By David N. Leff
Editor¿s note: Science Scan is a round-up of recently published biotechnology-relatedresearch.
Fetal Surgery Corrects SCID In UteroBy Implanting Killer CellProgenitors
At the University of Brescia, Italy, a team of pediatricians and immunologistsreport successfully treating a male fetus diagnosed with X-linked severecombined immune deficiency (SCID). Their account appears in The Lancetdated Nov. 30, 1996. Its title: “In-utero transplantation of parentalCD34 hematopoietic progenitor cells in a patient with severe combined immunodeficiency(SCIDXI).“
Originally known as the “bubble-boy syndrome,“ this rare diseasecan be cured in a baby born alive only by a transplant of bone-marrow cellsfrom a closely-matched donor, usually a relative. A previous male childborn to the Italian couple in this case had died while awaiting such acompatible bone marrow donor.
In this second pregnancy, the Brescia team injected paternal bone-marrowcells into the fetal peritoneum during the 21st week of gestation. Then,at 38 weeks, on July 22, 1996, “cesarean section delivered a healthy3.6-kilo [8-lb] boy with no clinical or laboratory signs of graft-vs.-hostdisease . . . At the last follow-up, on Nov. 7, 1996, the baby, aged 3.5months, was well.“
“Our report,“ the authors concluded, “should encourageapplication of this method to other inherited disorders.“
PCR Finds Chlamydia Top Sexually Transmitted Disease, Innocent OfSex Discrimination
Macho men used to say scornfully of gonorrhea that “a case of clapis no worse than a bad cold.“ Nowadays, they might equate a genitalchlamydial infection with a slightcold.
In fact, the Chlamydia trachomatisbacterium, for all its low-keyor even silent symptoms, is today the commonest male-to-female sexuallytransmitted disease (STD) pathogen in the U.S. It frequently moves intoboth male and female genital tracts following a cured attack by Neisseriagonorrhoeae.
Reversing common wisdom that men and boys inflict chlamydial infectionon women and girls much more than vice versa, an article in the currentJournal of the American Medical Association (JAMA),dated Dec. 4,1996, reports that the STD is no respecter of gender, but an equal-opportunityinfective agent. The paper¿s title: “Epidemiologic and microbiologiccorrelates of Chlamydia trachomatisinfection in sexual partnership.“
The evidence for this joint indictment, beyond a reasonable doubt, camefrom PCR detection of chlamydial DNA in secretions of men and women withthe infection.
At the National Institute of Health¿s Institute of Allergy and InfectiousDiseases, in Bethesda, Md., first author Thomas Quinn and his colleagues,over a four-year period, tested 958 individuals ¾ 494 couples ¾engaged in heterosexual partnerships. They were patients at two STD clinicsin Baltimore, predominantly young and African-American.
PCR detected chlamydia in 14.2 percent of male subjects, 15.8 percentof females. One out of five couples (20.4 percent) had at least one partnerwith the infection; 10.7 percent two or more.
Cell culture analysis was far less sensitive than PCR, diagnosing theinfection in only 8.5 percent of male participants, 12.9 percent of females.
An estimated 50 million new cases of C. trachomatisinfectionoccur in the world each year, four million of them in the U.S. It afflictsmainly young people: males under 25 years of age; females under 20.
The JAMAarticle reported that 43 percent of infected males and79 percent of infected females had no symptoms at all.
Although symptoms are relatively mild or subclinical compared to thebetter known STDs, gonorrhea and syphilis, chlamydial infection poses athreat to girls and women. It can cause pelvic inflammatory disease (PID),which may lead to infertility and ectopic (outside-the-uterus) pregnancy.And infants carried by chlamydial mothers may be born with conjunctivitis,pneumonia or rhinitis.
PID accounts for an estimated 2.5 million outpatient medical visitsa year in the U.S., at a cost to society of more than $5 billion.
Quinn and his co-authors make the urgent point that “the high rateof infection in sexual partners of individuals who have been routinelyscreened and found to test positive for chlamydia emphasizes the importanceof routine screening, contact tracing and treatment of all sexual partnersand chlamydia-infected individuals.“
Native American Population Models Progression To End-Stage KidneyDisease In Type 2 Diabetics
When the White Man settled Arizona¿s fertile Gila Valley in the mid-1800s,he diverted the river¿s irrigation water from friendly Pima Indians, whohad farmed in the region for a thousand years or more. Today, some 10,000Pimas live on the Gila River Indian reservation, wards of the U.S. government.
Their lifestyle now sedentary, they have the world¿s highest prevalenceof Type 2 (adult-onset, non-insulin-dependent) diabetes, and its attendantpathologies. These include 20 times more end-stage kidney disease thanthe U.S. population at large. (See BioWorld Today April 25, 1995,p. 1.)
A four-year study of 194 Pima patients, reported in the New EnglandJournal of Medicine (NEJM) ated Nov. 28, 1996, found that the bestpredictor of progressive kidney failure in Type 2 diabetics is excretionof protein in their urine. The paper¿s title: “Development and progressionof renal disease in Pima Indians with non-insulin-dependent diabetes mellitus.“
Scientists knew that in people with Type 1 (insulin-dependent, juvenile-onset)diabetes, the amount of blood the kidney filters ¾ the glomerularfiltration rate, or GFR ¾ goes up sharply. Sometimes, the urinecontains albumin, a normal blood protein, in quantity. This proteinuriaadds to the GFR¿s overload, and can lead to kidney failure.
So, investigators suspected that proteinuria rather than high GFR isthe true early warning sign of deteriorating renal function. “We wantedto know,“ said nephrologist Robert Nelson of the National Instituteof Diabetes and Digestive and Kidney Diseases, and senior author of theNEJMpaper, “whether a rise in GFR occurs in Type 2 diabetes,and whether this or albumin in the urine best predicts progressive kidneyfailure.“
The study determined that although GFR can remain elevated for yearsin people with Type 2 disease, it¿s the amount of albumin processed bythe kidney¿s glomerular blood vessels and excreted in the urine that mostreliably forewarns of advancing renal disease. It also reported that thiscourse toward kidney failure in Type 2 diabetes mimics that of Type 1.