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Biomedical subjects

D H Martin

Publications and source records attributed to D H Martin.

At least 91 records · Page 5Linked to original sources

Determination of cocarcinogenic activity of benzo[e]pyrene for respiratory tract mucosa.

As benzo[e]pyrene (B[e]P) has been shown to enhance the carcinogenic effects of benzo[a]pyrene (B[a]P) on mouse skin [26], it therefore seemed important to determine if it would also act as a cocarcinogen in another target tissue, namely respiratory tract mucosa. Tracheal mucosa of rats was concomitantly exposed to B[a]P and B[e]P for up to 6 months. At B[a]P/B[e]P ratios of 1 : 1 and 0.5 : 1, B[e]P had no cocarcinogenic effects on tracheal epithelium. At the higher B[a]P/B[e]P ratio, B[e]P appeared to reduce the carcinoma incidence from 65% (B[a]P alone) to 40% (B[a]P plus B[e]P). In sharp contrast to the carcinoma incidence, the tracheal and peritracheal sarcoma incidence was enhanced 2-3-fold by B[e]P. Thus, while not cocarcinogenic for tracheal epithelium, B[e]P was cocarcinogenic for connective tissue. Together with other results [26], these point to the importance of the target tissue as a determining factor of cocarcinogenic activity of test substances.

Animals↗

Cellular immune response during uncomplicated genital infection with Chlamydia trachomatis in humans.

A lymphocyte transformation (LT) assay for the study of the cellular immune response to Chlamydia trachomatis in humans is described. Subjects studied included 9 newborns whose mothers were C. trachomatis culture negative, 16 seronegative, sexually inexperienced adults, and 107 patients seen at a sexually transmitted disease clinic, including 31 men presenting with acute nongonococcal urethritis and 76 women with known or suspected uncomplicated gonorrhea or with uncomplicated C. trachomatis genital infection. LT stimulation indices (SI) were less than 3.5 in newborns and normal adults, as well as 11 of 12 seronegative, isolation-negative sexually transmitted disease clinic subjects. LTSI greater than 3.5 was found only with subjects who were sero- or culture positive for C. trachomatis. Among men with nongonococcal urethritis, the LTSI correlated better with culture than with antibody. Among women, the LTSI correlated better with antibody than with culture. LTSI decline significantly 3 to 4 weeks after curative therapy in men with nongonococcal urethritis, suggesting that LT response is short-lived and that the LTSI may be an indicator of acute C. trachomatis infection. The sensitivity, specificity, and predictive value of a positive LT assay and of serum and local antibody tests, in terms of C. trachomatis infection defined as positive isolation, were also compared. The predictive value of a positive LTSI for C. trachomatis infection was generally low in the sexually transmitted disease clinic patients: 62% in men with nongonococcal urethritis and 37% in women. However, this study did show the LT assay to be a useful specific test for monitoring the cellular immune response to C. trachomatis infection.

Antibodies, Bacterial↗

Puerperal infectious morbidity: relationship to route of delivery and to antepartum Chlamydia trachomatis infection.

We investigated the relationship of route of delivery and of antepartum Chlamydia trachomatis cervical infection to selected forms of puerperal infectious morbidity, including intrapartum fever, or early (less than 48 hours) postpartum fever not attributable to infections of sites outside the uterus and late (48 hours to 6 weeks) postpartum endometritis. Infectious morbidity occurred in 27 (44%) of 62 women who underwent cesarean section and in 33 (10%) of 329 who underwent vaginal delivery (p less than 0.001). Postsection infectious morbidity was not correlated with C. trachomatis infection and was largely limited to early postpartum fever. Among women who underwent vaginal delivery, infectious morbidity occurred in 10 (34%) of 29 women with and in 23 (8%) of 300 without C. trachomatis infection (p less than 0.001), and chlamydial infection was associated only with intrapartum fever and late postpartum endometritis. Separate matched case-control analyses confirmed that cesarean section was associated with an increased risk of early postpartum fever (p = 4 x 10(-8)); whereas among women who underwent vaginal delivery, antepartum C trachomatis infection was associated with an increased risk of development of intrapartum fever or late postpartum endometritis (p = 0.002).

Cesarean Section↗

Cutaneous manifestations in rats with advanced vitamin A deficiency.

Specific-pathogen-free rats kept on a vitamin A-deficient diet for approximately 5 months developed cutaneous alterations, especially in the periorbital and eyelid skin. These lesions were characterized grossly by erythema, partial alopecia, and crusting, and histologically by hyperorthokeratinization, acanthosis, and a three-fold increase in incorporation of labeled DNA precursors into the epidermal basal layer. Electron microscopy showed an increased number of Langerhans cells with and without Birbeck granules, as well as the presence of cytoplasmic dense bodies of probable lipid nature in keratinocytes of all epidermal strata. The similarities of these ultrastructural alterations with some features of vitamin A-sensitive human dermatoses point to probable common mechanisms in the pathogenesis of these skin diseases.

Animals↗

Sexual differences in the distribution of epithelial alterations in vitamin A-deficient rats.

Male and female rats maintained on a vitamin A-deficient diet showed sex-related differences in several pathological features. Males developed severe manifestations of hypovitaminosis A earlier than females. They also presented more extensive squamous metaplasia of the trachea and more severe sialoadenitis, especially of the submaxillary gland. Females, on the other hand, presented earlier and more extensive squamous metaplasia of the renal pelvis. The underlying causes of sexual dimorphism in these pathological features are not known, but hormonal influences are suggested.

Aging↗

Alterations of nucleic acid and protein syntheses in vivo in the chick embryo mediated by captan.

1. The objective of this investigation was to measure the effects of captan on DNA, RNA and protein biosyntheses in limbs of developing chick embryo, in vivo. 2. Captan (12p.p.m.) was injected into the egg on day 4 of incubation and macromolecular syntheses were measured on days 8--14. 3. Total DNA content was unaffected by captan, but incorporation of [3H]thymidine was inhibited over the entire time range; the period of peak specific activity (day 11) was inhibited in treated samples to 67% of control. 4. Total RNA content was reduced in the earlier days but returned to normal by day 14, whereas incorporation of [3H]uridine was lowered throughout the period. The timing of peak specific activity for RNA synthesis was delayed by 2 days in treated eggs and was inhibited by 32% when peak days were compared. 5. Total protein concentration was slightly lowered by captan treatment in the mid-range of the days measured and the incorporation of [3H]valine was retarded in the early days; peak periods of synthesis were similar in magnitude but were shifted from days 9--10 in control to day 11 in treated embryos.

Animals↗

Enzootic and epizootic Venezuelan equine encephalomyelitis virus in horses infected by peripheral and intrathecal routes.

Forty-five horses were infected peripherally or intrathecally with enzootic or epizootic strains of Venezuelan equine encephalomyelitis (VEE) virus. Low titers of virus appeared in cerebrospinal fluid (CSF) after peripheral inoculation of enzootic or epizootic VEE virus strains. Intrathecal infection with either epizootic or enzootic VEE virus produced higher titers of virus in CSF than did peripheral infection. In contrast to peripheral infections with enzootic strains, intrathecal infections with these strains caused death. The animals that died had widespread histopathologic changes and large amounts of virus in brain tissue. The attenuated VEE virus vaccine strain, TC-83, also multiplied in the brain of horses inoculated intrathecally but caused no clinical disease and little histopathologic damage.

Animals↗

A randomized controlled trial of selective planned delivery.

A prospective randomized controlled trial designed to investigate selective planned delivery is reported: 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it. The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia. Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid. However, the infants in the two groups had similar Apgar scores at birth. There was one stillbirth in the control group; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity.

Apgar Score↗

Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity.

Seven aromatic polycyclic hydrocarbons (PCHs) were investigated for their toxic effects on respiratory mucosa: benzo(e)pyrene (BeP), pyrene, anthracene, benz(a)anthracene(BaA), dibenz(a,c)anthracene(DBacA), benzo (a)pyrene (BaP), and dimethylbenz(a)anthracene (DMBA). The compounds were chosen because they comprise a spectrum of PCHs ranging from noncarcinogens, to initiators, to weak and strong carcinogens. All of them except DMBA are environmentally relevant chemicals. The chemicals were tested over an 8-week period. Heterotopic tracheal transplants were continously exposed and the histopathologic effects induced by the various PCHs were periodically assessed semiquantitatively. All PCHs exhibited varying degrees of toxicity for respiratory epithelium and submucosa. BeP clearly showed the least toxicity followed by pyrene and anthracene. BaA and DBacA caused marked epithelial and submucosal changes. In addition to epithelial hyperplasia, undifferentiated epithelium and squamous metaplasia developed. Marked mononuclear infiltration occurred in the subepithelial connective tissue. With BaP the epithelial and submucosal changes were similar but were much stronger. DMBA was the most toxic substance, causing epithelial necrosis followed by generalized keratinizing squamous metaplasia; the subepithelial changes consisted of an early acellular exudate and, later (at 8 weeks), marked condensation and hyalinization of the lamina propria. The toxic response pattern of the tracheal mucosa to carcinogenic agents was characterized by the chronicity of epithelial and connective tissue damage, as opposed to the short-lived hyperplastic and inflammatory response elicited by the noncarcinogens and weak initiators.

9,10-Dimethyl-1,2-benzanthracene↗

Quantitative exposure of grafted rat tracheas to 7, 12-dimethylbenz(a)anthracene.

A method was developed for continuously exposing tracheal epithelium to measured amounts of carcinogen. Beeswax was the vehicle for sustained release of carcinogen, and tracheas transplanted to s.c. sites were target tissues. In the experiment reported here, transplanted rat tracheas were exposed to a potent carcinogen, 7,12-di-methyl benz(a)anthracene (DMBA). The rate of release of DMBA from the beeswax carrier within the tracheal lumen approached first order when the initial concentration of carcinogen was high (3200 to 325 microng in a 24.45-mg pellet). With lower concentrations, where the carcinogen was dissolved in the beeswax, initial release was rapid, and most of the carcinogen was delivered within 4 weeks. At high DMBA dose levels, the entire tracheal epithelium was uniformly replaced by keratinizing squamous metaplasia after 1 week of exposure, and after 2 months, when from 280 to 910 microng DMBA had been delivered, all transplants had developed invasive squamous carcinomas. Sarcomas also developed in 19% of the transplants. At lower dose levels the epithelial reactions were more varied, and tumor development was more protracted. The lowest DMBA dose presently known to diduce carcinomas in this experimental model is 40 microng, which is in the dose range used for tumor initiation in skin carcinogenesis studies in mice.

9,10-Dimethyl-1,2-benzanthracene↗

Induction of preneoplastic and neoplastic lesions in grafted rat tracheas continuously exposed to benzo(a)pyrene.

Heterotopically transplanted rat tracheas were continuously exposed to measured amounts of benzo(a)pyrene over a period of 1 to 6 months. The cumulative doses ranged from 10 to 2490 microng. The morphological response of the tracheal epithelium was characterized by hyperplasis during the first 2 weeks, followed by atrophy. Squamous metaplasias did not appear until after 4 months of exposure; at 4 and 6 months numerous dysplastic lesions and noninvasive carcinomas resembling those seen in the airways of humans were found in the higher carcinogen dose groups. The first invasive carcinomas developed at 4 months in the groups given 1250 microng or more benzo(a)pyrene. The lowest dose tested that produced a carcinoma within the observation period of 22 months was 300 microng benzo(a)pyrene. The majority of the neoplasms were squamous cell carcinomas, although several adenocarcinomas and sarcomas also developed. Since a variety of metaplastic and dyplastic lesions can be induced by carcinogenic polycyclic hydrocarbons in the transplanted rat tracheas, this experimental model appears to be well suited for the study of the sequential epithelial changes that lead to respiratory tract neoplasia.

Animals↗

Selective planned induction in conditions of civil strife.

Selective planned induction may be defined as the initiation of labour by artificial means for reasons not strictly medical. Where the indications are merely social or for conveniencewhether patient's, hospital's, or doctor'sīt is doubtful that the procedure is acceptable until we have more detailed knowledge of its effects on the mother and fetus. However, the civil strife that occurred in Belfast in 1972 provided conditions in which the present study of the technique seemed justified. The results suggest that, provided the selection criteria are sufficiently rigorous and meticulously applied, there are no serious maternal risks. The main fetal risk is of unexpected prematurity; this can be avoided, but the precautions applied in this preliminary study reduced significantly the number of patients for whom the method could be used. A second series, with controls and using less rigorous selection criteria, is at present being studied.

Apgar Score↗

Experimental tumor induction in a circumscribed region of the hamster trachea: correlation of histology and exfoliative cytology.

A method for the induction of carcinomas in a circumscribed region of the hamster trachea is reported. By means of a special catheter, a solution of N-nitroso-N-methylurea was applied twice a week to about a 6-mm length of the trachea 10- to 16-mm distal from teh vocal cords. Slight alteration of this catheter allowed sampling of cytologic specimens directly from the surface of the carcinogen0exposed epithelium. This procedure permitted the simple and accurate correlation of sequential histologic and cytologic changes observed during tumor development in the hamsters. Noninvasive dysplastic and metaplastic lesions were seen in animals killed after 5 and 10 weeks of carcinogen application. These epithelial changes could be readily correlated with abnormal exfoliated cells abundantly present in cytologic specimens from these animals. Exposure to carcinogen for 15 weeks induced a 100% tumor incidence exclusively at the application site. More than 75% of the malignancies appeared within 15-20 weeks after the start of carcinogen administration. Most tumors were epidermoid carcinomas but some anaplastic large-cell carcinomas were also observed. Cytologic specimens of tumor-bearing animals had many cells conclusive of malignancy. The new experimental system lends itself to study of the effect of topically applied anticarcinogenic or cocarcinogenic agents on different carcinogen-induced epithelial lesions whose regression or progression can be followed by exfoliative cytology.

Animals↗

Species differences in the effect of benzo(alpha)pyrene-ferric oxide on the respiratory tract of rats and hamsters.

When given intratracheal injections of a suspension of benzo(alpha)pyrene-ferric oxide, rats and hamsters showed striking species differences in the response of their respiratory tracts to the carcinogen. Hamsters produced squamous metaplasia of the trachea and large bronchi; in contrast, squamous cell nodules of bronchioloalveolar origin developed in rats within a few weeks after carcinogen application. The different sites of the early proliferative and metaplastic responses correlated in their location with the sites of later tumor development. There were no obvious differences between the two species in retention of benzo(alpha)pyrene in the lungs or tracheas. A species difference was observed, however, in the localization of the benzo(alpha)pyrene in the tracheal tissues using ultraviolet fluorescence microscopy. Carcinogen was found to be present in the epithelium of hamsters but not in the epithelium of rats, suggesting a species difference in penetration of carcinogen from the lumen into the tracheal tissues.

Animals↗