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Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 235 records · Page 13Linked to original sources

The effect of surgical biopsy on the cell production rate of a murine tumour.

The rate of cell production of a mammary adenocarcinoma following surgical biopsy has been investigated using vincristine sulphate as a metaphase arrest agent. Small implants of the tumour were implanted into the inguinal region of young mice of both sexes and were seen to have a constant rate of cell production both between different tumour generations and during tumour growth. Such a constant rate of tumour cell production provides an extremely useful model for exploring the effects of surgical biopsy. Measurement of the cell production rate showed a 60 per cent decrease for the first 48 hours following biopsy after which recovery ensued to reach control levels again. Sham-anaesthetized controls and sham-resected controls demonstrated none of these changes. Similar depression in the rate of cell production was seen following biopsy of one tumour in mice bearing bilateral tumours. The 48-hour depression was observed both in the ipsilateral remnant tumour and in the contralateral implant which has not been biopsied.

Adenocarcinoma↗

The incidence, pathology and transplantation of hepatomas in CBA mice.

Two hundred and seventy-five male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied at intervals over the whole range of their natural life span of about 2 1/2 yr. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight then decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were very prominent, suggestive of an on-going immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all the mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear plemorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumour metastasised to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1-6 wk (range 1-3-1-8 wk). These hepatomas were transplantable and grew with a doubling of 2-25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumour in situ in old CBA mice might have resulted from a breakdown in "immunological surveillance" the same tumour was transplanted simultaneously to a group of young and old recipients. The tumour grew more slowly (doubling time, 2-5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumours in situ in old mice.

Age Factors↗

Hyperosmolality and intraventricular haemorrhage in premature babies.

Serial investigations of electrolytes, osmolality and nutritional status were undertaken in 28 babies less than 33 weeks gestation. 6 died with intraventricular haemorrhage, 9 died without intraventricular haemorrhage, and 13 survived. Significant hypersomality was detected in the babies who died with intraventricular haemorrhage, whereas babies who died without intraventricular haemorrhage and survivors had values within normal limits. No relation was found between hyperosmolality and sodium concentrations. Total fluid intake and caloric intake were comparable in the three groups, but protein intake was much reduced in babies with intraventricular haemorrhage due to a lower milk intake. The hyperosmolality could have resulted from tissue breakdown following protein starvation and may be a factor in the occurrence of intraventricular haemorrhage. In premature babies an osmolality of over 320 mOsm/l carried a grave prognostic implication.

Birth Weight↗

The proliferation of transplanted haematopoietic cells derived from bone marrow and fetal liver.

The proliferation of transplanted murine haematopoietic cells, derived from the femoral bone marrow of young adults and from the liver on the sixteenth day of gestation, has been compared under standardized conditions. Suspensions of bone marrow cells contained 9-6+/-0-9 CFU per 10(5) cells (sm) and suspensions of fetal liver cells contained 3-7+/-0-5 CFU per 10(5) cells (Sl).Sl/Sm = 0-4. The mean diameter of colonies established by cells derived from bone marrow was 1-3+/-0-3 mm (established mean volume, Vm = 1-2 mm3) and the mean diameter of colonies established by cells derived from fetal liver was 1-7+/-0-1 mm (estimated mean volume, Vl ;-6 mm3). Vl/Vm ;-2. The relationship between the weight of the spleen and the number of bone marrow cells injected into lethally irradiated recipients 10 days previously has been confirmed, and a similar relationship between the weight of the spleen and the number of fetal liver cells injected has been demonstrated. An arbitrarily defined difference of 50 mg between the weight of the spleen in untreated irradiated controls and the weight of the spleen in irradiated recipients of haematopoietic cells has been observed 10 days after the administration of 2-2 x 10(6) bone marrow cells (Dm) or 3-0 x 10(6) fetal liver cells (Dl). Dm/Dl = 0-7. The calculated values of Dm/Dl (relative proliferative capacity), Sl/Sm (relative stem cell content) and Vl/Vm (relative clone size) are in good agreement with the values estimated using the equation Dm/Dl = Sl/Sm x Vl/Vm.

Animals↗

Rauwolfia derivatives and breast cancer.

During the course of a collaborative study initiated in investigate the relationship of breast cancer and the use of hormones, it was possible to study the possible relationship of rauwolfia derivatives, mainly reserpine, to breast cancer. Interviews were administered to breast cancer patients admitted to five hospitals in the Baltimore metropolitan area. The study of reserpine use was conducted for a period of approximately one and a half years and information on reserpine use was obtained on 164 breast cancer cases. Each case was matched with a control with respect to age, color, hospital of admission, and admission date. An additional set of controls was drawn from women residing in the same neighborhood as the cases. Neither reserpine, methyldopa, nor thiazides were found to be significantly associated with breast cancer. The exclusion from the analysis of hospital controls with a diagnosis of hypertensive disease and their matched cases did not significantly alter the results. Those cases who used reserpine, used more for longer periods of time than did the controls, however this was judged inconclusive due to a considerable amount of missing data. After comparison of these results with previously reported studies, it did not appear that reserpine was strongly associated with breast cancer. However, because of methodological problems and differences between the studies, a possible small overall relationship could not be definitely excluded.

Adolescent↗

Modulation in the rates of incorporation of lipid precursors during the cell cycle.

The rates of incorporation of 3H-choline into phospholipid and of 3H-fucose into glycolipid have been measured during the cell cycle of the murine mastocytoma, P815Y, synchronized by either velocity sedimentation or excess thymidine blockade. The rate of 3H-choline incorporation into acid-insoluble material exhibited two distinct maxima coincident with the early S and G2 periods, whereas the rate of incorporation of 3H-fucose into lipid extractable material was maximal during the G2 period. Variation in rate of incorporation of 3H-choline could not be accounted for by changes in membrane permeability.

Cell Division↗

A model of cell cycle control: effects of thymidine on synchronous cell cultures.

Further evidence is presented in support of a model for growth control in which commitment for cell division is determined by an event in the preceding cell cycle. A study was made of conditions affecting synchronous growth following treatment of murine mastocytoma cells with excess thymidine at different phases of the cell cycle. Cells were synchronized by a physical procedure involving velocity sedimentation in a zonal rotor. Pulse treatment of such cultures with thymidine at times corresponding to the S, G2, and M periods had no effect on further growth. However, addition at G1, although having no immediate effect, arrested cell growth in the next cell cycle. This temporal effect may account for the decay of synchrony observed during double thymidine blockade or thymidine-FUdR blockade. When the time interval between two such blocks was 7 hr or less, P815Y cells were arrested after one synchronous division. At this critical time a majority of cells were at, or near, G1. It is suggested that thymidine exerts a hitherto unrecognized effect at the G1 interval.

Animals↗

Prolonged effects of nitrogen mustard on mouse haematopoietic and lymphoid tissues.

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 mug (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20-30 d, 46-73 d, and 75-100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40-50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10-18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.

Animals↗

Survival after massive pulmonary haemorrhage in the neonatal period.

4 babies with massive pulmonary haemorrhage were seen in an 18 month period. 2 had severe rhesus maemolytic disease, and the other 2 severe respiratory problems. There was evidence of a profound respiratory acidosis and hypoxia prior to the onset of the haemorrhage. 2 babies survived the episode and subsequently developed normally. Adequate ventilation and attendance to the treatment of blood coagulation disorders may have been a factor in their survival.

Carbon Dioxide↗

Onchocerciasis: prevalence of microfilaruria and other manifestations in village of Cameroon.

Onchoecercal microfilaruia was studied in the course of an epidemiologic investigation of diseases, infections, and general health conditions in a rural village on the Adamaoua Plateau in northern Cameroon. Microfilariae of Onchocerca volvulus were observed in nearly one half of the skin snips taken from the village residents. The prevalence of onchocerciasis as diagnosed from skin snips increased with age, and was greater for males than females. The number of microfilariae per skin snip also increased wth age. The presence of subcutaneous nodules, inguinal lymphadenopathy, microfilariae in the urine, ocular lesions and prolonged itching all were related to both age and the presence of microfilariae in skin biopsy specimen, as well as to intensity of infection. Microfilaruria was not restricted to individuals with severe onchocerciasis.

Adolescent↗

The effects of antilymphocyte sera on bone marrow allograft rejection.

Prior sensitization can be a problem in successful graft take in bone marrow therapy. Spleen weight and femoral marrow cellularity have been used as indices of successful graft take in lethally irradiated mice receiving bone marrow allografts. Recovery if poor in mice sensitized, at least 6 days before irradiation and bone marrow therapy, to an intraperitoneal injection of allogenic bone marrow cells. Rabbit anti-mouse lymphocyte serum, normal rabbit serum and pig anti-mouse lymphocyte serum but not normal pig serum partially ablate tis immunity when administered 8 and 10 days after sensitization. Normal rabbit serum is, however, ineffective when administratered 26 and 28 days after sensitization whereas rabbit anti-mouse lymphocyte serum completely ablates this immunity. These findings demonstrate the marked radioresistance of the secondary response to bone marrow allografts and further show the effectiveness of antilymphocyte sera in ablating this immunity.

Animals↗

Rapid changes in nucleoside transport induced by growth inhibitors. Studies with neoplastic mast cells.

Aqueous extracts of murine embryonic or uterine tissue, or [(6)N]O(2)'-dibutyryl 3',5'-adenosine monophosphate (dbc-AMP) which were cytostatic for the murine mastocytoma P815Y in vitro also induced rapid changes in the incorporation of exogenous nucleosides into acid-insoluble material. However, these alterations were not a consequence of growth arrest. Different dose-response curves were obtained for cytostasis and inhibition of [(3)H]-nucleoside incorporation, and changes in [(3)H]thymidine uptake were detected within 15 min of treatment with the inhibitors. Also, there were differential effects of each inhibitor on the incorporation of (3)H-labeled thymidine, uridine, adenosine, or choline into acid-insoluble material.

Adenosine↗