"The man who made Peekskill famous": Dr. C.R. Johnston--first blind chiropractor.

Can a blind person be taught the art and science of chiropractic? If so, can a blind chiropractor be successful in practice? In 1918, Charles Robinson "C.R." Johnston, at the age of thirty-nine, was graduated from the Palmer School of Chiropractic--becoming not only the first blind D.C., but also one of the best known and most successful of his era. He practiced for twenty-five years in the small Hudson Valley community of Peekskill, New York, where his reputation as a "miracle healer" attracted hundreds of patients each week. The local press dubbed him "The Man Who Made Peekskill Famous." C.R. Johnston had come a long way from the Nevada mining camp where he was born. Accidentally blinded at age twenty-seven, he achieved notable success as a merchant before seeming to defy logic in choosing to begin again in a controversial new profession. But his attainments in chiropractic became equally inspirational... and the stuff of legend.

Kansas coconuts: legalizing chiropractic in the first state, 1910-1915.

When the Kansas Supreme Court averred that, under existing law, chiropractic was the practice of medicine, the matter was settled. The beleaguered chiropractic profession of that state had two choices: it could risk continued harassment by the medical establishment or seek legislation. In a small frontier town in western Kansas, a benchmark trial would clearly demonstrate the public's feeling about chiropractic's right to exist on its own merits, separate and distinct from medicine. That coveted goal seemed to have been achieved by passage of the Chiropractic Act of 1913, the world's first such law. However, a board of examiners could not be legally seated. It would be a combination of brilliant legal strategy on the part of the chiropractors and the medical board's own negligence that would end the dilemma, allowing licensure in Kansas by 1915.

Effect of current direction and K+ on polarization of the frog gastric mucosa proton pump.

When current was sent from serosa (S) to mucosa (M) across the frog stomach, there was a polarization (POL) of the open circuit potential (OCPD). POL was not affected by NaCl-free solutions, but was decreased by inhibitors of the H+ pump. In present experiments, current was sent to clamp the PD (VC) across the mucosa in steps of 20 mV up to 100 mV below the control OCPD, that is, current was sent from M to S. All experiments were performed in NaCl-free solutions. The POL was expressed as a % of the difference between the VC PD and the control OCPD. In 4 mM K+ control solutions, the POL was 11.8%; with 10(-3) M omeprazole (H+/K+ pump inhibitor), 1.1; with 10(-5) M SCH 28080 (H+/K+ pump inhibitor), 3.6; with 10(-3) M famotidine (H2 blocker), 1.6; and with 10(-2) M SCN-, 25.4 (inhibition of H+ sec, but not of the pump); in 79 mM K+ control solutions, 26.2; with 10(-3) M omeprazole, 4.2; with 10(-5) M SCH 28080, 15.9; with 10(-3) M famotidine, 5.6; and with 10(-2) M SCN-, 29.9. POL was higher in high K+ than in low K+ solutions contrary to what was observed in previous experiments with current sent from S to M. Results are explained on the basis of an electrogenic H+/K(+)-ATPase pump which includes a H+ channel, permeable to K+. With high K+ solutions, K+ is driven through the H+ channel onto the antiporter (ATPase) when current is sent from M to S, resulting in a greater POL of the pump.

Price of dissension: the private wars of Dr. Leo L Spears, 1921-1956.

Anathema to the Denver medical community, favorite of the 1950s-era sensationalist press, Leo Spears and his hospital represented the complexities of chiropratic. A dynamic achiever in the face of adversity, this 1921 Palmer School graduate built the profession's first large hospital complex and had plans for an institution that would have been among the largest healthcare facilities in existence.

Chiropractic goes to Washington: with Dr. Emmett J. Murphy, 1938-1964.

Articulate, urbane, naturally companionable, and always prepared, Dr. Emmett J. Murphy was perfectly suited to the office he created as chiropractic's first full-time national lobbyist. As labor relations director of the National Chiropractic Association from 1938 to 1964, he worked diligently to increase awareness of chiropractic among legislators, the federal bureaucracy, veterans organizations, labor and other groups equally concerned about the affairs of government. Many of his accomplishments, especially for chiropractic students, were pioneering efforts.

Electrogenicity of the frog gastric mucosa proton pump based on polarization responses in the presence of H(+)-secretion inhibitors.

Recently, we have shown that polarization of an electrogenic H+/K(+)-ATPase pump located in the secretory (luminal) membrane of the frog gastric mucosa is the major factor contributing to the increase in open circuit potential difference (OCPD) induced by voltage clamping. While this transmucosal polarization was not affected by removal of Cl- and Na+ and minimally affected by increasing the K+ concentration to 79 mM in both nutrient and secretory solutions, it was markedly reduced by 10(-3) M famotidine (beta blocker) or 10(-4) M omeprazole (H+/K(+)-ATPase inhibitor) in the nutrient solution. In present experiments, the effects of three other inhibitors of H+ secretion were examined, namely, cimetidine (beta blocker), SCH 28,080 (H+/K(+)-ATPase inhibitor) and SCN- (non-specific inhibitor). While cimetidine and SCH 28,080 markedly reduced the polarization induced by voltage clamp, SCN- affected the polarization to a lesser extent. These data further support the electrogenicity of the frog gastric mucosa proton pump and the lack of a direct effect of SCN- on the pump.

Effect of inhibitors of gastric secretion on polarization of gastric potential by voltage clamping.

Voltage clamping across the frog gastric mucosa, nutrient positive to secretory, results in an increase in the open-circuit potential difference (OCPD). The increase in OCPD, or polarization, induced by voltage clamping could be caused by a redistribution of ions across the plasma membrane or by a polarization of pump electromotive forces, such as the Na(+)-K(+)-adenosinetriphosphatase (ATPase) located in the nutrient (serosal) membrane or the proton pump located in the secretory (luminal) membrane. The polarization induced by voltage clamping was not affected by removing Cl- and Na+ or by increasing the K+ concentration to 79 mM but was markedly reduced by placing in the nutrient solution 10(-3) M famotidine or 10(-4) M omeprazole. These data suggest that there is a strong contribution of the proton pump to the polarization induced by voltage clamping with some contribution of ion redistribution and/or the Na(+)-K(+)-ATPase. The data support the electrogenicity of the proton pump.

Effect of amphotericin B and Cl- removal on basolateral membrane K+ conductance in frog corneal epithelium.

Increase in stromal K+ concentration from 4 to 79 mM in an in vitro preparation of the frog cornea, in Cl(-)-free solutions, did not change the apical membrane fractional resistance, fR0, or the transepithelial conductance, gt; it depolarized the intracellular potential, V0, by 38 mV and decreased the short-circuit current, Isc by 2.9 microA/cm2. These changes were similar to those observed for the same increase in stromal K+ in control solutions except for the increase in gt in the latter. When stromal K+ was increased with 10(-5) M amphotericin B, AmB, in the tear solution, fR0 increased by 0.27 in control solutions and by 0.08 in Cl(-)-free solutions; respectively, gt increased by 0.40 and by 0.17 mS/cm2; Isc decreased by 12 and by 11 mS/cm2; V0 depolarized by 9 and by 9.5 mV. These results support the concept that: (i) entrance of Cl- into the cell is responsible in part for the bioelectrical changes observed when stromal K+ is increased; and (ii) AmB decreases the partial K+ conductance in the basolateral membrane of the frog cornea epithelium by a decrease in intracellular K+.

Role of polarization of gastric EMFs in evaluation of contemporary HCl models.

The neutral proton pump (NP) model postulates a neutral exchange of K+ for H+ across the secretory membrane and the electrogenic proton pump (EP) model an electrogenic proton pump. Previous evidence is briefly reviewed and polarization of EMFs by transmucosal voltage clamping (VC) is presented. During VC, open circuit potential difference (PD) (VOC) is obtained by breaking the circuit for 2 s (after dielectric capacitors have discharged). The magnitude of polarization in Cl- media is less than in Cl(-)-free media, presumably due to the high conductance of Cl- paths. The magnitude in Cl(-)-free media is from 35 to 50 mV for a VC of 100 mV (nutrient side positive). The Na+/K(+)-ATPase is not essential because with choline sulphate media polarization is typical. With Cl(-)-free media, VOC versus IH (H+ rate) is exponential but (VC-VOC) versus IH is linear. Polarization on the basis of the NP model would be due to changes in K+ diffusion potentials. However, with 80 mM K+ on both sides (Cl(-)-free media) polarization is typical. We conclude that polarization cannot be due to a change in K+ diffusion potentials but to polarization of the EP model. The problem remains of how to incorporate the important finding of the H+/K(+)-ATPase into a model for the intact tissue.

Microelectrode studies of amphotericin B on Na+ and K+ conductance in bullfrog cornea.

Addition of 10(-5) M amphotericin B to the tear solution of an in vitro preparation of the frog cornea increased the transepithelial conductance, gt, and decreased the apical membrane fractional resistance, f(R0), in the presence or absence of tear Na+ and Cl-. In the presence of tear Na+ and Cl-, amphotericin B increased the short-circuit current, Isc, from 3.9 to 8.8 microA.cm-2 and changed the intracellular potential, V0, from -48.5 to -17.9 mV probably due to a higher increase in the Na+ than in the K+ conductance. In the absence of tear Na+ and Cl-, amphotericin B decreased Isc from 5.5 to about 0 microA.cm-2 due to K+ (and possibly Na+) flux from cell to tear and changed V0 from -35.4 to -63.6 mV due to the increase in conductance of both ions. Increase in the tear K+ from 4 to 79 mM (in exchange for choline), in the presence of amphotericin B and absence of tear Na+ and Cl-, decreased f(R0) from 0.09 to 0.06, increased gt from 0.23 to 0.31 mS, increased Isc from 0.63 to 7.3 microA.cm-2, and changed V0 from -65.5 to -17.3 mV due to the change in EK in the presence of a high conductance in the tear membrane. Similar effects were observed with an increase of tear Na+. Results support the concept that the Na+ conductance opened by amphotericin B in the apical membrane is greater than the K+ conductance. Previously observed transepithelial effects of the ionophore may be explained mostly on the basis of its effect on the apical membrane.

Potential difference responses to nutrient K+, Na+ and Cl- changes with varying nutrient HCO3- in resting frog stomach.

The effects of changes in nutrient concentrations of K+, Na+ and Cl- on the transmucosal potential difference (PD) and resistance were compared for 25 and 5 mM nutrient HCO3- in resting fundus. With 25 mM HCO3-, increase of K+ from 4 to 40 mM, decrease of Na+ from 100 to 10 mM and decrease of Cl- from 81 to 8.1 mM gave, 10 min after the change, delta PD values of -23.2, -15.1 and -21.3 mV, respectively. With 5 mM HCO3-, the same changes in nutrient ion concentration gave delta PD values of -11.9, -9.4 and -10.0 mV, respectively. From these results, in going from 25 to 5 mM HCO3-, it follows that the resistances of the ionic pathways for K+, Na+ and Cl- increased. The anomalous PD response following the increase in nutrient K+ from 4 to 40 mM with 5 mM nutrient HCO3- gave further evidence that the resistance of the simple K+ conductance pathway increased prior to the increase to 40 mM K+. The fact that 2 mM Ba2+ in the 25 mM HCO3- nutrient gave a smaller increase in resistance, compared to the decrease in nutrient HCO3- from 25 to 5 mM, supported the inference that resistances of ion pathways other than that of the K+ pathway increased.

Direct current electrical measurement in epithelia: steady-state and transient analysis.

A method has been presented for the determination of resistance of biological tissues in which the PD response to step currents is determined. The delta PD after the dielectric capacitors are charged, divided by the current, gives the resistance, provided the current density is low enough so that the tissue behaves as a linear-bilateral system. In the gastric mucosa the PD continues to increase after the dielectric capacitors are charged and it is shown that this part of the delta PD is due to polarization of EMFs and should not be used in determining the resistance. It has been shown that (1) resistance measurements have enabled us to demonstrate that during acid secretion there is a neutral mechanism(s) for the movement of HCO3- out of and the entrance of Cl- into the oxyntic cells, (2) the transmucosal resistance varies inversely with the rate of acid secretion, and (3) the low resistance of the secreting frog fundus is due to the low resistance of the lumen-tubular cell pathway--the parallel pathways (the TIC or paracellular and surface cell pathways) have high resistances. The results of both the resistance and PD measurements have recently been analyzed with respect to the problem of whether the proton pump is neutral or electrogenic in the intact tissue.

Potential difference responses to nutrient K+, Cl- and Na+ changes in secreting and resting states of frog stomach.

The effects of changes in nutrient concentrations of K+, Cl- and Na+ on the transmucosal potential difference (PD) and the resistance were compared for secreting fundus and resting fundus of Rana pipiens. Increase of K+ from 4 to 40 mM, decrease of Cl- from 81 to 8.1 mM and decrease of Na+ from 102 to 10 mM gave, 10 min after the change in the secreting fundus, delta PD values of -28.2, -19.8 and -7.5 mV, respectively. In the resting fundus with SCN- inhibition, the same changes in nutrient ion concentration gave delta PD values of -20.1, -17.0 and -10.2 mV, respectively. Changes in Na+ concentration were considered in a set of experiments of high acid secreting stomachs (4 to 6 mu equiv. . h-1 . cm-2). Here, delta PD gave for 10-fold decreases in Na+ concentration in secreting fundus -4.8 mV and in resting fundus with SCN- inhibition -22.6 mV. Omeprazole inhibition gave results quite similar to those with SCN- inhibition. From these results in going from secretion to inhibition, it follows that the increment of K+ conductance if it increased was lower than the increase in NaCl symport conductance since the change in delta PD for K+ decreased and that for Na+ increased. Also HCO3- conductance increased with inhibition. After SCN- inhibition the transmucosal resistance initially increased and later decreased. The decrease can be accounted for by the increase in conductance of the NaCl symport pathway and of the HCO3- pathway.

Primary site of the huge increase in resistance upon inhibition of gastric acid secretion with hypotonic secretory solution.

In summary, in this paper previous as well as some new results are presented for analysis. It has been shown for the in vitro frog gastric mucosa, with secretory solutions hypotonic relative to the nutrient solution, that inhibition of acid secretion produces a large increase in the transmucosal resistance, Rt. We have shown on the basis of electrophysiological findings that the large increase in Rt is due to an increase in the resistance of the pit and tubular lumina and that the primary factor in this increase is a decrease in luminal area. We have shown that the low transmucosal resistance of the fundus (the acid-secreting portion of the stomach) under standard conditions is due to a low resistance of the lumen-tubular (acid-secreting) cell pathway and that the parallel pathways have high resistances. The latter conclusion is important in deciding among the various models for the mechanism of acid secretion. The histological findings are qualitatively predicted by the electrophysiological results. The limitations of present histological techniques for a quantitative determination of the area of the lumina have also been discussed.

Effect of amphotericin B and tear K+ on PD responses to changes in stromal K+ in frog cornea.

Data have been presented in this paper that support the hypothesis that normal or anomalous responses to changes in stromal K+ are a result of the relative conductances of the simple K+ and the (Na+ + K+)-ATPase pathways located in the basolateral membrane of the corneal epithelium. The simple K+ conductance may be changed by changing the tear K+ concentration in the presence of amphotericin B and by the use of Ba2+ in the stromal solution.

Microelectrode studies of potential difference responses to changes in stromal K+ in bullfrog cornea.

The effects of changing stromal K+ were studied using microelectrodes in an in vitro preparation of frog cornea. The intracellular potential (V0) responded in two opposite ways under short-circuit conditions: (1) depolarization (normal response) when stromal K+ was increased from 4 to 20 or to 79 mM, about 30 mV per 10-fold K+ concn. change; (2) a hyperpolarization (anomalous response) of 10 mV maximum when stromal K+ was increased from 0 to 4 mM. The increase from 4 to 20 or 79 mM decreased or even reversed the short-circuit current (Isc). The transepithelial conductance (gt) increased when K+ was increased to 79 mM but no change occurred in the apical membrane fractional resistance (fRo). Increase of stromal K+ from 0 to 4 mM increased Isc and minimally changed gt and fRo. Ouabain (10(-3) M) abolished the anomalous responses, that is, the increases in V0 and Isc when stromal K+ was increased from 0 to 4 mM. These results are interpreted in terms of two K+ conductive pathways in the basolateral membrane of the corneal epithelium, a Nernstian conductance and an electrogenic (Na+ + K+)-ATPase pump transporting more Na+ than K+ ions per cycle. The normal or anomalous potential difference responses to changes in stromal K+ appear to depend on the relative resistance of the two pathways at the time stromal K+ is changed.

Inhibition of acid secretion of fundus of Rana pipiens with a high concentration of potassium on the secretory side.

Inhibition of acid secretion of the frog fundus is generally accompanied by an increase in transmucosal resistance, Rt, and in potential difference, PD (nutrient normally positive). These results are predicted for the intact tissue by an electrogenic proton pump. It has been suggested that the increase in PD with inhibition can also be explained by a neutral proton pump. The latter model postulates a K+ diffusion potential across the secretory (lumen-facing) membrane tending to make the secretory side positive. Upon inhibition, the [K+] in the lumen is assumed to increase, which decreases the diffusion potential, resulting in an increase in the positivity of the nutrient side. To test this theory, we determined the effects of inhibition with a high [K+] on the secretory side. With a high [K+] in the lumina, inhibition would result in only a small change in the ratio of K+ in the cell to that in the lumina, and hence a small change in the diffusion potential. We found, however, that inhibition increased the PD essentially the same as in the controls. With inhibition the resistance also increased with high secretory K+. Elevating the secretory K+ during secretion produced a 44% decrease in Rt indicating a large increase in luminal K+. We conclude that the results are not compatible with the K+ diffusion potential model but are those predicted by the electrogenic concept.

Potential difference responses to secretory K+, Na+ and HCO3- changes in secreting and resting states of frog stomach in Cl(-)-free media.

The effects of changes in secretory concentrations of K+, Na+ and HCO3- on transmucosal potential difference (PD) and resistance in Cl(-)-free (SO4(2-)) solutions were compared for secreting fundus and resting fundus of Rana pipiens. In the resting fundus experiments, histamine was not present in the nutrient solution and cimetidine was primarily used to obtain acid inhibition. Increase of K+ from 4 to 80 mM, decrease of Na+ from 156 to 15.6 mM and decrease of HCO3- from 25 to 5 mM gave, 10 min after the change, in the secreting fundus delta PD values of 39.7, -11.9 and 3.2 mV, respectively. In the resting fundus, 1.5 to 2 h after the addition of cimetidine, the same changes in secretory ion concentration gave delta PD values of 12.2, -5.6 and 1.5 mV, respectively. Replacement of cimetidine with SCN and without histamine yielded a delta PD somewhat lower than that in cimetidine, namely 9 mV for a K+ change from 4 to 80 mM. Subsequent addition of histamine with SCN present gave a delta PD of about 21 mV. The change in PD was attributed to histamine increasing the secretory membrane area, leading to an increase in K+ conductance. Another possibility is that histamine increases the K+ conductance per se.