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GASTRIC MUCIN-A CHEMICAL AND HISTOLOGIC STUDY FOLLOWING BILATERAL VAGECTOMY, GASTRIC RESECTION AND THE COMBINED PROCEDURE* WALTER L. MERSHEIMER, M. D., GEORGE B. JERZY GLASS, M.D., FRANCES D. SPEER, M.D., JAMES M. WINFIELD, M.D., AND LiNN J. BOYD, M.D. NEW YORK, N. Y. FROM THE DEPARTMENTS OF SURGERY, MEDICINE AND PATHOLOGY, NEW YORK MEDICAL COLLEGE, FLOWER AND FIFTH AVENUE HOSPITALS, NEW YORK DURING THE PAST FEW YEARS we have conducted rather extensive studies of the secretion of gastric mucin and its fractions in the human stomach. The recent intro- duction of a simple fractionation technic for the isolation of various mucous constit- uents6 , 9, 19 and a colorimetric quantitative method for their determination has made these studies possible.8 Information that is predominantly of surgical significance will be presented at this time. The classification of the various mucous substances of the stomach is based upon information obtained in earlier studies by our group." 8 Figure 1 shows the deriva- tion, site of origin and mutual relationship of the main mucous fractions present in the gastric contents. The sum of the mucous substances se- creted by the gastric mucosa is termed the total gastric mucin. This occurs in two grossly distinct forms: (1) visible mucus, (2) dissolved mucin. Visible mucus is secreted by the colum- nar surface epithelium and appears jelly- like, tenacious and adherent, forming the protective lining of the gastric mucosa. When precipitated by hydrochloric acid it forms lumps and shreds. Dissolved mucin can be isolated from the gastric juice only by chemical methods of separation, either by salting it out or by pre- cipitation with organic solvents such as al- cohol or acetone. The trichloracetic acid filtrate of the gastric juice is precipitated by acetone. The precipitate is taken up by alkali and the total mucin content is deter- mined colorimetrically by the Folin-Ciocal- teu phenol reaction using tyrosine solution as a standard.6' 7 According to earlier studies,1 8, 9, 19 dis- solved mucin is a mixture of at least three different components: (1) Soluble mucus is the physical dissolution product of the vis- ible mucus derived from the surface epithe- lial mucous lining of the stomach; (2) Dis- solved mucoproteose is the degradation and further dissolution product of the visible mucus formed by the enzymatic digestion; the hypothetic "gastric mucolysin"2 may be the responsible enzyme; (3) Glandular mucoprotein is the only mucous compo- nent secreted by the mucous cells in the neck of the glands in the fundus and corpus of the stomach. Its secretion is strongly in- fluenced by the vagus nerves.3 4,'7 Each of these fractions can be easily separated by the fractionation technic of Glass and Boyd8 and has an electrophoretic pattern of its own.5 Each has its own physico-chem- ical properties which distinguish each from the other.8 668 * Read before the American Surgical Associa- tion White Sulphur Springs, W. Va., April 18, 1952.
Transcript

GASTRIC MUCIN-A CHEMICAL AND HISTOLOGIC STUDY FOLLOWINGBILATERAL VAGECTOMY, GASTRIC RESECTION AND

THE COMBINED PROCEDURE*WALTER L. MERSHEIMER, M. D., GEORGE B. JERZY GLASS, M.D.,

FRANCES D. SPEER, M.D., JAMES M. WINFIELD, M.D.,AND LiNN J. BOYD, M.D.

NEW YORK, N. Y.

FROM THE DEPARTMENTS OF SURGERY, MEDICINE AND PATHOLOGY, NEW YORK MEDICAL COLLEGE,

FLOWER AND FIFTH AVENUE HOSPITALS, NEW YORK

DURING THE PAST FEW YEARS we haveconducted rather extensive studies of thesecretion of gastric mucin and its fractionsin the human stomach. The recent intro-duction of a simple fractionation technicfor the isolation of various mucous constit-uents6 , 9, 19 and a colorimetric quantitativemethod for their determination has madethese studies possible.8 Information that ispredominantly of surgical significance willbe presented at this time.The classification of the various mucous

substances of the stomach is based uponinformation obtained in earlier studies byour group." 8 Figure 1 shows the deriva-tion, site of origin and mutual relationshipof the main mucous fractions present in thegastric contents.The sum of the mucous substances se-

creted by the gastric mucosa is termed thetotal gastric mucin. This occurs in twogrossly distinct forms: (1) visible mucus,(2) dissolved mucin.

Visible mucus is secreted by the colum-nar surface epithelium and appears jelly-like, tenacious and adherent, forming theprotective lining of the gastric mucosa.When precipitated by hydrochloric acid itforms lumps and shreds.

Dissolved mucin can be isolated from thegastric juice only by chemical methods ofseparation, either by salting it out or by pre-cipitation with organic solvents such as al-cohol or acetone. The trichloracetic acidfiltrate of the gastric juice is precipitatedby acetone. The precipitate is taken up byalkali and the total mucin content is deter-mined colorimetrically by the Folin-Ciocal-teu phenol reaction using tyrosine solutionas a standard.6' 7According to earlier studies,1 8, 9, 19 dis-

solved mucin is a mixture of at least threedifferent components: (1) Soluble mucus isthe physical dissolution product of the vis-ible mucus derived from the surface epithe-lial mucous lining of the stomach; (2) Dis-solved mucoproteose is the degradation andfurther dissolution product of the visiblemucus formed by the enzymatic digestion;the hypothetic "gastric mucolysin"2 may bethe responsible enzyme; (3) Glandularmucoprotein is the only mucous compo-nent secreted by the mucous cells in theneck of the glands in the fundus and corpusof the stomach. Its secretion is strongly in-fluenced by the vagus nerves.3 4,'7 Each ofthese fractions can be easily separated bythe fractionation technic of Glass andBoyd8 and has an electrophoretic pattern ofits own.5 Each has its own physico-chem-ical properties which distinguish each fromthe other.8

668

* Read before the American Surgical Associa-tion White Sulphur Springs, W. Va., April 18,1952.

Volume 136 GASTRINumber 4

Our investigations have included secre-tory studies in human beings on both maincomponents of the dissolved gastric mucin,i.e., mucoproteose and glandular mucopro-tein as well as histochemical studies of thegastric mucosa in dogs. In this report em-phasis will be placed, however, on the re-sults relating to the secretion of the glandu-lar mucoprotein component as they are ofgreater significance. One part of thesestudies were reported earlier in moredetail.3

STUDIES IN HUMAN BEINGS

Method. Under fasting conditions, thespecimens were obtained by emptying thestomach as completely as possible througha Levin tube and 20 minutes later obtaininga second fasting specimen. Then, 16 unitsof insulin were injected intravenously andspecimens were obtained by aspiration 20,40 and 60 minutes later. Each of the fivespecimens were tested for free hydrochloricacid by titration with twentieth normalsodium hydroxide using Toepfer's reagentand phenolphthalein. The glandular muco-protein was determined by the colorimetrictyrosine method8 including its volumetricmodification17 when contamination of gas-tric juice by bile, blood or food was present.

In 25 patients, partial gastrectomy wasperformed by a modified Hoffmeister tech-nic, resecting the distal three-quarters ofthe stomach, including almost the entirelesser curvature, with closure of the upperhalf of the transected stomach and anasto-mosing the lower half to the side of thejejunum. The short efferent antecolic loopof jejunum was brought to the lesser curva-ture of the stomach. The gastric secretorycurves of acid and glandular mucoproteinfollowing insulin stimulation were testedbefore and at various times after theoperation.

In five patients a bilateral vagectomyalone was performed (transabdominally inthree instances and transthoracically in two

[C MUCIN

instances) . The insulin tests were per-formed at various times after the operation.The combined procedure of partial gas-

trectomy and bilateral vagectomy was per-formed on five patients. Gastrectomy wasdone as previously described, and the bilat-eral vagectomy by the transabdominal ap-proach. Each of these patients was studiedwith insulin test pre- and postoperatively.

Results. The secretory response of freeHC1 and glandular mucoprotein to insulinstimulation in the normal stomach is illus-trated in Figure 2. Glandular mucoproteinis strongly influenced by the vagus nervesand in the intact stomach its concentrationrises sharply after insulin stimulation.4' 17Similarly, there is a sharp rise in the con-centration of free hydrochloric acid. Thisrise of both mucoprotein and free acid ischaracteristic of the positive pattern ofresponse.

Reference to Figure 2 will further showthe effect of successful bilateral vagectomy.There is depression of the secretion of bothmucoprotein and free acid under fastingconditions and the response to insulin stim-ulation is abolished. This is typical of thenegative pattern of response.3 In twovagectomized patients studied one and one-half years and four years after operation,we have observed partial restoration of acidresponse to insulin stimulation, while theresponse of glandular mucoprotein was stillabolished.

Study of 25 patients following partialgastrectomy (Fig. 3) has demonstrated de-pression of the free acidity under fastingconditions and the depression or abolitionof its normal response to insulin stimula-tion. On the other hand, there is little alter-ation in the concentration of glandularmucoprotein under fasting conditions, andits characteristic response to insulin stimu-lation is preserved. This loss or decrease inacid response and the retention of muco-protein response to insulin is termed thedissociated pattern of response,17 and it is

669

MERSHEIMER, GLASS, SPEER, WINFIELD AND BOYD

frequently observed in the partially resectedstomach.3' 11

After partial gastrectomy combined withbilateral vagectomy (five cases) there wascomplete depression of free acid and gland-ular mucoprotein and the response to in-sulin was lost-the negative pattern.3 17

(Fig. 3).

TOTAL GASTRIC MUCIN

VISIBLE MUCUS DISSOLVED MUCIN(JELLY-LIKE AND ,PRECIPITATED BY HCL) ,-' ,

*0A

o SOLUBLE (DIGESTION) DISSOLVED GLANIw MUCUS MUCOPROTEOSE MUCOPf

S .

Columnar surface Mucoid necepitheliol cells of gastric 1

IDULARROTEIN

glands|

FIG. 1.-Derivation and mutual relationship ofmucous substances of the stomach.

Comment. The study of the glandularmucoprotein response to insulin stimula-tion appears to be of definite value to eval-uate the completeness of vagectomy. Thisis particularly true in cases in which com-

bined vagectomy and partial gastric resec-

tion were done, and in which the negativeacid response to insulin was obtained. Whenthis occurs the negative acid test may de-pend not only on severance of vaginerves12, 14, 18, 21 but also upon (a) neutral-ization of the acid by the regurgitated duo-denal content and bile, (b) on abolition(by resection of the antrum) of the acidstimulating hormonal gastrin mechanism,"or (c) on the post-resection achlorhydria,due usually to atrophic lesions in the pre-

served fundal area of the stomach. The test-ing of acid and mucoprotein response toinsulin and of the acid response to hista-mine may give complete information on themechanism of the secretory dysfunction ob-served (Table I) .

If the insulin test shows absence of acidresponse, and presence of mucoprotein re-

sponse and the histamine test shows thepresence of acid, then the absence of theacid response to insulin does not dependupon severance of vagi but merely uponneutralization achlorhydria or removal ofthe gastric antrum with its hormonal medi-ating secretory mechanism. When thisoccurs, the preservation of the secretory re-

sponse of glandular mucoprotein to insulinindicates that the vagi nerves were notcompletely cut.On the other hand, if not only acid but

also the mucoprotein response is abolishedafter insulin, but both are preserved afterhistamine, then complete severance of vaginerves can be postulated (Fig. 3).

If, finally, both acid and mucoprotein re-

sponse are absent following insulin, andboth are also absent following histaminestimulation, then no conclusion concerningthe completeness of vagectomy can bemade, since the abolition of the response tohistamine indicates an associated postgas-trectomy atrophic lesion of the gastric mu-

cosa. The absence of the acid as well as

mucoprotein response to insulin can dependupon an atrophic lesion as well as on thevagectomy.The disturbances of gastric secretion ob-

served after partial gastrectomy may be ex-plained as follows: The glandular mucopro-tein response is retained because part of themucoprotein secreting area in the fundusof the stomach is preserved. The acid re-sponse is depressed because the pyloricantrum, site of hormonal mediation, is re-moved.The normal secretory pattern and the

alterations that occur following surgicalprocedures upon the stomach have beendiscussed. However, the secretory patternsare altered also in the non-operated patho-logic stomach.When a duodenal ulcer is present the re-

sponse of free acid and glandular mucopro-670

Annals of SurgeryOctob er, 1952

GASTRIC MUCIN

NORMALS(25 CASES)

Z

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FIG. 2. - Concentration ofglandular mucoprotein and freeacid in the gastric juice of nor-

A mals and patients following bi-lateral vagectomy. Each curve

)° represents the mean value.

FIG. 3. - Concentration of60' glandular mucoprotein and free

acid in the gastric juice follow-ing subtotal gastrectomy andsubtotal gastrectomy combinedwith bilateral vagectomy. Eachcurve represents the mean value.

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tein to insulin is frequently exaggerated'5(Fig. 4). On the other hand, atrophic in-flammatory or degenerative lesions of thegastric mucosa either alone (perniciousanemia,'3 atrophic gastritis) 23 or associatedwith carcinoma of the stomach24 may abol-ish the response of free acid and glandularmucoprotein to insulin-the negative pat-tern of response (Fig. 4). The significance

67.

of the absence of response of glandular mu-coprotein to insulin in patients with per-

nicious anemia has been reported in greaterdetail elsewhere.'0

After bilateral vagectomy no free acidand mucoprotein are secreted after stimula-tion with insulin (Fig. 2). On several va-

gectomized individuals we have observedthat the secretion of glandular mucoprotein

Volume 136Number 4

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and free hydrochloric acid are preservedafter histamine administration (Fig. 5).Therefore, in the vagectomized stomach theglandular mucoprotein and acid are not se-creted in response to central nervous stim-ulation, but their secretion is preserved fol-lowing humoral stimuli.

TABLE I.-Gastric Secretory Responses FollowingSurgical Procedures Upon the Stomach.

Causes of Secretory DisturbancesNeutrali-

Severance zation Removal Atrophyof Vagus Achlor- of ofNerves hydria Antrum Mucosa

Insulin test:Acid response - - 4 or-

Insulin test:Mucoproteinresponse - + +

Histamine test:Acid response + + + or 4i

STUDIES IN DOGS

Because the secretion of glandular muco-protein is abolished when atrophy of thegastric mucosa is present in the non-oper-ated stomach," 13. 23. 24 the question arises:Are the alterations in the secretion of gland-ular mucoprotein observed after vagectomydependent exclusively upon severance ofthe vagus nerves, or also upon pathologic,atrophic lesions in the cells responsible forits secretion? To answer this question, whichhad been raised by Dr. Wangensteen at aprevious discussion on this subject,22 wehave studied the cytology of the variousmucous cells of the canine stomach beforeand after bilateral vagectomy, partial gas-trectomy and the combined procedure (va-gectomy and partial gastrectomy).Method. Thirty-three dogs were studied:

15 were investigated before and after par-tial gastrectomy, nine before and after bilat-eral vagectomy, and five before and afterthe combined procedure. Four dogs servedas controls.

Postoperative specimens were obtainedfrom the cardia, fundus, corpus and pylorusat varying intervals up to 11 months after

operation. The majority of the dogs weresacrificed after fasting 18 hours, and a fewsacrificed during the digestion period(about two hours after a meal).The specimens were prepared in two

ways: (1) fixed in acid formalin, stainedwith 0.1 per cent cresyl violet and counter-stained with hematoxylin and eosin; (2)fixed in absolute alcohol, stained with muci-carmine and counterstained with picricacid. More than 250 slides were preparedand studied, with special considerationgiven to the columnar cells of the surfaceepithelium, source of the surface epitheliummucus, and to the mucus cells of the neckof the fundic glands, source of glandularmucoprotein.

Results. The study reported at this timepertains only to the fundic glands. Theresults of the study of the glands of thecardiac and pyloric area will be reportedseparately. A representative tabulation ofour data appears in Table II.No relevant cytologic lesion could be

demonstrated in postoperative gastric spe-cimens that could account for the secretoryalterations previously discussed. Regard-less as to whether partial gastrectomy alone,vagectomy alone, or the combined proce-dure was performed, we noted that thecolumnar surface epithelium maintained itsintegrity and that the granules in themucous cells of the neck of fundic glandswere well preserved. The same was true ofzymogen granules of the peptic cells.When animals were sacrificed 18 hours

after fasting, the appearance of the cells wastypical of the resting stage of the secretorycycle (Figures 6 through 9). There was noatrophic lesion of the secretory cells of thefundic glands, i.e. of the chief peptic cells,the parietal cells, and the mucous neck cellsfollowing gastrectomy, bilateral vagectomyor the combined procedure.When the dogs were sacrificed during the

secretory phase of the digestive cycle (twohours after feeding) the staining of the

672

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FIG. 4. - Concentration ofglandular mucoprotein and freeacid in the gastric juice of pa-tients with atrophic gastritisalone or associated with carci-noma of the mid-portion of thestomach, and in individuals with

40' 60' duodenal ulcer. Each curverepresents the mean value.

FIG. 5. - Concentration ofglandular mucoprotein and freeacid in the gastric juice of a pa-tient with bilateral vagectomyafter intravenous administrationof 16 units insulin and subcu-taneous administration of 1 mg.histamine.

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mucous granules in the neck cells of theglands was less intense, indicating that thecells were partly depleted of their secretoryproducts. This was typical for the animalssacrificed at the height of digestion, regard-less of the operative procedure performed(Figures 10 through 13).Comment. In the dogs sacrificed under

fasting conditions, the secretory granulesare present within the surface epithelium

and neck cells, proving the absence of anyorganic-atrophic lesion following partialgastrectomy alone, vagectomy alone, or thecombined procedure. In the vagectomizedanimal sacrificed under fasting conditions,the "resting appearance" of these cells indi-cates that the material is produced nor-

mally within the cells, but in the absence offood stimulation it is not discharged intothe gastric juice. If we are permitted to

674

Annals of Surgery0 c t o b e r, 1952

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FIG. 6 FIG. 7

FiG. 8 FIG. 9

FIG. 6.-Dog sacrificed during the rest period, stained with cresyl violet, low power mag-nification. Postoperative specimen from the fundus of dog following combined partial gas-trectomy and bilateral vagectomy.

FIG. 7.-Same as Figure 6, but with high power magnification.FIG. 8.-Dog sacrificed during the rest period, stained with mucicarmine and picric acid,

low power magnification. Specimen source same as Figure 6.FIG. 9.-Same as Figure 8, but high power magnification.

675

Volume 136Number 4

MERSHEIMER, GLASS, SPEER, WINFIELD AND BOYD

FIG. 10 FIG. 1 1

Annals of Surgery0 c t o b e r, 1952

FIG. 12 FIG. 1:3

FIG. 10.-Dog sacrificed during secretory period, stained with cresyl violet, low powermagnification. Postoperative specimen from the fundus of dog following bilateral vagectomy.

FIG. 11.-Same as Figure 10, but with high power magnification.FIG. 12.-Dog sacrificed during secretory period, stained with mucicarmine and picric acid,

low power magnification. Specimen source same as Figure 10.FIr, 13.-Same as Figure 12, but with high power magnification.

676

MERSHEIMER, GLASS, SPEER, WINFIELD AND BOYD Annas of Surgery0 .1952

Stomach. Bull. New York Acad. Med., 25:459, 1949.

6----: Studies on Dissolved Mucin (Muco-protein) of the Gastric Juice. I. PreliminaryTests and Rationale for a New ColorimetricQuantitative Method for the Determination ofDissolved Gastric Mucin. Rev. Gastroen-terol., 15: 396, 1948.. Studies on Dissolved Mucin (Muco-

protein) of the Gastric Juice. II. A NewQuantitative Colorimetric Method for theDetermination of Total Dissohied GastricMucin. Rev. Gastroenterol., -15: 511, 1948.

8 Studies on Dissolved Mucin of theGastric Juice. IV. Relationship of the Mu-coid of the Visible Gastric Mucus, its SplitProducts, and the Salivary Mucin to theDissolved Gastric Mucoproteose and Muco-protein of the Gastric Juice. Bull. New YorkM. Coll. Flower & Fifth Ave. Hosps., 12:1, 1949.

9----. : A Study of the Alleged Deficiencyof Gastric Mucin in the Stomach of Humanswith Peptic Ulcer. Gastroenterology, 16: 697,1950.

10------: The Three Main Components of theHuman Gastric Mucin: Dissolved Mucopro-teose, Dissolved Mucoprotein, and Mucoidof the Gastric Visible Mucus. Part I. Differ-entiation; Some Physical and ChemicalCharacteristics; Classification. Part II. Meth-od for Separation and Quantitative Deter-mination of Each Mucous -Component of theGastric Juice. Part III. Preliminary Data onPhysiological and Clinical Significance ofSeparate Quantitative Determination of theDissolved Mucoproteose and Dissolved Mu-coprotein in the Gastric Juice of Man. Gas-troenterology, 12: 821, 1949.

Glass, G. B. J., L. J. Boyd, A. Heisler and I. J.Drekter: Studies on Dissolved Mucin of theGastric Juice. III. Heterogeneity of the Gas-tric Dissolved Mucin and Its Differen'iationand Separation into Two Main Fractions:Dissolved Mucoproteose and Dissolved Mu-coprotein. Bull. New York M. Coll. Flower&.Fifth Ave. Hosps., 11: 8, 1948.

12 Glass, G. B. J., W.L. Mersheimer and C. S. Svi-gals: Effect of Vagotomy and Subtotal GastricResection on the Secretion of Mucin in theHuman Stomach; Arch. Surg., 62: 658, 1951.

13 Glass, G. B. J., L. J. Boyd, M. A. Rubinstein

and C. S. Svigals: Relationship of GlandularMucoprotein from Human Gastric Juice toCastle's Intrinsic Anti-anemic Factor. Sci-ence, 115: 101, 1952.

14 Glass, G. B. J., L. J. Boyd and C. S. Svigals:The Absence of Glandular Mucoprotein andthe Presence of Mucoproteose from SurfaceEpithelium in the Gastric Juice of Patientswith- Pernicious Anemia. Bull. N. Y. Med.Coll. Flower & Fifth Ave. Hosps., 13: 15,1950.

15 Glass, G. B. J., and S. Wolf: Hormonal Media-tion in Nervous Mechanism of Gastric AcidSecretion in Humans. Proc. Soc. Exper. Biol.& Med., 73: 535, 1950.

16 Hollander, F.: Insulin Test for Presence of In-tact Nerve Fibers after Vagal Operations forPeptic Ulcer. Gastroenterology, 7: 607, 1946.

17.-----: Laboratory Procedures in the Studyof Vagotomy (with Particular Reference tothe Insulin Test). Gastroenterology, 11:419, 1948.

18 Jemerin, E. E., F. Hollander and V. A. Wein-stein: A Comparison of Insulin and Food asStimuli for the Differentiation of Vagal andNonvagal Gastric Pouches. Gastroenterology,1: 500, 1943.

19 Jennings, M. A., and H. W. Florey: The In-fluence of the Vagus on the Secretion ofMucus by the Stomach. Quart. J. Exper.Physiol., 30: 329, 1940.

20 Morton, G; M., and G. W. Stavraky: A Histo-physiological Study of the Effect of Intra-arterial Injection of Acetylcholine Upon theGastric Mucosa of the Dog. Gastroenter-ology, 12: 800, 1949.

21 Pugh, B. L., G. B. J. Glass and S. Wolf: Electro-phoretic Studies of the Mucin Fractions fromthe Human Gastric Juice. Proc. Soc. Exper.Biol. & Med., 79: 674, 1952.

2 Wangensteen, 0. H.: Discussion. S'urgicalForum 36th Clin. Congress, Am. Coll. Surg.,Boston, Mass., 1950.

23 Weinstein, V. A., F. Hollander, F. V. Lauberand R. Colp: Correlation of Insulin TestStudies and Clinical Results -in a Series ofPeptic Ulcer Cases Treated by Vagotomy.Gastroenterology, 14:-214, 1950.

24 Wolf, S., G. B. J. Glass, G. McNeer and L.Bowden: Disturbances in the Secretion ofGastric Mucous Substances in Cancer of theStomach. J. Nat. Cancer Inst., in press.

DIscusSION.-DR. GEORGE B. JERZY GLASS, NewYork, N. Y.: The disturbances in the secretion ofglandular mucoprotein following vagectomy andgastrectomy are of some significance, we believe,

for the interpretation of the hematologic disturb- -ances which may or may not occur after operationson the stomach.

It appears from the data which we have re-678

MERSHEIMER, GLASS, SPEER, WINFIELD AND BOYD Annas of Surgery0 ,1952

Stomach. Bull. New York Acad. Med., 25:459, 1949.

6----: Studies on Dissolved Mucin (Muco-protein) of the Gastric Juice. I. PreliminaryTests and Rationale for a New ColorimetricQuantitative Method for the Determination ofDissolved Gastric Mucin. Rev. Gastroen-terol., 15: 396, 1948.. Studies on Dissolved Mucin (Muco-protein) of the Gastric Juice. II. A NewQuantitative Colorimetric Method for theDetermination of Total Dissohied GastricMucin. Rev. Gastroenterol., -15: 511, 1948.

8 Studies on Dissolved Mucin of theGastric Juice. IV. Relationship of the Mu-coid of the Visible Gastric Mucus, its SplitProducts, and the Salivary Mucin to theDissolved Gastric Mucoproteose and Muco-protein of the Gastric Juice. Bull. New YorkM. Coll. Flower & Fifth Ave. Hosps., 12:1, 1949.._----- A Study of the Alleged Deficiencyof Gastric Mucin in the Stomach of Humanswith Peptic Ulcer. Gastroenterology, 16: 697,1950.

10 ------: The Three Main Components of theHuman Gastric Mucin: Dissolved Mucopro-teose, Dissolved Mucoprotein, and Mucoidof the Gastric Visible Mucus. Part I. Differ-entiation; Some Physical and ChemicalCharacteristics; Classification. Part II. Meth-od for Separation and Quantitative Deter-mination of Each Mucous -Component of theGastric Juice. Part III. Preliminary Data onPhysiological and Clinical Significance ofSeparate Quantitative Determination of theDissolved Mucoproteose and Dissolved Mu-coprotein in the Gastric Juice of Man. Gas-troenterology, 12: 821, 1949.

Glass, G. B. J., L. J. Boyd, A. Heisler and I. J.Drekter: Studies on Dissolved Mucin of theGastric Juice. III. Heterogeneity of the Gas-tric Dissolved Mucin and Its Differentiationand Separation into Two Main Fractions:Dissolved Mucoproteose and Dissolved Mu-coprotein. Bull. New York M. Coll. Flower&.Fifth Ave. Hosps., 11: 8, 1948.

12 Glass, G. B. J., W.L. Mersheimer and C. S. Svi-gals: Effect of Vagotomy and Subtotal GastricResection on the Secretion of Mucin in theHuman Stomach' Arch. Surg., 62: 658, 1951.

13 Glass, G. B. J., L. J. Boyd, M. A. Rubinstein

and C. S. Svigals: Relationship of GlandularMucoprotein from Human Gastric Juice toCastle's Intrinsic Anti-anemic Factor. Sci-ence, 115: 101, 1952.

14 Glass, G. B. J., L. J. Boyd and C. S. Svigals:The Absence of Glandular Mucoprotein andthe Presence of Mucoproteose from SurfaceEpithelium in the Gastric Juice of Patientswith- Pernicious Anemia. Bull. N. Y. Med.Coll. Flower & Fifth Ave. Hosps., 13: 15,1950.

15 Glass, G. B. J., and S. Wolf: Hormonal Media-tion in Nervous Mechanism of Gastric AcidSecretion in Humans. Proc. Soc. Exper. Biol.& Med., 73: 535, 1950.

16 Hollander, F.: Insulin Test for Presence of In-tact Nerve Fibers after Vagal Operations forPeptic Ulcer. Gastroenterology, 7: 607, 1946.

17------: Laboratory Procedures in the Studyof Vagotomy (with Particular Reference tothe Insulin Test). Gastroenterology, 11:419, 1948.

18 Jemerin, E. E., F. Hollander and V. A. Wein-stein: A Comparison of Insulin and Food asStimuli for the Differentiation of Vagal andNonvagal Gastric Pouches. Gastroenterology,1: 500, 1943.

19 Jennings, M. A., and H. W. Florey: The In-fluence of the Vagus on the Secretion ofMucus by the Stomach. Quart. J. Exper.Physiol., 30: 329, 1940.

20 Morton, G; M., and G. W. Stavraky: A Histo-physiological Study of the Effect of Intra-arterial Injection of Acetylcholine Upon theGastric Mucosa of the Dog. Gastroenter-ology, 12: 800, 1949.

21 Pugh, B. L., G. B. J. Glass and S. Wolf: Electro-phoretic Studies of the Mucin Fractions fromthe Human Gastric Juice. Proc. Soc. Exper.Biol. & Med., 79: 674, 1952.

22 Wangensteen, 0. H.: Discussion. S'urgicalForum 36th Clin. Congress, Am. Coll. Surg.,Boston, Mass., 1950.

23 Weinstein, V. A., F. Hollander, F. V. Lauberand R. Colp.: Correlation of Insulin TestStudies and Clinical Results -in a Series ofPeptic Ulcer Cases Treated by Vagotomy.Gastroenterology, 14:-214, 1950.

24 Wolf, S., G. B. J. Glass, G. McNeer and L.Bowden: Disturbances in the Secretion ofGastric Mucous Substances in Cancer of the'Stomach. J. Nat. Cancer Inst., in press.

DIscusSION.-DR. GEORGE B. JERZY GLASS, NewYork, N. Y.: The disturbances in the secretion ofglandular mucoprotein following vagectomy andgastrectomy are of some significance, we believe,

for the interpretation of the hematologic disturb- -ances which may or may not occur after operationson the stomach.

It appears from the data which we have re-678


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