Experiments on the Theory of Osteogenesis

Huggins, Charles; McCarroll, H. Relton; Blocksom, B. H.

doi:10.1001/archsurg.1936.01180240003001

Cited by 51 publications

(5 citation statements)

References 28 publications

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“…According to Huggins, fibroblasts are attracted to the transitional epithelial transplants and are stimulated by the alkaline phosphatase activity of the transitional cells to become osteoblasts. The process is quite rapid, and bone formation has been observed in the fibroblastic layer adjacent to autotransplants of bladder epithelium to muscle after only 13 days (Huggins & Compere, 1930;Huggins, McCarroll & Blocksom, 1936). Spongy bone is formed with Haversian canals containing fibrous and haemopoietic bone marrow (Huggins, 1931).…”

Section: Biological Potentialities Of the Bladder Epithelium ( I mentioning

confidence: 99%

The Mammalian Urinary Bladderan Accommodating Organ

1975

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Summary 1. Urinary bladders are found in the amphibia, chelonian reptiles and mammals. In these orders liquid urine is stored in the bladder and eliminated at intervals from the body by micturation. 2. In the amphibia and chelonian reptiles, the urinary bladder is a functional extension of the renal tubules. The composition of the urine in the bladder is modified by the active movement of water and ions across the bladder wall, and these transporting processes are under hormonal control. The bladder acts as a water reservoir which can be drawn upon in times of water shortage. 3. The mammalian bladder separates two widely differing water phases, namely the urine which is frequently hypertonic to the blood and the tissue fluids which are isotonic. Its function is uniquely one of storage, and no adjustment to the composition of the urine is made by active transport of either water or ions across the bladder wall. 4. The epithelium lining the mammalian bladder is the site of the osmotic barrier between urine and tissue fluids. This functional barrier is dependent on the structure of the epithelium and is maintained despite large alterations in the surface area of the epithelium as the bladder rapidly contracts, or slowly dilates. 5. The epithelium is of mixed mesodermal and endodermal origin, is transitional in type and is usually 3 or 4 cell‐layers thick. If this urothelium is damaged, it has a high capacity for regeneration and rapidly re‐establishes an intact barrier over the luminal surface. 6. The superficial cell layer of this epithelium is composed of large, polyploid, highly differentiated squamous cells which have a long life span. These cells are limited on their free surface by an unusual, angular, semi‐rigid luminal membrane. This membrane is assembled in the Golgi complex. 7. The luminal membrane is composed of thickened, discoidal plaques, separated by narrow bands of thinner membrane. When the bladder contracts, the membrane folds along the thinner ‘hinge’ regions, and the rigid discoidal plates invaginate to form fusiform, cytoplasmic vacuoles. The thickened plaques contain a hexagonal lattice of sub‐units, spaced at 14 nm centre‐to‐centre. Each sub‐unit in the lattice is itself composed of 12 smaller particles. These particles may be envisaged as small rods 3 nm in diameter and 12 nm long, and are inserted into matrix from which they project on the luminal face by about 3 nm. Each rod has a central hydrophobic portion separating distal hydrophilic ends. 8. The chemical composition of this luminal membrane is unusual. Cerebroside is a major component of the polar lipid fraction and there is an unusually high proline content in the protein fraction. When the mucoproteins are adequately dispersed, and the proteins separated by electrophoresis, a few major proteins are revealed in 33000–80000 dalton range of molecular weight. 9. If the normal structure of the luminal membrane is altered, either by physical damage or by failure of the cells to produce it, the barrier function of the epithelium is lost. 10...

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Section: Biological Potentialities Of the Bladder Epithelium ( I mentioning

confidence: 99%

The Mammalian Urinary Bladderan Accommodating Organ

1975

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“…The frequent occurrence of bone in primary mammary tumors of dogs while it is absent in metastases can be explained by the direct osteogenic stimulation of connective tissues by the tumor tissue. It has been shown that there exist functionally different types of connective tissue with respect to ossification through the influence of transplants of the epithelium of the urinary bladder; in certain regions, notably the abdominal and thoracic wall, fibroblastic areas readily ossify when exposed to this epithelium whereas the connective tissue cells of liver, spleen, and lung (25,26) do not form bone under these circumstances. Transplantation of the mammary cancerous cysts to rectus sheath stimulated bone formation in areas closely adjacent to the epithelium--a pattern reproducing the effect of urinary bladder transplants in a small way.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Mammary Tumors of Dogs

Huggins

Moulder

1944

Journal of Experimental Medicine

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The object of this study was tq determine the extent to which function of the mammary gland and especially its involution are dependent on the ovaries and on the suprarenal glands.. The observations were made on dogs for several reasons, namely; spontaneous mammary tumors are frequent and the neoplasms while originally local often metastasize; normal dogs have an interesting lactational rhythm in that non-pregnant females secrete milk (pseudopregnancy) twice a year; and further both suprarenal glands can be removed surgically with prolonged survival of the animal in good health, an operation as yet impossible in man (1).In dogs secretion was frequently obtained from the mammary papillae with which tumors of the breast communicate. This fluid was studied cytologically and chemically, being compared with normal milk. The amount and duration of the secretion were studied as an index of activity of the neoplastic breast. It was necessary also to collect data on the timing and extent of lactation in normal dogs, pregnant and non-pregnant. In dogs after lactation has ceased, the mammary glands do not undergo involution immediately but we found that they remain capable of stimulation by the lactogenic hormone of the hypophysis for varying lengths of time. The functional test with prolactin was of value since it is impossible from external examination of the breast of dogs in which lactation has stopped to tell whether the breast has undergone appreciable regression or is dormant and capable of functioning. This test was applied to series of normal and cancerous dogs, both intact and following removal of ovaries and suprarenal glands.Laaalio~ in Dogs.--In the dog ovulation occurs spontaneously and is followed by corpus luteum formation and the luteal phase is prolonged (35). The secretion of milk by virgin dogs was described by Heape (2) and Loisel (3) who thereby established that the presence of the fetus or decidua is not necessary for lactation. Loisel observed a female dog for more than 2 years, and discovered that vaginal bleeding and lactation occurred in a regular sequence semiannually.

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“…As mentioned already, Huggins [1936] supposed that the al kaline phosphatase of transitional epithelium plays a significant role in its osteogenctic activity. The alkaline phosphatase cannot be re garded as the most im portant factor in the mechanism of normal osteogenesis, but nevertheless, there is no doubt th at this enzyme plays some role in bone calcification (Robison [1923]) as well as in its organic m atrix building (Siffert [1951]).…”

Section: Morphological and Histochemical Properties Of The Connectivementioning

confidence: 94%

“…T hat is why the influences of the epithelium, which are responsible for this histochemical characteristic of connective tissue, must be different from those causing bone induction. It should be taken into account that osteogenesis can be induced also by the grafts of gall bladder epi thelium (Huggins [1936]) which gives negative histochemical reaction for alkaline phosphatase and does not induce the diffuse phosphatase activity in the underlying connective tissue in the course of trans plantation (Friedenstein [1957]). …”

Section: Morphological and Histochemical Properties Of The Connectivementioning

confidence: 99%

Osteogenetic Activity of Transplanted Transitional Epithelium

Friedenstein¹

1961

Cells Tissues Organs

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Experiments on the Theory of Osteogenesis

Cited by 51 publications

References 28 publications

The Mammalian Urinary Bladderan Accommodating Organ

The Mammalian Urinary Bladderan Accommodating Organ

Studies on the Mammary Tumors of Dogs

Osteogenetic Activity of Transplanted Transitional Epithelium

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