there was no statistical superiority noted for the supplemented group in respect to either the gingival or plaque index, although the gingival index approached significance (P = 0.062).

Adult↗

Human T-cell leukemia-lymphoma virus type 1 and adult T-cell leukemia-lymphoma in Okinawa.

A serological survey for the presence of antibodies against the human T-cell leukemia virus, type 1 (HTLV-1) in patients seen at the Chubu Hospital in Okinawa was undertaken. All patients with the clinicopathological diagnosis of adult T-cell leukemia-lymphoma were positive. These cases had the characteristic features of adult T-cell leukemia-lymphoma: diffuse histology, often mixed cell or pleomorphic, and a high frequency of hypercalcemia, leukemic phase, diffuse visceral involvement, and opportunistic infections. The median survival of these patients was short, being only 18 weeks. Of the other patients with cancers screened, two of five other non-Hodgkin's lymphoma patients were positive and three of eight patients with other hematological cancers were positive. In addition, three of the four immediate family members of one adult T-cell leukemia-lymphoma case had antibodies. Of the other persons (both in- and outpatients) without hematological cancers, those under the age of 50 had a much lower antibody prevalence (4%) than those over 50 (30%). There was no significant difference in antibody prevalence between the two sexes in either the younger or older age group. These findings further document that Okinawa is an endemic area for HTLV-1. None of the 157 individuals screened for antibodies to HTLV-3 were positive, consistent with the fact that no cases of the acquired immune deficiency syndrome have been reported from Okinawa.

Acquired Immunodeficiency Syndrome↗

Antigenicity of human T-cell leukemia virus-associated gp52: greater response in leukemia patients compared to healthy donors exposed to the virus.

Monoclonal antibody HT462 recognizes a human T-cell leukemia virus type I (HTLV-I)-associated Mr 52,000 glycoprotein (HA-gp52), which is found on the surface of HTLV-infected cells. Whether HA-gp52 is encoded by the virus or by the infected cells has not yet been established. Using monoclonal HT462 in a competitive binding assay, natural human antibodies specific for HA-gp52 were detected in 97% of the patients from the United States, the Caribbean, and Japan with adult T-cell leukemia but not in healthy donors not exposed to HTLV-I. In contrast, antibodies to HA-gp52 occur in healthy virus-exposed donors, but at a lower prevalence than that observed in patients. Among Japanese from HTLV-I-endemic areas and exposed to the virus as indicated by the presence of antibodies to disrupted HTLV-I, 93% of adult T-cell leukemia patients were also seropositive for HA-gp52 compared to only 16% of healthy individuals. Differing sensitivities in the methods of assaying antibodies to HTLV and HA-gp52 were not responsible for these observations as shown by the lack of correlation of HTLV-I antibody titer with the presence of antibody to HA-gp52. Among adult T-cell leukemia patients, antibody titers to HTLV-I and HA-gp52 also varied independently. These results indicate that HA-gp52 in humans is antigenic and correlated with disease. Detection of antibody to this protein in asymptomatic individuals may be indicative of a predisease condition.

Animals↗