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Biomedical subjects

T G Baker

Publications and source records attributed to T G Baker.

At least 19 recordsLinked to original sources
PubMed1988

The logistics of broader pre-clinical evaluation of potential anti-cancer agents with reference to anti-tumour activity and toxicity of mitozolomide.

Anti-tumour responses with CCRG81010, M & B 39565, NSC 353451, 8-carbamoyl-3-(2-chloroethyl)imidazo [5,1-d]-1,2,3,5-tetrazin-4(3H)-one (Mitozolomide) in a panel of 4 murine colon tumours of varying growth characteristics and chemosensitivity and a spontaneous murine lymphoma are similar to those seen with standard nitrosoureas. The moderately well differentiated colon adenocarcinoma MAC 16 is nonresponsive to mitozolomide and methylCCNU. Responses in the other 4 lines studied are only achieved near to maximum tolerated dose and at this level there is severe host toxicity. Haemopoietic toxicity is clearly demonstrated by analysis of peripheral blood counts and by CFU-S assays and severe testicular and ovarian toxicity was also seen at dose levels necessary to achieve anti-tumour effects. Using mitozolomide as an example, the study has demonstrated the feasibility of conducting simple but thorough toxicity evaluation for the determination of the therapeutic index. This approach would provide invaluable guidelines for the selection for clinical trial of the most appropriate members of a series of new cytotoxic compounds.

Adenocarcinoma↗
PubMed1988

A histological study of the gonads of T16H/XSxr hermaphrodite mice.

A proportion of mice with the genotype T16H/XSxr develop as hermaphrodites (Ward et al. 1987). In this study, histological sections were prepared of the gonads and reproductive tract from a number of such animals. Examination of the sections showed a wide range of development. The most common types of gonad found were sterile testes resembling those found in XXSxr males and apparently normal ovaries. However, between these two extremes were some gonads which were classified as ovotestes. These ovotestes covered such a range of sexual development that they were for convenience divided into two groups. Type I ovotestes were similar in appearance to the Sxr-type testes with the exception that oocytes surrounded by granulosa-like cells were present in some seminiferous tubules. Also, many tubules had shed their Sertoli cell lining. The structure of Type II ovotestes was even more bizarre; regions of both testicular and ovarian somatic tissue and widespread areas of haemorrhage were seen. In general, the histological structure of the reproductive ducts approached the normal pattern. The epididymal ducts were small and haemorrhage was present in some epididymides associated with the Type II ovotestes.

Animals↗
PubMed1987

A comparison of the structural integrity of several commonly used preparations of rat small intestine in vitro.

The structural integrities of various preparations of rat small intestine for the study of absorption in vitro have been compared after incubation or perfusion. Perfused intestines removed from anaesthetized rats, and thus never deprived of a supply of oxygen, maintain their structural integrity even after perfusion for 1 h provided that a Krebs-Henseleit bicarbonate perfusate is used. However, intestines removed from freshly killed rats show severe villus disruption and oedema after perfusion for only 20 min. Extensive damage to both crypts and villi is observed in everted sacs of small intestine incubated for 20 min, regardless of the buffer system used. Intestinal rings show damage at the tips of the villi after incubation for 2 min, but otherwise remain morphologically intact; this damage is progressive with time. It is concluded that the exact mode of preparation of intestinal tissue is critical for preservation of structural and functional integrity and that this is especially important in quantitative studies on transport processes. Further, it is recommended that routine monitoring of the integrity of intestinal preparations in vitro is desirable and that histological assessment is an appropriate technique.

Animals↗
PubMed1987

Gonadal development in T16H/XSxr hermaphrodite mice.

Sexual development was studied in 25 hermaphrodite mice with the genotype T16H/XSxr. The majority of the animals had a male phenotype similar to that seen in XXSxr males. A few, however, had feminized external genitalia and were classified as females. Examination of the gonads and reproductive tracts of the male hermaphrodites revealed a strong tendency for the left gonad to be more masculine than the right. Most of the gonads in male and female hermaphrodites appeared to be ovaries or testes rather than ovotestes.

Animals↗
PubMed1985

Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women.

Postnatally, XO mice have approximately half as many oocytes as their XX sisters. A quantitative histological analysis of XO and XX ovaries throughout oogenesis (14 1/2-24 1/2 days post coitum) revealed that this oocyte deficiency in XO mice is due to excess atresia of oocytes at the late pachytene stage (19 1/2 days post coitum). Female mice heterozygous for a large X inversion (In(X)/X mice) were also found to have excess atresia at late pachytene. It was suggested that in XO mice it is the presence of an unpaired X chromosome, and in In(X)/X mice, the incompleteness of X chromosome pairing, which leads to this excess oocyte atresia. A new quantitative histological procedure which was developed for the analysis of perinatal mouse ovaries is also described.

Animals↗
PubMed1985

Intersexuality in five pigs, with particular reference to oestrous cycles, the ovotestis, steroid hormone secretion and potential fertility.

Reproductive tissues, steroid hormone secretion, and sexual behaviour have been examined in five gilts, in each of which the right gonad was an ovotestis. Although from different females, these animals were sired by the same boar and each possessed an XX sex chromosome constitution as determined by karyotype analysis of blood cells. Despite variable amounts of testicular tissue in the ovotestis and unilateral development of a prominent epididymis, four of the animals had oestrous cycles of normal duration (20-22 days) and extended periods of standing oestrus (3-6 days). The fifth animal did not have detectable oestrous cycles but was extremely aggressive in the presence of a mature boar. Two of the gilts were mated, and there were small numbers of embryos in each uterine horn 23 and 26 days later. Removal of the ovary did not prompt compensatory hypertrophy in the ovarian portion of the ovotestis, nor did injection of pregnant mare serum gonadotrophin stimulate detectable follicular growth in ovarian tissue adjoining testicular tissue. Concerning the aetiology of this intersex condition, the unilateral appearance of an ovotestis precludes any simple involvement of a translocated portion of the Y chromosome or systemic effects of unusual titres of the putative H-Y antigen. However, bearing in mind a predisposition to gonadal asymmetry in eutherian mammals, a case is advanced for apposition or incorporation of adrenocortical tissue in the right embryonic ovary. The resultant virilization of neighbouring reproductive tissues would stem from adrenocortical androgen synthesis.

Animals↗
PubMed1984

Cutaneous malignant melanoma in West Yorkshire: II. A prospective study of recurrence and prediction of lymph nodal metastasis.

One hundred and fifty patients with cutaneous malignant melanoma, in clinical stage I at diagnosis, were studied prospectively to determine the lymph nodal metastatic pattern of the disease, and to find that combination of clinical and pathological variables best predictive of the probability of its occurrence when combined in a linear logistic regression equation based upon a model by Cox. Details of the general pattern of melanoma recurrence are included to provide a necessary background to the nodal metastatic study. Of 66 patients showing melanoma recurrence in 48 (19 males and 29 females) it took the form of lymph nodal metastasis. Of these 50% showed lymph nodal metastasis within 1.1 years of the primary operation and 90% within 3.8 years. Nineteen clinical and pathological variables were tested for association with lymph nodal metastasis, 15 of which showed a significant association and in 7 of these the association was highly significant (P less than or equal to 0.0001). All 19 variables were included in the logistic regression analysis, 6 being selected as providing the best regression 'goodness of fit' and of these 'maximum tumour thickness (Breslow' and 'sex' emerged as the dominant variables. It is concluded that the analysis described provides surgeons, oncologists, and pathologists with a practical method to assess the likelihood in an individual patient of melanoma recurrence to regional lymph nodes. This should enable surgery or other adjunctive therapeutic regimens to be selected at an early stage.

Adult↗
PubMed1984

Meiotic pairing and gametogenic failure.

In males spermatogenic impairment is associated with a wide range of chromosomal anomalies, including XYY trisomy, XO monosomy with sex reversal and heterozygosity for many structural rearrangements. Common to all these anomalies is the presence of unpaired chromosome segments during pachytene. The stage at which spermatogenic cells are lost varies markedly from one anomaly to the next. The present paper considers the possibility that there may be a common mechanism underlying these various manifestations of spermatogenic failure. An analysis of meiotic data from XYY mice had previously pointed to a causal relationship between the presence of unpaired elements at pachytene, and a failure to reach metaphase II (MII). In apparent contradiction to this is the observation that sex-reversed XO mice form reasonable numbers of round spermatids (implying progression beyond MII) despite the presence of the unpaired X. However, evidence is presented that the round spermatids of XO Sxr mice are diploid, the second meiotic division having been omitted. Most of these spermatids degenerate during spermiogenesis, but a few very abnormal sperm are produced. The female counterparts of male sterile chromosome anomalies are usually fertile, so the mechanism causing the spermatogenic failure has been presumed to be inoperative in females. However, recent work on female XO mice has revealed that although they are fertile as adults, there is nevertheless extensive oogenic failure (a 60% reduction as compared to controls) during late pachytene. It is proposed that there is a mechanism operating in both males and females which selectively removes gametogenic cells in which there has been meiotic pairing failure. In females the mechanism is not completely efficient, so that sufficient of the 'at risk' oocytes usually survive to allow fertility. In males the severity and stage of spermatogenic loss is presumed to be related to the extent of the pairing failure at pachytene. In male mammals spermatogenesis is disrupted by a wide range of karyotypic anomalies. These include XYY trisomy; XO monosomy with sex reversal; X- or Y-autosome translocations; partial or complete autosomal trisomies; heterozygosity for some autosome-autosome translocations; double heterozygosity for some Robertsonian translocations and heterozygosity for some other structural rearrangements (e.g. rings, insertions, some inversions). Common to all these anomalies is the presence of incompletely paired (synapsed) regions at pachytene. The severity of the spermatogenic impairment and the stage most affected vary widely.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

OpScan-MIMS. A data network system.

The expansion of a unique system for medical, epidemiological, and laboratory information management is described. The system utilizes an automated, optically scanned data entry mode (OpScan), and a generalized, interactive storage and retrieval software package (MIMS). Aggregate medical, epidemiological, and laboratory information are monitored, with the permission of the locality, via telephone terminals at four sexually transmitted disease clinics. OpScan-MIMS combines an efficient, rapid, and cost-effective method for data entry with a user-friendly computer system that requires no specialized training in computer language.

Centers for Disease Control and Prevention, U.S.↗
PubMed1983

Cutaneous malignant melanoma in West Yorkshire: I. A prospective study of variables, survival and prognosis.

A prospective study was made of 150 cases of primary invasive cutaneous malignant melanoma in clinical stage I diagnosed during the period 1966-1980. Thirty-six of the patients were male, the remaining 114 female, and thus the age-standardized male:female ratio was 2.9:1. One hundred and forty cases were part of the first author's personal series while the data for the remaining 10 patients were provided by colleagues and were subject to the same prospective approach. As a preliminary to multivariate analysis 19 clinical and pathological variables were subject to contingency table analysis to determine significant associations between pairs of variables. Sixty-six nominally significant associations were found of which 28 were highly significant (P less than or equal to 0.0001). Survival to 3, 5, and 7 years was examined by the life table method and a better survival was found in females than in males. Linear logistic regression analyses with dependent variables of 3, 5, and 7 years were carried out by 2 modifications of Cox's regression model, that with survival to 5 years as the dependent variable showing the best goodness of fit. In this study "level of microinvasion" and "patient's sex" emerged as the primary dominant variables in the 5-year regression model. Possible reasons for this and other apparent anomalies between different Cox's models are discussed.

Adolescent↗
PubMed1982

Morphology, histology and steroid hormones of the gonads in intersex pigs.

Studies of 3 genetically female, intersex pigs revealed that only one showed oestrous cycles and lordosis, the other 2 exhibited various components of male sexual behaviour. Each uterus was a patent bicornuate structure, but 5 of the oviducts were incompletely formed. Two of the animals had bilateral ovotestes, whilst the third had a functional ovary on the right and an ovotestis on the left. The small ovarian portion of each ovotestis contained Graafian follicles which did not respond to a systemic injection of PMSG. The major portion of each ovotestis consisted of extensive interstitial tissue and seminiferous tubules devoid of germ cells. A structure closely resembling an epididymis adjoined the ovotestes. Concentrations of oestradiol and progesterone in plasma corresponded with those expected in the follicular phase of an oestrous cycle, but concentrations of testosterone represented approximately one-tenth of the values found in mature boars.

Animals↗
PubMed1982

The ultrastructure of rat thyroid glands under experimental conditions in organ culture.

A technique has been described which permits the maintenance for up to 6 days in organ culture of explanted thyroid glands. This provided a suitable model for an electron microscope study to be carried out on glands under experimental conditions. The appearance of the control gland was consistent with stimulation by TSH. The formation of 'intracytoplasmic' follicles was caused by injection of TSH into the culture. Parafollicular (light) cells were described for the first time in organ cultured thyroid glands.

Animals↗
PubMed1981

Oocyte depletion in XO mice and their XX sibs from 12 to 200 days post partum.

The total number of oocytes (healthy and atretic) in XO and XX mice at ages ranging from 12 to 200 days after birth was determined using a quantitative histological technique. For each oocyte the stage of the enveloping follicle was recorded. The results demonstrated that throughout the period studied XO mice had approximately half the number of oocytes found in XX mice. No increase in the incidence of atresia was detected in XO ovaries. In XO mice at 12 days of age the establishment of the population of growing follicles was clearly retarded.

Aging↗