Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Vertical lengthening of the unilateral cleft lip after a triangular flap repair

Summary A triangular flap repair for unilateral cleft lip is stated to have the potential problem of creating a lip that is too long. Although preoperative measurements were performed with calipers, the gap created in the medial segment was directly measured during the procedure, in order to determine the size of the flap more precisely. Ninety patients with complete unilateral cleft lips underwent a triangular flap repair using this method. The symmetry of the Cupid's bow was evaluated at a follow-up period averaging between six years and three months. Sixty-two lips obtained symmetry and the remaining 28 cases showed a lip which was too long; none of the lips were too short. The comparison between 27 primary palate clefts (UCLA) and 63 primary and secondary palate clefts (UCLP) showed no significant difference in the surgical result. The preoperative shortness of the lip on the cleft side was significantly greater in the too long group (5.01 ± 0.95 mm) than in the symmetry group (4.40 ± 0.87 mm). The width of the flap used was significantly larger in the too long group (3.76 ± 0.79 mm) than in the symmetry group (3.42 ± 0.69 mm). The triangular flap repair with intraoperative measurements is considered to be beneficial, although preoperative measurements provide an optimal design in most cases. It is suggested that the use of a wider triangular flap results in a lip which tends to be too long in spite of the preoperative shortness on the cleft side.     

An interpretation of acute changes in plasma45Ca following parathyroid hormone administration to thyroparathyroidectomized rats

Acute changes in plasma calcium and⁴⁵Ca were studied in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma⁴⁵Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide (1 h⁴⁵Ca), 18 h later (18 h⁴⁵Ca) and more than 6 days later (6 day⁴⁵Ca). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into fed rather than into fasted rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma⁴⁵Ca concentrations. This increase was the same in the 1 h⁴⁵Ca and the 18 h⁴⁵Ca groups. (3) Plasma⁴⁵Ca rose at least temporarily following PTH injection in the 18 h⁴⁵Ca group. (4) The⁴⁵Ca rise following PTH was always greater in fed than in fasted groups. (5) Plasma⁴⁵Ca specific activities (S.A.) tended to rise in the 6 day⁴⁵Ca group and to fall in the 18 h⁴⁵Ca group, following PTH injection. However, the⁴⁵Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which³²P was injected with⁴⁵Ca, specific activity changes in plasma⁴⁵Ca following PTH injection werenot accompanied by similar changes in³²P specific activity.These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.     

173. Tierexperimentelle Ergebnisse mit einem voll implantierbaren Distraktionsgerät zur operativen Beinverlängerung

Zusammenfassung Zur operativen Beinverlängerung wurde ein neues Femur-Distraktionsgerät entwickelt. Das Gerät besteht aus einem elektronisch programmierbaren Distraktionsaggregat einschließlich Kraftquelle und einer zweiteiligen Führungsschiene. Das Gesamtsystem ist voll versenkbar und schafft Übungsstabilität während der Distraktionsphase. Die Funktionen Vorlauf — Stop —Rücklauf können transcutan induktiv gesteuert werden. Ein für das Tierexperiment speziell entwickelter Prototyp des Gerätes wurde an Schafen erfolgreich erprobt.     

242. Korrelation klinischer und biochemischer Befunde mit dem Schweregrad einer bakteriellen Peritonitis

Zusammenfassung Anhand von Verlaufsdaten 66 chirurgischer Patienten mit einer bakteriologisch gesicherten Peritonitis sollten harte und weiche Kriterien zur Beurteilung des Schweregrades differenziert werden. Untersuchungskriterien: 1) regionale Ausbreitung, 2) Entwicklung eines Organod. Systemversagens, 3) Leukocytose/Thrombopenie, Körpertemperatur, 4) die Plasmamediatoren Endotoxin/Prostaglandin F₂ (PGF₂), 5) Anamnesedauer (Erstsymptom bis OP), 6) Anzahl erforderlicher Reoperationen und 7) Lebensalter. Zuzuordnende Schweregrade: Grad 1: überlebt, Grad 2: mit Komplikationen überlebt, Grad 3: nicht überlebt. Danach erweisen sich als harte Kriterien: 1) Lokalisation, 2) Anamnesedauer, 3) Leukocytose, 4) Endotoxin > 100 Eu/ml, PGF₂ > 500 pg/ml, 5) Körpertemperatur 38,5°C.     

“High spinal” dysrhaphism

Summary High spinal (cervical and upper thoracic) dysrhaphism usually involves either a meningocele or a dermal sinus tract. These high spinal lesions can have a complex intradural anatomy at the level of the lesion (as this case reports) and are associated with an increased incidence of lower spinal occult dysrhaphic anomalies. It is therefore recommended that patients with high spinal dysrhaphism undergo radiological evaluation of the entire spine to identify those patients with intradural anomalies, define the anatomy for surgery, and investigate the lower spine for associated occult anomalies.     

The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2ml saline (control), 2.5 or 5.0mg·kg^–1 dizocilpine in saline, or 20 or 40mg·kg^–1 ketamine is saline 20min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20min was 49% (n = 51) in saline (control) group, 6.7 (P 0.01 vs control, n = 30) and 15.0% (P 0.01, n = 40) in 2.5 and 5.0mg·kg^–1 dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40mg·kg^–1 ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0mg·kg^–1, respectively), which may be a novel finding.(Komatsu H, Nogaya J, Anabuki D, et al.: The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enflurane-induced opisthotonus in mice. J Anesth 7: 519–522, 1993)     

Prognostic evaluation before operative extirpation and radiotherapy of solitary brain metastasis

Summary This is a retrospective study of 134 patients operated on for solitary brain metastasis at the University Hospital in Uppsala, Sweden between 1963 and 1982. All the patients underwent postoperative radiation therapy. A statistical evaluation of different prognostic factors was made in order to create a prognostic model, a so-called risk profile, to be used for future patients. The most important factors for the making of risk profiles were found to be the histological diagnosis followed by the location in the brain, then the state on admission and the age at admission in that declining order. All these variables separately and together,i.e., as risk profiles, were matched against the outcome during survival as Karnofsky's scores and against the length of survival time. The results are shown in a diagram giving the surgeon grounds for his decision-making for or against operation and also for pre-operative information.     

New method of anesthesia in neurosurgery

Zusammenfassung Die Endotrachealnarkose ist die Methode der Wahl bei allen Operationen am Gehirn und Rückenmark.Eine extreme Blutdrucksenkung mil Pendiomid birgt die Gefahr einer anoxischen Schädigung parenchymalöser Organe in sich. Es ist daher die kontrollierte Blutdrucksenkung bei gleichzeitiger Stoffwechselsenkung durch Anwendung von Phenothiazine vorzuziehen.Die Dämpfung der vegetativen und psychischen Funktionen durch die Phenothiazine ist als Operationsvorbereitung besser als die Anwendung von Opiaten oder Barbituraten.

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Summary The endotracheal anesthesia is the preferred method for all operations on brain and spinal cord.An excessive lowering of the blood pressure by means of Pendiomid may lead to an anoxic damage of the parenchymatous organs.Therefore the controlled hypotension is preferred with a simultaneous metabolic decrease by means of Phenothiazine.It is better to prepare the patient for the operation with decreasing of the vegetative and psychical functions by means of Phenothiazine than using opiates or barbiturates.

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Resumen La narcosis endotraqueal es el método preferido para todas las intervenciones sobre el cerebro y médula espinal.Una disminución excesiva de la presión arterial por medio del Pendiomid Ileva en sí el peligro de un daño anóxico sobre los órganos parenquimatosos. Por esto, es preferible lá hipotensión controlada, con contemporánea disminución del recambio material con el empleo de Phenothiazina.La obnubilación de las funciones vegetatives y psíquicas como preparación a la intervención se obtiene mejor con la Phenothiazina que no con opiáceos y barbitúricos.

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Résumé La narcose intratrachéale est la méthode préférée pour toutes les interventions sur le cerveau et sur la moëlle épinière.Une diminution extrême de la tension artérielle au moyen du «Pendiomid» peut devenir la cause d'une anossie des organes parenchymateux. Voilá la raison parce que une ipotension contrôlée avec diminution simultanée du métabolisme tissulaire au moyen de la «Phénothiazine» est une méthode á préférer. Afin de diminuer les fonctions végétatives et psychiques pour la préparation á l'intervention, il vaut mieux employer la «Phénothiazine» que les opiacées ou les barbituriques.

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Riassunto L'anestesia endotracheale è il melodo di preferenza per tutti gli interventi sul cervello e sul midollo spinale.Una eccessiva diminuzione della pressione arteriosa per mezzo del Pendiomid porta con sè il pericolo di una anossia degli organi parenchimatosi. Perciò è da preferire l'ipotensione controllata con contemporanea riduzione del metabolismo tissulare per mezzo della Phenothiazina.L'obnubilamento delle funzioni vegetative e psichiche come preparazione all'intervento si ottiene meglio con la Phenothiazina che non con oppiacei o barbiturici.

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Vorgetragen auf der 30. Tagung der Bayerischen Chirurgenvereinigung vom 24. und 25. Juli 1953 in München.     

A versatile procedure for the closure of small skin defects

The author describes a method for the primary, direct closure of wide skin lesions, combining the lazy S, crown, and the H-advancement flap techniques. The lazy S edges of the flaps permit the satisfactory use of adjacent surrounding skin with good aesthetic results, when the flaps alone would otherwise be placed under too much strain.     

Demonstration of the 5-flap technique

Summary Demonstration of the 5-flap technique which is double opposed Z-plasty and Y – V advancement is presented. A 4×4 gauze serves to demonstrate this technique.The authors dedicate this paper to the dear memory of their teacher, the late Prof. Zvi Neuman, who passed away untimely on March 22, 1977     

Low peripheral perfusion: The cause of pressure sores in patients after open-heart surgery

Summary Pressure sores occurring in patients undergoing open-heart surgery have been accepted as accidental diathermy burns. This etiologic factor is an incorrect explanation. The mechanism must be similar to the one causing urethral strictures in these patients, namely, low peripheral perfusion during pump time. Statistical workup is not available to determine the exact magnitude of the problem, but there seems to be a difference in incidence in various cardiac surgery units. Most of the sores heal spontaneously. Prevention is strongly advocated.     

PTSD among vietnam veterans: An early look at treatment outcome using direct therapeutic exposure

Vietnam combat veteran inpatients were evaluated after being treated in a PTSD special treatment unit. Selected pretreatment measures that included mental and physical problems, combat variables, PTSD symptoms, and the standard MMPI scales found no clinically meaningful differences between a group that was found to be successes and another group found to be failures, based on predetermined cutoff scores on the VETS scale, a reliable outcome measure for veteran patients. At 3 months post-therapy, a significantly greater number of subjects treated with Direct Therapeutic Exposure (DTE) (flooding therapy) as compared to another group treated with a more conventional individual therapy, were identified as successes as opposed to failures, based on the VETs scale. Also, the number of failures was greater for those treated with the more conventional therapy and the number of successess was greater for those treated with DTE, when compared to all other subjects in the sample. These preliminary results were interpreted as indicating that DTE, when offered as part of an inpatient milieu, shows promise as an effective treatment for chronic/severe combat veteran PTSD sufferers.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Secretory territories and rate of matrix production of osteoblasts

The secretory territories of rat osteoblasts on the parietal bone were measured directly using scanning electron microscopy. The mean territory of 4620 cells in 19 fields was 154 m² per osteoblast. The range for the fields was 136 to 177 m² per osteoblast. Four hundred cells were measured individually—for these the mean value per osteoblast was 143 m² with a standard deviation of 33. The daily rate of apposition over an 8 day period was 3.12 m (standard deviation 0.22) measured by tetracycline marking of the mineral front. This gave a daily matrix production rate of approximately 470 m³ per osteoblast.

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Zusammenfassung Die Ausscheidungsbereiche von Ratten-Osteoblasten des Scheitelbeines wurden mit dem Raster-Elektronenmikroskop direkt gemessen. Der durchschnittliche Bereich von 4620 Zellen in 19 Gesichtsfeldern war 154 m² per osteoblast. Der Streubereich lag in den verschiedenen Gesichtsfeldern zwischen 136 und 177 m² per Osteoblast. 400 Zellen wurden einzeln gemessen. Bei diesen war der Durchschnittswert per Osteoblast 143 m², mit einer Standard-Abweichung von 33. Die tägliche Anlagerungsrate während einer Periode von 8 Tagen war 3,12 m (Standard-Abweichung 0,22); sie wurde mittels Tetracyclinmarkierung der Mineralisierungsfront gemessen. Dies ergab eine tägliche Produktionsrate der Matrix von etwa 470 m³ per Osteoblast.

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Résumé Les territoires sécrétoires des ostéoblastes d'os pariétal de rats sont déterminées en utilisant la microscopie électronique à balayage. Le territoire moyen de 4.620 cellules, dans 19 territoires, est de 154 m² par ostéoblaste. Les valeurs extrêmes par champ varient de 136 à 177 m² par ostéoblaste. Quatre cent cellules sont mesurées individuellement; la valeur moyenne par ostéoblaste est de 143 m³ avec une déviation standard de 33. Le taux d'apposition journalier, mesuré par la tétracycline pendant 8 jours, est de 3.12 m (déviation standard 0.22). Ce qui correspond à une production matricielle journalière d'environ 470 m³ par ostéoblaste.

     

Replacement of the anterior cruciate ligament

Summary Eighty-seven patients have been examined 2 years on average after knee ligament reconstruction for a torn anterior cruciate ligament. The patients were divided into four groups according to the type of operation that had been carried out. In the first group an extra-articular lateral repair (MacIntosh tenodesis) had been performed, in the second group an intra-articular over-the-top repair using the quadriceps and the patellar tendon, in the third group a modified Eriksson procedure using the patellar tendon, and in the fourth group a combined intra- and extra-articular repair using carbon fibres as a graft. The results of the operations in the different groups are compared. The best results were obtained with the Eriksson procedure, closely followed by the over-the-top repair. Limited range of motion and retropatellar pain resulting from changes in the alignment of the patella were the main problems. The results after the use of carbon fibres were less good. In two cases the graft tore without further trauma, and there were also problems because of restricted range of motion and retropatellar pain. The worst results were found after extra-articular lateral repair, due to insufficient stability in many cases. However, the best results with regard to the range of motion were found in this group.

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Zusammenfassung Es wurden 87 Patienten im Durchschnitt 2 Jahre nach Ersatzplastik bei zerrissenem vorderem Kreuzband und chronischer Instabilität nachkontrolliert. Die Patienten wurden in vier Gruppen eingeteilt. In jeder Gruppe war eine andere Art von Ersatzplastik durchgeführt worden. In der ersten Gruppe war es ein extraartikulärer lateral repair (sog. MacIntosh-Plastik), in der zweiten Gruppe eine intraartikuläre over the top geführte Plastik mit der Quadriceps- und der Patellarsehne, in der dritten eine modifizierte Eriksson-Plastik unter Verwendung der Patellarsehne und in der vierten Gruppe eine kombinierte intra- und extraartikuläre Plastik mit Carbon fibres. Die Resultate der Operationen in allen vier Gruppen werden miteinander verglichen. Die besten Ergebnisse zeigte das Vorgehen nach Eriksson, dicht gefolgt vom over the top-repair. Probleme, die in diesen zwei Gruppen auftraten, betrafen eingeschränkte Kniebeweglichkeit und retropatelläre Schmerzen wegen veränderter Führung der Patella. Die Resultate in der Gruppe mit Verwendung der carbon fibres waren weniger gut. In zwei Fällen ist das Transplantat ohne Trauma gerissen, zudem traten auch hier Beschwerden auf wegen eingeschränkter Beweglichkeit und retropatellärer Schmerzen. Am wenigsten gut waren die Resultate nach extraartikulärem lateral repair. In vielen Fällen konnte durch these Methode keine genügende Stabilität erreicht werden. Andererseits war die Beweglichkeit des Kniegelenkes nach dieser Operation kaum je eingeschränkt.

     

Scanning electron microscopy-electron probe microanalysis study of the interface between apatite and wollastonite-containing glass-ceramic and rabbit tibia under load-bearing conditions after long-term implantation

Glass-ceramic implants containing oxy- and fluoroapatite [Ca₁₀(PO₄)₆(O, F₂)] and -wollastonite (CaSiO₃) were studied under load-bearing conditions in a segmental replacement model in the tibia of the rabbit. A 16-mm segment of the middle of the tibial shaft was resected at a point distal to the junction of the tibia and the fibula. The defect was replaced by a 15 mm-long hollow, cylindrical implant that was fixed by intramedullary nailing using Kirschner wire. The implants were 9 mm in diameter and 15 mm long bearing a central hole 3.05 mm in diameter. The rabbits used were killed 6 months, 1 year, 18 months, and 2 years after implantation. The interface between the bone and the glass-ceramic was investigated by scanning electron microscopy-electron-probe microanalysis (SEM-EPMA).None of the glass-ceramic implants broke, and the glass-ceramic had bonded directly to the bone tissue without any intervening soft tissue. A calcium-phosphorus layer (Ca-P layer) was observed at the glass-ceramic/bone interface. This layer was 30–100 m thick at 6 months after implantation, 60–110 m thick at 1 year after implantation, 80–200 m thick at 18 months, and 120–350 m thick at 2 years. At the lateral surface of the glass-ceramic uncovered by the bone, the calcium-phosphorus layer was 50–80 m thick at 6 months after implantation, 250–450 m thick at 1 year, 300 400 m thick at 18 months, and 300 m thick at 2 years. The thickness of the calcium-phosphorus layer increased moderately after long-term implantation. However, it was difficult to estimate the rate of increase in the thickness of calciumphosphorus layer.     

An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: Report of a case

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-, -, and - in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-, -, and - immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC- and - was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies and , which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.     

The role of TGF-β in patterning and growth of the mammary ductal tree

Evidence that transforming growth factor beta (TGF-)⁴ influences pattern formation in the developing mammary gland and negatively regulates ductal growth is reviewed. In the mouse, overexpression of TGF- transgenes during puberty reduces the rate of growth of the ductal tree and simplifies the pattern of arborization, while expression during pregnancy also interferes with lactation. Expression studies in the normal mouse gland indicate that TGF- is synthesized in the mammary epithelium, with the three isoforms showing somewhat different spatial and temporal distributions. Exogenous TGF- applied directly to the glandin situ inhibits epithelial cell division within hours, and strongly stimulates extracellular matrix synthesis over a longer time course. Normal human breast cells as well as certain breast cancer cell lines also secrete TGF- and are themselves inhibited by it, suggesting an autoregulatory feedback circuit, that in some cases appears to be modulated by estradiol. Taken together, the evidence suggests a model in which growth and patterning of the mammary ductal tree are regulated, at least in part, by TGF- operating through an autocrine feedback mechanism and by paracrine circuits associated with epithelial-stromal interactions.