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Biomedical subjects

J J Ho

Publications and source records attributed to J J Ho.

63 records · Page 4Linked to original sources

Origin of the decline in pancreatic amylase secretion with time in vitro.

The release of alpha-amylase (EC 3.2.1.1) into the medium bathing strips of rabbit pancreas decreased gradually with time in vitro so that after 3 h of incubation the secretory rate was only 20% of that seen initially. This decrease was not the result of an intrinsic loss of cellular responsiveness or viability, because a cholinergic agonist was still able to augment amylase secretion from the tissue after this incubation period to the same, or greater, degree than from "fresh" tissue. Rather, the inhibition of secretion was apparently due to the release of a nondialyzable substance from the tissue, which appears to be amylase itself. The observations that led to this conclusion are 1) replacing the bathing medium every 30 min eliminated the time-dependent decrease in enzyme secretion, 2) this replacement was ineffective if the tissue was separated from the medium by a dialysis membrane, and 3) adding an excess of the amylase substrate glycogen to the medium also prevented the falloff in amylase secretion, the effect of glycogen presumably being due to the formation of an enzyme-substrate complex in the medium. These observations are consistent with other observations that demonstrate that the rate of enzyme secretion by the pancreas depends on the rate of removal of product from the site of its secretion [Isenman and Rothman, Proc. Natl. Acad. Sci. USA 74: 4068-4072, 1977; Isenman and Rothman, Science 204: 1212-1215, 1979; Ho and Rothman, Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G32-G39, 1982].

Amylases↗

Nature of flow dependence of protein secretion by the exocrine pancreas.

It has been proposed that bidirectional and concentration-dependent fluxes of digestive enzymes across pancreatic acinar cell membranes account for secretion. One implication of such a model is that protein secretion should be a function of fluid outflow, inasmuch as flow would be required to generate the necessary concentration gradient by carrying away secreted material. In an earlier study (Science 204: 1212, 1979) when fluid flow was decreased by a backpressure applied to fluid in the pancreatic duct, proportional reductions in protein secretion occurred. The present study uses metabolic rather than mechanophysical methods to decrease flow, reduction of the sodium concentration of the medium bathing the pancreas, or addition of the Na+-K+-ATPase inhibitor ouabain. Both treatments produced similar results: decreases in protein output synchronous with and proportional to the observed decreases in flow. Essentially the same relationship was seen when flow was reduced during protein secretion augmented by the secretagogue cholecystokinin-pancreozymin. These results suggest that the reduction in flow rate (whether produced mechanically or chemically) was the variable directly responsible for the decrease in protein secretion by the acinar cell.

Animals↗

Hydrolysis of the hen egg vitelline membrane by cock sperm acrosin and other enzymes.

A technique utilizing Pregnant Mare's Serum Gonadotropin and Human Chorionic Gonadotropin treatment of hens (Gallus domesticus), followed by manual ovulation of the excised follicles, was developed to obtain a large number of mature ova. The intact ova were used to test whether acrosin, partially purified from the spermatozoa of the cock (Gallus domesticus), partially purified rabbit testicular acrosin and commercial preparations of several hydrolytic enzymes could dissolve the inner vitelline membrane. Enzymes were applied to pieces of filter paper placed on the ovum. Cock acrosin and endopeptidases such as trypsin, chymotrypsin, collagenase and elastase hydrolyzed the membrane whereas exopeptidases such as leucine aminopeptidase and carboxypeptidase A did not. Phospholipase A, sulfatase, hyaluronidase, beta-glucuronidase and rabbit testicular acrosin also failed to hydrolyze the membrane. Cock acrosin hydrolysis of the ovum surface was inhibited by soybean trypsin inhibitor. The surface of the ovum over the germinal disc region was hydrolyzed more quickly by cock acrosin than the surface over other regions of the ovum. Acrosin from cock sperm caused the release of trichloroacetic acid soluble material absorbing at 280 nm from sonicated preparations of inner vitelline membranes. Hydrolysis was greatest at pH 8.0 and was inhibited by soybean trypsin inhibitor.

Acrosin↗

A population-based study of birth defects in Malaysia.

Birth defects are one of the leading causes of paediatric disability and mortality in developed and developing countries. Data on birth defects from population-based studies originating from developing countries are lacking. One of the objectives of this study was to determine the epidemiology of major birth defects in births during the perinatal period in Kinta district, Perak, Malaysia over a 14-month period, using a population-based birth defect register. There were 253 babies with major birth defects in 17,720 births, giving an incidence of 14.3/1000 births, a birth prevalence of 1 in 70. There were 80 babies with multiple birth defects and 173 with isolated birth defects. The exact syndromic diagnosis of the babies with multiple birth defects could not be identified in 18 (22.5%) babies. The main organ systems involved in the isolated birth defects were cardiovascular (13.8%), cleft lip and palate (11.9%), clubfeet (9.1%), central nervous system (CNS) (including neural tube defects) (7.9%), musculoskeletal (5.5%) and gastrointestinal systems (4.7%), and hydrops fetalis (4.3%). The babies with major birth defects were associated with lower birth weights, premature deliveries, higher Caesarean section rates, prolonged hospitalization and increased specialist care. Among the cohort of babies with major birth defects, the mortality rate was 25.2% during the perinatal period. Mothers with affected babies were associated with advanced maternal age, birth defects themselves or their relatives but not in their other offspring, and significantly higher rates of previous abortions. The consanguinity rate of 2.4% was twice that of the control population. It is concluded that a birth defects register is needed to monitor these developments and future interventional trials are needed to reduce birth defects in Malaysia.

Case-Control Studies↗

Radioimmunotherapy of orthotopically transplanted pancreatic cancer with 131I-labeled chimeric monoclonal antibody Nd2.

Recombinant mouse/human chimeric antibody Nd2 was previously reported to have the same specificity and reactivity against pancreatic cancer as murine Nd2 without HAMA production which induced serious problems in clinical application. We established orthotopic SW1990 transplanted mice to represent the progression of pancreatic cancer. We examined anti-tumor effect of 131I-labeled chimeric Nd2 in an orthotopic transplant model. 131I-labeled chimeric Nd2 inhibited the growth of orthotopically transplanted tumors and extended the survival time of the mice. These results suggest that 131I-labeled chimeric Nd2 has high clinical applicability in the therapy of pancreatic cancer.

Animals↗