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Biomedical subjects

J W Johnson

Publications and source records attributed to J W Johnson.

At least 19 recordsLinked to original sources

Excessive maternal weight and pregnancy outcome.

OBJECTIVES: This study was undertaken to determine the influences of increased maternal prepregnancy weight and increased gestational weight gain on pregnancy outcome. STUDY DESIGN: This was a longitudinal retrospective study of 7407 term pregnancies delivered from 1987 through 1989. After excluding cases with multiple fetuses, stillbirths, fetal anomalies, no prenatal care, selected medical and surgical complications, and those with incomplete medical records, 3191 cases remained for analyses by determination of odds ratios for obstetric outcomes, by chi 2 tests for significant differences and by adjustment for risk factors with stepwise logistic regression. RESULTS: Both increased maternal prepregnancy weight (body mass index) and increased maternal gestational weight gain were associated with increased risks of fetal macrosomia (p less than 0.0001), labor abnormalities (p less than 0.0001), postdatism (p = 0.002), meconium staining (p less than 0.001), and unscheduled cesarean sections (p less than 0.0001). They were also associated with decreased frequencies of low birth weight (p less than 0.001). The magnitude of the last was less than that of the other outcomes. CONCLUSIONS: Increased maternal weight gain in pregnancy results in higher frequencies of fetal macrosomia, which in turn lead to increased rates of cesarean section and other major maternal and fetal complications. Because these costs of increased maternal weight gain appear to outweigh benefits, weight gain recommendations for pregnancy warrant careful review.

Apgar Score

131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma.

Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.

3-Iodobenzylguanidine

Equilibrium and kinetic study of glycine action on the N-methyl-D-aspartate receptor in cultured mouse brain neurons.

1. The characteristics of the activation of the N-methyl-D-aspartate (NMDA) response by glycine were studied using whole-cell and outside-out patch clamp recording techniques. 2. Glycine concentration-response (C-R) curves were measured in the presence of 10 microM-NMDA and fitted with the Hill equation modified to account for the response to NMDA observed in the absence of added glycine. The mean value of the apparent dissociation constant (KD) was 150 nM, and the mean value of the Hill coefficient (nH) was 1.1. When the KD was corrected for the concentration of contaminating glycine in nominally glycine-free solutions, estimated assuming that there is no response in the absence of glycine, the value was 130 nM. 3. The question of how many glycine binding sites there are on each NMDA receptor-channel complex was addressed by examining the curvature at the foot of the glycine C-R curve. An equation that allowed estimation of both the concentration of contaminating glycine and of the value of nH was fitted to glycine C-R data up to 50 nM. The mean value of nH was found to be 1.0, consistent with the idea that there is one glycine binding site. 4. The kinetics of the interaction of glycine with the NMDA receptor were measured by fitting single exponential curves to the current relaxation following a jump in glycine concentration in the presence of 10 microM-NMDA. The plot of the inverse of the relaxation time constant as a function of glycine concentration after the concentration jump was linear. The association rate constant was estimated from these data as 1.2 x 10(7) M-1 s-1 and the dissociation rate as 1.0 s-1. 5. Experiments were devised to allow the evaluation of the KD and dissociation rates of glycine in the absence of NMDA. They led to a value for KD of 80 nM, slightly but significantly lower than the value of 150 nM estimated in the presence of 10 microM-NMDA. The glycine dissociation rate in the absence of NMDA was found to be 0.7 s-1, not significantly different from that measured in the presence of 10 microM-NMDA. 6. The results are consistent with a model of the NMDA receptor with a single glycine binding site. The characteristics of glycine binding are similar in the absence and the presence of 10 microM-NMDA, although NMDA binding may cause a small increase in the glycine KD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reproduction in the older gravida. A literature review.

Infertility, spontaneous abortions and trisomic anomalies increase with maternal age, as do ectopic pregnancy, low birth weight, macrosomia, abruptio placentae and labor dysfunction. However, those phenomena are multifactorial in origin and cannot be ascribed solely to advancing age. Older pregnant women are also at increased risk for diabetes and hypertension. Whereas the older gravida is at increased risk for maternal mortality and morbidity and for fetal and infant mortality, those problems are explainable in large part by coexisting medical complications. The healthy older pregnant woman who receives appropriate prepregnancy counseling and up-to-date perinatal care can achieve results comparable to those achieved by younger ones.

Abortion, Spontaneous

Giant adult malignant sacrococcygeal teratoma. Successful treatment by combined abdominosacral resection.

This report describes the successful removal of the largest adult sacrococcygeal teratoma (18.75 kg) the authors could find on record. The patient was 58 years of age. The tumor had been present at birth and had been biopsied at the time of her cesarean section 34 years earlier without further treatment. Special planning was necessary for moving and positioning the patient for operation to prevent injury due to the size and weight of the tumor. A combined abdominosacral resection with preliminary ligation of the internal iliac arteries and a diversionary colostomy were performed without difficulty or undue blood loss. The defect was closed primarily and drained. The tumor proved to be malignant on pathologic examination.

Adenocarcinoma

Lymphoscintigraphy in melanoma: initial evaluation of a low protein dose monoclonal antibody cocktail.

A low protein dose (73 +/- 10 micrograms total) 131I-labeled monoclonal antibody cocktail made of equal microgram quantities of 225.28S (IgG2a) and 763.24T (IgG1) murine monoclonal antibodies, which bind additively to a high molecular weight antigen of melanoma, was evaluated as a lymphoscintigraphic agent in 17 patients with intermediate to thick (mean Breslow depth, 3.39 +/- 0.64 mm) melanomas or clinical Stage II disease scheduled for nodal dissection. Eleven of the patients were clinically Stage I while 6 were clinically Stage II. 131I antibody cocktail, 258 +/- 10 microCi, was administered s.c. at the site of the primary melanoma or its scar following surgical removal. In eight patients, 63 +/- 8 microCi of 125I nonspecific normal sheep IgG was coadministered s.c. Gamma camera imaging was conducted beginning immediately after and continuing for several days following injection. Surgical resection, weighing, and gamma counting of the draining lymph nodes were undertaken in all patients. On gamma scans, early nodal uptake of antibody was most pronounced and of longest duration in the tumor pathologically positive patients (5 of 7 had visible nodal uptake, 4 of 7 visually stable or rising with time), with the t 1/2 of nodal clearance by gamma scan significantly (P less than 0.05) longer than in the negative patients in whom 4 of 10 showed some, although generally transient (0 of 10 stable or rising), nodal uptake. Scans were not easily interpretable when the injection site was very near the draining nodal group, in part due to the detection of scatter activity from the injection site. In several instances the scan was correct and the clinical examination was incorrect as regards nodal disease. Quantitative analysis of the surgically excised draining nodes showed significantly (P less than 0.001) more 131I anti-melanoma antibody uptake in the 21 tumor-involved nodes [0.01217% injected dose (ID)/node median] than in the 512 tumor-negative nodes (0.00051% ID/node median). Median percentage ID/g of anti-melanoma antibody in tumor-involved nodes was significantly greater (P less than 0.01) than in tumor-negative nodes (0.01984 versus 0.003215% ID/g). 125I-labeled nonspecific antibody did not accumulate significantly more in the tumor-involved nodes on a per node or per g basis in the 283 of 533 nodes studied using the dual-label approach (0.0036 versus 0.00092% ID/g). These data demonstrate that by external imaging and by tissue counting that a radiolabeled anti-melanoma monoclonal antibody cocktail can specifically accumulate to melanoma-involved lymph nodes following s.c. administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

The case for routine umbilical blood acid-base studies at delivery.

One of the major goals of obstetricians is to prevent fetal asphyxia. Unfortunately, the commonly used clinical indicators (fetal heart rate monitoring, meconium staining of the amniotic fluid, and Apgar scores) do not have acceptable accuracy in establishing the presence of fetal asphyxia. These subjective assessments often overdiagnose fetal asphyxia and on occasion may fail to detect its presence. The only scientific, objective means of diagnosing fetal asphyxia at delivery is through umbilical blood acid-base studies. This test is convenient, noninvasive, and accurate. The routine use of umbilical blood acid-base studies is a major asset to the obstetric team in determining (1) the presence of asphyxia and its consequences, (2) the efficacy of interventions to prevent fetal asphyxia, and (3) the mechanisms responsible for fetal acidosis.

Acid-Base Equilibrium

Cases with ruptured membranes that "reseal".

Among patients with a diagnosis of preterm prepartal rupture of the membranes, an occasional case ceases to leak amniotic fluid before the onset of labor. The purpose of this case-control study was to determine the characteristics and obstetric outcomes of this unique group of patients. This diagnosis was made in 24 such patients who gave birth in 1984 and 1985 at Shands Hospital. Compared with matched control subjects who continued to leak fluid, there were no significant differences in maternal race, age, marital status, socioeconomic status, smoking status, or past obstetric performance. Amniotic fluid volumes, as assessed by ultrasound studies, were less in the group that failed to "reseal." The "reseal" group had longer durations of pregnancy, larger babies, longer maternal hospitalization, less neonatal hospitalization, and less perinatal mortality and morbidity. The occurrence of "resealing" appears to bode well for the mother and infant. Such cases should be sought aggressively but managed conservatively.

Adult

Pelvic lymphadenectomy for staging clinically localized prostate cancer. Indications, complications, and results in 217 cases.

We reviewed the findings of 217 consecutive pelvic lymphadenectomies performed in patients with clinically localized prostatic carcinoma focusing particular attention on the importance of completely removing the hypogastric lymph nodes and on the operative complications associated with a more extensive dissection. Metastatic disease was identified in the lymph nodes of 127 patients (58.6%). The hypogastric nodes were involved in two thirds of the patients with lymph node metastases, and in 29 percent the hypogastric nodes were the only site of metastasis. No increased operative morbidity was documented as a result of extending the level of the pelvic lymphadenectomy to include the lower hypogastric nodes. We conclude that although the lower hypogastric lymph nodes have not been routinely included in most pelvic lymphadenectomies, their removal is important in detecting metastases.

Adenocarcinoma

Purification of bovine trophoblast protein-1 complex and quantification of its microheterogeneous variants as affected by culture conditions.

The bovine trophoblast protein-1 complex (bTP-1) is a group of glycosylated interferon-alpha 11, molecules secreted by the bovine conceptus that plays a critical role in preventing luteolysis during early pregnancy. In the current studies, secretion of individual variant forms of bTP-1 was quantified under a variety of culture conditions that could affect yields of bTP-1 for preparative-scale production of bTP-1. Additionally, a purification scheme for bTP-1 was developed. Conceptuses from Day 17 produced 13 proteins in the molecular weight and pI range characteristic of bTP-1, with 4-5 isoforms (pI = 5.6-6.6) at each of three molecular weight classes (21, 23.2 and 25.8 kDa). The major forms of bTP-1 were two variants of 23.2 kDa having pIs of 6.2 and 6.6. The relative proportion of bTP-1 variants was generally unaffected by culture conditions. Cultured conceptuses secreted bTP-1 at a sustained rate for 3 days and gaseous environment was without major effect on bTP-1 secretion. Conceptuses from superovulated cows also produced bTP-1 at Day 17 of pregnancy, suggesting that superovulation might be a useful method for increasing total bTP-1 yield per cow. The purification scheme that was developed utilized ultrafiltration with Centricon devices to achieve rapid molecular weight fractionation, desalting and concentration of conceptus secretory proteins prior to purification of bTP-1 using anion-exchange and gel filtration HPLC. The resultant preparation of bTP-1 included 9 variant forms of bTP-1 as well as a slight amount of a 45-kDa contaminant. Purified bTP-1 possessed antiviral activity but the specific activity was apparently reduced when conceptus-conditioned medium used for purification was stored for prolonged periods.

Animals

Glycine-insensitive desensitization of NMDA responses in cultured mouse embryonic neurons.

The influence of glycine on the desensitization of NMDA-induced currents was studied using cultured embryonic mouse neurons. Although glycine often appeared to reduce desensitization in the whole-cell mode, it had no effect on desensitization in outside-out patches. Various interpretations can be proposed for this discrepancy, such as the presence in intact cells of an intracellular factor regulating desensitization, or the masking of desensitization in intact cells by restricted diffusion of the agonist in the extracellular space. The fact that glycine potentiates the NMDA responses under conditions where it does not regulate desensitization indicates that the potentiation cannot be explained by a reduction of desensitization.

Animals

Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels.

The N-methyl-D-aspartate (NMDA)-activated channel, which is known to be blocked by extracellular Mg ions, is shown also to be blocked by intracellular Mg ions. The block by intracellular Mg can be explained by assuming that Mg ions from the intracellular side enter the membrane electrical field before binding to the blocking site. The dissociation constant of the binding site for intracellular Mg is 8 mM at 0 mV, which is close to the value previously calculated for the extracellular Mg blocking site. The unbinding rates of intracellular and extracellular Mg are different, and their effects are additive, suggesting that the corresponding binding sites are distinct. Both blocks occur at physiological concentrations of Mg, making the NMDA-activated channel a bidirectional rectifier.

Animals

Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor.

1. Kynurenate (Kyn), 7-chlorokynurenate (7-Cl-Kyn), 3-amino-1-hydroxypyrrolid-2-one (HA-966) and D-cycloserine are known to bind to the glycine site that modulates the N-methyl-D-aspartate (NMDA) response of vertebrate central neurones. The effects of these compounds were investigated with patch-clamp and fast-perfusion techniques on mouse cortical neurones in primary culture in an effort to establish whether they act as antagonists, partial agonists and/or inverse agonists of glycine. A fast drug application method allowed the study of both steady-state and transient responses. 2. The analysis of steady-state responses indicates that the main effects of Kyn and 7-Cl-Kyn are those expected from competitive antagonists of glycine, with a dissociation constant of 15 microM for Kyn, and of 0.3 microM for 7-Cl-Kyn. Concentration jumps indicate that at all concentrations of glycine, and in particular in the absence of added glycine, the blockade by Kyn and 7-Cl-Kyn develops at a rate which is close to the rate of dissociation of glycine from its binding site and is independent of antagonist concentration. 3. The main effects of D-cycloserine and of HA-966 are those of partial agonists of high and low efficacy, respectively. In the absence of added glycine, D-cycloserine always produced a potentiation, while HA-966 produced either a potentiation or an inhibition. This can be explained by assuming the presence of a variable level of contaminating glycine. With both D-cycloserine and HA-966, concentration jumps produced biphasic relaxations in which the onset rate of the slow component was, here again, close to the rate of dissociation of glycine from its binding site. 4. These results can be interpreted by assuming that (1) Kyn and 7-Cl-Kyn are competitive antagonists of glycine, (2) HA-966 and D-cycloserine are partial agonists, (3) in the absence of added glycine some glycine is present in the extracellular solution and (4) the response in the total absence of glycine is very small or negligible.

Action Potentials

Measurement of nonuniform current densities and current kinetics in Aplysia neurons using a large patch method.

A large patch electrode was used to measure local currents from the cell bodies of Aplysia neurons that were voltage-clamped by a two-microelectrode method. Patch currents recorded at the soma cap, antipodal to the origin of the axon, and whole-cell currents were recorded simultaneously and normalized to membrane capacitance. The patch electrode could be reused and moved to different locations which allowed currents from adjacent patches on a single cell to be compared. The results show that the current density at the soma cap is smaller than the average current density in the cell body for three components of membrane current: the inward Na current (INa), the delayed outward current (Iout), and the transient outward current (IA). Of these three classes of ionic currents, IA is found to reach the highest relative density at the soma cap. Current density varies between adjacent patches on the same cell, suggesting that ion channels occur in clusters. The kinetics of Iout, and on rare occasions IA, were also found to vary between patches. Possible sources of error inherent to this combination of voltage clamp techniques were identified and the maximum amplitudes of the errors estimated. Procedures necessary to reduce errors to acceptable levels are described in an appendix.

Action Potentials

Binding of liposomes to human bladder tumor epithelial cell lines: implications for an intravesical drug delivery system for the treatment of bladder cancer.

Present therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether liposomes can bind to human bladder cancer cells and thereby provide a mechanism to improve the delivery of anticancer agents to diseased urothelium. Negatively charged large multilamellar vesicles (MLVs) bound to four different human bladder tumor cell lines (253J, J82, T24, TCCSUP) more avidly than did small sonicated vesicles or vesicles consisting of uncharged phosphatidylcholine (PC). Of the three types of negatively charged MLVs tested, phosphatidylcholine/phosphatidylserine (7:3, mol ratio) (PC/PS) MLVs bound the most. MLV binding to tumor cells was saturable and appeared to be specific. In contrast, the binding of liposomes to normal fetal bladder cells was minimal. These data suggest that targeting of drugs to superficial bladder cancer can be achieved by the intravesical administration of PC/PS MLV.

Drug Carriers

Intrauterine infusion of highly enriched bovine trophoblast protein-1 complex exerts an antiluteolytic effect to extend corpus luteum lifespan in cyclic cattle.

Intrauterine infusion of enriched bovine trophoblast protein-1 complex (bTP-1) resulted in extension of interoestrous intervals and corpus luteum function in cyclic cattle. Conceptus proteins were obtained by culture of Day 17-18 conceptuses for 72 h. Media from the first (n = 28), second (n = 26) and third (n = 19) 24 h of conceptus incubations were utilized. A highly enriched preparation of bTP-1 was obtained by a combination of ammonium sulphate precipitation, ion-exchange chromatography, and h.p.l.c. gel filtration. Degree of purity of the final preparation was confirmed by gel electrophoresis and immunoblotting with antiserum to ovine trophoblast protein-1. Jersey cattle (3 per group) received intrauterine infusions, twice daily from Day 15.5 to 21.0, of bovine serum albumin, the entire array of bovine conceptus secretory proteins (bCSP) from the 3 days of conceptus culture, or bTP-1. Infusions were via a catheter into the uterine horn ipsilateral to the corpus luteum. Oestrous cycle length in bTP-1-treated cows (26.1 +/- 1.3 days) was greater than for cows given BSA (19.5 +/- 1.3 days) or bCSP (21.5 +/- 1.3 days). Similarly, progesterone concentrations in serum remained elevated for a longer period of time for bTP-1-treated cows than for cows treated with BSA or bCSP. Residual variance associated with vena cava concentrations of PGF-2 alpha at Days 19-21 after oestrus (which included the variance between 15-min periods within cows) was reduced in cows treated with bTP-1 as compared to other groups. Lack of a bCSP effect may have been due to low amounts of bTP-1 in conceptus-conditioned medium from cultures of greater than 24 h. None the less, purified bTP-1 was effective in extending luteal function and appears to be the antiluteolytic agent of early pregnancy.

Animals

Toxicity from treatment of neuroblastoma with 131I-meta-iodobenzylguanidine.

Toxic effects from 131I-meta-iodobenzylguanidine (131I-MIBG) treatments of neuroblastoma in six patients were recorded. The toxicity was largely confined to the hematologic system where circulating leukocytes and platelets regularly declined after each dose of 131I-MIBG; the values reached nadirs between three and seven weeks and recovered slowly over subsequent weeks. Prior bone marrow transplantation and infiltration of bone marrow by neuroblastoma appeared to make the hematologic system more vulnerable to the radiation. Dosimetry revealed greater absorbed radiation by the whole body than by the blood and bone marrow. These observations are explained by a relatively rapid exit of 131I-MIBG from the blood to other tissues (but not to the bone marrow). Since treatment of an aggressive and lethal tumor such as neuroblastoma should be pushed to a degree of toxicity, careful dosimetry in each case will be necessary as a guide to reach the point of maximally tolerable toxicity.

3-Iodobenzylguanidine